Hemato-Oncology Trials: AOP Health Presents New Results at Top Congress ASH




Hemato-Oncology Trials: AOP Health Presents New Results at Top Congress ASH

VIENNA–(BUSINESS WIRE)–#AOPHealth—AOP Health continues to advance its clinical research program in myeloproliferative neoplasms, a special group of rare blood cancers. The company, specialized in rare diseases, presented the results of two scientific investigations at the 67^th American Society of Hematology Association (ASH) Annual Meeting 2025 held in Orlando, FL, USA. The results provide new insights in treatment strategies.

ROP-ET and BESREMI PASS

One of the clinical studies, ROP-ET, examined the use of ropeginterferon alfa-2b in people with essential thrombocythemia (ET), a disease in which the body produces too many platelets. The trial, a prospective, multicenter, single-arm phase III study, investigated the safety and efficacy of ropeginterferon alfa-2b in ET patients unable to receive available cytoreductive therapies¹.

The other investigation, the BESREMi-PASS study, looked at how the medicine performs in everyday clinical practice among people with polycythemia vera (PV). PV is a rare cancer of the blood-building stem cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets.

Solutions for unmet medical need

Both studies provide new insights into how ropeginterferon alfa-2b may help people living with these chronic blood cancers.

Martin Steinhart, CEO of AOP Health, concludes: “AOP Health was founded to address unmet patient needs in rare indications. Our continued investment in research and development is a testament to that commitment, resulting in new findings that we are now proud to share with the scientific community at ASH.”

About Ropeginterferon alfa-2b

Ropeginterferon alfa-2b is the first interferon approved for polycythemia vera, a myelo­proliferative neoplasm (MPN), indicated in the European Union as monotherapy in adults for treatment of polycythaemia vera without symptomatic enlarged spleen.

Ropeginterferon alfa-2b is a long-acting, mono-pegylated proline interferon (ATC L03AB15). It is administered once every 2 weeks initially, or up to every 4 weeks after stabilization of blood values. It is designed to be self-administered subcutaneously with a pre-filled pen.

About AOP Health

AOP Health is a global enterprise group with roots in Austria, where the headquarters of AOP Orphan Pharmaceuticals GmbH (“AOP Health”) is located. Since 1996, the AOP Health Group has been dedicated to developing innovative solutions to address unmet medical needs, particularly in the fields of rare diseases and intensive care medicine. The group has established itself internationally as a pioneer in integrated therapy solutions and operates worldwide through subsidiaries, representations, and a strong network of partners. With the claim “Needs. Science. Trust.” the AOP Health Group emphasizes its commitment to research and development, as well as the importance of building relationships with physicians and patient advocacy groups to ensure that the needs of these stakeholders are reflected in all aspects of the company’s actions. (aop-health.com)

¹ Kiladjian JJ, Marin FF, Al-Ali HK, et al. ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options. Annals of Hematology. 2024 Mar 4:1-2.

Needs. Science. Trust.

AOP Orphan Pharmaceuticals GmbH

Member of the AOP Health Group

Contacts

Further inquiry

DI Isolde Fally

Isolde.Fally@aop-health.com
+43-676-500 4048

Incyte Announces New Positive Data for INCA033989, its First-In-Class mutCALR-Targeted Monoclonal Antibody, in Patients with Myelofibrosis Presented at ASH 2025




Incyte Announces New Positive Data for INCA033989, its First-In-Class mutCALR-Targeted Monoclonal Antibody, in Patients with Myelofibrosis Presented at ASH 2025

• Rapid and robust reductions in spleen volume and symptoms, and improvements in anemia were observed with INCA033989 as monotherapy and in combination with ruxolitinib (Jakafi^®) in patients with myelofibrosis (MF) harboring a CALR mutation (mutCALR)
• Results demonstrate a favorable safety profile for INCA033989 as a monotherapy and in combination with ruxolitinib – no dose limiting toxicities were reported and a maximum tolerated dose was not reached
• A reduction in peripheral blood mutCALR variant allele frequency (VAF) from baseline was observed in MF patients in the INCA033989 monotherapy arm with ≥1 post-baseline VAF measurement
• Exploratory analyses from the clinical studies of INCA033989 demonstrate the potential for disease-modifying activity in MF patients with a CALR mutation
• Incyte will host an investor event and webcast highlighting these data today, Sunday, December 7, 2025, from 11:00 a.m.-12:30 p.m. ET

WILMINGTON, Del.–(BUSINESS WIRE)–$INCY #ASH2025–Incyte (Nasdaq:INCY) today announced new clinical data from two Phase 1 studies evaluating the safety, tolerability and efficacy of INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, for patients with mutCALR-expressing myeloproliferative neoplasms (MPNs). These preliminary results are from the dose escalation portion of the studies evaluating INCA033989 as a monotherapy in patients with myelofibrosis (MF) harboring a CALR mutation who are resistant, intolerant to or ineligible for JAK inhibitor treatment, and INCA033989 in combination with ruxolitinib (Jakafi^®) in patients who experienced a suboptimal response to ruxolitinib monotherapy. These data are being featured in oral presentations (Session 634, Publication #484; Session 631, Publication #71) at the 2025 American Society of Hematology (ASH) Annual Meeting in Orlando.

“These positive study results reinforce our confidence in INCA033989’s transformative potential, both as a targeted monotherapy and combination therapy for MF, building on the positive results previously reported in essential thrombocythemia (ET),” said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. “Our goal is to bring new targeted treatment options to patients across the MPN disease spectrum. In line with this commitment, we plan to initiate a registrational program evaluating INCA033989 for the treatment of patients with MF in 2026.”

The preliminary analysis (data cut off September 25, 2025) evaluated the safety and efficacy of INCA033989 in patients with MF as measured by spleen volume reduction ≥25% (SVR25) and ≥35% (SVR35), change in MPN-Symptom Assessment Form (SAF), total symptom score (TSS), anemia response and mutCALR variant allele frequency (VAF) reduction.

In the monotherapy arm of the trials, patients with MF treated with INCA033989 (dose range 24 to 2,500 mg) experienced rapid and robust spleen and anemia responses and symptom improvements. Specifically:

• At Week 24, 41.7% (15/36) of all evaluable MF patients achieved SVR25, and 33.3% (12/36) achieved SVR35. Among MF patients not previously treated with a JAK inhibitor, 71.4% (5/7) achieved SVR25 and 57.1% (4/7) achieved SVR35. Among those resistant or intolerant to JAK inhibitor treatment, 34.5% (10/29) and 27.6% (8/29) achieved SVR25 and SVR35 at Week 24, respectively.
• Anemia response occurred in more than half (56%; 14/25) of evaluable anemic MF patients, with 40% (10/25) of patients achieving a major response with INCA033989 treatment.
• Nearly all MF patients treated with INCA033989 (93.3%; 42/45) experienced improved symptoms, with 60% (27/45) achieving a ≥50% reduction in TSS (TSS50) as best response. At Week 24, 39.4% (13/33) of patients achieved a TSS50.
• Most patients (89.4%; 42/47) with ≥1 post-baseline VAF measurement experienced a reduction in mutCALR VAF, and 10.6% (5/47) achieved a ≥25% best reduction in VAF.
• Most patients (76.5%; 39/51) in the studies had co-occurring mutations. Of those, 40.5% (15/37) of response eligible patients achieved SVR35 or an anemia response. Single-cell analyses in MF patients with high clonal complexity, including high-risk mutations, showed consistent reductions in all CALR-mutant clones, regardless of the presence of co-occurring variants.

Similarly, in the INCA033989 (dose range 70 to 2,500 mg) and ruxolitinib combination arm of the trials, most MF patients experienced spleen volume reductions and symptom improvements:

• At Week 24, half (50%; 6/12) of all evaluable MF patients achieved SVR25 and 25% (3/12) achieved SVR35.
• Among the 14 evaluable patients, 86% had stable anemia and one (1) patient with non-transfusion dependent anemia had a major anemia response.
• The majority of MF patients (81.3%; 13/16) treated with INCA033989 in combination with ruxolitinib experienced symptom improvement, and 33.3% (3/9) achieved TSS50 at Week 24.

Additionally, exploratory analyses in a subset of MF patients from the studies showed that INCA033989 reduced circulating mutCALR-positive hematopoietic stem and progenitor cells (HSPC) and mutCALR-positive platelet producing cells called megakaryocytes (MK) in the bone marrow, and improved marrow architecture, as measured by increased wild type (mutCALR-negative) MK. Among evaluable anemic MF patients (n=12), erythroid progenitor cells (CD71+ by IHC) in the bone marrow increased, correlating with hemoglobin increase and clinical anemia response. Together, these findings demonstrate the disease-modifying activity of INCA033989 in patients with mutCALR-expressing MF.

INCA033989 was well-tolerated, both as a monotherapy and in combination with ruxolitinib, in patients with MF who were resistant or intolerant to prior JAK inhibitor therapy or ineligible for JAK inhibitor treatment, with no dose-limiting toxicities observed.

• In the monotherapy arm (n=52), 86.5% (45) of patients were still receiving treatment and 13.5% (7) discontinued treatment. Only two (2) patients discontinued treatment due to treatment-emergent adverse events (TEAEs). Two (2) dose and three (3) infusion interruptions due to TEAEs were reported, and a maximum tolerated dose was not reached (dose range 24 to 2,500 mg). Fifty (50) patients across the monotherapy dose cohorts reported a TEAE, 30 of which were deemed treatment related.
  • The most common TEAEs (>20%) were anemia, fatigue, thrombocytopenia, arthralgia, AST elevations, cough, diarrhea, headache, leukopenia, nausea and pruiritis – nearly all were Grade 1. Sixteen (16) patients had Grade ≥3 TEAEs, with neutropenia being the most frequent (9.6%).
• In the combination therapy arm (n=20), 85.0% (17) patients were still receiving treatment and 15.0% (3) discontinued treatment. Only two patients discontinued treatment due to TEAEs. One (1) dose and one (1) infusion interruption due to TEAEs were reported, and a maximum tolerated dose was not reached (dose range 70 to 2,500 mg). Twenty (20) patients across the combination therapy dose cohorts reported a TEAE, 13 of which were deemed treatment related.
  • The most common TEAEs (>20%) were anemia, thrombocytopenia, ALT increase, diarrhea and fatigue. Eleven (11) patients experienced Grade ≥3 TEAEs, with anemia (30%) being the most frequent.

“Widely regarded as the most aggressive type of MPN – a group of rare, chronic blood cancers – MF is characterized by bone marrow fibrosis, anemia and splenomegaly, which can lead to debilitating symptoms and increased mortality,” said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mt. Sinai and Director, Center of Excellence for Blood Cancers and Myeloid Disorders, The Tisch Cancer Institute. “The Phase 1 data evaluating INCA033989 alone and in combination with ruxolitinib offer compelling proof-of-concept for a differentiated, targeted treatment approach in MF. The early signals observed suggest the potential to meaningfully influence the MF disease course, and I look forward to seeing this therapy advance in future clinical studies.”

More information regarding Incyte’s presentations at the 2025 ASH Annual Meeting can be found on the ASH website: https://www.hematology.org/meetings/annual-meeting/schedule-and-program/programs.

In addition to MF, INCA033989 is also being evaluated in Phase 1 studies for the treatment of patients with essential thrombocythemia (ET). The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation to INCA033989 for the treatment of patients with ET harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy. The company plans to initiate a registrational program evaluating INCA033989 for the treatment of patients with ET harboring a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in 2026.

Incyte Conference Call and Webcast

Incyte will host an investor event and webcast on Sunday, December 7, 2025, from 11:00 – 12:30 p.m. ET to discuss key mutCALR data presented at ASH.

The event will be webcasted and can be accessed via the Events and Presentations tab of the Investor section of Incyte.com and it will be available for replay for 30 days.

About Myeloproliferative Neoplasms (MPNs) and Mutations in Calreticulin (mutCALR)

Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),¹ a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.^2,3 Among two types of MPNs, essential thrombocythemia (ET) and myelofibrosis (MF), mutCALR drives 25-35% of all cases.^1,2

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

About the INCA033989 Trial Program

The clinical trial program for INCA033989 includes two multicenter, open-label Phase 1 studies, INCA33989-101 (NCT05936359) and INCA33989-102 (NCT06034002). The studies are evaluating the safety, tolerability and efficacy of INCA033989 in ~455 adult (≥18 years old) patients with mutCALR-expressing myeloproliferative neoplasms (MPNs), including myelofibrosis (MF) and essential thrombocythemia (ET).

The primary endpoint of the studies is measured by the number of participants with dose limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs) and the number of participants with TEAEs leading to dose modification or discontinuation. Secondary endpoints include response rates, mean change of ET total symptom score, percentage of MF patients achieving spleen volume reduction, MF patient anemia response, mean change in disease-related allele burden and various pharmacokinetics measures.

For more information on the studies, please visit: https://clinicaltrials.gov/study/NCT05936359 and https://clinicaltrials.gov/study/NCT06034002.

About Jakafi^® (ruxolitinib)

Jakafi^® (ruxolitinib) is a JAK1/JAK2 inhibitor approved by the U.S. FDA for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea; intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults; steroid-refractory acute GVHD in adult and pediatric patients 12 years and older; and chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Jakafi is a registered trademark of Incyte.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi^® (ruxolitinib) may cause low platelet, red blood cell, and white blood cell counts. If you develop bleeding, stop taking Jakafi and call your healthcare provider. Your healthcare provider will do a blood test to check your blood counts before you start Jakafi and regularly during your treatment. Your healthcare provider may change your dose of Jakafi or stop your treatment based on the results of your blood tests. Tell your healthcare provider right away if you develop or have worsening symptoms such as unusual bleeding, bruising, tiredness, shortness of breath, or a fever.

Infection: You may be at risk for developing a serious infection during treatment with Jakafi. Tell your healthcare provider if you develop any of the following symptoms of infection: chills, nausea, vomiting, aches, weakness, fever, painful skin rash or blisters.

Cancer: Some people have had certain types of non-melanoma skin cancers during treatment with Jakafi. Your healthcare provider will regularly check your skin during your treatment with Jakafi. Tell your healthcare provider if you develop any new or changing skin lesions during treatment with Jakafi.

Increases in cholesterol: You may have changes in your blood cholesterol levels during treatment with Jakafi. Your healthcare provider will do blood tests to check your cholesterol levels about every 8 to 12 weeks after you start taking Jakafi, and as needed.

Increased risk of major cardiovascular events such as heart attack, stroke or death in people who have cardiovascular risk factors and who are current or past smokers while using another JAK inhibitor to treat rheumatoid arthritis: Get emergency help right away if you have any symptoms of a heart attack or stroke while taking Jakafi, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back, severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw, pain or discomfort in your arms, back, neck, jaw, or stomach, shortness of breath with or without chest discomfort, breaking out in a cold sweat, nausea or vomiting, feeling lightheaded, weakness in one part or on one side of your body, slurred speech.

Increased risk of blood clots: Blood clots in the veins of your legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) have happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with Jakafi, including: swelling, pain, or tenderness in one or both legs, sudden, unexplained chest or upper back pain, shortness of breath or difficulty breathing.

Possible increased risk of new (secondary) cancers: People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers. People who smoke or who smoked in the past have an added risk of new cancers.

The most common side effects of Jakafi include: for certain types of myelofibrosis (MF) and polycythemia vera (PV) – low platelet or red blood cell counts, bruising, dizziness, headache, and diarrhea; for acute GVHD – low platelet counts, low red or white blood cell counts, infections, and swelling; and for chronic GVHD – low red blood cell or platelet counts and infections including viral infections.

These are not all the possible side effects of Jakafi. Ask your pharmacist or healthcare provider for more information. Call your doctor for medical advice about side effects.

Before taking Jakafi, tell your healthcare provider about: all the medications, vitamins, and herbal supplements you are taking and all your medical conditions, including if you have an infection, have or had low white or red blood cell counts, have or had tuberculosis (TB) or have been in close contact with someone who has TB, had shingles (herpes zoster), have or had hepatitis B, have or had liver or kidney problems, are on dialysis, have high cholesterol or triglycerides, had cancer, are a current or past smoker, had a blood clot, heart attack, other heart problems or stroke, or have any other medical condition. Take Jakafi exactly as your healthcare provider tells you. Do not change your dose or stop taking Jakafi without first talking to your healthcare provider.

Women should not take Jakafi while pregnant or planning to become pregnant. Do not breastfeed during treatment with Jakafi and for 2 weeks after the final dose.

Please see the Full Prescribing Information, which includes a more complete discussion of the risks associated with Jakafi.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

You may also report side effects to Incyte Medical Information at 1-855-463-3463.

About Incyte

A global biopharmaceutical company on a mission to Solve On., Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia.

For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn, X, Instagram, Facebook, YouTube.

Incyte Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the presentation of data for Incyte’s anti-mutCALR monoclonal antibody (INCA033989), the potential this monoclonal antibody offers for patients, and expectations regarding ongoing and future clinical trials, contain predictions, estimates, and other forward-looking statements.

These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials and the ability to enroll subjects in accordance with planned schedules; the timing of clinical trials, including initiation and completion; determinations made by the FDA, EMA and other regulatory agencies; Incyte’s dependence on its relationships with and changes in the plans of its collaboration partners; the efficacy or safety of Incyte’s products and the products of Incyte’s collaboration partners; the acceptance of Incyte’s products and the products of Incyte’s collaboration partners in the marketplace; market competition; unexpected variations in the demand for Incyte’s products and the products of Incyte’s collaboration partners; the effects of announced or unexpected price regulation or limitations on reimbursement or coverage for Incyte’s products and the products of Incyte’s collaboration partners; sales, marketing, manufacturing and distribution requirements, including Incyte’s and its collaboration partners’ ability to successfully commercialize and build commercial infrastructure for newly approved products and any additional products that become approved; greater than expected expenses, including expenses relating to litigation or strategic activities; variations in foreign currency exchange rates; and other risks detailed in Incyte’s reports filed with the Securities and Exchange Commission, including its annual report on form 10-K and our quarterly report on Form 10-Q for the quarter ended September 30, 2025. Incyte disclaims any intent or obligation to update these forward-looking statements.

Contacts

Media
media@incyte.com

Investors
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Incyte’s First-in-Class mutCALR-Targeted Monoclonal Antibody, INCA033989, Granted Breakthrough Therapy Designation by U.S. FDA




Incyte’s First-in-Class mutCALR-Targeted Monoclonal Antibody, INCA033989, Granted Breakthrough Therapy Designation by U.S. FDA

• The Company plans to initiate a Phase 3 program evaluating INCA033989 in essential thrombocythemia (ET) patients with all types of CALR mutations in mid-2026, following alignment with regulators
• Updated safety and efficacy data for INCA033989 in ET, and new data in myelofibrosis (MF), will be presented at the upcoming 2025 ASH Annual Meeting

WILMINGTON, Del.–(BUSINESS WIRE)–$INCY #ASH2025–Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to INCA033989, a first-in-class mutant calreticulin (mutCALR)-targeted monoclonal antibody, for the treatment of patients with essential thrombocythemia (ET) harboring a Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy.

ET is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. CALR mutations are the second most common oncogenic driver mutation and are observed in 25% of patients with ET. A 52-bp deletion, also known as a Type 1 mutation, occurs in 55% of patients with a CALR mutation, and is associated with the highest risk of transformation to myelofibrosis (MF) among all ET patients.

“Incyte has long been committed to improving outcomes for patients with MPNs, and this Breakthrough Therapy designation underscores the potential of INCA033989 to be a novel therapy that could significantly transform the treatment of ET patients, who today have limited treatment options,” said Pablo J. Cagnoni, M.D., President and Head of Research and Development, Incyte. “The designation allows us to expedite the development pathway for INCA033989 in patients with Type 1 mutations. Looking ahead, we plan to initiate a Phase 3 program evaluating INCA033989 in ET patients with all types of CALR mutations in mid-2026, following alignment with regulators in the first half of next year.”

The FDA Breakthrough Therapy Designation was supported by the early Phase 1 data evaluating INCA033989 in ET patients with a Type 1 CALR mutation available at the time of submission.

The preliminary Phase 1 data were presented earlier this year at the 2025 European Hematology Association (EHA) Congress. In the study, INCA033989 was well-tolerated and demonstrated rapid and durable normalization of platelet counts across evaluated doses, with greater responses seen at higher doses across both mutation types. Updated results from the Phase 1 dose escalation and expansion trial are planned for presentation at the 2025 ASH Annual Meeting in Orlando (Session 634; Publication #1024; December 8, 4:30-6:00 p.m. ET).

Incyte plans to develop INCA033989 for patients with Type 1 and non-Type 1 CALR mutations and, following discussions with regulatory agencies, plans to initiate a registrational program evaluating patients with ET with a Type 1 or non-Type 1 CALR mutation who are resistant or intolerant to at least one cytoreductive therapy in the first half of next year.

About Essential Thrombocythemia

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by persistently elevated platelet counts due to abnormal blood cell production in the bone marrow. People living with ET are at increased risk for blood clots and bleeding and a proportion of patients may progress over time to myelofibrosis or acute leukemia.

About Mutations in Calreticulin (mutCALR)

Calreticulin (CALR) is a protein involved in the regulation of cellular calcium levels and normal protein folding. Somatic, or non-inherited, DNA mutations in the CALR gene (mutCALR) can result in abnormal protein function and lead to the development of myeloproliferative neoplasms (MPNs),¹ a closely related group of clonal blood cancers in which the bone marrow functions abnormally, overproducing blood cells.^2,3 In Essential thrombocythemia (ET) and myelofibrosis (MF), CALR mutations occur in ~25-35% of patients.^1,2

Incyte is at the forefront of developing novel therapies for patients with mutCALR ET or MF that target only malignant cells, sparing normal cells, including INCA033989, a first-in-class, mutCALR-specific therapy.

About Incyte

A global biopharmaceutical company on a mission to Solve On., Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia.

For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn, X, Instagram, Facebook, YouTube.

Incyte Forward-Looking Statements

Except for the historical information set forth herein, the matters set forth in this press release, including statements regarding the presentation of data for INCA033989 studies, the potential this monoclonal antibody offers for patients, and expectations regarding ongoing and future clinical trials contain predictions, estimates, and other forward-looking statements.

These forward-looking statements are based on Incyte’s current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA, EMA, and other regulatory authorities; the efficacy or safety of Incyte and its partners’ products; the acceptance of Incyte and its partners’ products in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; and other risks detailed from time to time in our reports filed with the U.S. Securities and Exchange Commission, including our annual report on Form 10-K and our quarterly report on Form 10-K for the quarter ended September 30, 2025. Incyte disclaims any intent or obligation to update these forward-looking statements.

Contacts

Media
media@incyte.com

Investors
ir@incyte.com

Yescarta® Delivers Consistent Safety, Efficacy, and Quality of Life Benefits Across Broad Range of Relapsed/Refractory Large B-cell Lymphoma Patients in New Analysis at ASH 2025




Yescarta® Delivers Consistent Safety, Efficacy, and Quality of Life Benefits Across Broad Range of Relapsed/Refractory Large B-cell Lymphoma Patients in New Analysis at ASH 2025

– Benefits Seen Regardless of Eligibility for Previous Standard of Care of High-Dose Chemotherapy and Stem Cell Transplant for Second-Line Treatment –

SANTA MONICA, Calif.–(BUSINESS WIRE)–Kite, a Gilead Company (Nasdaq: GILD), presented a new analysis today demonstrating that second-line Yescarta^® (axicabtagene ciloleucel) therapy offers consistent benefits in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL), even among those ineligible for the previous standard of care, high-dose chemotherapy followed by an autologous stem cell transplant (ASCT).

Results were shared from the combined analysis of four-year data from the landmark ZUMA-7 Phase 3 pivotal study of Yescarta for R/R LBCL and two-year data from the Phase 2 ALYCANTE study, designed by French collaborative group LYSA and sponsored by LYSARC, for transplant-ineligible patients. The findings were presented (Abstract #3714) during the 67th American Society of Hematology (ASH) Annual Meeting and Exposition.

“Patients with large B-cell lymphoma who are ineligible for stem cell transplants face limited treatment options and poor outcomes due to age, co-morbidities and other factors,” said Professor Roch Houot, Head of Haematology Department, University Hospital of Rennes, France and coordinator of the ALYCANTE study. “This analysis reinforces that Yescarta should be considered earlier in a patient’s treatment paradigm given its curative potential as a one-time treatment and further establishes CAR T as the new standard of care for second-line treatment of large B-cell lymphoma.”

The efficacy analyses included 178 and 69 patients from the ZUMA-7 and ALYCANTE trials, respectively.

After two years:

• Overall survival (OS) rate, meaning the percentage of patients in the trials who were still alive, was 64.9% in the pooled analysis, 62.8% in ZUMA-7, and 70.8% in ALYCANTE. Historically, the prognosis for R/R LBCL was very poor; prior to the introduction of new therapies like CAR Ts, the two-year survival rate was only about 20%.
• Event-free survival (EFS) rate, meaning the percentage of patients who were still alive and had not seen their disease worsen or experienced other major complications, was 45.2% in the pooled analysis, 45.4% in ZUMA-7, and 44.7% in ALYCANTE.
• Progression-free survival (PFS) rate, meaning the percentage of patients who were still living without their disease getting worse, was 47.4% in the pooled analysis, 47.6% in ZUMA-7, and 46.8% in ALYCANTE.

Additionally:

• After three months, 55.6% of the patients in the pooled analysis showed a complete metabolic response (CMR), meaning their disease was barely, if at all, detectable. CMR was 51.2% in ZUMA-7 and 67.7% in ALYCANTE.
• After one year after treatment, overall response rate (ORR), meaning patients saw their cancer significantly shrink or completely disappear, was 46.6% in the pooled analysis, 46.5% in ZUMA-7, and 46.8% in ALYCANTE.
• For those patients who responded well to treatment, 61% saw that positive response continue after a full year. Pooled 12-month duration of response (DOR) was 61.0%, 60.6% in ZUMA-7, and 62.1% in ALYCANTE.

In the safety analysis, which included 170 ZUMA-7 and 62 ALYCANTE Yescarta-infused patients, safety outcomes were comparable between the two studies. The incidence of grade ≥3 treatment-emergent adverse events (TEAEs) was similar between the ZUMA-7 and ALYCANTE patients, 91.2% and 88.7% respectively, with a pooled incidence of 90.5%. Pooled incidence of grade ≥3 neurologic events, neutropenias, and anemia were 19.8% (ZUMA-7 21.2%, ALYCANTE 16.1%), 64.7% (ZUMA-7 70.0%, ALYCANTE 50.0%), and 27.6% (ZUMA-7 30.0%, ALYCANTE 21.0%), respectively.

Across both studies, patients generally experienced similar long-term improvements in their quality of life after initial treatment challenges. At Day 50 after treatment, patients in both trials showed a transient decline (-7.2 in ZUMA-7 and -6.3 in ALYCANTE) for EORTC QLQ-C30 global health status, and -12.9 for physical function in both. However, patients in ALYCANTE reported a meaningful improvement in their overall well-being (EQ-5D-5L VAS) by Day 100 (+9.9), while ZUMA-7 patients reached a similar meaningful improvement (+9.9) at Day 150, which continued through Month 12. By month 24, both ALYCANTE and ZUMA-7 showed continued improvements of global health status.

“This analysis offers compelling evidence of Yescarta’s consistent, durable efficacy and safety profile across a broad range of patients, including those with difficult-to-treat relapsed or refractory disease who historically faced very limited options and a poor prognosis,” said Gallia Levy, MD, PhD, Senior Vice President and Global Head of Development, Kite. “These robust data further reinforce Yescarta’s potential as a treatment with curative intent, reflecting Kite’s deep commitment to transforming patient outcomes.”

About LBCL

Globally, LBCL is the most common type of non-Hodgkin lymphoma. In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30-40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.

About ALYCANTE Study

ALYCANTE (NCT04531046) is a Phase 2 study evaluating the efficacy and safety of Yescarta in patients with R/R LBCL after one prior line of therapy who were deemed ineligible for high-dose chemotherapy and ASCT, sponsored by the LYSA/LYSARC collaborative group. The primary endpoint was the complete metabolic response at three months from Yescarta infusion. The study was funded by Kite, a Gilead Company, and carried out with Yescarta manufactured by Kite.

About LYSA and LYSARC

The Lymphoma Study Association (LYSA) is an independent, multidisciplinary network and an international leader in clinical lymphoma and CLL/WM research. With over 500 experts and a network of 90 centers across France, Belgium, and Portugal, it conducts clinical trials ranging from early-stage treatment evaluation to the development of new therapeutic strategies.

The Lymphoma Academic Research Organization (LYSARC), based in France, is the largest European academic organization dedicated to clinical lymphoma and CLL/WM research. As the operational arm of LYSA, LYSARC sponsors and leads research initiatives and operates specialized platforms in pathology, biology, and imaging. It manages and coordinates numerous clinical trials (phases 1 to 4) each year, as well as non-interventional and data reuse studies. LYSARC is a key research expert, leading innovative projects on an international scale.

About ZUMA-7 Study

Based on the primary efficacy endpoint results of ZUMA-7, the U.S. Food & Drug Administration approved Yescarta as initial treatment of R/R LBCL in April 2022. The EU granted approval in October 2022, followed by approvals in several other countries including Australia, Canada, Great Britain, Israel, Japan and Switzerland.

ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus standard of care (SOC) for second-line therapy in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The SOC for initial treatment of R/R LBCL has been a multi-step process involving platinum-based salvage combination chemotherapy regimen, and for responders, HDT and ASCT. In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or SOC second-line treatment. The primary endpoint was EFS as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate and OS. Additional secondary endpoints included patient-reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of OS occurred at the time of the primary EFS.

About Yescarta

Please see full Prescribing Information, including BOXED WARNING below and Medication Guide.

YESCARTA is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

• Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.
• Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Limitations of Use: YESCARTA is not indicated for the treatment of patients with primary central nervous system lymphoma.

U.S. IMPORTANT SAFETY INFORMATION

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, and SECONDARY HEMATOLOGICAL MALIGNANCIES

• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving YESCARTA. Do not administer YESCARTA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving YESCARTA, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with YESCARTA. Provide supportive care and/or corticosteroids, as needed.
• T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA.

CYTOKINE RELEASE SYNDROME (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with YESCARTA. CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma (NHL), including ≥ Grade 3 CRS in 9%. CRS occurred in 93% (256/276) of patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in 9%. Among patients with LBCL who died after receiving YESCARTA, 4 had ongoing CRS events at the time of death. For patients with LBCL in ZUMA-1, the median time to onset of CRS was 2 days following infusion (range: 1-12 days) and the median duration was 7 days (range: 2-58 days). For patients with LBCL in ZUMA-7, the median time to onset of CRS was 3 days following infusion (range: 1-10 days) and the median duration was 7 days (range: 2-43 days).

CRS occurred in 84% (123/146) of patients with indolent non-Hodgkin lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 CRS in 8%. Among patients with iNHL who died after receiving YESCARTA, 1 patient had an ongoing CRS event at the time of death. The median time to onset of CRS was 4 days (range: 1-20 days) and median duration was 6 days (range: 1-27 days) for patients with iNHL.

Key manifestations of CRS (≥ 10%) in all patients combined included fever (85%), hypotension (40%), tachycardia (32%), chills (22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious events that may be associated with CRS include, cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), renal insufficiency, cardiac failure, respiratory failure, cardiac arrest, capillary leak syndrome, multi-organ failure, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

The impact of tocilizumab and/or corticosteroids on the incidence and severity of CRS was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received tocilizumab and/or corticosteroids for ongoing Grade 1 events, CRS occurred in 93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients experienced a Grade 4 or 5 event. The median time to onset of CRS was 2 days (range: 1-8 days) and the median duration of CRS was 7 days (range: 2-16 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Thirty-one of the 39 patients (79%) developed CRS and were managed with tocilizumab and/or therapeutic doses of corticosteroids with no patients developing ≥ Grade 3 CRS. The median time to onset of CRS was 5 days (range: 1-15 days) and the median duration of CRS was 4 days (range: 1-10 days). Although there is no known mechanistic explanation, consider the risk and benefits of prophylactic corticosteroids in the context of pre-existing comorbidities for the individual patient and the potential for the risk of Grade 4 and prolonged neurologic toxicities.

Confirm that 2 doses of tocilizumab are available prior to infusion of YESCARTA. Monitor patients at least daily for 7 days following infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for 2 weeks after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated.

NEUROLOGIC TOXICITIES

Neurologic toxicities including immune effector cell-associated neurotoxicity syndrome (ICANS) that were fatal or life-threatening occurred following treatment with YESCARTA. Neurologic toxicities occurred in 78% (330/422) of patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.

Neurologic toxicities occurred in 87% (94/108) of patients with LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to onset was 4 days (range: 1-43 days) and the median duration was 17 days for patients with LBCL in ZUMA-1. The median time to onset for neurologic toxicity was 5 days (range: 1-133 days) and median duration was 15 days in patients with LBCL in ZUMA-7. Neurologic toxicities occurred in 77% (112/146) of patients with iNHL, including ≥ Grade 3 in 21%. The median time to onset was 6 days (range: 1-79 days) and the median duration was 16 days. Ninety-eight percent of all neurologic toxicities in patients with LBCL and 99% of all neurologic toxicities in patients with iNHL occurred within the first 8 weeks of YESCARTA infusion. Neurologic toxicities occurred within the first 7 days of infusion in 87% of affected patients with LBCL and 74% of affected patients with iNHL.

The most common neurologic toxicities (≥ 10%) in all patients combined included encephalopathy (50%), headache (43%), tremor (29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia (10%). Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred. Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred.

The impact of tocilizumab and/or corticosteroids on the incidence and severity of neurologic toxicities was assessed in 2 subsequent cohorts of LBCL patients in ZUMA-1. Among patients who received corticosteroids at the onset of Grade 1 toxicities, neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had Grade 3 neurologic toxicities; no patients experienced a Grade 4 or 5 event. The median time to onset of neurologic toxicities was 6 days (range: 1-93 days) with a median duration of 8 days (range: 1-144 days). Prophylactic treatment with corticosteroids was administered to a cohort of 39 patients for 3 days beginning on the day of infusion of YESCARTA. Of those patients, 85% (33/39) developed neurologic toxicities; 8% (3/39) developed Grade 3 and 5% (2/39) developed Grade 4 neurologic toxicities. The median time to onset of neurologic toxicities was 6 days (range: 1-274 days) with a median duration of 12 days (range: 1-107 days). Prophylactic corticosteroids for management of CRS and neurologic toxicities may result in higher grade of neurologic toxicities or prolongation of neurologic toxicities, delay the onset, and decrease the duration of CRS.

Monitor patients for signs and symptoms of neurologic toxicities following infusion at least daily for 7 days; and for 2 weeks thereafter and treat promptly. Advise patients to avoid driving for at least 2 weeks following infusion.

HYPERSENSITIVITY REACTIONS

Allergic reactions may occur with the infusion of YESCARTA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) or residual gentamicin in YESCARTA.

SERIOUS INFECTIONS

Severe or life-threatening infections occurred after YESCARTA infusion. Infections (all grades) occurred in 45% of patients with NHL. Grade 3 or higher infections occurred in 17% of patients, including ≥ Grade 3 infections with an unspecified pathogen in 12%, bacterial infections in 5%, viral infections in 3%, and fungal infections in 1%. YESCARTA should not be administered to patients with clinically significant active systemic infections. Monitor patients for signs and symptoms of infection before and after infusion and treat appropriately. Administer prophylactic antimicrobials according to local guidelines.

Febrile neutropenia was observed in 36% of patients with NHL and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

In immunosuppressed patients, including those who have received YESCARTA, life-threatening and fatal opportunistic infections including disseminated fungal infections (e.g., candida sepsis and aspergillus infections) and viral reactivation (e.g., human herpes virus-6 [HHV-6] encephalitis and JC virus progressive multifocal leukoencephalopathy [PML]) have been reported. The possibility of HHV-6 encephalitis and PML should be considered in immunosuppressed patients with neurologic events and appropriate diagnostic evaluations should be performed.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, has occurred in patients treated with drugs directed against B cells, including YESCARTA. Perform screening for HBV, HCV, and HIV and management in accordance with clinical guidelines before collection of cells for manufacturing.

PROLONGED CYTOPENIAS

Patients may exhibit cytopenias for several weeks following lymphodepleting chemotherapy and YESCARTA infusion. Grade 3 or higher cytopenias not resolved by Day 30 following YESCARTA infusion occurred in 39% of all patients with NHL and included neutropenia (33%), thrombocytopenia (13%), and anemia (8%). Monitor blood counts after infusion.

HYPOGAMMAGLOBULINEMIA

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving YESCARTA. Hypogammaglobulinemia was reported as an adverse reaction in 14% of all patients with NHL. Monitor immunoglobulin levels after treatment and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement.

The safety of immunization with live viral vaccines during or following YESCARTA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment.

SECONDARY MALIGNANCIES

Patients treated with YESCARTA may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including YESCARTA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Kite at 1-844-454-KITE (5483) to obtain instructions on patient samples to collect for testing.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 20%) in:

• patients with LBCL in ZUMA-7 included fever, CRS, fatigue, hypotension, encephalopathy, tachycardia, diarrhea, headache, musculoskeletal pain, nausea, febrile neutropenia, chills, cough, infection with unspecified pathogen, dizziness, tremor, decreased appetite, edema, hypoxia, abdominal pain, aphasia, constipation, and vomiting.
• patients with LBCL in ZUMA-1 included CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections with pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.

Please see full Prescribing Information, including BOXED WARNING and Medication Guide.

About Gilead and Kite Oncology

Gilead and Kite Oncology are working to transform how cancer is treated. We are innovating with next-generation therapies, combinations and technologies to deliver improved outcomes for people with cancer. We are purposefully building our oncology portfolio and pipeline to address the greatest gaps in care. From antibody-drug conjugate technologies and small molecules to cell therapy-based approaches, we are creating new possibilities for people with cancer.

Forward-Looking Statements

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the ability of Gilead and Kite to initiate, progress or complete clinical trials within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical studies, including those involving Yescarta (such as ZUMA-7 and ALYCANTE); uncertainties relating to regulatory applications and related filing and approval timelines, including pending or potential applications for indications currently under evaluation; the possibility that Gilead and Kite may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead and Kite, and Gilead and Kite assume no obligation and disclaim any intent to update any such forward-looking statements.

Yescarta, Gilead, the Gilead logo, Kite, the Kite logo are trademarks of Gilead Sciences, Inc., or its related companies.

For more information on Kite, please visit the company’s website at www.kitepharma.com. Follow Kite on social media on

Contacts

Ashleigh Koss, Media

public_affairs@gilead.com

Jacquie Ross, Investors

investor_relations@gilead.com

Read full story here

NMDP℠ Demonstrates Scientific Leadership in Expanding Patient Access to Lifesaving Cell Therapy at ASH 2025




NMDP℠ Demonstrates Scientific Leadership in Expanding Patient Access to Lifesaving Cell Therapy at ASH 2025

New results from the Phase II ACCESS trial represent a significant milestone in solving one of transplant medicine’s biggest challenges: finding a donor for every patient in need of a blood stem cell transplant

One-year overall survival exceeds 80% among trial participants receiving 4/8-7/8 mismatched unrelated donor transplant

Ninety-nine percent of patients with common blood cancers can find a suitable donor and safely and effectively access transplant

MINNEAPOLIS–(BUSINESS WIRE)–New research from NMDP, a global nonprofit leader in cell therapy, and conducted by CIBMTR® (Center for International Blood and Marrow Transplant Research®) at the 67^th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Fla., demonstrates that patients receiving allogeneic transplantation using more deeply mismatched unrelated donors (MMUD), followed by post-transplant chemotherapy, can achieve outcomes comparable to those receiving transplants from more closely, but still not fully, matched donors. The data also show that virtually every patient searching international registries now has a greater than 99% likelihood of identifying a suitable blood stem cell donor. Notably, ASH selected this abstract for presentation at its 2026 Highlights of ASH® program in January.

While exact donor-patient genetic matching was historically considered essential for preventing life-threatening complications after transplant, results from the NMDP-sponsored ACCESS study [#936] showed strong, consistent outcomes among adults receiving donor grafts across all mismatch levels (4/8–7/8). At one-year post-transplant, overall survival (OS) exceeded 80% across all match levels, achieving a significant 86% for <7/8 mismatches and 79% for 7/8 mismatches.

“We are fundamentally changing what’s possible in transplant medicine and creating a new standard of care for curing common blood cancers,” said Steven M. Devine, M.D., chief medical officer, NMDP, and executive lead, CIBMTR. “For the first time, we have clear evidence that patients can safely receive a range of mismatched unrelated donor grafts and achieve survival outcomes on par with those from fully matched donors—this is a giant leap forward for transplant science and medicine.”

The most important factor that determines donor-recipient compatibility in unrelated donor transplantation is matching at human leukocyte antigens (HLA), the proteins that help the immune system distinguish its cells from another’s. When HLA mismatch occurs, the donor’s immune system can recognize the patient’s tissues as foreign, triggering graft-versus-host disease (GVHD), a potentially life-threatening complication.

Historically, achieving an 8/8 HLA match resulted in the best transplant outcomes, while using donors with fewer matching alleles (<7/8) was associated with poor survival and higher rates of GVHD. However, NMDP research published in the Journal of Clinical Oncology in June demonstrated that patients receiving <7/8 matched graft achieved outcomes comparable to, or even exceeding, historical 8/8 benchmarks of 75% survival—supporting broader donor eligibility.

Finding a fully or closely matched donor remains a major barrier for many patients, as HLA markers are inherited. If there are no suitable matches within the family, physicians must search international registries, now totaling more than 42 million potential donors and more than 760,000 cord blood units. Unfortunately, patients of non-European ancestry have historically had much lower chances of finding a suitable donor.¹

ACCESS trial demonstrates safe and effective use of MMUDs

Presenting author Antonio Jimenez-Jimenez, M.D. will deliver the oral presentation on Monday, Dec. 8, at 4 p.m. EST sharing detailed results from ACCESS (NCT04904588). This prospective, multicenter trial evaluated 268 adult patients with common blood cancers who received 4/8 to 7/8 HLA-MMUD peripheral blood stem cell (PBSC) grafts with post-transplant cyclophosphamide (PTCy). While prior studies explored PTCy for GVHD prevention in related individuals with HLA mismatches, the ACCESS trial is the first to evaluate this approach in patients receiving PBSC transplants from unrelated donors with as few as 4/8 HLA matches. Notably, 61% of participants in the <7/8 cohort self-identified as other than non-Hispanic White.

“These results challenge long-held assumptions about the risks of HLA mismatching and demonstrate that PTCy-based regimens can safely extend donor eligibility to nearly all patients in need of transplant, including those from varied backgrounds who are most in need of a suitably matched donor,” said Dr. Jimenez-Jimenez, associate professor of medicine in the division of Transplantation & Cellular Therapy at Sylvester Comprehensive Cancer Center, at the University of Miami Miller School of Medicine.

Non-relapse mortality (7/8=13.7%; <7/8=8.4%), relapse (7/8=17.1%; <7/8=22.8%), and moderate-to-severe chronic GVHD (7/8=11.3%; <7/8=7.7%) rates were similarly favorable between cohorts, regardless of conditioning regimen.

An additional CIBMTR analysis included in the presentation depicted the ACCESS results within the context of current donor availability on international registries. For patients highly unlikely to find an 8/8 match, allowing a <7/8 match offers a significantly higher pool of potential donors available, even if these patients had ethnically diverse backgrounds. Sixty-two percent of patients included in this five year analysis were ethnically diverse, and the median number of available donors increased from two at the 7/8 level to 83 at the 6/8 level, illustrating the profound impact of broadening acceptable match levels.

Donor for All: Research advances outcomes and access for all patients

NMDP’s Donor for All initiative unites clinical research, data science and operational innovation to close long-standing gaps in access for patients, especially for those of diverse ancestry. The ACCESS, OPTIMIZE (NCT06001385) and ACCELERATE (NCT06859424) trials are key Phase II trials at the core of the Donor for All initiative; additional ACCESS findings and in-progress updates from ACCELERATE will be presented at ASH, including:

• Results from the reduced-intensity conditioning (RIC) cohort [#4232] of the ACCESS study in a poster presentation. Findings demonstrated one-year OS at 79.6% and relatively low rates of non-relapse mortality (12.5%), chronic GVHD (15.6%) and severe GVHD (3.7%) across HLA match levels. Results confirmed that PTCy-based MMUD transplantation delivers consistent and reproducible outcomes across conditioning intensities and centers, further supporting its use as a safe and scalable approach to expand donor access.
• A poster presentation of the ACCESS PRO (“Living the Recovery”) [#6042] will also show findings that complemented these positive clinical outcomes. The study examined patient-reported outcomes to better understand survivorship and quality of life one year after transplant. Among 268 patients, self-reported quality-of-life scores, physical function and fatigue returned to or exceeded baseline levels, with overall results comparable to population norms. Financial well-being also remained stable from baseline to one year. Patients who experienced moderate or severe chronic GVHD reported greater symptom burden and reduced physical function, underscoring the importance of continued efforts to reduce GVHD incidence and strengthen supportive care strategies.
• Another poster presentation will show the latest from the in-progress ACCELERATE trial, [#6035] which represents the next step in optimizing transplant. This multicenter platform protocol will evaluate multiple PTCy-based GVHD prevention regimens—testing reduced-dose PTCy with novel agents such as abatacept and ruxolitinib—across up to 60 U.S. centers. The goal: to refine efficacy, minimize toxicity and further improve long-term outcomes for patients receiving mismatched donor transplants. ACCELERATE is still enrolling at sites across the U.S.

“These collective studies move us closer to a future where donor match limitations no longer determine who receives a cure,” said Dr. Devine. “With donor matching no longer as restrictive, clinicians can now prioritize other factors, such as donor age and cell quality, to optimize outcomes and further individualize transplant care. Through our Donor for All initiative, NMDP is combining rigorous science with a commitment to equity so that every searching patient, regardless of ancestry, can find their cure.”

Additional studies presented at ASH 2025

Other research presented by NMDP and CIBMTR at ASH further support the organizations’ aim to make safe and effective cell therapy available to every patient in need.

In an oral presentation to be presented Sunday, Dec. 7 at 10:30 a.m., Kai Yu, Ph.D., Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, will share results from the MEASURE Genome Atlas study [#455], which sought to advance understanding of the genomic landscape of acute myeloid leukemia (AML). Using whole genome sequencing (WGS) from 255 adult patients across 18 U.S. cancer centers, the study demonstrated that WGS can function as a single, comprehensive diagnostic platform for AML—reproducing 93% of standard prognostic markers while identifying additional alterations, including KMT2A partial tandem duplications and cryptic gene fusions missed by traditional testing. This comprehensive atlas of adult AML genomics provides novel insights into disease biology, creates an evidentiary basis to support clinical testing improvements, and is a resource for both diagnostic and drug development. NMDP supported this study, with CIBMTR facilitating the research.

Other notable presentations include:

• Longer telomeres in donors aged ≤35 years reduce graft failure and non-relapse mortality after allogeneic HCT (oral)—Found that longer telomeres in younger donors correlated with reduced graft failure and non-relapse mortality.
• Impact of HLA alloimmunization on availability of HLA well-matched and mismatched unrelated allogeneic hematopoietic cell donors for transplantation (DSA match) (poster)—Examined how donor-specific antibodies affect donor match feasibility and clinical outcomes.
• Vδ2 unconventional T cells in the donor graft are associated with improved overall survival after unrelated donor allo-HCT for AML and MDS: An analysis from the DKMS and NMDP Graft Composition Study (oral)—Demonstrated that higher frequencies of Vδ2 T cells in donor grafts are associated with improved survival after unrelated donor transplantation.

About CIBMTR®

CIBMTR® (Center for International Blood and Marrow Transplant Research®) is a nonprofit research collaboration between NMDP^SM, in Minneapolis, and the Medical College of Wisconsin®, in Milwaukee. CIBMTR collaborates with the global scientific community to increase survival and enrich quality of life for patients. CIBMTR facilitates critical observational and interventional research through scientific and statistical expertise, a large network of centers, and a unique database of long-term clinical data for more than 630,000 people who have received hematopoietic cell transplantation and other cellular therapies. Learn more at cibmtr.org.

About NMDP^SM

At NMDP^SM, we believe each of us holds the key to curing blood cancers and disorders. As a global nonprofit leader in cell therapy, NMDP creates essential connections between researchers and supporters to inspire action and accelerate innovation to find life-saving cures. With the help of blood stem cell donors from the world’s most diverse registry and our extensive network of transplant partners, physicians and caregivers, we’re expanding access to treatment so that every patient can receive their life-saving cell therapy. NMDP. Find cures. Save lives. Learn more at nmdp.org.

Contacts

Media Contact:
Jess Ayers

media@nmdp.org

ReAlta Announces Promising Phase 2 Data Demonstrating Rapid Clinical Responses and Target Engagement in Steroid-Refractory Acute GvHD at the ASH 2025 Annual Meeting




ReAlta Announces Promising Phase 2 Data Demonstrating Rapid Clinical Responses and Target Engagement in Steroid-Refractory Acute GvHD at the ASH 2025 Annual Meeting

Pegtarazimod demonstrates significant clinical improvement and reduction in inflammatory markers in patients with lower gastrointestinal acute GvHD

NORFOLK, Va.–(BUSINESS WIRE)–ReAlta Life Sciences, Inc. (“ReAlta” or the “Company”), a clinical-stage biopharmaceutical company dedicated to saving lives by rebalancing the inflammatory response to address rare and acute inflammatory diseases, today announced a presentation of interim Phase 2 clinical data on RLS-0071 (pegtarazimod) for the treatment of acute graft-versus-host disease (aGvHD) at the 67th American Society of Hematology (ASH) Annual Meeting.

The new findings will be presented in a poster titled “Anti-inflammatory drug pegtarazimod (RLS-0071) demonstrates clinical improvement in lower gastrointestinal acute graft-versus-host disease (aGvHD) and target engagement of key inflammatory marker myeloperoxidase (MPO).” The data highlight interim results from ReAlta’s Phase 2 clinical trial, an open-label, prospective, dose-escalation study evaluating pegtarazimod in hospitalized patients with steroid-refractory aGvHD, underscoring the program’s continued clinical momentum.

The study design features multiple cohorts exploring different dosing strategies, including a treatment optimization cohort of 6 patients receiving 10mg/kg of pegtarazimod with ruxolitinib for 7 days. Preliminary efficacy of pegtarazimod was evaluated by clinical response in the lower GI, skin and liver, and characterized as Grade II, III or IV, per Mount Sinai Acute GVHD International Consortium (MAGIC) guidelines. Plasma levels of MPO were evaluated as a pharmacodynamic (PD) measurement of drug activity in a qualified assay.

Key Highlights from ASH 2025 Poster Presentation:

• Clinical MAGIC Stage improvement observed for 6 of 6 patients with steroid-refractory aGvHD, with 4 of 5 participants demonstrating lower GI MAGIC Stage improvement of 1, 2, or 3 stages over 7 days of treatment
• Median plasma MPO levels decreased by 68% (p = 0.02), suggesting modulation of neutrophil-driven inflammatory mechanisms
• Safety profile characterized by no dose-limiting toxicities or serious adverse events attributed to the study drug

“Pegtarazimod treatment shows compelling clinical improvements for patients with steroid-refractory aGvHD, particularly in lower gastrointestinal involvement,” said Robert Zeiser, M.D., from the Medical Center, University of Freiburg and lead author of the study. “The statistically significant decrease in plasma myeloperoxidase levels suggests a direct pathway to reducing tissue damage and potentially improving outcomes for patients with this life-threatening condition.”

Kenji Cunnion, M.D., Chief Medical Officer of ReAlta, said, “This data demonstrates pegtarazimod’s unique ability to target multiple inflammatory pathways simultaneously, particularly in lower gastrointestinal aGvHD, a condition with historically poor patient outcomes. By selectively inhibiting complement activation and neutrophil-driven mechanisms, we are exploring a novel therapeutic approach that could transform the clinical management of this complex and life-threatening disease.”

About Pegtarazimod (RLS-0071)

Pegtarazimod (RLS-0071) is a pipeline-in-a-product that represents a paradigm shift in treating immune-mediated inflammatory disease. Pegtarazimod inhibits C1 and MBL activation within the classical and lectin pathways to block the initiation of the inflammatory cascade at its earliest stages, while simultaneously blocking myeloperoxidase (MPO) in order to prevent the activation of toxic reactive oxidative species (ROS) and formation of neutrophil extracellular traps (NETs) that are known to accelerate tissue damage.

With demonstrated biomarker validation across neurology, immunology and pulmonology, pegtarazimod is currently advancing through multiple Phase 2 clinical trials, including ongoing studies in newborns with moderate to severe hypoxic ischemic encephalopathy (HIE) and patients with steroid-refractory acute graft-versus-host disease (aGvHD), along with a recently completed Phase 2 proof-of-concept study in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).

ReAlta has secured multiple FDA Orphan Drug and Fast Track Designations for pegtarazimod in HIE and aGvHD, as well as European Medicines Agency Orphan Drug Designations for both indications, positioning ReAlta to deliver transformative outcomes for patients facing life-threatening inflammatory conditions with no adequate treatment options.

About ReAlta Life Sciences

ReAlta Life Sciences is clinical-stage biopharmaceutical company redefining the treatment possibilities for patients with devastating and historically untreatable inflammation-driven diseases by developing first-in-class tailored peptides designed to achieve life-changing outcomes. The company’s lead candidate, pegtarazimod (RLS-0071) is a next-generation dual-targeting intervention that represents a potential solution that rebalances the body’s inflammatory response and prevents tissue damage by selectively blocking both complement- and neutrophil-mediated pathways at the outset, disrupting inflammation at the core. To learn more about ReAlta, visit https://realtalifesciences.com and follow us on LinkedIn.

Contacts

Investors
John Rickman

Chief Financial Officer

jrickman@realtals.com

Media
Harrison Wong

ICR Healthcare

ReAltaPR@icrhealthcare.com

Genetix Participates in the American Society of Hematology’s (ASH) Exclusive Press Program & Shares Recent Patient Experience Data from U.S. Commercial Gene Therapy Implementation




Genetix Participates in the American Society of Hematology’s (ASH) Exclusive Press Program & Shares Recent Patient Experience Data from U.S. Commercial Gene Therapy Implementation

• Data presented was selected for ASH’s exclusive program to highlight the most impactful research submitted for this year’s meeting
• Real-world data reinforces the value of durable, one-time gene therapy
• 369 patients enrolled and 115 treated since FDA approval of ZYNTEGLO™ and LYFGENIA™
• Lessons learned from ZYNTEGLO launch informed Genetix’s revamped commercial strategy and ongoing infrastructure expansion driving LYFGENIA adoption

SOMERVILLE, Mass.–(BUSINESS WIRE)–Genetix Biotherapeutics Inc. today announced their participation in the American Society of Hematology’s (ASH) exclusive press program ahead of the 67^th ASH annual meeting in Orlando, Florida (December 6-9, 2025). Genetix’s abstract Accelerating access to gene therapy: Lessons from commercial implementation in sickle cell disease and transfusion-dependent thalassemia was selected by the ASH Program Committee as one of the meeting’s most impactful datasets submitted this year.

“We’re honored to be selected for ASH’s exclusive program, a recognition that underscores the significance of our data, which is the first to analyze commercial gene therapy adoption for the treatment of hemoglobinopathies,” said Joanne Lager, MD, Chief Medical Officer. “These findings from patients prescribed ZYNTEGLO and LYFGENIA demonstrate the growing demand and scalability of our durable one-time therapies, setting a new benchmark for delivering commercial gene therapy to patients seeking curative therapies. Building on lessons learned from our first launch of ZYNTEGLO, we’ve accelerated access to LYFGENIA for sickle cell patients, shortening timelines and expanding treatment availability. While initial progress has been made, the vast majority of the thousands of individuals who would benefit from receiving LYFGENIA have not yet been treated. Genetix remains determined and committed to invest in its commercial infrastructure throughout the U.S. to further expand access to LYFGENIA to those in need.”

Since FDA approval of ZYNTEGLO (August, 2022) and LYFGENIA (December, 2023), nearly 370 patients have initiated the treatment journey of which 115 have been treated as of mid-November. Lessons learned from the ZYNTEGLO launch along with Genetix’s revamped commercial strategy and ongoing expansion of infrastructure is enabling faster, broader access to LYFGENIA for patients with sickle cell disease.

LYFGENIA Commercial Launch Metrics Compared to ZYNTEGLO

• 2x faster lead time from FDA approval to first patient enrollment
• 167% faster enrollment rates in the first quarter post approval
• 6x more treatment center activations in the first quarter post approval

Genetix will present the full dataset in an oral presentation at the annual ASH meeting. See details below.

Abstract Title: Accelerating Access to Gene Therapy: Lessons from Commercial Implementation in Sickle Cell Disease and Transfusion-Dependent Thalassemia (Abstract #948)

Date & Time: Monday, December 8^th at 4:00pm EST

Please refer to the ASH 2025 online program for full session details and visit the Genetix booth (#1261) onsite.

About LYFGENIA™ (lovotibeglogene autotemcel)

LYFGENIA is a one-time ex-vivo lentiviral vector (LVV) gene addition therapy approved for eligible patients with sickle cell disease, in which a functional β-globin gene is added to patients’ own hematopoietic (blood) stem and progenitor cells (HSPCs). This addition results in the production of adult hemoglobin with anti-sickling properties (HbA^T87Q) which has a similar oxygen-binding affinity to wild-type HbA. LYFGENIA has been shown to limit sickling of red blood cells and reduce or eliminate vaso-occlusive events (VOEs).

LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of VOEs.

Limitations of Use

Following treatment with LYFGENIA, patients with α-thalassemia trait (-α3.7/-α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions.

IMPORTANT SAFETY INFORMATION FOR LYFGENIA (lovotibeglogene autotemcel)

Boxed WARNING: HEMATOLOGIC MALIGNANCY

Hematologic malignancy has occurred in patients treated with LYFGENIA. Monitor patients closely for evidence of malignancy through complete blood counts at least every 6 months and through integration site analysis at Months 6, 12, and as warranted.

Hematologic Malignancy

Hematologic malignancy has occurred in patients treated with LYFGENIA (Study 1, Group A). At the time of initial product approval, two patients treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A) developed acute myeloid leukemia (AML). One patient with α-thalassemia trait (Study 1, Group C) has been diagnosed with myelodysplastic syndrome (MDS).

The additional hematopoietic stress associated with mobilization, conditioning, and infusion of LYFGENIA, including the need to regenerate the hematopoietic system, may increase the risk of a hematologic malignancy. Patients with sickle cell disease have an increased risk of hematologic malignancy as compared to the general population.

Patients treated with LYFGENIA may develop hematologic malignancies and should have lifelong monitoring. Monitor for hematologic malignancies with a complete blood count (with differential) at least every 6 months for at least 15 years after treatment with LYFGENIA, and integration site analysis at Months 6, 12, and as warranted.

In the event that a malignancy occurs, contact Genetix Biotherapeutics at 1-833-999-6378 for reporting and to obtain instructions on collection of samples for testing.

Post-Marketing Long Term Follow-Up Study: Patients who intend to receive treatment with LYFGENIA are encouraged to enroll in the study, as available, to assess the long-term safety of LYFGENIA and the risk of malignancies occurring after treatment with LYFGENIA by calling Genetix Biotherapeutics at 1-833-999-6378. The study includes monitoring (at pre-specified intervals) for clonal expansion.

Delayed Platelet Engraftment

Delayed platelet engraftment has been observed with LYFGENIA. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia. Two patients (4%) required more than 100 days post treatment with LYFGENIA to achieve platelet engraftment.

Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.

Neutrophil Engraftment Failure

There is a potential risk of neutrophil engraftment failure after treatment with LYFGENIA. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 0.5 × 109 cells/L obtained on different days by Day 43 after infusion of LYFGENIA. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with LYFGENIA, provide rescue treatment with the back-up collection of CD34+ cells.

Insertional Oncogenesis

There is a potential risk of lentiviral vector-mediated insertional oncogenesis after treatment with LYFGENIA.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of LYFGENIA. The dimethyl sulfoxide (DMSO) or dextran 40 in LYFGENIA may cause hypersensitivity reactions, including anaphylaxis.

Anti-retroviral Use

Patients should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization and until all cycles of apheresis are completed. There are some long-acting anti-retroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

Hydroxyurea Use

Patients should not take hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed. If hydroxyurea is administered between mobilization and conditioning, discontinue 2 days prior to initiation of conditioning.

Iron Chelation

Drug-drug interactions between iron chelators and the mobilization process and myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of mobilization or conditioning. Do not administer myelosuppressive iron chelators (e.g., deferiprone) for 6 months post-treatment with LYFGENIA. Non-myelosuppressive iron chelation should be restarted no sooner than 3 months after LYFGENIA infusion. Phlebotomy can be used in lieu of iron chelation, when appropriate.

Interference with PCR-based Testing

Patients who have received LYFGENIA are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a possible false-positive PCR assay test result for HIV. Therefore, patients who have received LYFGENIA should not be screened for HIV infection using a PCR-based assay.

Adverse Reactions

The most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia.

Three patients died during LYFGENIA clinical trials; one from sudden cardiac death due to underlying disease and two from acute myeloid leukemia who were treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure (Study 1, Group A).

Pregnancy/Lactation

Advise patients of the risks associated with myeloablative conditioning agents, including on pregnancy and fertility.

LYFGENIA should not be administered to women who are pregnant, and pregnancy after LYFGENIA infusion should be discussed with the treating physician.

LYFGENIA is not recommended for women who are breastfeeding, and breastfeeding after LYFGENIA infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before LYFGENIA administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of LYFGENIA.

Advise patients of the options for fertility preservation.

Please see full Prescribing Information, including Boxed WARNING and Medication Guide for LYFGENIA.

About ZYNTEGLO™ (betibeglogene autotemcel)

ZYNTEGLO is a first-in-class, one-time ex-vivo LVV gene addition therapy approved for eligible patients with transfusion-dependent beta-thalassemia who require regular red blood cell (RBC) transfusions, in which functional copies of a modified form of the beta-globin gene (β^A-T87Q-globin gene) is added into a patient’s own HSPCs. This addition results in the production of adult hemoglobin (HbA^T87Q) enabling total hemoglobin to reach normal or near normal levels. ZYNTEGLO has been shown to eliminate the need for regular RBC transfusions.

ZYNTEGLO is indicated for the treatment of adult and pediatric patients with beta-thalassemia who require regular RBC transfusions.

IMPORTANT SAFETY INFORMATION FOR ZYNTEGLO (betibeglogene autotemcel)

Delayed Platelet Engraftment

Delayed platelet engraftment has been observed with ZYNTEGLO treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in patients with prolonged thrombocytopenia; 15% of patients had ≥ Grade 3 decreased platelets on or after Day 100.

Patients should be made aware of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding according to standard guidelines. Conduct frequent platelet counts until platelet engraftment and platelet recovery are achieved. Perform blood cell count determination and other appropriate testing whenever clinical symptoms suggestive of bleeding arise.

Risk of Neutrophil Engraftment Failure

There is a potential risk of neutrophil engraftment failure after treatment with ZYNTEGLO. Neutrophil engraftment failure is defined as failure to achieve three consecutive absolute neutrophil counts (ANC) ≥ 500 cells/microliter obtained on different days by Day 43 after infusion of ZYNTEGLO. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a patient treated with ZYNTEGLO, provide rescue treatment with the back-up collection of CD34+ cells.

Risk of Insertional Oncogenesis

There is a potential risk of lentiviral vector (LVV)-mediated insertional oncogenesis after treatment with ZYNTEGLO.

Patients treated with ZYNTEGLO may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) at Month 6 and Month 12 and then at least annually for at least 15 years after treatment with ZYNTEGLO, and integration site analysis at Months 6, 12, and as warranted.

In the event that a malignancy occurs, contact Genetix Biotherapeutics at 1 833-999-6378 for reporting and to obtain instructions on collection of samples for testing.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of ZYNTEGLO. The dimethyl sulfoxide (DMSO) in ZYNTEGLO may cause hypersensitivity reactions, including anaphylaxis.

Anti-retroviral and Hydroxyurea Use

Patients should not take prophylactic HIV anti-retroviral medications or hydroxyurea for at least one month prior to mobilization, or for the expected duration for elimination of the medications, and until all cycles of apheresis are completed. If a patient requires anti-retrovirals for HIV prophylaxis, then confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.

Interference with Serology Testing

Patients who have received ZYNTEGLO are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a false-positive test for HIV. Therefore, patients who have received ZYNTEGLO should not be screened for HIV infection using a PCR-based assay.

Adverse Reactions

The most common non-laboratory adverse reactions (≥20%) were mucositis, febrile neutropenia, vomiting, pyrexia, alopecia, epistaxis, abdominal pain, musculoskeletal pain, cough, headache, diarrhea, rash, constipation, nausea, decreased appetite, pigmentation disorder, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (>50%) include neutropenia, thrombocytopenia, leukopenia, anemia, and lymphopenia.

Drug Interactions

Drug-drug interactions between iron chelators and the myeloablative conditioning agent must be considered. Iron chelators should be discontinued at least 7 days prior to initiation of conditioning. The prescribing information for the iron chelator(s) and the myeloablative conditioning agent should be consulted for the recommendations regarding co-administration with CYP3A substrates.

Some iron chelators are myelosuppressive. After ZYNTEGLO infusion, avoid use of these iron chelators for 6 months. If iron chelation is needed, consider administration of non-myelosuppressive iron chelators. Phlebotomy can be used in lieu of iron chelation, when appropriate.

Pregnancy/Lactation

Advise patients of the risks associated with conditioning agents, including on pregnancy and fertility.

ZYNTEGLO should not be administered to women who are pregnant, and pregnancy after ZYNTEGLO infusion should be discussed with the treating physician.

ZYNTEGLO is not recommended for women who are breastfeeding, and breastfeeding after ZYNTEGLO infusion should be discussed with the treating physician.

Females and Males of Reproductive Potential

A negative serum pregnancy test must be confirmed prior to the start of mobilization and re-confirmed prior to conditioning procedures and before ZYNTEGLO administration.

Women of childbearing potential and men capable of fathering a child should use an effective method of contraception (intra uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of ZYNTEGLO.

Advise patients of the option to cryopreserve semen or ova before treatment if appropriate.

Please see full Prescribing Information and Patient Information for ZYNTEGLO.

About Genetix Biotherapeutics

Genetix Biotherapeutics Inc. is a privately-held, commercial-stage biotechnology company dedicated to delivering genetic therapies for patients with severe rare diseases. Backed by more than 30 years of pioneering genetic therapy innovation, the company has FDA-approved treatments for sickle cell disease, β-thalassemia, and cerebral adrenoleukodystrophy that directly treat the underlying cause of disease. Genetix is committed to commercial execution, scaling patient access, and improving the treatment experience for patients and providers. Genetix is headquartered in Somerville, Massachusetts.

Contacts

For media inquiries:
info@GenetixBioTx.com

Website: www.GenetixBioTx.com

Vertex Presents New Data on CASGEVY®, Including First-Ever Data in Children Ages 5-11 Years, at the American Society of Hematology Annual Meeting and Announces Plan for Global Regulatory Submissions




Vertex Presents New Data on CASGEVY®, Including First-Ever Data in Children Ages 5-11 Years, at the American Society of Hematology Annual Meeting and Announces Plan for Global Regulatory Submissions

– Data from pivotal studies of CASGEVY in children ages 5-11 years with severe sickle cell disease or transfusion-dependent beta thalassemia demonstrates the transformative potential of the therapy in younger patients –

– Efficacy and safety data in children 5-11 years are consistent with the durable and positive benefit/risk profile established from clinical studies in patients 12 years of age and older –

– Vertex expects to initiate global regulatory submissions for CASGEVY in children 5-11 years in 1H 2026 –

BOSTON–(BUSINESS WIRE)–Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced data from multiple studies demonstrating the clinical benefits of CASGEVY^® (exagamglogene autotemcel) in people ages 5 years and older living with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The results, including the first presentation of clinical data from pivotal studies in children ages 5-11 years, and longer-term data from the pivotal studies of people with severe SCD and TDT ages 12 years and older, will be presented at the American Society of Hematology (ASH) Annual Meeting. CASGEVY is currently approved for eligible people ages 12 years and older with SCD or TDT in the United States, Great Britain, the European Union, the Kingdom of Saudi Arabia, the Kingdom of Bahrain, Kuwait, Qatar, Canada, Switzerland and the United Arab Emirates.

“These results — the first clinical data ever presented on any genetic therapy for children ages 5-11 years with SCD — again demonstrate the transformative potential of CASGEVY,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “With dosing completed in the 5-11 age group and the Commissioner’s National Priority Voucher for CASGEVY in this population in hand, we are excited to begin global regulatory filings in the first half of next year and bring this potentially transformative therapy to eligible children as soon as possible.”

“As an investigator in the clinical program for patients 12 years and older and after having real-world experience with CASGEVY as an early commercial treatment center, I have seen firsthand the transformative impact this therapy has had on older patients with SCD or TDT. I am excited to hopefully be able to offer this option to my younger patients soon, early in life, before some of the most devastating impacts of these diseases begin,” said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital, Member of Vertex’s SCD Program Steering Committee, and presenting author of the 5-11 years old CASGEVY data at ASH.

First presentation of data in children ages 5-11 years treated with CASGEVY

• In children with SCD, 11 patients have been dosed with CASGEVY in the Phase 3 CLIMB-151 clinical study, and all (4/4) patients with sufficient follow-up achieved the primary endpoint of being free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12).
  • No patient experienced a VOC following infusion with CASGEVY, with the longest duration of VOC-free of approximately two years (range 3.2–24.1 months).
• In children with TDT, 13 patients have been dosed with CASGEVY in the Phase 3 CLIMB-141 clinical study, and all (6/6) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin (Hb) of at least 9 g/dL (TI12).
  • Following CASGEVY infusion, 12/13 are transfusion free, with the longest duration of transfusion free just under two years (range 2.3–22.5 months).
  • One patient died from pneumonia in the setting of multi-organ failure due to severe veno-occlusive disease related to the busulfan conditioning.
• The safety profile of CASGEVY in younger patients is consistent with myeloablative conditioning and autologous transplant in both SCD and TDT, as established in clinical studies in older patients.
• Consistent with studies in older patients, children treated with CASGEVY have durable increases in fetal hemoglobin (HbF) and stable allelic editing.

Longer-term data for people with SCD and TDT ages 12 years and older treated with CASGEVY

New longer-term data from the pivotal clinical studies of CASGEVY in people 12 years and older will also be presented at ASH. These data, as of April 2025, continue to demonstrate the transformative, durable clinical benefits that CASGEVY provides to people living with SCD or TDT. In SCD, 100% of patients (45/45) achieved VF12 in either CLIMB-121 or the long-term follow-up study CLIMB-131, with a mean duration of VOC-free for 35.3 months (range 12.9–67.7 months). In TDT, 98.2% (55/56) achieved TI12 in either CLIMB-111 or CLIMB-131 with a mean duration of transfusion independence of 41.4 months (range 13–72.3 months). The safety profile remained consistent with myeloablative conditioning and autologous transplant in both SCD and TDT.

About Sickle Cell Disease (SCD)

SCD is a debilitating, progressive and life-shortening disease. It is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or “sickled” red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires a lifetime of treatment and results in a reduced life expectancy. In the U.S., the median age of death for patients living with SCD is approximately 45 years. SCD patients report health-related quality of life scores well below the general population, and the lifetime health care costs in the U.S. of managing SCD for patients with recurrent VOCs is estimated between $4 and $6 million.

About Transfusion-Dependent Beta Thalassemia (TDT)

TDT is a serious, life-threatening genetic disease. It requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In the U.S., the median age of death for patients living with TDT is 37 years. TDT patients report health-related quality of life scores below the general population and the lifetime health care costs in the U.S. of managing TDT are estimated between $5 and $5.7 million.

About CASGEVY^® (exagamglogene autotemcel)

CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

The use of CASGEVY in children ages 5-11 years is investigational.

About the CLIMB Studies

The Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients will be followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5-11-years-old cohort in both studies with the plan to extend to ages 2-4 years.

Each patient will be asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion.

Next steps for CASGEVY in children ages 5-11 years

Enrollment and dosing are complete for the 5-11 years cohort in both studies. Vertex expects to initiate global regulatory filings for this age group, including a supplemental Biologics License Application (sBLA) in the U.S., in the first half of next year. Vertex recently received a Commissioner’s National Priority Voucher for CASGEVY in the 5-11 years age group from the U.S. Food and Drug Administration to accelerate the review of the sBLA once submitted. Products under the program will be subject to a 1–2-month review clock from the start of FDA’s review and will also benefit from enhanced communication opportunities with the agency.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people ages 12 years and older with:

• sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs
• beta thalassemia (β-thalassemia) who need regular blood transfusions

CASGEVY is made specifically for each patient, using the patient’s own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

• Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells:
  • severe headache
  • abnormal bruising
  • prolonged bleeding
  • bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood

• Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells:
  • fever
  • chills
  • infections

You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

• Do not donate blood, organs, tissues, or cells at any time in the future

What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

• Low levels of platelet cells, which may reduce the ability of blood to clot and may cause bleeding
• Low levels of white blood cells, which may make you more susceptible to infection

Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

• fever
• chills
• infections
• severe headache
• abnormal bruising
• prolonged bleeding
• bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood

These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases and conditions. The company has approved therapies for cystic fibrosis, sickle cell disease, transfusion-dependent beta thalassemia and acute pain, and it continues to advance clinical and research programs in these areas. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.

Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry’s top places to work, including 16 consecutive years on Science magazine’s Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and X.

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Carmen Bozic, M.D., and Haydar Frangoul, M.D., M.S., and statements regarding expectations for the clinical benefits of CASGEVY, plans to initiate global regulatory submissions for children 5-11, including in the U.S., in the first half of 2026, expectations that the use of a Priority Voucher will accelerate the review of the sBLA, expectations for the design of the CLIMB studies, including plans to follow patients after infusion, expectations that each patient will be asked to participate in the CLIMB-131 study and expectations that the studies will be extended to children 2-4 years of age. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company’s beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company’s research and development programs may not support registration or further development of its potential medicines in a timely manner, or at all, due to safety, efficacy or other reasons, that the company may be unable to make the anticipated regulatory submissions on the expected timeline, or at all, and other risks listed under the heading “Risk Factors” in Vertex’s most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at www.sec.gov and available through the company’s website at www.vrtx.com. You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

Contacts

Vertex Pharmaceuticals Incorporated

Investors:

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Stoke Therapeutics and Biogen Present Data that Further Support the Disease-Modifying Potential of Zorevunersen, an Investigational Medicine for the Treatment of Dravet Syndrome, at the 2025 American Epilepsy Society (AES) Annual Meeting




Stoke Therapeutics and Biogen Present Data that Further Support the Disease-Modifying Potential of Zorevunersen, an Investigational Medicine for the Treatment of Dravet Syndrome, at the 2025 American Epilepsy Society (AES) Annual Meeting

—Long-term Phase 1/2a and open label extension (OLE) data for zorevunersen on top of standard of care anti-seizure medicines (ASMs) demonstrate durable seizure reductions, including increases in seizure-free days, in addition to improvements in cognition, behavior and quality of life—

—Propensity score weighted analysis comparing the effects of zorevunersen to natural history showed reductions in seizures and improvements in cognition and behavior with dose levels and timepoints similar to and consistent with the ongoing Phase 3 EMPEROR study—

—Analysis of electroencephalogram (EEG) supports a disease-modifying mechanism of action—

BEDFORD, Mass. & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, and Biogen Inc. (Nasdaq: BIIB) today announced data presentations that further support the potential of zorevunersen, an investigational antisense oligonucleotide, as a disease-modifying medicine for Dravet syndrome. These data were presented at the 2025 American Epilepsy Society (AES) Annual Meeting in Atlanta, Georgia.

Long-term results from the ongoing Phase 1/2a and open label extension (OLE) studies demonstrated durable seizure reductions, including increases in seizure-free days, in addition to improvements in cognition, behavior and quality of life in patients treated with zorevunersen on top of standard of care anti-seizure medicines (ASMs). A new propensity score weighted analysis provides the first direct comparison between patients with Dravet syndrome treated with zorevunersen and a matched cohort from the BUTTERFLY natural history study and showed reductions in seizures and improvements in cognition and behavior with dose levels and timepoints similar to and consistent with the ongoing Phase 3 EMPEROR study.

“Over the last four years we have gained an increasing appreciation for the potential to change the course of Dravet syndrome with new disease-modifying medicines. Open-label data from the zorevunersen clinical studies have been highly encouraging, bringing hope and anticipation to the Dravet community,” said M. Scott Perry, M.D., Head of Neurosciences and Director of the Jane and John Justin Institute for Mind Health and Medical Director of the Genetic Epilepsy Clinic at Cook Children’s Medical Center. “In addition, the new propensity score weighted analysis comparing zorevunersen treatment to patients treated with the current standard of care gives us further context for the improvements we’re seeing in patients living with this devastating disease.”

Propensity Score Weighted Analysis

A propensity score weighted analysis, designed to mimic randomization by adjusting for baseline differences between treated and untreated (natural history) patient groups, showed patients receiving two loading doses of zorevunersen (70mg) experienced statistically significant reductions in major motor seizure frequency at six months compared to natural history. Six months is consistent with the Week 28 Phase 3 primary endpoint measuring the effects of zorevunersen on seizure frequency. With continued dosing at 45mg, improvements in five key assessments of cognition and behavior as measured by Vineland-3 were shown at 18 months, with several reaching statistical significance. At the 18-month timepoint, cumulative dosing is similar to and consistent with a key secondary endpoint in the Phase 3 EMPEROR study. Durable effects were demonstrated through 24 months, the longest evaluable timepoint in the BUTTERFLY natural history study.

“Data from this analysis, which allows us to match patients treated with zorevunersen directly to natural history, add to a growing body of information shaping our understanding of Dravet syndrome and the effects of zorevunersen over time,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “As we continue to progress our Phase 3 EMPEROR program and await safety and efficacy data from this larger, sham-controlled study, results presented at AES give us additional confidence in what zorevunersen may one day offer to patients and their families.”

“In addition to these important efficacy findings, we are also encouraged by the accumulating long-term safety data, with some patients treated with up to 15 doses over more than four years,” said Katherine Dawson, M.D., Head of the Therapeutics Development Unit at Biogen. “The totality of clinical data, in addition to the new EEG findings, demonstrates zorevunersen’s potential to restore protein function and address the underlying cause of Dravet syndrome to improve debilitating symptoms like seizures and cognitive impairment.”

Electroencephalogram (EEG) Results

Data from an analysis of EEGs performed in patients treated with zorevunersen highlighted the dose-dependent effects of zorevunersen in decreasing abnormal brain activity that is persistently higher in patients with Dravet syndrome. The analysis also showed that a reduction in abnormal EEG activity in the brain was associated with an increased probability of achieving a meaningful reduction in seizure frequency.

Summary of Zorevunersen Safety Data

Eighty-one patients received at least one dose of zorevunersen and have been evaluated for safety, and more than 800 doses have been administered to date. Zorevunersen has been generally well tolerated across the Phase 1/2a and OLE studies. Study drug related treatment emergent adverse events (TEAEs) were observed in 30% (24/81) and 53% (40/75) of patients treated in the Phase 1/2a and OLE studies, respectively. The most common study drug related TEAE was CSF protein elevations reported in 14% (11/81) of patients in the Phase 1/2a studies and 45% (33/75) of patients in the OLE studies. CSF protein elevations (>50 mg/dL) occurred in 42% (34/81) of patients in the Phase 1/2a studies and 86% (62/72) of patients in the OLE studies. No related clinical manifestations have been observed although one patient discontinued treatment due to elevated CSF protein levels. Treatment-emergent serious adverse events (TESAEs) were reported in 22% (18/81) and 29% (22/75) of patients in the Phase 1/2a and OLE studies, respectively, all of which were assessed to be unrelated to zorevunersen except one patient who experienced SUSARs. Three patient deaths have been reported across the Phase 1/2a and OLE studies, two from sudden unexpected death in epilepsy (SUDEP) and one from malnutrition. All were unrelated to zorevunersen.

Details of the AES Presentations:

• Title: Zorevunersen Continues to Demonstrate Potential as a Disease-modifying Therapy in Long-term Open-label Extension Studies of Patients with Dravet Syndrome
  
  Oral Presentation Date & Time: Friday, December 5, 3:30-5:55 PM EST
  
  Oral Presenter: M. Scott Perry, M.D., Head of Neurosciences and Director of the Jane and John Justin Institute for Mind Health and Medical Director of the Genetic Epilepsy Clinic at Cook Children’s Medical Center

• Title: Zorevunersen Demonstrates Disease-modifying Potential in Patients with Dravet Syndrome with Increases in Seizure-free Days, Improvements in Quality of Life, and Benefits in Overall Clinical Status
  
  Poster Presentation Date & Time: Saturday, December 6, 12:00-2:00 PM EST
  
  Poster Presenter: Kelly Knupp, M.D., MSCS, Professor of Pediatrics and Neurology at the University of Colorado Anschutz and the Dravet Program Director and Epilepsy Program Lead at Children’s Hospital Colorado
  
  Poster Number: 1.379

• Title: Zorevunersen Continues to Demonstrate Potential as a Disease-modifying Therapy in Long-term Open-label Extension Studies of Patients with Dravet Syndrome
  
  Poster Presentation Date & Time: Sunday, December 7, 12:00-2:00 PM EST
  
  Poster Presenter: M. Scott Perry, M.D., Head of Neurosciences and Director of the Jane and John Justin Institute for Mind Health and Medical Director of the Genetic Epilepsy Clinic at Cook Children’s Medical Center
  
  Poster Number: 2.341

• Title: Spectral Electroencephalogram Abnormalities Across Development in Patients with Dravet Syndrome
  
  Poster Presentation Date & Time: Sunday, December 7, 12:00-2:00 PM EST
  
  Poster Presenter: Pieter van Mierlo, Founder and Chief Scientific Officer, Epilog, Clouds of Care, Associate Professor, Ghent University
  
  Poster Number: 2.432

• Title: Electrophysiological Improvements in Patients with Dravet Syndrome Following Treatment with Zorevunersen, an Investigational Antisense Oligonucleotide
  
  Poster Presentation Date & Time: Monday, December 8, 12:00-1:45 PM EST
  
  Poster Presenter: Nigel Colenbier, Senior Data Scientist, Epilog, Clouds of Care
  
  Poster Number: 3.489

About Dravet Syndrome

Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. Even when treated with the best available anti-seizure medicines (ASMs), up to 57 percent of patients with Dravet syndrome do not achieve ≥50 percent reduction in seizure frequency. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments often include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP; up to 20 percent of children and adolescents with Dravet syndrome die before adulthood due to SUDEP, prolonged seizures, seizure-related accidents or infections¹. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan. ² There are no approved disease-modifying therapies for people living with Dravet syndrome.

About Zorevunersen

Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the non-mutated (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition, and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights.

About the EMPEROR Study

The EMPEROR Phase 3 Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety, and tolerability of zorevunersen in children ages 2 to <18 with Dravet syndrome with a confirmed variant in the SCN1A gene not associated with gain-of-function. The trial is currently enrolling patients within the United States and is expected to enroll participants across Japan, United Kingdom and European Union, with participants being randomized 1:1 to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an 8-week baseline period. Following the completion of the study, eligible participants will be offered ongoing treatment with zorevunersen as part of an OLE study. The primary endpoint of the study is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen as compared to sham. The key secondary endpoints are the durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains, including expressive communication, receptive communication, interpersonal relationships, coping skills and personal skills. Additional endpoints include safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C), and the Bayley Scales of Infant Development (BSID-IV). For more information, visit https://www.emperorstudy.com/.

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/.

About Biogen

Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.

We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media – Facebook, LinkedIn, X, YouTube.

Stoke Therapeutics Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; the potential benefits, safety and efficacy of zorevunersen; the timing and expected progress of clinical trials, data readouts, regulatory meetings, regulatory decisions and other presentations; and the participation of scientists associated with Stoke making presentations at AES 2025 and the presentation of data at AES 2025. Statements including words such as “plan,” “potential,” “will,” “continue,” “expect,” or similar words and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause Stoke’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: Stokes ability to advance, obtain regulatory approval and ultimately commercialize its product candidates; that if Biogen were to breach or terminate the collaboration, Stoke would not obtain the anticipated financial or other benefits; the possibility that Stoke and Biogen may not be successful in their development of zorevunersen and that, even if successful, they may be unable to successfully commercialize zorevunersen; positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; Stoke’s ability to protect its intellectual property; Stoke’s ability to fund development activities and achieve development goals to mid-2028; and the other risks and uncertainties described under the heading “Risk Factors” in its Annual Report on Form 10-K for the year ended December 31, 2024, its quarterly reports on Form 10-Q, and the other documents it files with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Stoke undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

Biogen Safe Harbor

This news release contains forward-looking statements, including, among others, relating to: the potential clinical effects of zorevunersen; the potential for zorevunersen to improve outcomes and for patients of Dravet syndrome; the potential benefits, safety and efficacy of zorevunersen and continued treatment with zorevunersen; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Dravet syndrome; the anticipated benefits, risks and potential of Biogen’s collaboration arrangements with Stoke Therapeutics; the potential of Biogen’s commercial business and pipeline programs, including zorevunersen; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,” “goal,” “guidance,” “hope,” “intend,” “may,” “objective,” “outlook,” “plan,” “possible,” “potential,” “predict,” “project,” “prospect,” “should,” “target,” “will,” “would” or the negative of these words or other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements. Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements.

These forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to differ materially from those stated or implied in this document, including, among others, uncertainty of our long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans, prospects and timing of actions relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; the potential impact of increased product competition in the biopharmaceutical and healthcare industry, as well as any other markets in which we compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our corporate strategy; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks related to commercialization of biosimilars, which is subject to such risks related to our reliance on third-parties, intellectual property, competitive and market challenges and regulatory compliance; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; and the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in other reports we have filed with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at www.sec.gov.

These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise.

Digital Media Disclosure

From time to time, we have used, or expect in the future to use, our investor relations website (investors.biogen.com), the Biogen LinkedIn account (linkedin.com/company/biogen-) and the Biogen X account (https://x.com/biogen) as a means of disclosing information to the public in a broad, non-exclusionary manner, including for purposes of the SEC’s Regulation Fair Disclosure (Reg FD). Accordingly, investors should monitor our investor relations website and these social media channels in addition to our press releases, SEC filings, public conference calls and websites, as the information posted on them could be material to investors.

References:

1. Symonds, J. et al. Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants. Brain. 2021;144(9):2879-2891.
2. Based on Stoke Therapeutics’ preliminary estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality.

Contacts

Stoke Media & Investor Contacts:
Susan Willson

Vice President, Corporate Communications

swillson@stoketherapeutics.com
415-509-8202

Doug Snow

Director, Communications & Investor Relations

IR@stoketherapeutics.com
508-642-6485

Biogen Media Contact:
Madeleine Shin

Public.affairs@biogen.com
+ 1 781 464 3260

Biogen Investor Contact:
Tim Power

IR@biogen.com
+1 781 464 2442

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Amylyx Pharmaceuticals Announces New Safety and Tolerability Cohort 1 Data of AMX0114 in ALS from First-in-Human LUMINA Trial




Amylyx Pharmaceuticals Announces New Safety and Tolerability Cohort 1 Data of AMX0114 in ALS from First-in-Human LUMINA Trial

– AMX0114 was generally well-tolerated, with no treatment-related serious adverse events

– Amylyx will proceed with opening enrollment of second cohort

– Data are being presented at the 36^th International Symposium on ALS/MND

CAMBRIDGE, Mass.–(BUSINESS WIRE)–$AMLX—Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) (“Amylyx” or the “Company”) today announced the presentation of early safety and tolerability data from its Phase 1 LUMINA trial of AMX0114 and results from ongoing work characterizing biomarkers of AMX0114 target engagement at the 36^th International Symposium on ALS/MND (MNDA) held from December 5-7 in San Diego, California. AMX0114 was generally well-tolerated in LUMINA trial participants enrolled in cohort 1 (n=12), with no treatment-related serious adverse events (SAEs). Based on these data, Amylyx expects to begin enrolling the second cohort of participants in Canada later this month and in the U.S. in January.

“LUMINA is a first-in-human study, and we are encouraged by these data as we continue to advance AMX0114 as a potential treatment for this rapidly progressive disease with high unmet need. The safety and tolerability analysis allows LUMINA to proceed with its next cohort of participants, which is critical given that this community has no time to wait,” said Sabrina Paganoni, MD, PhD, principal investigator of the LUMINA trial, investigator at the Sean M. Healey & AMG Center for ALS at Mass General Brigham, and member of the Scientific Advisory Board of the Network of Excellence for ALS (NEALS).

The LUMINA trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose clinical trial of AMX0114 – an investigational, potent antisense oligonucleotide (ASO) targeting calpain-2 – in people living with amyotrophic lateral sclerosis (ALS). LUMINA is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS and assessing both novel and broadly researched ALS biomarkers, including change from baseline in neurofilament light chain (NfL) levels. Amylyx expects biomarker data from the first cohort of LUMINA participants (n=12) in the first half of 2026.

“We appreciate the partnership with LUMINA sites and participants to achieve complete enrollment of the first cohort. In addition, we are pleased that to date no drug-related SAEs or dose-limiting toxicities were observed, which represent important early steps in this study,” said Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx. “AMX0114 is designed to inhibit calpain-2, a calcium-activated protease that is one of the fundamental drivers of axonal degeneration and consequent disease progression in ALS. Preclinical studies have demonstrated that treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in calpain-2 protein levels, translating to improved neuronal survival and reductions in extracellular NfL levels. We look forward to presenting cohort 1 biomarker data at a medical meeting in the first half of next year.”

The MNDA presentation details are as follows:

Friday, December 5, 2025, Session A, 5:30-7pm Pacific Time:

Title: A Phase 1, Multicenter, Randomized, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety and Tolerability of AMX0114 in Amyotrophic Lateral Sclerosis (LUMINA)

Presenting Author: Sabrina Paganoni, MD, PhD, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Harvard Medical School, Spaulding Rehabilitation Hospital, Harvard Medical School

Poster Number: CLT-14

Saturday, December 6, 2025, Session 6B: Biomarkers, 10:50-11:10am Pacific Time:

Title: Characterizing the CSF Biomarker Signature of Calpain-2 Activity in ALS and the Biomarker Impact of Calpain-2 Inhibition in a Preclinical Model of ALS

Presenting Author: Robert Bowser, PhD, Barrow Neurological Institute and nVector, Inc.

For MNDA conference information, visit https://symposium.mndassociation.org/. Abstracts have been published as an online open access supplement of Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. The presentations will be available on the “Events & Presentations” tab of the Amylyx website.

About AMX0114

AMX0114 is an investigational antisense oligonucleotide (ASO) with U.S. Food and Drug Administration (FDA) Fast Track designation for the potential treatment of ALS. AMX0114 targets calpain-2 (CAPN2), a calcium-activated protease that is one of the fundamental drivers of axonal degeneration and consequent disease progression in ALS. In preclinical studies, treatment with AMX0114 resulted in potent, dose-dependent, and durable reduction in CAPN2 mRNA and calpain-2 protein levels in disease-relevant cell models of axonal degeneration. This translated to improved neuronal survival, including in a model of TDP-43 ALS, and reductions in extracellular neurofilament light (NfL) levels across multiple disease models and paradigms of neuronal injury. AMX0114 was generally well-tolerated in LUMINA trial participants enrolled in cohort 1 (n=12), with no treatment-related serious adverse events (SAEs).

About LUMINA

The Phase 1 LUMINA clinical trial (NCT06665165) is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS. LUMINA will also assess change from baseline in calpain-2 levels, neurofilament light (NfL) levels, and other pharmacodynamic biomarkers of ALS. LUMINA is anticipated to enroll approximately 48 adult participants. Participants will be randomized 3:1 to receive AMX0114 or placebo by intrathecal administration once every four weeks for a total of up to 4 doses. Study sites are active in Canada and the United States, and the first cohort has been fully enrolled. Amylyx expects to begin enrolling the second cohort of participants in Canada in December and in the U.S. in January.

About ALS

Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) is a relentlessly progressive and fatal neurodegenerative disorder caused by motor neuron death in the brain and spinal cord. One of the ways ALS progresses is through axonal degeneration, which disrupts neural connectivity and contributes significantly to disease pathology. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis, and eventually, death. More than 90% of people with ALS have sporadic disease, showing no clear family history.

About Amylyx Pharmaceuticals

At Amylyx, our mission is to usher in a new era of treating diseases with high unmet needs. Where others see challenges, we see opportunities that we pursue with urgency, rigorous science, and unwavering commitment to the communities we serve. We are currently focused on three investigational therapies across several neurodegenerative and endocrine diseases in which we believe they can make the greatest impact. For more information, visit amylyx.com and follow us on LinkedIn and X. For investors, please visit investors.amylyx.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, Amylyx’ expectations regarding: the potential for AMX0114 as a treatment for ALS, the expected timeline for enrollment of future cohorts, and the expected timeline for data readout. Any forward-looking statements in this press release and related comments in the Company’s earnings conference call are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of Amylyx’ program development activities; Amylyx’ ability to execute on its regulatory development plans and expectations regarding the timing of results from its planned data announcements and initiation of clinical studies; the risk that early-stage results may not reflect later-stage results; Amylyx’ ability to fund operations, and the impact that global macroeconomic uncertainty, geopolitical instability, and public health events will have on Amylyx’ operations, as well as the risks and uncertainties set forth in Amylyx’ United States Securities and Exchange Commission (SEC) filings, including Amylyx’ Annual Report on Form 10-K for the year ended December 31, 2024, and subsequent filings with the SEC. All forward-looking statements contained in this press release and related comments in our earnings conference call speak only as of the date on which they were made. Amylyx undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

Contacts

Media
Amylyx Media Team

(857) 799-7274

amylyxmediateam@amylyx.com

Investors
Lindsey Allen

(857) 320-6244

Investors@amylyx.com