Marea Therapeutics Launches with $190 Million to Accelerate a New Generation of Medicines for Cardiometabolic Diseases

Leveraging large-scale human genetics to advance clinical-stage pipeline of first-in-class treatments that target critical, unaddressed and genetically validated causes of cardiometabolic diseases

Lead program, MAR001, is a first-in-class ANGPTL4 inhibitor in Phase 2 clinical development aiming to address the untreated lipid and metabolic drivers of cardiovascular events in high-risk patients

Company incubated by Third Rock Ventures with distinguished scientific founders and leading investor syndicate including Sofinnova Investments, Forbion, Perceptive Xontogeny Venture Fund, venBio, Omega Funds, Alpha Wave Global and Surveyor Capital (a Citadel company)

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Marea Therapeutics, a clinical-stage biotechnology company incubated by Third Rock Ventures to develop a new generation of medicines for cardiometabolic diseases, launched today with $190 million in combined Series A and B financings. The Series A round was led by Third Rock Ventures and the Series B round was led by Sofinnova Investments and co-led by Forbion, Perceptive Xontogeny Venture Fund and venBio, with the participation of Alpha Wave Global, Omega Funds, Surveyor Capital (a Citadel company) and founding investor Third Rock Ventures. This financing will fund the company’s MAR001 Phase 2 development plan and further progression of additional pipeline programs.

Marea aims to transform the way cardiometabolic diseases are treated by leveraging large-scale human genetics and expertise in adipose function and biology to pursue genetically validated targets focusing on central – but unaddressed – drivers of cardiometabolic disease risk,” said Josh Lehrer, M.D., M.Phil., FACC, chief executive officer of Marea. “This approach could be the next frontier for patients with cardiometabolic disease who remain at very high risk, despite currently available therapies.”

With initial clinical validation, world-class scientific founders and investors, and an experienced board and leadership team, Marea is poised to become a premier cardiometabolic disease company,” said Jeffrey Tong, Ph.D., board member and partner, Third Rock Ventures. “We aim to accelerate a new generation of medicines, including MAR001, that treat key unaddressed drivers of cardiometabolic disease, potentially providing important new therapeutic options for millions of patients.”

Targeting Cardiometabolic Diseases at their Source

Marea’s lead program, MAR001, is a monoclonal antibody that targets ANGPTL4, a protein that is highly expressed in adipose tissue. By inhibiting ANGPTL4 and thereby preferentially augmenting adipose tissue lipoprotein lipase (LPL) activity, MAR001 aims to lower remnant cholesterol, improve adipose tissue and metabolic function, and reduce cardiovascular events. Remnant cholesterol is carried by triglyceride-rich lipoproteins, is highly atherogenic, and drives cardiovascular events independent of classical risk factors like LDL cholesterol, diabetes or obesity1. There are currently no available targeted therapies to lower remnant cholesterol and improve metabolic function.

Human genetics has demonstrated ANGPTL4 as a highly promising therapeutic target to lower remnant cholesterol with loss of function alleles leading to remnant cholesterol clearance, improved triglyceride distribution, improved insulin sensitivity, and protection from both cardiovascular disease and type 2 diabetes all via an adipose specific mechanism.

Preclinical models with MAR001 demonstrated reduction in triglycerides, remnant cholesterol and ectopic fat (storage of triglycerides in tissues other than adipose tissue), and improved insulin sensitivity. MAR001 has demonstrated strong Phase 1 results and is in Phase 2 clinical development for adults with metabolic dysfunction.

ANGPTL4 human genetics shows the potential to essentially reverse the adipose dysfunction responsible for the metabolic syndrome- which is not adequately treated by current therapies including weight loss and LDL cholesterol treatment. More than five million cardiovascular patients in the U.S. alone have elevated remnant cholesterol putting them at risk for a heart attack,” said Ethan J. Weiss, M.D., co-founder and chief scientific officer of Marea. “MAR001 has the potential to provide unique benefit to these patients by correcting the underlying adipose dysfunction leading to both elevated remnant cholesterol and metabolic dysfunction.”

In a Phase 1 trial, a single dose of MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers. We are very excited about this compound’s potential,” said Maha Katabi, Ph.D., general partner, Sofinnova Investments. “Led by renowned experts in genetics and cardiometabolic diseases, Marea is well positioned to advance MAR001 and other pipeline programs, potentially unlocking a new era in cardiovascular care.”

Marea is also advancing a pipeline of additional candidates aimed to address additional untapped nodes driving cardiometabolic diseases.

Management and Organization

Marea is led by a dynamic team of scientists and company builders with deep know-how and experience in human genetics, adipocyte biology and cardiometabolic disease drug development.

Marea founders include:

  • Charles Homcy, M.D., partner emeritus, Third Rock Ventures
  • Sir Stephen O’Rahilly, M.D., FRS, professor of clinical biochemistry and medicine, University of Cambridge
  • Joshua Rabinowitz, M.D., Ph.D., professor of chemistry & integrative genomics, Princeton University
  • Ethan J. Weiss, M.D., chief scientific officer

Marea management team members include:

  • Christine Garrett, Ph.D., chief strategy officer
  • Mark Joing, MBA, chief development operations officer
  • Josh Lehrer, M.D., M.Phil., FACC, chief executive officer
  • Ethan J. Weiss, M.D., scientific founder and chief scientific officer

Marea board members include:

  • Ted Love, M.D., chairman, former president and chief executive officer of Global Blood Therapeutics (acquired by Pfizer) and chairman, Biotechnology Innovation Organization (BIO)
  • Antoine Boulanger, Ph.D., principal, Forbion
  • Jung Choi, MBA, entrepreneur in residence, Third Rock Ventures
  • Chris Garabedian, venture portfolio manager, Perceptive Advisors
  • Maha Katabi, Ph.D., general partner, Sofinnova Investments
  • Josh Lehrer, M.D., M.Phil., FACC, chief executive officer
  • Aaron Royston, M.D., managing partner, venBio
  • Jeffrey Tong, Ph.D., partner, Third Rock Ventures

With its focused scientific approach and differentiated first-in-class development programs, Marea has the potential to become a leading company in the cardiometabolic disease space,” said Dr. Love. “I am thrilled to partner with this talented board and management team to advance MAR001 and other programs for patients who are in need of breakthrough cardiometabolic disease therapies.”

About Marea

Marea Therapeutics is a clinical-stage biotechnology company harnessing the latest advances in human genetics to develop first-in-class, next-generation medicines for cardiometabolic diseases. The company’s lead program, MAR001, is in Phase 2 clinical development to lower remnant cholesterol in adults with metabolic dysfunction and high risk for cardiovascular disease. Marea is led by a dynamic team of scientists and company builders with deep know-how and experience in cardiometabolic diseases, human genetics and adipocyte biology. To learn more, please visit www.mareatx.com and follow us on LinkedIn and X.

1 https://doi.org/10.1161/CIRCIMAGING.121.012615Circulation: Cardiovascular Imaging. 2021;14:e012615

Contacts

Media:

1AB

Katie Engleman

katie@1abmedia.com

Investors:

1AB

Steve Klass

steve@1abmedia.com

Geron Announces FDA Approval of RYTELO™ (imetelstat), a First-in-Class Telomerase Inhibitor, for the Treatment of Adult Patients with Lower-Risk MDS with Transfusion-Dependent Anemia

  • Approval across ESA ineligible and ESA relapsed/refractory patients with LR-MDS with transfusion-dependent anemia, regardless of ring sideroblast (RS) status
  • Durable and sustained red blood cell transfusion independence, increases in hemoglobin levels and reduction in transfusion burden observed across key LR-MDS subgroups in the IMerge Phase 3 clinical trial; the most common Grade 3/4 adverse reactions were thrombocytopenia and neutropenia, which were generally manageable and short-lived
  • Lower-risk MDS is a progressive blood cancer with high unmet need, where many patients with anemia become dependent on red blood cell transfusions, which can be associated with clinical consequences and decreased quality of life
  • Conference call with Geron management scheduled at 8am ET on Friday, June 7, 2024

FOSTER CITY, Calif.–(BUSINESS WIRE)–Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, today announced that the U.S. Food and Drug Administration (FDA) has approved RYTELO™ (imetelstat) for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent (TD) anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).

With the approval and availability of RYTELO, we believe eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia,” said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. “The approval of RYTELO as the first telomerase inhibitor is a testament to the power of our science and the passion of our people to innovate in the field of blood cancer. As we celebrate today’s momentous milestone, I would like to thank the patients and families, advocates, clinicians, study coordinators and site personnel, scientists, and Geron employees and collaborators past and present whose participation was integral to this achievement and to supporting our transformation into a commercial company.”

Lower-risk myelodysplastic syndromes (LR-MDS) is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue1. These symptomatic LR-MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short- and long-term clinical consequences that reduce quality of life and shorten survival2,3. There is a high unmet need for many LR-MDS patients, particularly those with characteristics having poorer prognosis. Current treatment options for those failing ESA are limited to select sub-populations and there is an unmet need for treatments that can provide extended and continuous red blood cell transfusion independence.

Approval Based on Results from IMerge Phase 3 Clinical Trial

For patients with lower-risk MDS and anemia who are transfusion dependent, we have very few options today and often cycle through available therapies, making the approval of RYTELO potentially practice changing for us,” said Rami Komrokji, MD, Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, who was an investigator of the pivotal IMerge clinical trial. “What is exciting about RYTELO is the totality of the clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias. The treatment goal for patients with LR-MDS and anemia is transfusion-independence and before today, this wasn’t possible for many patients.”

The FDA approval of RYTELO is based on results from the IMerge Phase 3 clinical trial, published in The Lancet4. The IMerge trial met its primary and key secondary endpoints, with RYTELO demonstrating significantly higher rates of red blood cell transfusion independence (RBC-TI) versus placebo for at least eight consecutive weeks (RYTELO 39.8% [95% CI 30.9–49.3]; placebo 15.0% [7.1–26.6]; p<0.001) and for at least 24 weeks (RYTELO 28.0% [95% CI 20.1-37.0]; placebo 3.3% [95% CI 0.4-11.5]; p<0.001). RBC-TI was durable and sustained in the RYTELO treated population, with a median RBC-TI duration for 8-week responders and 24-week responders of approximately 1 year and 1.5 years, respectively.

In an exploratory analysis of RYTELO-treated patients achieving ≥8-week RBC-TI, median increases in hemoglobin were 3.6 g/dL for RYTELO and 0.8 g/dL for placebo. Clinically meaningful efficacy results were observed across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category.

In the IMerge trial, the safety profile of RYTELO was well-characterized with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The most common Grade 3/4 adverse reactions were neutropenia (72%) and thrombocytopenia (65%), which lasted a median duration of less than two weeks, and in more than 80% of patients were resolved to Grade < 2 in under four weeks. Cytopenias were generally manageable with dose modifications. The intravenous administration of RYTELO every four weeks aligns to routine blood count monitoring for these patients.

The most common adverse reactions (incidence ≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets (thrombocytopenia), decreased white blood cells, decreased neutrophils (neutropenia), increased aspartate aminotransferase (AST), increased alkaline phosphatase (ALP), increased alanine aminotransferase (ALT), fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache. Clinically relevant adverse reactions in < 5% of patients who received RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension.

Conference Call Details

A conference call with Geron management is scheduled at 8am Eastern Time on Friday, June 7, 2024, to discuss the FDA approval and launch of RYTELO. To access the webcast and slides, please visit the Investors & Media page. Participants may access the webcast by registering online using the following link, https://events.q4inc.com/attendee/923992744.

About RYTELO™ (imetelstat)

RYTELO™ (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration.

Geron aims to ensure broad access to RYTELO for eligible patients. Accordingly, our REACH4RYTELO™ Patient Support Program provides a range of resources that support access and affordability to eligible patients prescribed RYTELO.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.

Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.

Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.

Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).

Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at https://pi.geron.com/products/US/pi/rytelo_pi.pdf.

About Geron

Geron is a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer. Our first-in-class telomerase inhibitor RYTELO™ (imetelstat) is FDA-approved for the treatment of adult patients with lower-risk MDS with transfusion dependent anemia. We are also conducting a pivotal Phase 3 clinical trial of imetelstat in JAK-inhibitor relapsed/refractory myelofibrosis (R/R MF), as well as studies in other hematologic malignancies. Inhibiting telomerase activity, which is increased in malignant stem and progenitor cells in the bone marrow, aims to potentially reduce proliferation and induce death of malignant cells. To learn more, visit www.geron.com or follow us on LinkedIn.

Use of Forward-Looking Statements

Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) Geron’s belief that eligible patients with lower-risk MDS can potentially experience meaningful clinical benefit with RYTELO, particularly the potential for greater than 24 weeks of freedom from the burden of red blood cell transfusions and symptomatic anemia; (ii) an unmet need for new treatments for patients with LR-MDS that can provide extended and continuous red blood cell transfusion independence; (iii) that RYTELO could be practice-changing for hematologists who treat patients with lower-risk MDS and anemia who are transfusion dependent; (iv) the potential for RYTELO to offer a totality of clinical benefit across LR-MDS patients irrespective of ring sideroblast status or high transfusion burden, including sustained and durable transfusion independence and increases in hemoglobin levels, all within a well-characterized safety profile of generally manageable cytopenias; (v) that inhibiting telomerase activity aims to potentially reduce proliferation and induce death of malignant cells; (vi) that Geron aims to ensure broad access to RYTELO; (vii) that imetelstat has the potential to demonstrate disease-modifying activity in patients; (viii) that IMpactMF has registrational intent; and (ix) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron is successful in commercializing RYTELO (imetelstat) for the treatment of patients with LR-MDS with transfusion dependent anemia; (b) whether Geron overcomes potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for and meet expected timelines and planned milestones; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether any future safety or efficacy results of imetelstat treatment cause the benefit-risk profile of imetelstat to become unacceptable; (e) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (f) that Geron may seek to raise substantial additional capital in order to continue the development and commercialization of imetelstat; (g) whether Geron meets its post-marketing requirements and commitments in the U.S. for RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact commercialization of RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia or the continuation of the IMpactMF trial; (i) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (j) whether the EMA will approve RYTELO for the treatment of patients with LR-MDS with transfusion dependent anemia and whether the FDA and EMA will approve imetelstat for other indications on the timelines expected, or at all. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s quarterly report on Form 10-Q for the quarter ended March 31, 2024, and subsequent filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events, or circumstances.

1 Lewis R, Bewersdorf JP, Zeidan AM. Clinical Management of Anemia in Patients with Myelodysplastic Syndromes: An Update on Emerging Therapeutic Options. Cancer Manag Res. 2021 Jan 25;13:645-657. doi: 10.2147/CMAR.S240600. PMID: 33531837; PMCID: PMC7846829.

2 Cogle CR, Reddy SR, Chang E, et al. Early treatment initiation in lower-risk myelodysplastic syndromes produces an earlier and higher rate of transfusion independence. Leuk Res. 2017;60:123-128.

3 Balducci, L. (2006), Transfusion independence in patients with myelodysplastic syndromes. Cancer, 106: 2087-2094. https://doi.org/10.1002/cncr.21860
4 Platzbecker, U. et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet. Volume 403, Issue 10423, P249-260. Jan 20, 2024.

Contacts

Aron Feingold

Vice President, Investor Relations and Corporate Communications

Kristen Kelleher

Associate Director, Investor Relations and Corporate Communications

investor@geron.com
media@geron.com

Tiziana Life Sciences Announces Six-Month Qualitative Improvement in Neuroimaging in 80% of Multiple Sclerosis Patients Receiving Intranasal Foralumab

  • Qualitative improvements in PET imaging seen in 80% of non-active Secondary Progressive Multiple Sclerosis (na-SPMS) Expanded Access patients receiving intranasal foralumab for at least 6-months.
  • FDA Allowance for an additional 20 Patients to be enrolled in the intranasal foralumab Multiple Sclerosis Expanded Access Program will allow further data collection and analysis.
  • Applied for FDA Orphan Drug Designation of foralumab for na-SPMS

NEW YORK, June 06, 2024 (GLOBE NEWSWIRE) — Tiziana Life Sciences, Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced the qualitative results for all 10 non-active Secondary Progressive Multiple Sclerosis (na-SPMS) patients enrolled in the intermediate-size patient population Expanded Access (EA) Program receiving foralumab for at least six months.

Tarun Singhal, M.B.B.S., M.D., Director of the PET Imaging Program in Neurologic Diseases, associate neurologist and nuclear medicine physician at Brigham and Women’s Hospital, a founding member of Mass General Brigham Healthcare System, and Associate Professor of Neurology at Harvard Medical School, commented, “Based on currently available data from the latest cohort of four Expanded Access patients, three out of the four subjects had findings that suggest a qualitative reduction in the microglial PET signal over a period of six months of treatment with nasal foralumab. When combined with my assessment of the first six Expanded Access patients at six months, eight of the ten suggest a qualitative reduction in microglial PET signal. Further studies are needed to confirm these findings using additional cases and quantitative approaches.”

Gabriele Cerrone, Chairman, acting CEO, and founder of Tiziana Life Sciences, added, “I am thrilled that 80% of the na-SPMS patients who received intranasal foralumab treatment for at least 6-months have a qualitative reduction of microglial activity as confirmed in these latest PET images. I am also greatly appreciative of Dr. Singhal’s research and look forward to the additional quantitative analysis of the data. With the allowance of an additional 20 patients in the EA program, the application for Orphan Drug Designation for na-SPMS, and the ongoing Phase 2a trial, Tiziana is rapidly progressing its intranasal foralumab program in multiple sclerosis.”

About Foralumab

Activated T cells play an important role in the inflammatory process. Foralumab, the only fully human anti-CD3 monoclonal antibody (mAb), binds to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. This effect has been demonstrated in patients with COVID and with multiple sclerosis, as well as in healthy normal subjects. The non-active SPMS intranasal foralumab Phase 2 trial (NCT06292923) began screening patients in November of 2023. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of neuroinflammatory and neurodegenerative human diseases.[1],[2]

About Tiziana Life Sciences

Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal approach has the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s lead candidate, intranasal foralumab, which is the only fully human anti-CD3 mAb, has demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.

For further inquiries:

Tiziana Life Sciences Ltd
Paul Spencer, Business Development and Investor Relations
+44 (0) 207 495 2379
email: info@tizianalifesciences.com

Investors:
Irina Koffler
LifeSci Advisors, LLC
646.970.4681
ikoffler@lifesciadvisors.com

[1] https://www.pnas.org/doi/10.1073/pnas.2220272120
[2] https://www.pnas.org/doi/10.1073/pnas.2309221120

Osteal Therapeutics Closes $50M Series D Financing to Support Approval and Commercial Launch of Lead Candidate

Financing led by Zimmer Biomet with participation from existing investors Johnson & Johnson Innovation – JJDC, Inc., Gideon Strategic Partners, and HM Capital.

Proceeds will support NDA submission and commercial launch of lead candidate, VT-X7, a 7-day treatment for periprosthetic joint infection.

DALLAS, June 05, 2024 (GLOBE NEWSWIRE) — Osteal Therapeutics, Inc. (“Osteal”), a clinical-stage biopharmaceutical company developing a new category of combination drug/device therapies for orthopedic infections, announced today the completion of an oversubscribed $50 million Series D preferred stock equity financing. Zimmer Biomet led the round, joined by returning investors Johnson & Johnson Innovation – JJDC, Inc., Gideon Strategic Partners, and HM Capital. In conjunction with the financing, a representative of Zimmer Biomet will join Osteal’s Board of Directors.

The proceeds of the financing will be used to advance the development of Osteal’s portfolio of therapies, including the submission of a New Drug Application (NDA) for, and accelerated commercial launch of, VT-X7 for the treatment of periprosthetic joint infection (PJI) of the hip and knee. VT-X7 has been the subject of two multicenter, randomized, controlled trials, APEX and APEX-2. APEX-2 recently met its primary endpoint and will be completed in late 2024. The study builds upon the safety and efficacy evidence obtained from APEX, a similarly designed clinical study that successfully met its primary endpoint in 2023. Both studies were designed in close consultation with the FDA, which previously granted VT-X7 Breakthrough Therapy, Orphan Drug, Fast Track, and Qualified Infectious Disease Product designations. The company expects to seek FDA approval upon completion of APEX-2.

“This round of financing represents an inflection point in the company’s progress towards introducing VT-X7 to the market,” said David Thompson, Chairman and Chief Executive Officer. “From the beginning, Osteal has been extremely fortunate to have the support of a world-class group of financial and strategic partners who share our vision and recognize the tremendous impact our programs will have on patient care. I am delighted to welcome Zimmer Biomet as a partner and look forward to working closely with their exemplary team.”

About Periprosthetic Joint Infection (PJI)

Affecting over 40,000 people in the U.S. annually, PJI is a rare and potentially devastating complication of joint replacement surgery in which pathogenic bacteria colonize the joint prosthesis, forming difficult-to-remove structures called biofilms. Biofilm infections are challenging to resolve, requiring long, invasive and expensive treatments that are often unsuccessful, resulting in high rates of permanent disability and early death. Recent retrospective analyses demonstrate that the current gold standard for treatment of PJI, two-stage exchange arthroplasty, takes an average of 16 weeks and has a success rate under 50% after 12 months, highlighting the unmet need for faster and more efficacious treatment options.

About VT-X7

VT-X7 (vancomycin hydrochloride and tobramycin sulfate for irrigation/VT-X7 irrigation system) is a novel drug/device combination product designed to deliver therapeutic concentrations of vancomycin and tobramycin, well-established, broad-spectrum antibiotics, directly to the joint space and surrounding tissue to treat PJI. VT-X7 is a seven-day therapy designed to address the unmet clinical need for a rapid, reliable treatment for these challenging infections. In clinical studies of VT-X7, 100% of patients were treated and received a new permanent joint prosthesis in seven days with >90% remaining infection-free after one year. The US Food and Drug Administration has granted VT-X7 Breakthrough Therapy, Orphan Drug, Fast Track and Qualified Infectious Disease Product designations. This initial application of VT-X7 represents a first-of-its-kind, multibillion-dollar opportunity to dramatically improve outcomes for a serious unmet medical need.

About Osteal Therapeutics, Inc.

Osteal Therapeutics is a privately held, clinical-stage biopharmaceutical company developing novel musculoskeletal therapeutics to treat orthopedic infections and their consequences. The company is leveraging the ability of concentrated, locally delivered antimicrobials to treat the bacterial biofilms typically responsible for musculoskeletal infections while minimizing off-target tissue exposure and associated adverse effects. Osteal employs a low-risk development strategy by using approved drugs with long histories of safety and efficacy as candidates for new routes of local delivery. The company’s lead candidate, VT-X7, is in late-stage clinical development to treat periprosthetic joint infections, a serious complication of joint replacement surgery. For more information, please visit: www.ostealtx.com

Corporate Contact:

Todd Saunders
Vice President of Marketing
Osteal Therapeutics, Inc.
Phone: 469-809-2630
Email: info@ostealtx.com

RS Oncology Announces Positive Data from a Phase 1 Clinical Trial of RSO-021, a First-in-Class Therapeutic for Malignant Pleural Mesothelioma

  • First-in-human MITOPE clinical study meets primary objective of Phase 1 safety and tolerability
  • First-in-Class therapy shows early signs of efficacy and offers new hope to patients with malignant pleural mesothelioma with pleural effusion and other cancers.

CAMBRIDGE, Mass.–(BUSINESS WIRE)–#LungcancerRS Oncology, a privately held biopharmaceutical company focusing on novel treatments for rare and aggressive cancers presented positive results from its Phase 1 study in patients with Malignant Pleural Mesothelioma (MPM) with Malignant Pleural Effusion (MPE) or MPE associated with other solid tumors at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

The Phase 1 data was presented by Professor Dean Fennell, MRCP, FRCP (MD/PhD) on behalf of all the MITOPE investigators at an oral presentation session. In the 15 recruited patients safety data demonstrated weekly treatment of RSO-021 was well tolerated at 90 mg. The pharmacokinetic data showed minimal systemic exposure to RSO-021 after intrapleural administration. Efficacy data showed a long-term partial response in one patient as well as encouraging survival in 7 of the 10 evaluable patients. In addition to responses in mesothelioma, the drug showed promising responses in non-target lesions and other cancers with metastatic disease to the lung.

“The MITOPE trial would not have been possible without the support of the outstanding investigation teams throughout the UK who are dedicated to the treatment of patients with mesothelioma. We thank all of the MITOPE trial participants and their supportive families, and look forward to hearing about their continued benefit,” said George Naumov, PhD, RS Oncology Chief Operations Officer.

“RSO-021 represents a new class of drugs with a first-in-class anticancer mechanism. The safety and efficacy observed in the Phase 1 trial is supported by strong pre-clinical rationale” said Brian Cunniff, PhD, Chief Science Officer for RS Oncology.

MPM is a rare and aggressive form of cancer that typically develops years after asbestos inhalation and/or exposure. Most cases (70%) originate in the pleura, but it can also be found the peritoneum and the pericardium. A mesothelioma prognosis remains poor with a shorter life expectancy and decreased quality of life.

Phase 2 exploration of this novel agent is ongoing at two doses, as a single agent and in combination with chemotherapy. Clinical trial information: NCT05278975.

About RS0-021

RSO-021 is a naturally occurring, sulfur-rich, cyclic oligopeptide of the thiopeptide class, which covalently inactivates PRX3, leading to catastrophic oxidative stress and cell death.

The oral and poster presentations will be available for viewing on RSOncology.com.

About the MITOPE study

MITOPE is an open-label, non-randomized, multicenter, translational Phase 1/2 dose-escalation and expansion study. It is designed to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of RSO-021 after intrapleural (IP) administration in patients with MPE associated with either MPM or other solid tumors.

About RS Oncology

RS Oncology is a private, clinical-stage biopharmaceutical company leading scientific discoveries and global collaborations to improve the lives of patients with the most aggressive cancers. Taking a fundamentally different approach to drug development, we are advancing a pipeline of programs based on mitochondrial dynamics and metabolic function that dictate cell processes including cell migration and tumor cell metastasis. The oral presentation will be posted to RSOncology.com or follow us on LinkedIn and X.

Contacts

Corporate contact:

Jarrett Duncan, CEO

j.duncan@rsoncology.com

Promising Anti-tumor Activity of Novel Costimulatory Bispecific Antibody REGN7075 (EGFRxCD28) in Combination with Libtayo® (cemiplimab) to be Reported at ASCO

Oral presentation to highlight activity of REGN7075 in combination with Libtayo from dose-escalation portion of trial in patients with microsatellite stable colorectal cancer, which has historically proven unresponsive to immunotherapy

Ongoing REGN7075 Phase 1/2 trial is investigating a potentially first-in-class combination across a range of advanced solid tumors

TARRYTOWN, N.Y., May 23, 2024 (GLOBE NEWSWIRE) — Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive new results from an ongoing Phase 1/2 trial evaluating its first-in-class costimulatory bispecific antibody, REGN7075 (EGFRxCD28), in combination with Libtayo® (cemiplimab) in patients with advanced solid tumors. Data from the dose-escalation portion of the trial showed the investigational combination led to anti-tumor responses in patients with microsatellite stable colorectal cancer (MSS CRC). REGN7075 is one of the first immunotherapies to demonstrate clinical activity in MSS CRC, including in a patient with liver metastases. The results will be shared during an oral session at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago.

“Microsatellite stable colorectal cancer has historically been unresponsive to immunotherapy,” said Neil H. Segal, M.D., Ph.D., Medical Oncologist and Research Director in the Division of Gastrointestinal Oncology at Memorial Sloan Kettering Cancer Center, and a trial investigator. “The early results for this novel investigational EGFRxCD28 costimulatory bispecific in combination with Libtayo are encouraging, showing anti-tumor responses in a highly difficult-to-treat cancer. This combination is one of the first immunotherapy regimens to show clinical activity in microsatellite stable colorectal cancer, and we are excited to advance this trial in additional tumor types.”

In the dose-escalation portion of the trial, patients with metastatic and locally advanced solid tumors – who had exhausted standard treatment options, and most of whom also had liver metastases – received combination therapy with REGN7075 and Libtayo, following a REGN7075 monotherapy lead-in dose. Among 94 patients treated as of data cutoff, 65% (n=61) had MSS CRC, of which 51 MSS CRC patients were treated at an active dose level. Efficacy results among these 51 patients were as follows:

  • 6% (n=3) overall response rate (ORR) and 29% (n=15) disease control rate (DCR). This included one complete response (CR), two partial responses (PR), and 12 patients with stable disease. At data cutoff, all responders were without liver metastases.
  • Among the subset of 15 patients without liver metastases, there was a 20% ORR (n=3) and 80% DCR (n=12).
  • Among the subset of 36 patients with liver metastases, three patients had stable disease as of data cutoff, and one patient achieved a PR following data cutoff.

Safety was assessed in 84 patients across multiple solid tumor types at a variety of doses of REGN7075. REGN7075 and Libtayo showed an acceptable safety profile, and the maximum tolerated dose was not reached. Treatment-emergent adverse events (TEAEs) of any grade occurred in 98% of patients; Grade 3 and 4 TEAEs occurred in 35% of patients. Treatment-related adverse events (TRAEs) occurred in 90% of patients, with 7% of cases reported as grade 3 or 4. The majority of TRAEs were Grade 1 to 2 (83%), with the most common being infusion-related reactions (58%) that were manageable with premedication and dosing adjustments. TRAEs led to discontinuation in 5% of patients, and three patients discontinued treatment due to Grade 2 infusion-related reactions. As of data cutoff, there have been no dose-limiting toxicities, no reports of cytokine release syndrome, and no treatment-related deaths.

“Regeneron is focused on developing a unique investigational portfolio of oncology medicines including checkpoint inhibitors, CD3 bispecifics and CD28 costimulatory bispecifics. Over the past several years, we have made progress in our programs across checkpoint inhibitors and the CD3 class and are now showing promising activity with two costimulatory bispecific antibodies,” said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Oncology at Regeneron. “Our costimulatory bispecifics were designed with the goal of turning cancer cells into antigen presenting cells, thereby converting historically immunotherapy unresponsive tumors from ‘cold’ to ‘hot’. These early data speak to the potential of REGN7075 in combination with Libtayo and add to a growing body of evidence supporting novel costimulatory bispecifics that are in clinical trials for a range of solid tumors and blood cancers.”

The combination of REGN7075 and Libtayo is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority. While the dose escalation portion of the trial across multiple solid tumor types including non-small cell lung cancer, colorectal cancer, head and neck cancer and other tumor types is ongoing, expansion cohorts in several tumor types have also been initiated.

About the Phase 1/2 Trial
The Phase 1/2, first-in-human, open-label trial investigating REGN7075 in combination with Libtayo is currently enrolling patients with metastatic and locally advanced solid tumors who have exhausted standard treatment options. The trial includes an ongoing Phase 1 dose-escalation portion and a Phase 2 dose-expansion period. In the Phase 1 dose-escalation portion, patients first receive a weekly lead-in dose of REGN7075 monotherapy for three weeks to assess its safety and efficacy alone. This is followed by treatment with combination therapy, with Libtayo dosed once every three weeks and REGN7075 dosed either every week or every three weeks. The primary endpoints are assessing safety and tolerability, while the secondary endpoints are assessing efficacy, pharmacokinetics and immunogenicity. Expansion cohorts in several tumor types have been initiated. For more information, visit the Regeneron clinical trials website, or contact via clinicaltrials@regeneron.com or 844-734-6643.

About Regeneron in Cancer
We aspire to turn revolutionary discoveries into medicines that can transform the lives of those impacted by cancer. Our team around the world is driven to solve the needs and challenges of those affected by one of the most serious diseases of our time.

Backed by our legacy of scientific innovation and a deep understanding of biology, genetics and the immune system, we’re pursuing potential therapies across more than 30 types of solid tumors and blood cancers. Our cancer strategy is powered by cutting-edge technologies and therapies that can be flexibly combined to investigate potentially transformative treatments for patients. Oncology assets in clinical development comprise nearly half of Regeneron’s pipeline, and include checkpoint inhibitors, bispecific antibodies and costimulatory bispecific antibodies. Our approved PD-1 inhibitor Libtayo serves as the backbone of many of our investigational combinations.

To complement our extensive in-house capabilities, we collaborate with patients, healthcare providers, governments, biopharma companies and each other to further our shared goals. Together, we are united in the mission to serve as a beacon of transformation in cancer care.

About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T cells and was invented using Regeneron’s proprietary VelocImmune® technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced non-small cell lung cancer (NSCLC), as well as in advanced cervical cancer in the European Union, Canada and Brazil. Libtayo is developed and marketed globally by Regeneron.

In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA). Outside of the U.S., the generic name of Libtayo in its approved indication is cemiplimab.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:

  • People with a type of skin cancer called cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
  • People with a type of skin cancer called basal cell carcinoma (BCC) when your BCC cannot be removed by surgery (locally advanced BCC) or when it has spread (metastatic BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with a HHI.
  • Adults with a type of lung cancer called non-small cell lung cancer (NSCLC).
    • LIBTAYO may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene.
    • LIBTAYO may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, or your lung cancer has spread to other areas of your body (metastatic lung cancer), and your tumor tests positive for high “PD-L1,” and your tumor does not have an abnormal “EGFR,” “ALK,” or “ROS1” gene.

It is not known if Libtayo is safe and effective in children.

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is the most important information I should know about LIBTAYO?
LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

  • Lung problems: cough, shortness of breath, or chest pain
  • Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
  • Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach-area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
  • Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
  • Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
  • Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
  • Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
  • Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include: nausea, vomiting, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
  • Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had
  • Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications

Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects.

Before you receive LIBTAYO, tell your healthcare provider about all your medical conditions, including if you:

  • have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
  • have received an organ transplant
  • have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
  • have received radiation treatment to your chest area
  • have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
  • are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby
  • are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO

Females who are able to become pregnant:

  • Your healthcare provider will give you a pregnancy test before you start treatment
  • You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk to your healthcare provider about birth control methods that you can use during this time
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of LIBTAYO when used alone include tiredness, muscle or bone pain, rash, diarrhea, and low levels of red blood cells (anemia). The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, and decreased appetite. These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296.

Please see full Prescribing Information, including Medication Guide.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spend decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo®, Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab-bbfg).

About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.
For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.

Dr. Segal has financial interests related to Regeneron Pharmaceuticals.

Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation REGN7075 in combination with Libtayo® (cemiplimab) and other of Regeneron’s Product Candidates discussed or referenced in this press release; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates and new indications for Regeneron’s Products, such as REGN7075 in combination with Libtayo in patients with advanced solid tumors and the other clinical programs discussed or referenced in the press release; uncertainty of the utilization, market acceptance, and commercial success of Regeneron’s Products and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates (such as REGN7075 in combination with Libtayo); the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron’s Products and Regeneron’s Product Candidates (such as REGN7075 in combination with Libtayo) in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron’s Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics (such as the COVID-19 pandemic) on Regeneron’s business; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney’s Office for the District of Massachusetts), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2023 and its Form 10-Q for the quarterly period ended March 31, 2024. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.
Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron’s media and investor relations website (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals).

Contacts:Media Relations
Taylor Skott
Tel: +1 914-409-2381
taylor.ramsey@regeneron.com
Investor Relations
Vesna Tosic
Tel: +1 914-847-5443
vesna.tosic@regeneron.com

iCell Gene Therapeutics Announces Positive Clinical Data from Investigator Initiated Phase 1 Trial Evaluating BCMA-CD19 Compound CAR in Patients with Systemic Lupus Erythematosus/Lupus Nephritis Published in Annals of the Rheumatic Diseases

BCMA-CD19 compound CAR (cCAR) therapy was safe and well tolerated and achieved proof of concept of complete humoral reset delivering long-term medication-free remission –

iCell’s BCMA-CD19 cCAR was the first CAR T evaluated in autoimmune disease with first SLE patient treated September 2019

Based on successful IIT study, iCell plans to file INDs in U.S. and China

STONY BROOK, N.Y.–(BUSINESS WIRE)–iCell Gene Therapeutics, a clinical stage biopharmaceutical company focused on immunotherapies for autoimmune disorders and cancer, today announced the publication in Annals of the Rheumatic Diseases of positive results of an investigator initiated clinical trial (IIT) for its BCMA-CD19 compound chimeric antigen receptor (cCAR) T cell immunotherapy.

The clinical trial evaluated the safety and efficacy of a complete humoral reset of both long-lived plasma cells and B cells in 13 systemic lupus erythematosus (SLE) patients treated with iCell’s cCAR, including 11 patients with SLE and lupus nephritis (LN). All patients (12/13) who received an initial dose of 3×106 cCAR cells/kg were negative for all autoantibodies, including those derived from long-lived plasma cells, 3-months post-cCAR, and the complement returned to normal levels. These patients achieved symptom-free and medication-free remission (MFR), with post-cCAR follow-up to 46 months. cCAR therapy was well tolerated with mild cytokine-release syndrome (no CRS >1). iCell considers this IIT to be a successful proof of concept; the Company plans to file an investigational new drug application (IND) for its BCMA-CD19 cCAR in the United States and China.

iCell’s cCAR, with two independently functioning CARs in a single construct targeting the B cell CD19 and the plasma cell BCMA surface antigens, is uniquely designed to completely reset humoral immunity and address the underlying cause of SLE/LN through the elimination of all elevated autoantibodies including those produced by long-lived plasma cells.

Unique armoring of iCell’s cCAR allows for safe pretreatment conditioning with cyclophosphamide only (no fludarabine was used in LN patients), and patients in the study discontinued all lupus medications, including glucocorticoids and immunosuppressants, prior to cCAR treatment and remained lupus medication-free post-infusion. There are currently no approved therapies that deliver MFR in SLE/LN patients who are at high risk of long-term organ damage and kidney transplant.

“This study demonstrates that the complete reset of humoral immunity results in elimination of all elevated autoantibodies, that long term medication free remission is achievable, and that treatment with a BCMA-CD19 compound CAR is well-tolerated in patients suffering from lupus nephritis. The data show humoral immunity recovering, a low rate of infections, no CRS greater than 1, and no ICANS observed to date,” said Yupo Ma, M.D., Ph.D., Chief Scientific Officer and Founder of iCell. “iCell now has the largest clinical dataset of autoimmune patients receiving CAR therapy, and we are excited to continue the advancement of our BCMA-CD19 cCAR.”

“iCell first envisioned the potential for CAR treatments in autoimmune diseases more than 10 years ago and subsequently became the first to patent a BCMA-CD19 compound CAR. Nearly five years ago, we were the first company worldwide to treat an autoimmune patient with a CAR, and we are delighted to see that this patient continues to do well,” said Greg Deener, Chief Executive Officer of iCell. “We look forward to receiving further follow up data confirming the promising results to date, and we plan to present this data on June 12th at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress.”

Study Details:

iCell designed its cCAR T Cell immunotherapy to express two distinct and fully functional CAR molecules in a single construct, one that targets the molecule CD19 present on B cells and one that targets BCMA present on plasma cells. Targeting both B cells and long-lived plasma cells is needed to eliminate all elevated autoantibodies, given they have separate and redundant memory. iCell’s cCAR is armored to safely promote T cell survival and function and to allow for cyclophosphamide-only conditioning.

The single arm IIT evaluating iCell’s BCMA-CD19 cCAR was conducted in two leading centers in China, Zhongshan People’s Hospital and Peking University Shenzhen Hospital. Initially two patients with SLE and comorbid localized lymphoma were treated with the BCMA-CD19 cCAR (the first in September 2019); 11 patients with LN with biopsy-confirmed active disease (Class III-V) and inadequate response to at least two lines of therapies were subsequently enrolled into the study and treated between June 2022 and February 2023. Ten LN patients received the target single cCAR dose of 3×106/kg.

Overall, the cCAR therapy was found to be generally safe and well-tolerated. The 10 LN patients receiving the target dose achieved depletion of B cells from peripheral blood within 10 days post-cCAR treatment and depletion of immunoglobulin within 42 days, and complete recovery of B cells and IgM was seen within 2-6 months post-cCAR. Excluding COVID-19, the only infection reported was a grade 1 urinary tract infection. In iCell’s overall cCAR safety database of 18 patients with autoimmune diseases (including the 13 patients with SLE or LN), there have been no CRS >1 and no ICANS or CRES.

All lupus patients (12/13) who received the target dose were negative for all autoantibodies, including those derived from long-lived plasma cells, 3-months post-cCAR, and the complement returned to normal levels. Patients achieved symptom-free and medication-free remission (MFR), with post-cCAR follow-up to 46-months. Mean Systemic Lupus Erythematosus SLE Disease Activity Index 2000 (SLEDAI-2K) reduced from 9.9 (baseline) to 2.3 (3 months), and mean renal function significantly improved in the 10 LN patients ≤90 days post-cCAR. The data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in SLE and LN patients.

About SLE/LN

Systemic lupus erythematosus is an antibody-mediated autoimmune disease, in which autoantibodies attack the body’s own tissues, resulting in widespread damage in affected organs including kidneys, lungs, joints, brain and blood vessels. According to the Lupus Foundation of America, an estimated 1.5 million Americans, and at least five million people worldwide, have SLE/LN. Lupus nephritis affects ~40% of SLE patients and disproportionately burdens nonwhite women from lower socioeconomic groups. LN patients have a 6-fold higher risk of mortality with 1 in 4 progressing to end stage renal disease There are currently no treatments targeting the underlying causes of the disease delivering MFR. Standard of care LN treatments have substantial side effects. Prolonged immunosuppression increases the risk of serious infections and cancers. Glucocorticoid associated adverse effects include osteoporotic fractures, avascular necrosis, diabetes mellitus, cataracts, glaucoma, and premature mortality.

About iCell Gene Therapeutics

iCell Gene Therapeutics is a clinical-stage biopharmaceutical company developing chimeric antigen receptor (CAR) immunotherapies designed to be innovative, first-in-class and lifesaving. iCell is focused on developing treatments for diseases where no treatment options exist and where dramatic improvements in quality and duration of life are needed, including autoimmune disorders, AML, and T-cell malignancies. The company is currently conducting clinical trials in the U.S. and China utilizing its CARvac, T-cell targeted CARs, compound CARs and non-gene edited universal CARs engineered as treatments for autoimmune diseases, cancer, and organ rejections. For more information, please visit http://icellgene.com/

Contacts

Investor Contact:

Greg Deener, CEO

greg.deener@icellgene.com

Media Contact:

Argot Partners

icellgene@argotpartners.com

Sinaptica Therapeutics Selected for StartUp Health’s Alzheimer’s Moonshot

Moonshot supported by Gates Ventures and Alzheimer’s Drug Discovery Foundation (ADDF) to accelerate innovation around Alzheimer’s

Sinaptica is one of 14 companies initially selected that are advancing innovative solutions for Alzheimer’s to commercialization and scalability

Collaboration will support the company’s Phase 3 clinical development plans based on unprecedented Phase 2 data in Alzheimer’s showing >80% disease slowing on cognitive & functional endpoints

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Sinaptica Therapeutics, Inc., a clinical-stage company leading the development of a new class of personalized neuromodulation therapeutics to treat Alzheimer’s (AD) and other neurodegenerative diseases, today announced that it has been selected to join StartUp Health’s Alzheimer’s Moonshot. This bold new initiative and global community of founders and funders collaborating to prevent, diagnose, manage, and ultimately cure Alzheimer’s disease is supported by the Alzheimer’s Drug Discovery Foundation (ADDF) and Gates Ventures.

The collaboration will help support the global development of Sinaptica’s patented neuromodulation therapy, which takes a precision medicine approach targeting the Default Mode Network in the brain. The company has prioritized mild/moderate Alzheimer’s Disease as its first indication and is preparing for a pivotal Phase 3 trial in 2025.

“Sinaptica is honored to be included in this hand-selected group of innovators working to end Alzheimer’s – a goal which we believe will require combinatorial approaches,” said Sinaptica CEO Ken Mariash. “Sinaptica brings a bold new personalized neuromodulation approach that can be combined with virtually any drug, given its near-total lack of side effects. Also, we know diagnostics are a key piece of the puzzle and will look to combine our novel electrophysiological biomarker with those of others in the Moonshot, to better characterize the disease and bring a more personalized, precision medicine approach to Alzheimer’s treatments.”

“We’re excited to welcome Sinaptica Therapeutics to the Alzheimer’s Moonshot and the StartUp Health family,” said Steven Krein, CEO and co-founder of StartUp Health. “We created the Alzheimer’s Moonshot to bring together trailblazers, support new approaches and rapidly accelerate progress in this challenging disease. Sinaptica is a perfect fit and we look forward to partnering with them.”

Sinaptica is building on unprecedented positive Phase 2 data in Alzheimer’s published by the company’s scientific co-founders, showing greater than 80% disease slowing on all four gold-standard AD cognitive and functional clinical endpoints, in the peer-reviewed Oxford University Press journal, Brain. Additional exciting 52-week data from the Phase 2 study will also be published in an upcoming issue of a peer-reviewed journal. Sinaptica’s technology has been granted FDA Breakthrough Device Designation, and the company is preparing for a larger Phase 3 clinical trial in Alzheimer s patients at multiple sites.

About StartUp Health

Since 2011, StartUp Health has been on a mission to solve the biggest health challenges of our time by creating and sustaining a global ecosystem of health moonshot communities. StartUp Health has provided support to more than 1,000 founders and contributed to the development of more than 500 health innovation companies. Our valued partners include The Helmsley Charitable Trust, Alzheimer’s Drug Discovery Foundation (ADDF) and Gates Ventures in addition to nearly 100 families and mission-aligned organizations. Visit startuphealth.com.

About Sinaptica Therapeutics

Sinaptica Therapeutics is a clinical-stage neuromodulation therapeutics company leading the development of a new class of personalized therapeutics to revolutionize the treatment of Alzheimer’s and neurodegenerative diseases. The company utilizes a patented novel, non-invasive approach to treating Alzheimer’s via precision neurostimulation of a key brain network involved in memory, the Default Mode Network. This novel approach slowed disease progression by >80% on all four gold-standard cognitive and functional clinical endpoints in a placebo-controlled Phase 2 clinical study, with results published in the peer-reviewed Oxford University Press journal, Brain. The technology was granted Breakthrough Device Designation by the FDA in 2022 and the company is preparing for a pivotal randomized controlled clinical trial in 2025. Sinaptica’s mission is to bring a safe, effective, and non-invasive neuromodulation therapy to Alzheimer’s patients that can help to significantly slow the progression of both cognitive and functional decline. Learn more at sinapticatx.com and follow us on LinkedIn and X @SinapticaTX.

The SinaptiStim™ System is for investigational use only. It has not been approved by the U.S. Food and Drug Administration and is not available for commercial sale in any geography.

Contacts

Kira Gordon, BrightPoint

kira@brightpointny.com
646-243-4920

Cimeio Therapeutics : CD45 ADC and Shielded HSCs Represent a Potentially Universal Therapy for Blood Cancers

— Selective and complete eradication of leukemic cells with an ADC targeting the pan-blood marker CD45 —

— Engineered hematopoietic Stem Cells (HSCs) shielded from the CD45-targeting ADC maintain full functionality —

— Represents a novel, potentially universal approach to treating blood cancers —

BASEL, Switzerland & CAMBRIDGE, Mass.–(BUSINESS WIRE)–Cimeio Therapeutics today announced a publication in Nature showing that its CD45 antibody-drug conjugate (ADC) eradicated aggressive leukemic cells in vivo, while hematopoiesis was fully preserved and protected from the ADC via shielded hematopoietic stem cells (HSCs). The findings point to a novel and potentially universal approach to treating blood cancers.

CD45 is highly expressed on blood cancers but also on healthy blood cells. This profile until now has prevented effective targeting for therapeutic purposes. Now, a group led by Dr. Lukas Jeker, and researchers at Cimeio have shown that acute myeloid leukemia (AML) cells can be eliminated using Cimeio’s proprietary CD45-targeting ADC. By transplanting engineered HSCs that are shielded from the CD45-directed therapy, the CD45 ADC was safely and effectively administered against the blood cancers.

This work is foundational for the emerging field called epitope shielding, which enables the development of curative therapies for patients with hematologic diseases, severe autoimmune conditions and potentially infectious diseases such as HIV. The core patent for epitope shielding is exclusively licensed to Cimeio by University of Basel.

“All AML cells express CD45 but since all healthy blood cells also express it, killing cells that express CD45 results in severe toxicity,” said Dr. Jeker, who is the co-founder of Cimeio and Professor of Experimental Transplantation Immunology & Nephrology at the Basel University Hospital, Switzerland. “We solved the problem by providing epitope-shielded HSCs, which enable the ADC to selectively deplete cancer cells while sparing the healthy ones.”

“We believe that this therapy could change the treatment paradigm for patients with AML, which is a difficult-to-treat disease with a five-year survival rate of only 25%,” said Stefanie Urlinger, Ph.D., Chief Scientific Officer at Cimeio. “By protecting a patient’s heme system from toxicity, we are able to develop new targeted treatments previously not possible.”

Cimeio Therapeutics is developing epitope engineered cells and paired targeted therapies for CD45 and CD117, and epitope engineered cells for CD33, CD52, and several other heme targets.

About Cimeio Therapeutics

Cimeio is an immunotherapy company developing Shielded-Cell & Immunotherapy Pairs™ (SCIP), novel immunotherapies which have the potential to transform treatment of hematologic diseases. Cimeio develops immunotherapies, along with paired, modified variants of naturally occurring cell surface proteins in HSCs. These novel epitopes edited variants maintain their function but are resistant to depletion when targeted by a paired immunotherapy which has high affinity for the wild-type version of these proteins. These immunotherapies have significant therapeutic potential, which Cimeio is using to develop curative treatments for patients with hematologic malignancies, autoimmune disorders, and genetic diseases. Shielded Cell and Immunotherapy Pairs and SCIP are trademarks of Cimeio Therapeutics, Inc. For more information, please visit www.cimeio.com.

Contacts

Steve Edelson

sedelson@versantventures.com
415-801-8088

AmorChem’s RNA Zipcode Delivery Technology Investment Exits via New York-Based Kodikaz Therapeutic Solutions, Inc.

MONTREAL–(BUSINESS WIRE)–AmorChem II Fund L.P. (”AmorChem”) is delighted to announce that its RNA Zipcode delivery program has been acquired by Kodikaz Therapeutic Solutions, Inc. (”Kodikaz”), a New York City biotech focused on targeted delivery of cancer therapeutics. The RNA Zipcode program was the first university-based investment of AmorChem’s second fund and was developed by Professors Eric Lécuyer (Montreal Clinical Research Institute), Mathieu Blanchette (McGill University), and Jérôme Waldispühl (McGill University).

”We invested in this technology ahead of current trends and prior to the pandemic of 2020, when the promise of RNA-based therapeutics was crystallized in an effort that saved millions of lives. Focus on RNA-based therapeutics has grown steadily since, though one of the major issues remains delivery – not only to the appropriate tissue – but also to the correct subcellular localization. The work of Kodikaz on targeted delivery of therapeutics to cancer cells using their DNA zipcode technology made them a most attractive receptor for our assets, and in fact, both groups saw synergy in combining the two approaches. It’s truly exciting to see our RNA Zipcode program now move forward in collaboration between the researchers and the Kodikaz group, which includes a seasoned management team already in place,” says Kevin McBride, General Partner & CSO at AmorChem.

”The success of our RNA Zipcode program highlights our specialized investment strategy: digging deep into Quebec academia searching for novel therapeutic approaches that will benefit patients. This often means that AmorChem bets on nascent technologies that have not yet been proven. In the RNA Zipcode case, our team spearheaded the collaboration between three teams from two major research institutions and AmorChem’s investment leveraged additional financial support from several granting agencies. Our mobilization of the appropriate human and financial resources allowed us to attract a valuable partner. This is now bringing a transformative academic technology one step closer to patients while building Kodikaz’s pipeline to a full suite of complementary delivery tools,” comments Inès Holzbaur, Managing Partner at AmorChem.

”This is a great opportunity to partner with world-renowned inventors that bring expertise in artificial intelligence and RNA delivery. We are excited to bring in the new capability that permits us to further control delivery not only to the targeted cell but also within the cell with high specificity,” says Anthony Johnson, Kodikaz President & CEO.

The transaction was made possible by the great collaboration of Axelys and McGill University’s Office of Innovation + Partnerships. The RNA Zipcode program was generously supported by grants from the Genomic Applications Partnership Program (Genome Canada and Genome Quebec), as well as the Programme de soutien aux organismes de recherche et d’innovation (Ministère de l’Économie, de l’Innovation et de l’Énergie) and Médicament Québec.

About AmorChem

AmorChem (www.amorchem.com) is a leading early-stage venture capital fund launched in 2011 in Montreal. The AmorChem team utilizes its deep understanding of fundamental science to uncover its therapeutic potential and focuses its core expertise in translational research to accelerate therapeutic drug discovery and development across a broad spectrum of disease areas. The fund capitalizes on both its venture capital expertise and its entrepreneurial experience to spark the creation of start-up companies and help shape them into the next generation of biotech companies. With over $85M under management, AmorChem has financed over 30 university projects and started up several biotechnology companies from the fruits of this innovative research.

For more information on Kodikaz, visit www.kodikaz.com.

Contacts

Media contact
Inès Holzbaur

514 513-7453

ines@amorchem.com