Deciphera Presents 2-Year Efficacy and Safety Results from MOTION Phase 3 Study of ROMVIMZA™ (vimseltinib) in Patients with Tenosynovial Giant Cell Tumor (TGCT) at the European Society for Medical Oncology Congress 2025




Deciphera Presents 2-Year Efficacy and Safety Results from MOTION Phase 3 Study of ROMVIMZA™ (vimseltinib) in Patients with Tenosynovial Giant Cell Tumor (TGCT) at the European Society for Medical Oncology Congress 2025

– Vimseltinib demonstrated statistically significant and clinically meaningful benefit vs placebo in antitumor response –

OSAKA, Japan & WALTHAM, Mass.–(BUSINESS WIRE)–Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; “Ono”), today announced the two-year efficacy and safety results from its MOTION Phase 3 study of vimseltinib in patients with TGCT in cases where surgical removal of the tumor is not an option will be presented as a poster during the 2025 European Society for Medical Oncology Congress (ESMO), taking place October 17-21 in Berlin, Germany.

“These long-term Phase 3 MOTION results add to the established body of evidence supporting vimseltinib as a best-in-class treatment for TGCT,” said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. “TGCT often causes debilitating pain, stiffness and impaired mobility and these results demonstrate the durable benefit that vimseltinib can offer patients.”

Summary of Data and Findings from the 2-year results of the MOTION Phase 3 Study

Methods

The global Phase 3 MOTION study (NCT05059262) aims to evaluate the efficacy and safety of vimseltinib for the treatment of TGCT in cases where surgical removal of the tumor is not an option.

The study consists of two parts. In Part 1, eligible study participants were assigned to receive either vimseltinib or matching placebo for 24 weeks. Participants assigned to placebo in Part 1 had the option to receive vimseltinib for Part 2. Part 2 was a long-term treatment phase in which all participants received open-label vimseltinib. Patients received vimseltinib 30 mg twice weekly in all periods. Objective response rate (ORR) based on best overall response was assessed by independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and per Tumor Volume Score (TVS). Duration of response (DOR) and safety were also evaluated.

Efficacy

In these two-year results from the MOTION Phase 3 trial, vimseltinib continued to demonstrate robust and durable antitumor efficacy with a manageable safety profile that was consistent with prior reports. These long-term results support vimseltinib as a treatment option for patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability, where it is approved. These results are reported with two years of follow-up in patients randomized to vimseltinib in Part 1 and crossed over from placebo to vimseltinib in Part 2. The data cutoff for this analysis was February 22, 2025.

In total, 118 patients received vimseltinib. At data cutoff, 51% (60/118) remained on treatment. With at least 2 years of follow-up, results demonstrate robust and durable antitumor activity with vimseltinib per RECIST v1.1 and per TVS, including in patients who crossed over to vimseltinib in Part 2.

• Of 83 patients randomized to vimseltinib in Part 1, 73 continued open-label treatment in Part 2. Median (range) treatment duration was 23.6 months (2 to 36).
• Of the 40 patients randomized to placebo in Part 1, 35 crossed over to vimseltinib in Part 2. Median treatment duration for this group was 19.1 months (1 to 30).
• ORR on study per RECIST v1.1 was 48% (40/83) for patients randomized to vimseltinib and 54% (19/35) for those who crossed over to vimseltinib. ORR on study per TVS was 81% (67/83) for patients randomized to vimseltinib and 71% (25/35) for those who crossed over to vimseltinib.
• The corresponding median DOR per RECIST v1.1 and per TVS was still not reached.

Safety

Vimseltinib continued to have a manageable safety profile that was consistent with prior reports with no new safety signals.

• Most treatment-emergent adverse events (TEAEs) were grade 1/2, and grade 3/4 TEAEs were similar between randomized vimseltinib and crossover groups.
• There were no new TEAEs in ≥15% of patients receiving vimseltinib and no new serious adverse events in more than one patient.
• Serum enzyme elevations were consistent with the known mechanism of action of CSF1R inhibition, and there was no evidence of cholestatic hepatotoxicity or drug-induced liver injury.

About Vimseltinib

Vimseltinib is an oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. Vimseltinib has been developed using Deciphera’s proprietary switch-control kinase inhibitor platform. It has been approved in the United States for adult patients with symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability.

About Tenosynovial Giant Cell Tumor (TGCT)

TGCT is caused by a dysregulation in colony-stimulating factor 1 (CSF1) gene leading to overproduction of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion.¹ TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS). TGCT is a rare, locally aggressive neoplasm that can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients, surgical resection will potentially cause worsening functional limitation or severe morbidity. Systemic treatment options are limited and new therapeutic options are needed.^1,2

About Deciphera Pharmaceuticals Inc.

Deciphera, a member of Ono Pharmaceutical Co., Ltd., is a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer. Deciphera is leveraging its proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology to develop a broad portfolio of innovative medicines. In addition to advancing multiple product candidates from Deciphera’s platform in clinical studies, QINLOCK® (ripretinib) is Deciphera’s switch-control kinase inhibitor approved in many countries including the European Union and the United States for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. ROMVIMZA™ (vimseltinib) is a kinase inhibitor approved in the United States for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability. For more information, visit www.deciphera.com and follow us on LinkedIn and X (@Deciphera).

About Ono Pharmaceutical Co., Ltd

Ono Pharmaceutical Co., Ltd. delivers innovative therapies for patients worldwide. Upholding its philosophy of “Dedicated to the Fight against Disease and Pain,” Ono targets areas with unmet medical needs including oncology, immunology, and neurology, and fosters partnerships with academic and biotech organizations to accelerate drug discovery. Through its affiliate, Deciphera Pharmaceuticals, Ono is accelerating clinical development and commercial operations in the US and Europe to drive global business expansion and further its commitment to patient care. For more information, please visit the company’s website at https://www.ono-pharma.com/en.

Cautionary Note Regarding Forward-Looking Statements

In this press release, statements made with respect to current plans, estimates, strategies and beliefs, and other statements that are not historical facts are forward-looking statements about the future performance of the company. These statements are based on current assumptions and beliefs in light of the information currently available and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in the business environment in the pharmaceutical market and amendments to relevant laws and regulations, (ii) disruptions to product supply due to stagnation or delays in production caused by natural disasters, fires, etc., (iii) the possibility that sales activities for new and existing products may not achieve the expected results, (iv) the emergence of new side effects in post-marketing drugs, and (v) infringements of intellectual property rights by third parties. Information about pharmaceutical products included in this press release is not intended to constitute an advertisement or medical advice.

1. Gelderblom H, Bhadri V, Stacchiotti S, et al. Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10445):2709-2719. doi:10.1016/S0140-6736(24)00885-7

2. Stacchiotti S, Dürr HR, Schaefer IM, et al. Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts. Cancer Treat Rev. 2023;112:102491. doi:10.1016/j.ctrv.2022.102491

Contacts

Ono Pharmaceutical Co., Ltd.
Media:
media_inquiries@ono-pharma.com

Deciphera Pharmaceuticals, Inc.
Media:
David Rosen

Argot Partners

david.rosen@argotpartners.com
646-461-6387

KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Demonstrates Durable 5-Year Survival Benefit Versus Chemotherapy for Patients With Advanced Endometrial Carcinoma Following One Prior Platinum-Based Regimen




KEYTRUDA® (pembrolizumab) Plus LENVIMA® (lenvatinib) Demonstrates Durable 5-Year Survival Benefit Versus Chemotherapy for Patients With Advanced Endometrial Carcinoma Following One Prior Platinum-Based Regimen

At five years, KEYTRUDA plus LENVIMA showed a 16.7% overall survival (OS) rate for these patients with mismatch repair proficient (pMMR) advanced endometrial carcinoma versus 7.3% for chemotherapy alone in the pivotal Phase 3 KEYNOTE-775/Study 309 trial

Five-year OS results in the pMMR subgroup were consistent with the all-comers study population, which demonstrated an OS rate of 19.9% for KEYTRUDA plus LENVIMA versus 7.7% for chemotherapy

RAHWAY, N.J. & NUTLEY, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Eisai today announced long-term follow-up data continued to show durable benefit of KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 therapy, plus LENVIMA^® (lenvatinib), the orally available multiple receptor tyrosine kinase inhibitor (TKI) discovered by Eisai, compared to chemotherapy for patients with advanced endometrial carcinoma following at least one prior platinum-based regimen in any setting. The findings, based on five years of follow-up from the Phase 3 KEYNOTE-775/Study 309 trial evaluating KEYTRUDA plus LENVIMA versus chemotherapy (treatment of physician’s choice of doxorubicin or paclitaxel), for these patients with advanced endometrial carcinoma are being presented during a poster session at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany (Presentation #1119P).

In the trial, a total of 827 patients (697 whose cancer was mismatch repair proficient [pMMR] and 130 whose cancer was mismatch repair deficient [dMMR]) were randomized to receive KEYTRUDA plus LENVIMA (n=411) or chemotherapy (n=416). The trial’s primary endpoints, overall survival (OS) and progression-free survival (PFS), were evaluated in patients with pMMR disease and in the intent-to-treat population (also known as the all-comers population), which included all randomized patients (both pMMR and dMMR).

In the pMMR subgroup, after a median follow-up of 68.8 months (range, 60.8–79.0 months for KEYTRUDA plus LENVIMA; range, 60.9–80.0 for chemotherapy), the five-year OS rate was 16.7% for KEYTRUDA plus LENVIMA versus 7.3% for chemotherapy alone. Median OS was 18.0 months (95% CI, 14.9-20.5) for KEYTRUDA plus LENVIMA versus 12.2 months (95% CI, 11.0-14.1) for chemotherapy alone (HR 0.70; 95% CI, 0.60-0.83). Five-year OS results in the pMMR subgroup were consistent with the all-comers population, which demonstrated an OS rate of 19.9% for KEYTRUDA plus LENVIMA versus 7.7% for chemotherapy; median OS was 18.7 months (95% CI, 15.6-21.3) for KEYTRUDA plus LENVIMA versus 11.9 months (95% CI, 10.6-13.3) for chemotherapy (HR 0.66; 95% CI, 0.57-0.77).

The long-term OS data were consistent with the primary analysis presented at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting and published in the New England Journal of Medicine. In the primary analysis, the median OS was 17.4 months (95% CI, 14.2-19.9) for KEYTRUDA plus LENVIMA versus 12.0 months (95% CI, 10.8-13.3) for chemotherapy in the pMMR subgroup, and 18.3 months (95% CI, 15.2-20.5) versus 11.4 months (95% CI, 10.5-12.9) in the all-comers population. In the five-year analysis, there were no new safety signals and the safety profile of KEYTRUDA plus LENVIMA was consistent with previously reported data on the combination.

“Endometrial carcinoma is difficult-to-treat in the recurrent or advanced stage, especially when tumors are mismatch repair proficient and therefore harder to target with immunotherapy alone,” said Dr. Vicky Makker, Principal Investigator and Gynecologic Medical Oncologist, Memorial Sloan Kettering Cancer Center. “Five-year follow-up data from the KEYNOTE-775/Study 309 trial show sustained survival benefit in patients treated with pembrolizumab plus lenvatinib and underscore the role of this combination as an effective treatment option for patients with advanced endometrial carcinoma who need further treatment after receiving prior platinum-based therapy.”

“Recent advances have led to steady improvement in outcomes for patients with advanced endometrial carcinoma,” said Dr. Gregory Lubiniecki, Vice President, Global Clinical Development, Merck Research Laboratories. “These five-year data highlight the durable survival benefit of KEYTRUDA plus LENVIMA in patients with advanced endometrial carcinoma who have received prior platinum-based therapy and are the result of our ongoing commitment to delivering impactful treatment options for people affected by women’s cancers.”

“The five-year results from KEYNOTE-775/Study 309 represent the longest reported follow-up for a trial evaluating an immunotherapy plus tyrosine kinase inhibitor combination in advanced endometrial carcinoma,” said Dr. Corina Dutcus, Senior Vice President, Oncology Global Clinical Development Lead at Eisai Inc. “These findings demonstrate the continued overall survival benefit observed with KEYTRUDA plus LENVIMA, further supporting the combination’s therapeutic value for patients facing this disease. We are deeply grateful to the patients, their families, and the dedicated investigators whose participation and commitment made this research possible.”

Treatment-related adverse events (TRAEs) occurred in 97.3% of patients receiving KEYTRUDA plus LENVIMA versus 93.8% of patients receiving chemotherapy and led to the discontinuation of KEYTRUDA and/or LENVIMA in 40.1% of patients (16.0% discontinued both drugs) versus the discontinuation of chemotherapy in 8.0% of patients. The most common adverse events (≥ 20%) in the KEYTRUDA plus LENVIMA group were hypertension (61.8%), hypothyroidism (55.7%), diarrhea (43.3%), nausea (40.1%), decreased appetite (37.9%), fatigue (28.8%), proteinuria (27.6%), vomiting (24.4%), arthralgia (23.9%), decreased weight (22.7%) and palmar-plantar erythrodysesthesia syndrome (20.7%).

Based on the primary analysis results in 2021 from the Phase 3 KEYNOTE-775/Study 309 trial, KEYTRUDA plus LENVIMA is approved in the U.S. for patients with advanced endometrial carcinoma that is pMMR or not microsatellite instability-high (MSI-H), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. KEYTRUDA plus LENVIMA is also approved in the European Union (EU) and Japan for certain patients with advanced or recurrent endometrial carcinoma regardless of mismatch repair status. Lenvatinib is approved as KISPLYX for advanced renal cell carcinoma in the EU.

Dr. Makker has provided consulting and advisory services for Merck and Eisai.

Study design and additional data from KEYNOTE-775/Study 309

KEYNOTE-775/Study 309 (ClinicalTrials.gov, NCT03517449) is a Phase 3, multicenter, open-label, randomized, active-controlled study evaluating KEYTRUDA plus LENVIMA for the treatment of patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. Participants may have received up to two platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade ≥3 fistula, uncontrolled blood pressure (>150/90 mmHg), significant cardiovascular impairment or event within the last 12 months or patients who had active autoimmune disease or a medical condition that required immunosuppression. The primary efficacy outcome measures were OS and PFS as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary efficacy outcome measures included objective response rate (ORR) as assessed by BICR and safety. The study randomized 827 patients 1:1 to receive:

• KEYTRUDA (200 mg intravenously every three weeks) plus LENVIMA (20 mg orally once daily); or
• Investigator’s choice, consisting of either doxorubicin (60 mg/m² every three weeks) or paclitaxel (80 mg/m² given weekly, three weeks on/one week off).

Treatment with KEYTRUDA plus LENVIMA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity or, for KEYTRUDA, a maximum of 35 cycles. Administration of KEYTRUDA plus LENVIMA was permitted beyond RECIST v1.1-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated.

In the pMMR subgroup, KEYTRUDA plus LENVIMA demonstrated a five-year PFS rate of 6.3% versus 2.1% for chemotherapy alone. Median PFS was 6.7 months (95% CI, 5.6-7.4) for KEYTRUDA plus LENVIMA versus 3.8 months (95% CI, 3.6-5.0) for chemotherapy alone. At five years, ORR was 32.4% (95% CI, 27.5-37.6) for KEYTRUDA plus LENVIMA compared with 14.8% (95% CI, 11.3-19.0) for chemotherapy.

In the all-comers population, KEYTRUDA plus LENVIMA demonstrated a five-year PFS rate of 9.8% versus 3.2% for chemotherapy alone. Median PFS was 7.3 months (95% CI, 5.7-7.6) for KEYTRUDA plus LENVIMA versus 3.8 months (95% CI, 3.6-4.2) for chemotherapy alone. At five years, ORR was 33.8% (95% CI, 29.3-38.6) for KEYTRUDA plus LENVIMA compared with 14.4% (95% CI, 11.2-18.2) for chemotherapy.

The long-term PFS data were also consistent with the primary analysis, in which the median PFS was 6.6 months (95% CI, 5.6-7.4) for KEYTRUDA plus LENVIMA versus 3.8 months (95% CI, 3.6-5.0) for chemotherapy in the pMMR subgroup, and 7.2 months (95% CI, 5.7-7.6) versus 3.8 months (95% CI, 3.6-4.2) in the all-comers population.

In the all-comers population, 44.8% of patients treated with KEYTRUDA plus LENVIMA and 51.2% of patients treated with chemotherapy used subsequent systemic anticancer therapy (compared with 28.0% and 48.1%, respectively, at the primary analysis). In the chemotherapy group, 10.1% of patients crossed over to receive KEYTRUDA plus LENVIMA. At the data cut-off (Feb. 26, 2025), 86 patients were alive after treatment with KEYTRUDA plus LENVIMA, compared to 53 patients treated with chemotherapy.

While the trial was not powered to compare KEYTRUDA plus LENVIMA with chemotherapy in the dMMR subgroup, a clinically meaningful improvement was observed across efficacy endpoints. The five-year OS rate was 36.5% for KEYTRUDA plus LENVIMA versus 9.8% for chemotherapy alone. Median OS was 31.9 months (95% CI, 15.6-47.7) for KEYTRUDA plus LENVIMA versus 8.6 months (95% CI, 5.5-13.4) for chemotherapy alone. KEYTRUDA plus LENVIMA demonstrated a five-year PFS rate of 26.4% versus 10.8% for chemotherapy. Median PFS was 14.8 months (95% CI, 5.6-31.9) for KEYTRUDA plus LENVIMA versus 3.7 months (95% CI, 3.1-4.4) for chemotherapy alone. The ORR at five years was 41.5% (95% CI, 29.4-54.4) for KEYTRUDA plus LENVIMA compared with 12.3% (95% CI, 5.5-22.8) for chemotherapy.

About endometrial carcinoma

Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. More than 90% of uterine body cancers occur in the endometrium. In the U.S., it is estimated there will be approximately 69,120 patients diagnosed with uterine body cancer and approximately 13,860 patient deaths from the disease in 2025. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall. Following primary treatment, patients face a risk of their cancer returning, often as distant metastasis, which is associated with poorer outcomes.

About KEYTRUDA^® (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA^® (pembrolizumab) Indications in the U.S.

Endometrial Carcinoma

KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting are not candidates for curative surgery or radiation.

KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.

Contacts

Media Contacts:

Merck:

Julie Cunningham

(617) 519-6264

John Infanti

(609) 500-4714

Eisai:

Michele Randazzo

(201) 248-2228

Investor Contacts:

Merck:

Peter Dannenbaum

(732) 594-1579

Steven Graziano

(732) 594-1583

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Genmab Announces New Data Demonstrating Investigational Rinatabart Sesutecan (Rina-S®) Achieved Anti-Tumor Activity in Heavily Pretreated Patients with Advanced Endometrial Cancer




Genmab Announces New Data Demonstrating Investigational Rinatabart Sesutecan (Rina-S®) Achieved Anti-Tumor Activity in Heavily Pretreated Patients with Advanced Endometrial Cancer

• Updated data from the Phase 1/2 RAINFOL™-01 trial showed rinatabart sesutecan (Rina-S^®) 100 mg/m² demonstrated 50% confirmed objective response rate (ORR), including two complete responses (CR), regardless of FRα expression
• A Phase 3 trial in endometrial cancer is underway
• U.S. FDA recently granted Breakthrough Therapy Designation to Rina-S for advanced endometrial cancer

COPENHAGEN, Denmark–(BUSINESS WIRE)–Genmab A/S (Nasdaq: GMAB) announced today updated data from cohort B2 of the Phase 1/2 RAINFOL™-01 trial evaluating rinatabart sesutecan (Rina-S^®), an investigational folate receptor alpha (FRα)-targeted, TOPO1-inhibitor antibody-drug conjugate (ADC). The study showed that at a median study follow-up of one year, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0% confirmed objective response rate (ORR), including two complete responses (CR), in heavily pretreated patients with advanced endometrial cancer (EC) who had progressed following platinum-based chemotherapy and an immune checkpoint inhibitor. Additionally, at a median study follow-up of one year, 63.6% of responders (including CRs) in the 100 mg/m² cohort maintained their responses and remain on treatment. The responses were observed regardless of FRα expression levels. The updated results were presented at the European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.

Continued evaluation of single-agent Rina-S 100 mg/m² in patients with advanced EC is ongoing in the Phase 2 RAINFOL-01 trial (NCT05579366) and the Phase 3 RAINFOL-03 trial (NCT07166094).

“Women with advanced endometrial cancer are often facing a difficult path, while doctors are confronted with not having enough treatment options,” said Noelle Cloven, M.D., Texas Oncology Fort Worth, Sarah Cannon Research Institute, and study investigator. “That’s why these data signals with Rina-S in the updated Phase 1/2 RAINFOL-01 data are encouraging – they point to the possibility of providing more choices for patients in the future.”

The B2 cohort of the Phase 1/2 RAINFOL-01 study (NCT05579366) is a dose expansion cohort evaluating the efficacy and safety of Rina-S in patients with advanced or recurrent endometrial cancer. In the study, 64 patients with heavily pretreated advanced or recurrent endometrial cancer whose disease had progressed on or after an anti-PD-(L)1 and platinum-based chemotherapy were enrolled and treated with Rina-S. Patients were administered either 100 mg/m² (n=22) (selected dose for Phase 3 clinical trial) or 120 mg/m² (n=42) of Rina-S. In the 100 mg/m² cohort, the confirmed ORR was 50.0%, including two CRs. Anti-tumor activity was also observed in patients treated with Rina-S 120 mg/m² Q3W, which resulted in 44.1% confirmed ORR and one CR. Study participants were previously treated with a median of three lines of therapy (range 1-8). Earlier results from this cohort were previously presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Common treatment emergent adverse events (TEAEs; all grades) consisted primarily of cytopenias and low-grade gastrointestinal (GI) events. To date, there have been no signals of ocular toxicities, neuropathy, or interstitial lung disease (ILD) observed in Rina-S clinical trials consistent with prior reports. Serious TEAEs (Grade 3 or higher), occurred in 36.4% and 52.4% of patients treated with Rina-S 100 mg/m² and 120 mg/m², respectively. Hematologic adverse events did not require significant dose reduction and were associated with low rates of treatment discontinuation.

“With this updated data, we are seeing additional momentum behind the possibilities of Rina-S,” said Tahi Ahmadi, M.D., Executive Vice President and Chief Medical Officer, Head of Experimental Medicines at Genmab. “As a wholly owned, novel antibody-drug conjugate, Rina-S reflects Genmab’s vision to accelerate our innovative, late-stage pipeline that has the potential to redefine possibilities for patients with certain gynecologic cancers.”

Rina-S is advancing through late-stage development supported by a growing portfolio of clinical trials, including the ongoing Phase 1/2 RAINFOL-01 trial (NCT05579366), the Phase 3 RAINFOL-03 trial (NCT07166094) in patients with endometrial cancer now underway and the Phase 3 RAINFOL-02 trial (NCT06619236) in patients with platinum resistant ovarian cancer (PROC). The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation (BTD) to Rina-S for the treatment of adult patients with recurrent or progressive EC who have disease progression on or following prior treatment with a platinum-containing regimen and a PD-(L)1 therapy.

About the RAINFOL^TM -01 Trial

RAINFOL™-01 (NCT05579366) is an open-label, multicenter Phase 1/2 study, designed to evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A dose escalation; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; Part D combination therapy cohorts; Part F a monotherapy endometrial cancer (EC) cohort.

About Endometrial Cancer

Endometrial cancer (EC) starts in the lining of the uterus, known as the endometriumⁱ and ranks as the second most prevalent gynecologic cancer globally, with increasing incidence and mortality rates^ii,iii. Patients with advanced or recurrent EC have a relatively poor prognosis and treatment options are limited for those patients who have progressed following treatment with chemotherapy and immune checkpoint inhibitor. FRα is overexpressed on multiple tumors, including EC, making it a promising therapeutic target. Anti-tumor activity with Rina-S was observed across a broad range of FRα expression, and there are currently no approved FRα-directed therapies approved for the treatment of endometrial cancer.

About Rinatabart Sesutecan (Rina-S; GEN1184)

Rinatabart sesutecan (Rina-S; GEN1184) is an investigational ADC. It is composed of a novel human monoclonal antibody directed at folate receptor α (FRα), a novel hydrophilic protease-cleavable linker, and exatecan, a topoisomerase I inhibitor payload. The clinical trial program for Rina-S continues to expand including ovarian, endometrial and other cancers of unmet need.

The safety and efficacy of rinatabart sesutecan has not been established. Please visit www.clinicaltrials.gov for more information.

About Genmab

Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For more than 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO) antibody medicines^®.

Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X.

This Media Release contains forward looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with preclinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab^®; the Y-shaped Genmab logo^®; Genmab in combination with the Y-shaped Genmab logo^®; HuMax^®; DuoBody^®; HexaBody^®; DuoHexaBody^®, HexElect^®, KYSO^® and RAINFOL™; Rina-S is a trademark of ProfoundBio, US, Co. and Genmab (Suzhou) Co., Ltd.

ⁱ Mayo Clinic. Endometrial Cancer. https://www.mayoclinic.org/diseases-conditions/endometrial-cancer/symptoms-causes/syc-20352461.

ⁱⁱ Ferlay J, Ervik M, Lam F, et al. Global cancer observatory: Cancer today (version 1.1). International Agency for Research on Cancer. 05/28/2024 (https://gco.iarc.who.int/today).

ⁱⁱⁱ Concin N, Matias-Guiu X, Vergote I, et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 2021;31(1):12-39. (In eng). DOI: 10.1136/ijgc-2020-002230.

Contacts

David Freundel, Senior Director, Global Communications & Corporate Affairs

T: +1 609 613 0504; E: dafr@genmab.com

Andrew Carlsen, Vice President, Head of Investor Relations

T: +45 3377 9558; E: acn@genmab.com

Salubris Biotherapeutics Announces Dose Escalation Data for JK06, a 5T4-Targeted Antibody Drug Conjugate, at the European Society for Medical Oncology 2025 Congress




Salubris Biotherapeutics Announces Dose Escalation Data for JK06, a 5T4-Targeted Antibody Drug Conjugate, at the European Society for Medical Oncology 2025 Congress

5 confirmed partial responses (PRs) among 13 evaluable non-small cell lung cancer (NSCLC) patients (ORR 38%); 1 confirmed PR among 7 breast cancer patients

Favorable safety and PK profile, with encouraging activity, demonstrate a therapeutic window for JK06

Company proceeding with expansion cohorts in NSCLC and breast cancer

GAITHERSBURG, Md.–(BUSINESS WIRE)–Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, today announced data from the dose escalation portion of the Phase 1/2 study of JK06, a 5T4-targeted antibody drug conjugate (ADC), in patients with unresectable locally advanced or metastatic cancer, including non-small cell lung cancer (NSCLC) and breast cancer, which is being presented at the European Society for Medical Oncology (ESMO) Congress.

Data presented at ESMO include 34 patients enrolled in Europe with advanced relapsed/refractory solid tumors who were treated with JK06, once every three weeks, across five dose levels (1.5-8.0 mg/kg) in dose escalation. Among the 34 patients, 29 were response-evaluable, all having failed standard of care therapy, and among whom 83% had received three or more prior lines of treatment and 59% had received four or more prior lines of therapy at the time of enrollment.

Key efficacy findings among the 29 response-evaluable patients include:

• 6 patients attained confirmed partial responses (PRs) (21%).
• Among 13 NSCLC patients, 5 attained confirmed PRs (ORR 38%), with the longest duration of response lasting 30 weeks.
• Among 7 response-evaluable breast cancer patients, 1 attained a confirmed PR with a duration of response lasting 18 weeks.
• PRs were observed at 3.0 mg/kg (1 NSCLC), 4.5 mg/kg (3 NSCLC and 1 breast cancer), and 6.0 mg/kg (1 NSCLC).

Treatment with JK06 has been generally well-tolerated with predominantly low grade (Grades 1 and 2), manageable toxicities, such as fatigue, alopecia, decreased appetite, dry eye and diarrhea. Among treatment-related adverse events (TRAEs) occurring in at least 5% of patients, only the following ≥ Grade 3 events were observed:

• At dose levels 1.5-3.0 mg/kg (n=12 patients), 1 patient with Grade 3 peripheral neuropathy.
• At dose level 4.5 mg/kg (n=15 patients), 1 patient with Grade 3 keratitis.
• At dose levels 6.0-8.0 mg/kg (n=7 patients), 1 patient with Grade 3 fatigue, 1 patient with Grade 3 ALT increase, and 1 patient with Grade 5 pneumonitis.
• Pharmacokinetic analysis demonstrated free monomethyl auristatin E (MMAE) levels that were favorable at dose levels up to 4.5 mg/kg.

“We are encouraged by the promising preliminary data demonstrating the combination of safety and efficacy of JK06 among heavily pre-treated metastatic solid tumors, including in NSCLC and breast cancer, supporting our belief that JK06 has the potential to be a first-in-class, differentiated therapy for patients with 5T4-expressing cancers,” said Sam Murphy, Chief Executive Officer of Salubris Biotherapeutics. “We look forward to advancing the study into dose expansion in tumor-specific cohorts for NSCLC and breast cancer, while continuing to explore activity in other solid tumors known to overexpress 5T4, as we aim to improve outcomes for these patients with advanced, aggressive disease and limited therapeutic options.”

The Phase 1/2 open-label, dose-escalation and expansion study (NCT06667960) to assess the safety, pharmacokinetics, and preliminary efficacy of JK06 is ongoing, and the cohort expansion phase, which is currently enrolling, will determine the recommended Phase 2 dose for further development.

Details of the ESMO presentation are as follows:

Title: A Phase 1/2 Study of JK06, a 5T4-Targeted Antibody Drug Conjugate (ADC), in Patients with Unresectable Locally Advanced or Metastatic Cancer

Presenter: Nuria Kotecki, M.D. at Institut Jules Bordet, Anderlecht, Belgium

Abstract #: 961P

Session: Developmental Therapeutics

Date/Time: Sunday, October 19, 2025 | 12:00 – 1:00 PM CEST

About JK06

JK06 is a first-in-class quadrivalent, biparatopic ADC that selectively targets 5T4 with a monomethyl auristatin E (MMAE) payload. 5T4 is an oncofetal protein that is overexpressed in a wide range of solid tumors, including NSCLC, breast, renal and genitourinary cancers, and is associated with more aggressive tumor progression and reduced survival. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies.

About SalubrisBio

SalubrisBio is a clinical-stage biotechnology company dedicated to discovering and developing complex biologics for cardiovascular disease and oncology. The Company is currently progressing multiple innovative and rationally designed first-in-class therapeutics through clinical development programs, including JK07, the potential first disease-modifying biologic for heart failure, and JK06, a quadrivalent, biparatopic ADC targeting 5T4 for the treatment of cancer. SalubrisBio is headquartered in Gaithersburg, Maryland. For more information about SalubrisBio, visit us at www.salubrisbio.com and connect with us on LinkedIn.

Contacts

For further information, please contact:
Argot Partners

212.600.1902 | SalubrisBio@argotpartners.com

Exelixis Announces Results from Subgroup Analysis of CABINET Phase 3 Pivotal Trial Evaluating CABOMETYX® (cabozantinib) in Advanced Lung and Thymic Neuroendocrine Tumors at ESMO 2025




Exelixis Announces Results from Subgroup Analysis of CABINET Phase 3 Pivotal Trial Evaluating CABOMETYX® (cabozantinib) in Advanced Lung and Thymic Neuroendocrine Tumors at ESMO 2025

– CABOMETYX reduced the risk of disease progression or death by 81% versus placebo in patients with advanced lung or thymic neuroendocrine tumors (NET) –

– The lungs are the second most common NET site of origin, yet limited treatment options are available¹ –

ALAMEDA, Calif.–(BUSINESS WIRE)–Exelixis, Inc. (Nasdaq: EXEL) today announced results from a subgroup analysis of the CABINET phase 3 pivotal trial evaluating CABOMETYX^® (cabozantinib) versus placebo in patients with previously treated advanced neuroendocrine tumors (NET) originating in the lungs or thymus. These data will be presented at the 2025 European Society for Medical Oncology Congress (ESMO) during the Monday Poster Session: Neuroendocrine Tumours on October 20, 2025, from 12:00 – 12:45 p.m. CEST.

“The regulatory approvals of cabozantinib in the United States and European Union earlier this year provide a much-needed targeted treatment option for patients with previously treated advanced NET,” said Jennifer Chan, M.D., M.P.H., study chair for the CABINET trial, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “These subgroup results showing that cabozantinib achieved a meaningful progression-free survival benefit in patients with lung or thymic NET are encouraging, as these subtypes of the disease can be particularly challenging to treat.”

In the phase 3 CABINET study, patients with locally advanced or metastatic pancreatic NET (pNET) or extra-pancreatic NET (epNET) were randomized 2:1 in separate cohorts to receive CABOMETYX 60 mg daily versus placebo. Patients with epNET had tumors arising in the gastrointestinal (GI) tract, lung, rare sites including the thymus and unknown primary sites. Of the 203 patients in the epNET cohort, 49 had lung or thymic NET. With a median follow-up for progression-free survival (PFS) of 5.5 months, CABOMETYX reduced the risk of disease progression or death by 81% versus placebo (stratified hazard ratio: 0.19; 95% confidence interval: 0.06-0.54; one-sided stratified log-rank P=0.0003). Median PFS was 8.2 months with CABOMETYX compared to 2.7 months with placebo. Confirmed objective response rates were 6% versus 0%, respectively.

“These subgroup data build upon the strong overall findings from the CABINET trial and reinforce the benefits of CABOMETYX for a heterogeneous NET patient population,” said Dana T. Aftab, Ph.D., Executive Vice President, Research & Development, Exelixis. “Lung and thymic NET are forms of cancer with limited treatment options, and we are pleased CABOMETYX helps address an unmet need for these patients. We are committed to continuing to serve the NET patient community with our ongoing STELLAR-311 pivotal trial examining zanzalintinib as a potential first-line oral targeted therapy versus everolimus for patients with locally advanced or metastatic NET.”

The safety profile of CABOMETYX observed in patients with lung or thymic NET was consistent with its known safety profile; no new safety signals were identified. The most frequent grade 3/4 adverse events attributed to CABOMETYX included fatigue (24%), hypertension (18%), diarrhea (9%) and palmar plantar erythrodysesthesia (9%).

In March 2025, the U.S. Food and Drug Administration approved CABOMETYX for the treatment of 1) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and 2) adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET, based on results from the CABINET study. In July 2025, the European Commission approved CABOMETYX for the treatment of adult patients with unresectable or metastatic, well-differentiated pNET and epNET who have progressed following at least one prior systemic therapy other than somatostatin analogues.

About CABINET (Alliance A021602)

CABINET (Randomized, Double-Blinded, Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network, as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase 3 pivotal trial that enrolled a total of 298 patients in two separate cohorts (pNET and epNET) in the U.S. at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo; each cohort was randomized separately and had its own statistical analysis plan. The trial was stopped early after an interim analysis showed superior efficacy associated with cabozantinib as compared to placebo in each of the two cohorts. Patients with epNET had primary tumors arising in the GI tract, lung, unknown primary sites and other organs. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.

About NET

NET are cancers that begin in the specialized cells of the body’s neuroendocrine system.² These cells have traits of both hormone-producing endocrine cells and nerve cells.² It is estimated that 161,000 to 192,000 people in the U.S. are living with unresectable, locally advanced or metastatic NET.³ The number of people diagnosed with NET has been increasing in recent decades.⁴ Functional NET release peptide hormones that can cause debilitating symptoms, like diarrhea, hypertension and flushing, while symptoms of non-functional NET are related primarily to tumor growth.^{5, 6, 7, 8, 9} Most NET take years to develop and grow slowly, but eventually all patients with advanced or metastatic NET will develop refractory and progressing disease.^{10, 11}

NET can start in the pancreas (pNET), where they tend to be more aggressive, with a five-year survival rate of only 19% for advanced disease.^2,12 NET can also develop in any part of the body, but most commonly start in the GI tract or in the lungs, where they have historically been referred to as carcinoid tumors and are more recently called epNET.² The five-year survival rate for advanced GI NET is 68%.¹³ For advanced NET patients, treatment options include somatostatin analogs, chemotherapy, molecular targeted therapy and peptide-receptor radionuclide therapy.¹⁴

Approximately 2,000-4,500 people will be newly diagnosed with lung NET in the U.S. each year.¹⁵ The five-year survival rate for advanced lung NET is 49%.¹⁶ Thymic NET are rare, typically aggressive tumors with a worse prognosis compared to that of lung NET.¹⁷

About CABOMETYX^® (cabozantinib)

In the U.S., CABOMETYX tablets are approved as monotherapy for the treatment of patients with advanced renal cell carcinoma (RCC) and in combination with nivolumab as a first-line treatment for patients with advanced RCC; for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible; for the treatment of adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pNET; and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated epNET. CABOMETYX tablets have also received regulatory approvals in over 65 countries outside the U.S. and Japan, including the EU. In 2016, Exelixis granted Ipsen Pharma SAS exclusive rights for the commercialization and further clinical development of cabozantinib outside of the U.S. and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize cabozantinib in the U.S.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: CABOMETYX can cause severe and fatal hemorrhages. The incidence of Grade 3-5 hemorrhagic events was 5% in CABOMETYX patients in RCC, HCC, and DTC studies. Discontinue CABOMETYX for Grade 3-4 hemorrhage and before surgery. Do not administer to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Perforations and Fistulas: Fistulas, including fatal cases, and gastrointestinal (GI) perforations, including fatal cases, each occurred in 1% of CABOMETYX patients. Monitor for signs and symptoms, and discontinue CABOMETYX in patients with Grade 4 fistulas or GI perforation.

Thrombotic Events: CABOMETYX can cause arterial or venous thromboembolic event. Venous thromboembolism occurred in 7% (including 4% pulmonary embolism) and arterial thromboembolism in 2% of CABOMETYX patients. Fatal thrombotic events have occurred. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or serious arterial or venous thromboembolic events.

Hypertension and Hypertensive Crisis: CABOMETYX can cause hypertension, including hypertensive crisis. Hypertension was reported in 37% (16% Grade 3 and <1% Grade 4) of CABOMETYX patients. In CABINET (n=195), hypertension occurred in 65% (26% Grade 3) of CABOMETYX patients. Do not initiate CABOMETYX in patients with uncontrolled hypertension. Monitor blood pressure regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled; when controlled, resume at a reduced dose. Permanently discontinue CABOMETYX for severe hypertension that cannot be controlled with antihypertensive therapy or for hypertensive crisis.

Diarrhea: CABOMETYX can cause diarrhea and it occurred in 62% (10% Grade 3) of treated patients. Monitor and manage patients using antidiarrheals as indicated. Withhold CABOMETYX until improvement to ≤ Grade 1; resume at a reduced dose.

Palmar-Plantar Erythrodysesthesia (PPE): CABOMETYX can cause PPE and it occurred in 45% of treated patients (13% Grade 3). Withhold CABOMETYX until PPE resolves or decreases to Grade 1 and resume at a reduced dose for intolerable Grade 2 PPE or Grade 3 PPE.

Hepatotoxicity: CABOMETYX in combination with nivolumab in RCC can cause hepatic toxicity with higher frequencies of Grades 3 and 4 ALT and AST elevations compared to CABOMETYX alone. With the combination of CABOMETYX and nivolumab, Grades 3 and 4 increased ALT or AST were seen in 11% of patients. Monitor liver enzymes before initiation of treatment and periodically. Consider more frequent monitoring as compared to when the drugs are administered as single agents. Consider withholding CABOMETYX and/or nivolumab, initiating corticosteroid therapy, and/or permanently discontinuing the combination for severe or life-threatening hepatotoxicity.

Adrenal Insufficiency: CABOMETYX in combination with nivolumab can cause primary or secondary adrenal insufficiency. Adrenal insufficiency occurred in 4.7% (15/320) of patients with RCC who received CABOMETYX with nivolumab, including Grade 3 (2.2%), and Grade 2 (1.9%) adverse reactions. Withhold CABOMETYX and/or nivolumab and resume CABOMETYX at a reduced dose depending on severity.

Proteinuria: Proteinuria was observed in 8% of CABOMETYX patients. Monitor urine protein regularly during CABOMETYX treatment. For Grade 2 or 3 proteinuria, withhold CABOMETYX until improvement to ≤ Grade 1 proteinuria; resume CABOMETYX at a reduced dose. Discontinue CABOMETYX in patients who develop nephrotic syndrome.

Osteonecrosis of the Jaw (ONJ): CABOMETYX can cause ONJ and it occurred in <1% of treated patients. Perform an oral examination prior to CABOMETYX initiation and periodically during treatment. Advise patients regarding good oral hygiene practices. Withhold CABOMETYX for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. Withhold CABOMETYX for development of ONJ until complete resolution; resume at a reduced dose.

Impaired Wound Healing: CABOMETYX can cause impaired wound healing. Withhold CABOMETYX for at least 3 weeks prior to elective surgery. Do not administer for at least 2 weeks after major surgery and until adequate wound healing. The safety of resumption of CABOMETYX after resolution of wound healing complications has not been established.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): CABOMETYX can cause RPLS. Perform evaluation for RPLS and diagnose by characteristic finding on MRI any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.

Thyroid Dysfunction: CABOMETYX can cause thyroid dysfunction, primarily hypothyroidism, and it occurred in 19% of treated patients (0.4% Grade 3). Assess for signs of thyroid dysfunction prior to the initiation of CABOMETYX and monitor for signs and symptoms during treatment.

Hypocalcemia: CABOMETYX can cause hypocalcemia, with the highest incidence in DTC patients. Based on the safety population, hypocalcemia occurred in 13% of CABOMETYX patients (2% Grade 3 and 1% Grade 4).

Monitor blood calcium levels and replace calcium as necessary during treatment. Withhold and resume CABOMETYX at a reduced dose upon recovery or permanently discontinue CABOMETYX depending on severity.

Embryo-Fetal Toxicity: CABOMETYX can cause fetal harm. Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.

ADVERSE REACTIONS

The most common (≥20%) adverse reactions are:

CABOMETYX as a single agent: diarrhea, fatigue, PPE, decreased appetite, hypertension, nausea, vomiting, weight decreased, and constipation.

CABOMETYX in combination with nivolumab: diarrhea, fatigue, hepatotoxicity, PPE, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

DRUG INTERACTIONS

Strong CYP3A4 Inhibitors: If coadministration with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage. Avoid grapefruit or grapefruit juice.

Strong or Moderate CYP3A4 Inducers: If coadministration with strong or moderate CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage. Avoid St. John’s wort.

USE IN SPECIFIC POPULATIONS

Lactation: Advise women not to breastfeed during CABOMETYX treatment and for 4 months after the final dose.

Hepatic Impairment: In patients with moderate hepatic impairment, reduce the CABOMETYX dosage. Avoid CABOMETYX in patients with severe hepatic impairment.

Pediatric Use: Physeal widening has been observed in children with open growth plates when treated with CABOMETYX. Physeal and longitudinal growth monitoring is recommended in children (12 years and older) with open growth plates. Consider interrupting or discontinuing CABOMETYX if abnormalities occur. The safety and effectiveness of CABOMETYX in pediatric patients less than 12 years of age have not been established.

Please see accompanying full Prescribing Information https://www.cabometyx.com/downloads/CABOMETYXUSPI.pdf.

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.

About Exelixis

Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules and biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX^® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com, follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements, including, without limitation, statements related to: the presentation of detailed results from the CABINET trial at the 2025 ESMO; the therapeutic potential of cabozantinib as a treatment across a wide range of patients with neuroendocrine tumors and the potential of cabozantinib to become a much-needed option for those with lung and thymic NET; and Exelixis’ scientific pursuit to create transformational treatments that give more patients hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the referenced times; complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere; Exelixis’ continuing compliance with applicable legal and regulatory requirements; the potential failure of cabozantinib to demonstrate safety and/or efficacy in future clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating cabozantinib; the costs of conducting clinical trials; Exelixis’ dependence on third-party vendors for the development, manufacture and supply of cabozantinib; Exelixis’ ability to protect its intellectual property rights; market competition, including the potential for competitors to obtain approval for generic versions of CABOMETYX; changes in economic and business conditions; and other factors affecting Exelixis and its development programs detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law.

Exelixis, the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis.

___________________________

¹ Lung neuroendocrine (carcinoid) tumors: Treatment and prognosis. UpToDate. Available at: https://www.uptodate.com/contents/lung-neuroendocrine-carcinoid-tumors-treatment-and-prognosis. Accessed October 2025.

² Neuroendocrine Tumors. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/22006-neuroendocrine-tumors-net. Accessed October 2025.

³ Population Estimate: Unresectable, Locally Advanced or Metastatic Extra-Pancreatic NET. June 2024 (internal data on file).

⁴ Pathak, S., Starr, J.S., Halfdanarson, T., et al. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab. September 2023;18(5):377-385.

⁵ Pancreatic Neuroendocrine Tumors (Islet Cell Tumors) Treatment (PDQ®)–Patient Version. NCI website. Available at: https://www.cancer.gov/types/pancreatic/patient/pnet-treatment-pdq. Accessed October 2025.

⁶ What Is a Pancreatic Neuroendocrine Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/about/what-is-pnet.html. Accessed October 2025.

⁷ Carcinoid Syndrome. Cleveland Clinic website. Available at: https://my.clevelandclinic.org/health/diseases/22103-carcinoid-syndrome. Accessed October 2025.

⁸ Signs and Symptoms of Gastrointestinal Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/signs-symptoms.html. Accessed October 2025.

⁹ Signs and Symptoms of Lung Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/signs-and-symptoms.html. Accessed October 2025.

¹⁰ McClellan, K., Chen, E.Y., Kardosh, A., et al. Therapy resistant gastroenteropancreatic neuroendocrine tumors. Cancers. 2022;14(19):4769.

¹¹ What is a Gastrointestinal Carcinoid Tumor? ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/about/what-is-gastrointestinal-carcinoid.html. Accessed October 2025.

¹² Survival Rates for Pancreatic Neuroendocrine Tumor. ACS website. Available at: https://www.cancer.org/cancer/types/pancreatic-neuroendocrine-tumor/detection-diagnosis-staging/survival-rates.html. Accessed October 2025.

¹³ Survival Rates for Gastrointestinal Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/gastrointestinal-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html. Accessed October 2025.

¹⁴ Neuroendocrine Tumor (NET). NCI website. Available at: https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-endocrine-tumor/carcinoid-tumor. Accessed October 2025.

¹⁵ Key Statistics for Lung Carcinoid Tumor. ACS. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/about/key-statistics.html. Accessed October 2025.

¹⁶ Survival Rates for Lung Carcinoid Tumors. ACS website. Available at: https://www.cancer.org/cancer/types/lung-carcinoid-tumor/detection-diagnosis-staging/survival-rates.html. Accessed October 2025.

¹⁷ Thymic neuroendocrine neoplasms. UpToDate. Available at: https://www.uptodate.com/contents/thymic-neuroendocrine-neoplasms. Accessed October 2025.

Contacts

Investors Contact:
Susan Hubbard
EVP, Public Affairs and

Investor Relations
Exelixis, Inc.
650-837-8194
shubbard@exelixis.com

Media Contact:
Claire McConnaughey
Senior Director, Public Affairs
Exelixis, Inc.
650-837-7052
cmcconn@exelixis.com

Genentech’s Phase III evERA Data Showed Giredestrant Significantly Improved Progression-Free Survival in People With ER-Positive Advanced Breast Cancer




Genentech’s Phase III evERA Data Showed Giredestrant Significantly Improved Progression-Free Survival in People With ER-Positive Advanced Breast Cancer

– Giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in ITT and ESR1-mutated populations, respectively, in a post-CDK inhibitor setting, compared with standard-of-care endocrine therapy plus everolimus –

– The giredestrant combination was well tolerated; no new safety signals were observed including no photopsia –

– Overall survival data were immature, but a clear positive trend was seen in both the ITT and ESR1-mutated populations –

– If approved, giredestrant plus everolimus could be the first and only oral selective estrogen receptor degrader combination in the post-CDK inhibitor setting –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today positive results from the Phase III evERA Breast Cancer study. Data showed giredestrant in combination with everolimus significantly reduced the risk of disease progression or death (progression-free survival; PFS) by 44% and 62% in the intention-to-treat (ITT) and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. The evERA study is evaluating the investigational giredestrant combination in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This is the first positive head-to-head Phase III trial investigating a selective estrogen receptor degrader-containing regimen versus a standard-of-care combination. The results are being presented in an oral session at the European Society for Medical Oncology Congress 2025. Data will be shared with health authorities, with the aim of bringing this potential treatment option to people as soon as possible.

“A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors. These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development.

“Resistance to standard-of-care therapies is common in the post-CDK inhibitor setting, and the results from evERA validate using a combination to address this challenge,” said Erica L. Mayer, M.D., Medical Oncologist at Dana-Farber Cancer Institute. “The clinically meaningful benefit observed with the giredestrant and everolimus all-oral combination is impressive and speaks to its potential to improve outcomes for patients in need of new treatment options.”

The giredestrant combination demonstrated a statistically significant and clinically meaningful improvement in PFS compared with standard-of-care endocrine therapy plus everolimus. In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arm, respectively (stratified hazard ratio [HR]=0.56; 95% CI: 0.44-0.71, p-value= <0.0001). In the ESR1-mutated population, the median PFS was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively (HR=0.38; 95% CI: 0.27-0.54, p-value= <0.0001). The PFS benefit was consistent across pre-specified subgroups in both populations. Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566). Follow-up for OS will continue to next analysis. Giredestrant in combination with everolimus also demonstrated improvements in key secondary endpoints (objective response rate and duration of response) compared with the comparator arm across both patient populations.

Adverse events for the giredestrant-based combination were manageable and consistent with the known safety profiles of the individual medicines. No new safety signals were observed, including no photopsia.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes. All-oral combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signaling pathways while helping to minimize the impact of treatment on people’s lives without the need for injections.

Our extensive giredestrant clinical development program spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.

About the evERA Breast Cancer study

evERA Breast Cancer [NCT05306340] is a Phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who have had previous treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomization to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.

About estrogen receptor (ER)-positive breast cancer

Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining feature of ER-positive breast cancer is that its tumor cells have receptors that attach to estrogen, which can contribute to tumor growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

About giredestrant

Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist.

Giredestrant is designed to block estrogen from binding to the estrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.

Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

• Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
• Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
• Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
• Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
• Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

About Genentech in Breast Cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in multiple types of breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including estrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.

About Genentech

Founded nearly 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Contacts

Media Contact: Jared Preston, (650) 467-6800

Advocacy Contact: Julie Burns, (860) 881-6594

Investor Contacts: Loren Kalm, (650) 225-3217

Bruno Eschli, +41 616875284

Genentech Presents New Phase III Pivotal Data for Vamikibart in Uveitic Macular Edema (UME), a Serious Cause of Vision Loss




Genentech Presents New Phase III Pivotal Data for Vamikibart in Uveitic Macular Edema (UME), a Serious Cause of Vision Loss

– Vamikibart is the first non-steroid targeted therapy designed to address inflammation driving UME and may offer a potential new treatment option for patients –

– Vision improvements were seen in both pivotal studies, achieving statistical significance in MEERKAT and nominal significance in SANDCAT –

– The MEERKAT and SANDCAT trials are ongoing and the data will be discussed with health authorities globally –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today results from two Phase III studies evaluating the efficacy and safety of two doses of investigational vamikibart (0.25 and 1 mg) compared with a sham procedure that mimics intravitreal (IVT) injections in people with uveitic macular edema (UME). UME is characterized by the buildup of fluid in the macula due to uveitis, an inflammatory condition of the eye, that can result in vision loss. Across both studies, the primary and secondary endpoint data support the potential for rapid improvements in vision and reductions in macular thickness (swelling in the back of the eye due to retinal fluid) with vamikibart treatment. The data were presented at the American Academy of Ophthalmology annual meeting (AAO 2025) in Orlando, FL.

“The totality of data from these pivotal vamikibart studies represent an important step towards addressing a clear unmet need for people with uveitic macular edema,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “UME is a major cause of vision loss and blindness in people of working age. We look forward to discussing the data for this potential first-in-class treatment with regulatory authorities.”

“UME is most commonly treated with steroids that, when injected in the eye, are associated with significant side effects such as increased pressure in the eye, which can lead to glaucoma and cataract formation,” said study investigator Eric Suhler, M.D., MPH, Professor of Ophthalmology at the Casey Eye Institute, Oregon Health & Science University, Portland, OR. “These data seen across multiple endpoints in both Phase III studies, along with the overall low rate of treatment-related ocular adverse events, suggest that vamikibart could provide a clinically relevant, locally injectable non-steroid treatment option for people with UME.”

In both trials, a numerically higher proportion of patients treated with vamikibart gained vision, with primary endpoint data demonstrating statistically significant superiority over sham in MEERKAT, though not in SANDCAT. Consistently across both trials, key secondary endpoints showed rapid and clinically meaningful improvements in average change from baseline in best corrected visual acuity (BCVA), and average change from baseline in central subfield thickness (CST), a key measure of macular edema, supporting the overall efficacy profile of vamikibart.

The underlying variability of BCVA as an endpoint, along with variations in patient baseline characteristics and concomitant medications, may have influenced the differences in trial primary outcomes and further analyses are currently underway.

Vamikibart was generally well tolerated in both studies, with a low incidence of treatment-related ocular adverse events (AEs) and intraocular inflammation (IOI) events, and no events of retinal occlusive vasculitis. The most common AEs (≥5%) in either trial in patients receiving vamikibart were conjunctival hemorrhage and raised intraocular pressure.

Key data from the pivotal vamikibart Phase III MEERKAT and SANDCAT studies:

About the MEERKAT and SANDCAT studies

MEERKAT (NCT05642312) and SANDCAT (NCT05642325) are identical Phase III, global, parallel, multicenter, randomized, double-masked, sham comparator-controlled trials of intravitreal (IVT) vamikibart in uveitic macular edema (UME). In both trials, patients were randomized and received treatment every four weeks with either 0.25 mg vamikibart, 1 mg vamikibart or sham IVT injection, for up to 16 weeks. The primary endpoint of both Phase III trials was the proportion of participants with a 15 letter or more improvement from baseline in best corrected visual acuity (BCVA) at week 16. Key secondary endpoints included the average change from baseline in BCVA and CST at week 16. The safety of vamikibart was assessed through adverse events (AEs) such as treatment related ocular AEs, intraocular inflammation (IOI) and retinal occlusive vasculitis. The studies included participants with and without prior IVT treatment history and included patients with history of raised IOP and glaucoma.

About Uveitic Macular Edema (UME)

UME is characterized by the buildup of fluid in the macula due to uveitis, an inflammatory eye condition. Although rare compared to other eye diseases, UME has a disproportionate impact on vision loss and blindness globally. It is the leading cause of moderate and severe vision loss in people with uveitis, and the most frequent sight threatening complication in uveitis. Uveitis accounts for 10% to 20% of blindness in the United States and Europe, and up to 25% of blindness in the developing world. UME has a significant negative impact on people’s quality of life, including physical and mental health, social functioning, and visual function for day-to-day activities such as driving and reading. Steroids, the current standard of care for UME, are associated with significant serious side effects such as increased pressure in the eye, glaucoma and cataracts, and have recognized efficacy limitations.

About Vamikibart

Vamikibart is an investigational monoclonal antibody that has been specifically engineered for IVT administration. It targets interleukin-6 (IL-6), a key cytokine in the inflammatory pathway in UME. In the Phase I DOVETAIL study, vamikibart provided rapid vision improvements and resolution of macular edema in people with UME. Vamikibart was also well tolerated, with no treatment-related serious adverse events reported. Based on the promising Phase I DOVETAIL data, Genentech initiated the two identical Phase III vamikibart studies MEERKAT and SANDCAT. Vamikibart is being investigated in retinal diseases with recognized inflammatory pathways, including in people with UME. Vamikibart has orphan drug designation in the United States and European Union.

About Genentech in Ophthalmology

Genentech is researching and developing new treatments for people living with a range of eye diseases that cause significant visual impairment and blindness, including wet age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), geographic atrophy (GA) and other retinal diseases, including rare and inherited conditions.

About Genentech

Founded nearly 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Contacts

Media Contact: Nicole Burkart (650) 467-6800

Advocacy Contact: Meg Harrison (617) 694-7060

Investor Contacts: Loren Kalm (650) 225-3217

Bruno Eschli +41 61 687 5284

TEZSPIRE approved in the US for chronic rhinosinusitis with nasal polyps




TEZSPIRE approved in the US for chronic rhinosinusitis with nasal polyps

Approval broadens indication for TEZSPIRE to a second disease characterized by epithelial-driven inflammation

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca and Amgen’s TEZSPIRE® (tezepelumab -ekko) has been approved in the US for the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP), a complex epithelial-driven inflammatory condition. TEZSPIRE is the first and only biologic that targets thymic stromal lymphopoietin (TSLP) to be approved for CRSwNP.

The approval by the US Food and Drug Administration (FDA) was based on efficacy and safety data from the WAYPOINT Phase III trial, which were presented at the 2025 American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress and simultaneously published in The New England Journal of Medicine.^1,2 In the trial, TEZSPIRE demonstrated a statistically significant and clinically meaningful reduction in nasal polyp severity, and showed near-elimination of the need for surgery and significant reduction in systemic corticosteroid use vs. placebo.^1,2

Dr. Joseph Han, Vice Chair of Department of Otolaryngology – Head and Neck Surgery, Old Dominion University, US, and co-primary investigator in the WAYPOINT trial, said: “Over 320 million lives globally are disrupted by chronic rhinosinusitis with nasal polyps. The FDA approval of TEZSPIRE brings forward a new treatment option that has demonstrated rapid and sustained symptom improvement, nearly eliminating the need for future surgeries and significantly reducing systemic steroid use. By targeting TSLP at the top of the inflammatory cascade, TEZSPIRE offers a novel option for patients who continue to endure the disruption of this disease despite available treatments.”

Kenneth Mendez, President and CEO of the Asthma and Allergy Foundation of America (AAFA), said: “Chronic rhinosinusitis with nasal polyps is a persistent and often-overlooked disease that can significantly impact daily life, robbing patients of their ability to breathe without congestion and full sense of smell. This approval introduces an innovative treatment option for patients with the potential to help address the ongoing cycle of debilitating symptoms, surgeries and systemic steroid use.”

Ruud Dobber, Executive Vice President, BioPharmaceuticals Business Unit, AstraZeneca said: “Today’s approval of TEZSPIRE in chronic rhinosinusitis with nasal polyps expands the reach of this innovative treatment option to patients living with an epithelial-driven inflammatory disease beyond severe asthma. Building on the widespread, established use of TEZSPIRE in severe asthma, this exciting milestone now reinforces its unique mechanism of action across both the upper and lower airways and reflects our commitment to transforming care for patients who face the daily burden of chronic respiratory and immune-mediated diseases.”

CRSwNP affects up to approximately 320 million people worldwide and is a complex epithelial-driven inflammatory condition characterized by persistent inflammation and benign polyp growths within the nasal cavity. People living with CRSwNP commonly experience airflow obstruction and symptoms including congestion and an impaired sense of smell.^3-7 For many patients, current therapies such as systemic and intranasal corticosteroids and repeated sinus surgeries do not offer lasting relief.⁴

The safety profile and tolerability of TEZSPIRE in the WAYPOINT trial was generally consistent with the known profile of the medicine.¹ The most frequently reported adverse events in the trial were COVID-19, nasopharyngitis and upper respiratory tract infection.¹

The Committee for Medicinal Products for Human Use (CHMP) recently adopted a positive opinion for the approval of TEZSPIRE in the EU for treatment of CRSwNP.⁸ Regulatory applications are currently under review in the EU, China, Japan and several other countries.

TEZSPIRE is currently approved for the treatment of severe asthma in the US, EU, Japan and more than 60 countries across the globe.^9-11

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Known hypersensitivity to tezepelumab-ekko or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions were observed in the clinical trials (eg, rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (ie, days). In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE.

Acute Asthma Symptoms or Deteriorating Disease

TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.

Abrupt Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves.

Live Attenuated Vaccines

The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 3%) are:

• Asthma: pharyngitis, arthralgia, and back pain.
• Chronic rhinosinusitis with nasal polyps: nasopharyngitis, upper respiratory tract infection, epistaxis, pharyngitis, back pain, influenza, injection site reaction and arthralgia

USE IN SPECIFIC POPULATIONS

There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATION

TEZSPIRE is indicated for:

• the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus
• the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP)

Please see accompanying full Prescribing Information, including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products.

Notes

Chronic Rhinosinusitis with Nasal Polyps (CRSwNP (nasal polyps))

CRSwNP is a complex inflammatory disorder, characterized by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps.^3,4 Nasal polyps can block nasal passages and lead to breathing problems, difficulty in sense of smell, nasal discharge, facial pain, sleep disturbance and other adverse effects on quality of life. ^5-7

Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis and impede the ability of the epithelium to act as a physical and immunological barrier against the external environment.^12,13 Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that has been implicated in shared pathophysiological processes underlying severe asthma and CRSwNP.^12,13

Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologics.^4,7,14-19

Phase III WAYPOINT trial

WAYPOINT was a double-blind, multi-center, randomized, placebo-controlled, parallel group trial designed to evaluate the efficacy and safety of tezepelumab in adults with uncontrolled CRSwNP.^1,2,20 Participants received tezepelumab or placebo, administered via subcutaneous injection. The trial also included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period.^1,20

The co-primary endpoints of the trial, were change from baseline in total nasal polyp size, measured by the endoscopic total Nasal Polyp Score, and change from baseline in bi-weekly mean nasal congestion, measured by the participant reported Nasal Congestion Score evaluated as part of the daily Nasal Polyposis Symptom Diary.^1,20 Key secondary endpoints included loss of smell; improvement in disease specific health-related quality of life as measured by Sino-Nasal Outcome Test (SNOT-22) score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and, in the population with co-morbid asthma, pre-bronchodilator FEV1 at Week 52.^1,20

TEZSPIRE

TEZSPIRE (tezepelumab) is being developed by AstraZeneca in collaboration with Amgen as a first-in-class human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, eosinophilic and other types of epithelial inflammation associated with severe asthma, CRSwNP and other inflammatory diseases.^12,13

TSLP is released by the epithelium in response to environmental triggers (including allergens, viruses and other airborne particles) associated with asthma, CRSwNP, chronic obstructive pulmonary disease (COPD), eosinophilic esophagitis (EoE) and other diseases.^13,21 Across these disease states, the expression of TSLP is increased and correlates with disease severity.^7,11

TEZSPIRE is approved as a single-use pre-filled syringe and auto-injector for self-administration in the US and EU.^9-11 Since 2021, over 100,000 patients have been treated with TEZSPIRE for severe asthma.²²

Beyond CRSwNP, TEZSPIRE is also being explored in Phase III trials in COPD and EoE.^23,24 In October 2021, TEZSPIRE was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of EoE.²⁵

Amgen Collaboration

The 2012 Collaboration Agreement between Amgen and AstraZeneca has been amended and updated over time. For TEZSPIRE, both companies continue to share costs and profits equally after payment by AstraZeneca of a mid single-digit inventor royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the agreement, Amgen and AstraZeneca jointly commercialize TEZSPIRE in the US. Amgen records product sales in the US, with AZ recording its share of US profits as Collaboration Revenue. Outside of the US, AstraZeneca records product sales, with Amgen recording profit share as Other/Collaboration revenue.

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.

References

1. Lipworth BJ, Han JK, et al. Tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps. N Engl J Med. 2025;392(12):1178-1188. DOI: 10.1056/NEJMoa2414482.
2. Lipworth BJ, Han JK, et al. Efficacy and safety of tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps: results from the Phase 3 WAYPOINT Study. [Late breaking oral presentation]. Presented at the American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress 2025 (28 February – 03 March).
3. Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016;4(4):621-628.
4. Del Toro E, Portela J. Nasal Polyps. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available at: https://www.ncbi.nlm.nih.gov/books/NBK560746/. Accessed October 2025.
5. Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4(4):565-572.
6. Abdalla S, et al. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012;37(4):276-282.
7. Chen S, et al. Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis. Curr Med Res Opin. 2020;36(11):1897-1911.
8. AstraZeneca news release. TEZSPIRE recommended for approval in the EU by CHMP for chronic rhinosinusitis with nasal polyps. Available at: https://www.astrazeneca.com/media-centre/press-releases/2025/TEZSPIRE-recommended-for-approval-in-eu-for-crswnp.html. Accessed October 2025.
9. TEZSPIRE (tezepelumab) US prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf. Accessed October 2025.
10. TEZSPIRE (tezepelumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/TEZSPIRE-epar-product-information_en.pdf. Accessed October 2025.
11. AstraZeneca news release. TEZSPIRE approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/TEZSPIRE-approved-in-japan-for-severe-asthma.html. Accessed October 2025.
12. Corren J, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936-946.
13. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
14. Xolair (omalizumab) Summary of Product Characteristics; Available at: https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf. Accessed October 2025.
15. Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf. Accessed: October 2025.
16. Nucala (mepolizumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/nucala-epar-product-information_en.pdf. Accessed October 2025.
17. Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf. Accessed October 2025.
18. Dupixent (dupilumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf. Accessed October 2025.
19. Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf. Accessed October 2025.
20. Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). Available at: https://clinicaltrials.gov/ct2/show/NCT04851964. Accessed October 2025.
21. Zhang M, et al. Hypoxia induces the production of epithelial-derived cytokines in eosinophilic chronic rhinosinusitis with nasal polyps. Int Immunopharmacol. 2023;121:110559.
22. AstraZeneca Data on file. 2025. REF-278452.
23. Clinicaltrials.gov. Tezepelumab COPD Exacerbation Study (COURSE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT04039113. Accessed October 2025.
24. Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Patients with Eosinophilic Esophagitis (CROSSING). Available at: https://clinicaltrials.gov/study/NCT05583227. Accessed October 2025.
25. AstraZeneca news release. Tezepelumab granted Orphan Drug Designation in the US for eosinophilic esophagitis. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/tezepelumab-granted-orphan-drug-designation-in-the-us-for-eosinophilic-esophagitis.html. Accessed October 2025.

Contacts

Media Inquiries
Fiona Cookson +1 212 814 3923

Jillian Gonzales +1 302 885 2677

US Media Mailbox: usmediateam@astrazeneca.com

Welldoc Expands AI-Powered Cardiometabolic Platform to Include Chronic Kidney Disease and MASH Support




Welldoc Expands AI-Powered Cardiometabolic Platform to Include Chronic Kidney Disease and MASH Support

The AI-powered platform elevates cardiometabolic care by extending its best-in-class weight management support to CKD and MASH.

COLUMBIA, Md.–(BUSINESS WIRE)–Welldoc^®, a leading AI-powered health tech company pioneering cardiometabolic care, today announced the expansion of its platform to include comprehensive support for the management of chronic kidney disease (CKD) and metabolic dysfunction-associated steatohepatitis (MASH). This expansion reinforces Welldoc’s commitment to delivering holistic, evidence-based AI-driven solutions that address the complex, interconnected nature of cardiometabolic conditions.

Building upon its clinical foundation in cardiometabolic health, which includes weight management with and without GLP-1 medications, Welldoc now provides individuals with integrated AI-driven coaching, education and health tracking specific to CKD and MASH. This support is especially vital given the expected expansion of GLP-1 therapies for broader cardiorenal and liver protection [1,2]. By directly addressing the cardiometabolic risk factors driving these conditions, Welldoc enables early detection, engagement and proactive provider interventions.

“As an endocrinologist, I see firsthand how interconnected and frequently undiagnosed these conditions are,” said Dr. Mansur Shomali, Welldoc Chief Medical Officer and practicing endocrinologist. “Our clinical foundation and advanced AI enable us to personalize the experience so individuals and their providers can manage all of their comorbid cardiometabolic conditions in one comprehensive platform and directly address the root causes driving CKD and MASH progression.”

This strategic expansion addresses urgent challenges posed by two often silent diseases that carry significant clinical and economic burdens:

• CKD’s Hidden Crisis: Approximately 9 out of 10 people with CKD are unaware they have the condition, meaning millions miss the critical early window for intervention [3]. This lack of awareness contributes to a substantial healthcare cost, with annual Medicare spending alone exceeding $115 billion [4].
• MASH’s Growing Epidemic: Fatty liver disease affects up to two-thirds of individuals with type 2 diabetes and up to 90% of individuals with severe obesity [5]. The condition is predicted to become the leading cause of liver transplant in the United States [6]. AI-powered health tech solutions offer the opportunity to support personalized lifestyle interventions, which are the cornerstone of early management.

The platform’s robust ability to support weight management is crucial for individuals diagnosed with MASH, where lifestyle and weight loss are cornerstone treatment strategies.

“Obesity is a major driving force behind MASH progression,” said Dr. Holly Lofton, Scientific Advisor at Welldoc and Director of the Medical Weight Management Program at NYU Langone Health. “The most impactful steps an individual diagnosed with fatty liver disease can take involve lifestyle changes to achieve weight loss. By integrating MASH support into their cardiometabolic and weight platform, Welldoc is providing a highly efficient way to reinforce the insights necessary to slow the progression of liver disease.”

References:

[1] Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW Trial). N Engl J Med. 2024. [Semaglutide reduced the risk of the primary composite kidney and CV death outcome by 24%].

[2] Sanyal AJ, et al. Semaglutide 2.4 mg in Patients with MASH and Fibrosis Stage F2 or F3: The ESSENCE Trial. N Engl J Med. 2025 (Interim Analysis). [Semaglutide achieved resolution of MASH without worsening of fibrosis in 62.9% of the treatment group].

[3] Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2023. Atlanta, GA: US Dept of Health and Human Services; 2023.

[4] National Kidney Foundation. Chronic Kidney Disease Data Analysis Strategy. [Reflects annual Medicare spending for beneficiaries with CKD/Kidney Failure].

[5] National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Definition & Facts of NAFLD & NASH. [Cites studies on prevalence in T2D/Obesity].

[6] Tesfay M, Goldkamp WJ, Neuschwander-Tetri BA. NASH: the emerging most common form of chronic liver disease. Mo Med. 2018;115(3):225-229. [Citing projections that MASH would become the leading cause of liver transplant by 2030].

About Welldoc

Welldoc^®, an AI powered health technology leader revolutionizing cardiometabolic care, integrates personalized, real-time, and actionable insights into the daily lives of individuals living with cardiometabolic conditions, facilitating improved health and outcomes. Welldoc’s comprehensive digital health platform provides AI-powered digital coaching across prediabetes, diabetes, hypertension, heart failure, weight and obesity management, CKD, and MASH, with integrated mental wellbeing and sleep support. As a FDA-cleared digital health solution, Welldoc guides individuals through the complex journey of living with diabetes, enabling self-management while enhancing connections with their healthcare team. The company partners with health plans, health systems and employers to extend care, improve health and reduce costs.

Welldoc has achieved 11 510(k) clearances for diabetes functionality within its digital health platform and holds an IP portfolio of 50+ patents for its advanced AI and first-in-class technology. With more than 90 clinical publications, Welldoc has built an extensive library of clinical research, including many publications focused on the value of combining CGM with AI-powered digital health solutions. Recognized as an industry thought leader, Welldoc has been featured in prestigious conferences and publications, including South by Southwest, the Wall Street Journal and the Economist. The company has been named the “Best Overall Digital Health Company” by MedTech Breakthrough for the past three years, and was a winner of the 2024 Healthcare AI Impact Awards, Innovation Awards by Business Intelligence Group, and Top 100 Healthcare Technology Companies by the Healthcare Technology Report. For more information, visit www.welldoc.com. Follow us on LinkedIn and X.

Contacts

Sylvia Aranda

Media@welldocinc.com

LucyRx Launches an Outcomes Accord, Uniting Consultants, Brokers and Employers to Raise PBM Accountability




LucyRx Launches an Outcomes Accord, Uniting Consultants, Brokers and Employers to Raise PBM Accountability

Dr. Mehmet Oz shares his vision to restore trust and accountability in prescription care

BETHESDA, Md.–(BUSINESS WIRE)–#HR—LucyRx, a next-generation pharmacy benefit manager (PBM) known for simplifying and improving access to prescription care, announced an Outcomes Accord to unite plan sponsors, consultants, brokers and LucyRx to a shared standard for PBM accountability. Unveiled at LucyRx’s 2025 Partner Summit, the Outcomes Accord defines how performance is measured and verified across plans and populations and moves beyond rebate math and claim discounts. The founding cohort includes dozens of employers spanning manufacturing, technology, insurance, health care delivery and transportation, leading pharmacy consultants and brokerage firms.

Dr. Mehmet Oz, Administrator of the Centers for Medicare & Medicaid Services, was the keynote speaker at LucyRx’s Summit and challenged the participants with the question, “How do we bring more transparency into the process, and what are the things that might move the needle for the American people to begin to trust the system again?”

“The Outcomes Accord confronts that reality with results,” said David Blair, CEO of LucyRx. “The clients and consultants who’ve joined as Founders are not just early adopters. They are architects of a model where outcomes are proven, not just promised.”

The six Outcomes Accord measurements are:

• PMPM cost and yearly trend: The actual, checked total pharmacy cost per member each month, net of discounts and rebates.
• Medication adherence: How well members stick to their medicine routines for important health conditions.
• Avoided care costs: Money saved by preventing unnecessary emergency room visits, hospital stays or health problems.
• Clinical savings: The direct health benefits and cost reductions from pharmacy actions.
• Member experience: How satisfied members are with their access to medicine and the support they receive.
• Biosimilar adoption: Safely switching to lower-cost, similar medicines to improve affordability and value.

The Outcomes Accord sets a new fiduciary standard by tying success directly to clinical outcomes, cost containment and member experience — shifting the focus from how savings are promised to how results are delivered. It is governed by three principles:

• Clarity, where every outcome is measurable, auditable and client verified.
• Commitment, where PBMs and plan sponsors align to shared metrics rather than marketing claims.
• Courage, where participants invite independent scrutiny and publish results on a regular cadence.

Those principles turn accountability into trust that can be verified. As the Summit’s keynote added: “Because if you lose trust, the changes that happen tend to be draconian. They often are legislative, and they’re not as nimble as if industry does it themselves,” said Dr. Oz.

“For too long, our industry has focused on good intentions instead of actual results,” said Susan Thomas, Chief Commercial Officer at LucyRx. “The Outcomes Accord changes the way we define and verify performance. It represents a collective dedication to evidence, transparency and a disciplined approach to measuring what truly matters.”

What launches today

• Joining Pathway: A simple request process for employers and advisors to officially sign up and get help with putting the Accord’s standards into action.
• Governance: A group made up of different stakeholders who regularly review and update the measurement rules and make sure verification is trustworthy.
• Metric Specification and FAQ: The working group will draft a guide that explains how success is measured and verified. It will be made publicly available when approved by the Accord Founders.
• Public Reporting: The Outcomes Accord will publish a yearly performance report — starting in 2026 — that shows verified, easy-to-understand results about cost savings and health improvements for participating clients.

In short, the Accord is a practical toolkit and a reporting process that turns health care goals into measurable, transparent outcomes for all involved.

Activation

Signatories can begin aligning to the standards today. LucyRx will coordinate onboarding with consultants and brokers, provide the metric specification and FAQ and convene the working group to finalize the 2026 public reporting plan.

Learn more and participate

• Read the Outcomes Accord FAQ and request the Version 1.0 metric specification.
• Contact LucyRx to join as a signatory or to align current programs to the framework.

About LucyRx

LucyRx is a fast-scaling, independent, next-generation pharmacy benefit manager (PBM) redefining prescription care. Fueled by innovation and decades of leadership experience, LucyRx delivers better outcomes through its integrated specialty network, formulary marketplace, and next-day home delivery solutions. Powered by its proprietary AI platform, LucyIQ™, the company provides real-time insights that support evidence-based clinical decisions, clear pricing, and exceptional service from U.S.-based pharmacy technicians. Partnering with more than 60,000 pharmacies, LucyRx serves over 1,200 clients nationwide.

This is prescription care, brilliantly reimagined.

Learn more at LucyRx.com.

Contacts

Media Contact

Tricia Bancroft

516-241-6157

press@lucyrx.com