BeOne Medicines Announces U.S. FDA Approval for TEVIMBRA-Based Regimen for First-Line HER2+ GEA

TEVIMBRA plus ZIIHERA and chemotherapy is the first and only immunotherapy-based regimen to deliver more than two years of median OS in first-line HER2+ GEA, regardless of PD-L1 statusRegimen poised to become standard of care in this difficult-to-treat disease.

BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for TEVIMBRA^® (tislelizumab) in combination with ZIIHERA^® (zanidatamab) and chemotherapy for the first-line treatment of adult patients with unresectable locally advanced or metastatic HER2-positive (HER2+) gastric, gastroesophageal junction, or esophageal adenocarcinoma (GEA). The approval is supported by results from the Phase 3 HERIZON-GEA-01 trial, which were published in The New England Journal of Medicine earlier this year.

GEA, which includes adenocarcinomas of the stomach, gastroesophageal junction and esophagus, remains an area of substantial unmet need in the United States, with more than 31,000 new stomach cancer cases diagnosed each year.¹ Approximately 20% of patients with GEA have HER2+ disease, a subtype that has historically been difficult to treat.^2,3,4

Despite recent advances, long-term outcomes for patients with advanced or metastatic HER2+ GEA remain challenging and the need for more effective first-line options is urgent. In the U.S., fewer than 40% of patients survive beyond two years. These outcomes highlight the need for additional treatment options that may help extend survival for patients facing this disease.

Jaffer A. Ajani, M.D., Professor of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, said:

“For patients with advanced HER2-positive gastroesophageal adenocarcinoma, first-line treatment represents a critical opportunity to make the greatest possible impact and change the course of disease at the start of care, making it especially important to provide the most effective treatment options and combinations upfront to give patients the best possible chance for improved outcomes. The median overall survival of more than two years observed with this regimen demonstrates meaningful progress in a setting where outcomes have historically been challenging to improve. With benefit observed across PD-L1 subgroups, this approval gives physicians greater freedom to select treatment regardless of PD-L1 status.”

Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne Medicines, said:

“Today’s approval is an important milestone for BeOne as we continue to expand the impact of TEVIMBRA for patients living with cancer. As the first approved foundational asset to emerge from our solid tumor portfolio, TEVIMBRA has demonstrated the potential to address significant unmet needs across tumor types, and today’s approval further reinforces our commitment to advancing innovative, practice changing combination regimens with TEVIMBRA for patients facing difficult-to-treat cancers. We are proud to bring this new first-line treatment option to physicians and patients with HER2-positive gastroesophageal adenocarcinoma in the United States.”

Aki Smith, Founder & Executive Director, Hope for Stomach Cancer, said:

“For people living with HER2-positive gastroesophageal cancer and their families, the possibility of more time can mean everything - more moments with loved ones, more milestones, and more confidence that progress is being made in a disease where additional options are urgently needed. As a caregiver to my father, who faced HER2-positive gastroesophageal cancer, I know personally the fear and urgency families feel when treatment begins and how much it means to have more options available from the very start. We welcome the availability of this new regimen and remain committed to helping patients and caregivers understand their treatment options and access the support they need throughout their journey.”

Approval supported by Phase 3 HERIZON-GEA-01 results

The approval is based on data from HERIZON-GEA-01, the global Phase 3 clinical trial evaluating ZIIHERA plus chemotherapy, with and without TEVIMBRA, compared with trastuzumab plus chemotherapy as first-line treatment for advanced or metastatic HER2+ GEA.

Key findings from the trial include:

• Overall survival (OS): TEVIMBRA plus ZIIHERA and chemotherapy demonstrated a statistically significant improvement in OS, with median OS of 26.4 months compared with 19.2 months in the control arm.
• Progression-free survival (PFS): TEVIMBRA plus ZIIHERA and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS, with a median PFS of 12.4 months compared with 8.1 months in the control arm.
• Consistent benefit regardless of PD-L1 status: improvements in OS and PFS were observed across patient subgroups, including patients with PD-L1-negative tumors (TAP <1%), where median OS was 29.7 months with TEVIMBRA plus ZIIHERA and chemotherapy compared with 15.8 months in the control arm.
• Consistent efficacy across HER2 expression levels: TEVIMBRA + ZIIHERA and chemotherapy showed benefit in both HER2 IHC (immunohistochemistry) 3+ and HER2 IHC 2+ populations.
• Safety: treatment with TEVIMBRA plus ZIIHERA and chemotherapy was generally consistent with the known safety profiles of the components of the regimen, and no new safety signals were identified.

About the HERIZON-GEA-01 Phase 3 Trial

HERIZON-GEA-01 (NCT05152147) is a global, randomized, open-label Phase 3 trial, conducted jointly with Jazz Pharmaceuticals, to evaluate and compare the efficacy and safety of ZIIHERAplus chemotherapy, with and without TEVIMBRA, to the standard of care (trastuzumab plus chemotherapy) as first-line treatment for adult patients with advanced/metastatic HER2+ GEA. The trial randomized 914 patients from approximately 300 trial sites in more than 30 countries. Patients for this trial had unresectable locally advanced, recurrent or metastatic HER2+ GEA (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISH positivity per central assessment. Patients were randomized to the three trial arms: ZIIHERAin combination with chemotherapy and TEVIMBRA; ZIIHERA in combination with chemotherapy; and trastuzumab plus chemotherapy. The trial is evaluating dual primary endpoints, PFS per blinded independent central review (BICR) and OS.

About ZIIHERA (zanidatamab-hrii)

ZIIHERA (zanidatamab) is a bispecific human epidermal growth factor receptor 2, or HER2-directed antibody that binds to two extracellular sites on HER2. Binding of zanidatamab with HER2 results in internalization leading to a reduction in HER2 expression of the receptor on the tumor cell surface. Zanidatamab induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.⁵

Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is approved in China for the treatment of patients who have unresectable, locally advanced, or metastatic HER2-high expression (IHC 3+) biliary tract cancer (BTC) and who have received prior systemic therapy. ZIIHERA has also been granted accelerated approval in the U.S. and conditional marketing authorization in the European Union for eligible BTC patients. Zanidatamab is being developed by Jazz and BeOne under license agreements from Zymeworks, which first developed the molecule. BeOne has licensed zanidatamab from Zymeworks in Asia (excluding India and Japan), Australia and New Zealand. Jazz Pharmaceuticals has rights in all other regions.

ZIIHERA is a registered trademark of Zymeworks BC Inc.

About TEVIMBRA (tislelizumab-jsgr)

TEVIMBRA is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.

TEVIMBRA is the foundational asset of BeOne’s solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global TEVIMBRA clinical development program includes almost 15,000 patients enrolled to date in 30+ countries and regions across 71 trials, including 21 registration-enabling studies. TEVIMBRA is approved in over 50 countries, and more than 2 million patients have been treated globally.

Select Important Safety Information

Serious and sometimes fatal adverse reactions occurred with TEVIMBRA treatment. Warnings and Precautions include severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, and solid organ transplant rejection. Other warnings and precautions include infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

The most common adverse reactions (≥20%), including lab abnormalities, in patients receiving TEVIMBRA + zanidatamab + chemotherapy were diarrhea, nausea, anemia, decreased appetite, vomiting, decreased neutrophil count, hypokalemia, fatigue, rash, decreased platelet count, peripheral neuropathy, infusion-related reaction, and increased aspartate aminotransferase.

Please see full U.S. Prescribing Information including the U.S. Medication Guide.

The information in this press release is intended for a global audience. Product indications vary by region.

About BeOne

BeOne Medicines is a global oncology company that is discovering and developing innovative treatments for cancer patients worldwide. With a portfolio spanning hematology and solid tumors, BeOne is expediting development of its diverse pipeline of novel therapeutics through its internal capabilities and collaborations. The Company has a growing global team spanning six continents who are driven by scientific excellence and exceptional speed to reach more patients than ever before. To learn more about BeOne, please visit www.beonemedicines.com and follow us on LinkedIn, X, Facebook and Instagram.

Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including the potential of TEVIMBRA to address significant unmet needs across tumor types; BeOne’s commitment to advancing combination regimens with TEVIMBRA; the potential of TEVIMBRA plus ZIIHERA and chemotherapyto become a new standard of care for treating HER2+ GEA; statements regarding the potential benefits of TEVIMBRA and ZIIHERA; and BeOne’s plans, commitments, aspirations, and goals under the heading “About BeOne.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeOne's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeOne's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeOne's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeOne's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeOne’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeOne’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeOne's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeOne undertakes no duty to update such information unless required by law.

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