NB-6253

BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines, today announced that BeiGene’s BTK inhibitor BRUKINSA (zanubrutinib) received approval from Swissmedic for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior line of therapy, or for treatment-naïve patients who are not suited for standard chemo-immunotherapy. BRUKINSA had previously been granted orphan drug status. “The authorization of BRUKINSA will bring a new option and an innovative medicine that has potential to offer deep and durable response for eligible patients with WM in Switzerland," said Pr. Davide Rossi, Deputy Head of the Division of Hematology of the Oncology Institute of Southern Switzerland IOSI. “BRUKINSA is a next-generation BTK inhibitor which has also provided meaningful improvements in tolerability for some patients with WM compared to ibrutinib, as treatment discontinuation remains a concern.” Reto Kessler, Country Manager, Switzerland at BeiGene added, “This approval is a significant development for people living with WM in Switzerland and for BeiGene’s expansion in Europe. Our teams are committed to collaborating with the Federal Office of Public Health and healthcare professionals to ensure access to BRUKINSA for patients in Switzerland.” The Marketing Authorization Application (MAA) is supported by data from the global Phase 3 ASPEN clinical trial, a Phase 3 randomized, open-label, multicenter trial (NCT03053440) that evaluated BRUKINSA compared to ibrutinib in patients with relapsed/refractory (R/R) or treatment-naïve (TN) WM who harbor a MYD88 mutation (MYD88MUT). In the ASPEN trial, BRUKINSA demonstrated a numerically higher very good partial response (VGPR) rate and a favorable safety pro ibrutinib, although the primary endpoint of statistical superiority related to deep response (VGPR or better) was not met. As assessed by independent review committee (IRC) per adaptation of the response criteria updated at the Sixth International Workshop on Waldenström’s Macroglobulinemia (IWWM), the combined complete response (CR) + VGPR rate in the overall intention-to-treat (ITT) population was 29% with BRUKINSA (95% CI: 20, 40), compared to 19% with ibrutinib (95% CI: 12, 30). In the ASPEN trial, of the 101 patients with WM randomized and treated with BRUKINSA, four percent of patients discontinued due to adverse events, including cardiomegaly, neutropenia, plasma cell myeloma, and subdural hemorrhage. Adverse events leading to dose reduction occurred in 14% of patients, with the most common being neutropenia (3%) and diarrhea (2%). The recommended dose of BRUKINSA is either 160 mg twice daily or 320 mg once daily, taken orally with or without food. The dose may be adjusted for adverse reactions and reduced for patients with severe hepatic impairment and certain drug interactions. About Waldenström’s Macroglobulinemia WM is a rare B-cell lymphoma that occurs in less than two percent of patients with non-Hodgkin lymphomas.2 The disease usually affects older adults and is primarily found in bone marrow, although lymph nodes and the spleen may be involved.1 Throughout Europe, the estimated incidence rate of WM is approximately seven for every one million men and four for every one million women.2 About BRUKINSA BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues. BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering more than 40 countries and regions, including the U.S., European Union, China, Australia, Great Britain and Switzerland. Currently, more than 40 additional regulatory submissions are in review around the world. BeiGene Oncology BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of approximately 2,900 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 14,500 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology and solid tumor targeted therapies and immuno-oncology are key focus areas for the Company, with both mono- and combination therapies prioritized in our research and development. BeiGene currently has three approved medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the United States, China, the EU and U.K., Canada, Australia and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the PARP inhibitor pamiparib in China. BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including with Mirati Therapeutics, Seagen, and Zymeworks. In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, including a biologics license application (BLA) under FDA review, BeiGene and Novartis announced an option, collaboration and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis Oncology products across designated regions of China. About BeiGene BeiGene is a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide. With a broad portfolio of more than 40 clinical candidates, we are expediting development of our diverse pipeline of novel therapeutics through our own capabilities and collaborations. We are committed to radically improving access to medicines for two billion more people by 2030. BeiGene has a growing global team of over 8,000 colleagues across five continents. References: 1 Lymphoma Research Foundation. Getting the Facts: Waldenström Macroglobulinemia. Accessed July 2021. Available at 2 Buske, C, et al. Treatment and outcome patterns in European patients with Waldenström’s macroglobulinaemia: a large, observational, retrospective chart review. The Lancet Haematology 2018; 5: e0299-309.

Bristol Myers Squibb’s cancer drug pipeline includes various immuno-oncology programs, including one that addresses TIGIT, a protein that’s become a hot target for the field. But the pharmaceutical giant sees promise in a preclinical TIGIT-targeting antibody from Agenus, and it has agreed to pay $200 million up front to acquire global rights to that asset. According to terms of the agreement announced Tuesday, BMS will become responsible for further development of the drug, AGEN1777. If it’s approved, BMS will also handle commercialization. Lexington, Massachusetts-based Agenus could earn up to $1.36 billion in milestone payments, plus royalties from sales. According to Agenus, the deal is the largest one struck for a preclinical asset in about three years. By acquiring the Agenus drug, BMS adds to its pipeline another approach to blocking checkpoint proteins. Found on immune cells, these proteins stop the immune cell from targeting tumors, providing one of the ways that cancers escape detection by the immune system. Drugs that block these proteins free immune cells to recognize and target tumors. The first wave of immunotherapies included drugs, such as BMS’s Opdivo, that block the checkpoint protein PD-1. But that approach doesn’t always work, and TIGIT has become another promising target as drug hunters seek to expand the reach of checkpoint inhibition. In preclinical research, Agenus said AGEN1777 showed potential in tumor models where a PD-1 inhibitor or an anti-TIGIT antibody alone were ineffective. The Agenus drug is a bispecific antibody that binds to two targets, TIGIT, and a second one that the company has not disclosed. The company says this bispecific antibody is engineered to have an enhanced affinity for binding to Fc receptors of cells. Binding to these receptors activates the immune system. Agenus said that its molecule is designed for improved activation of T cells and natural killer cells. While the company believes the drug has the potential to be used as a monotherapy, as well as part of a combination treatment, executives aren’t revealing additional details. “We haven’t disclosed the other arm of the bispecific, so hence we have to be careful not to release too much in terms of what we think the bispecific does in this context, because we don’t want others to be able to guess what that additional arm is,” Agenus CEO Garo Armen said, speaking on a conference call. It’s rare, though not unprecedented, for big pharma companies to strike large deals for preclinical assets. Usually, companies wait to see human data before putting up a large sum of cash. But the bidding for AGEN1777 was a competitive process involving “several major biopharma companies,” Armen said. He added BMS stood out as the suitor best positioned to develop the drug. Opdivo is the anchor of BMS’s cancer immunotherapy portfolio. The New York-based pharma giant has also advanced to human testing with a TIGIT-blocking drug, BMS-986207. That molecule is a monoclonal antibody. In grabbing rights to Agenus’s TIGIT blocker, BMS gets another shot at blocking TIGIT , and potentially a better one. Armen said that the company has data showing that its bispecific antibody is superior, by itself and in combination with other therapies, to other TIGIT-targeting molecules that have been studied in preclinical research. Speaking on the conference call, Agenus Chief Operating Officer Jennifer Buell described AGEN1777 as unique and differentiated. “It provides what we believe to be the potential for a superior blockade of tumor escape,” she said. “And Bristol is very well positioned to create value given the complementarity of molecules in their portfolio.” In a prepared statement, Debbie Law, BMS’s senior vice president and head of the company’s tumor microenvironment thematic research center, said that AGEN1777’s “differentiated mechanism of action provides the potential for potent anti-tumor activity.” Other companies chasing TIGIT with antibody drug candidates include Roche, Merck, iTeos Therapeutics, Seattle Genetics, and Arcus Biosciences. Agenus is readying AGNEN1777 for an investigational new drug application later in the current quarter. When BMS gets the program, it plans to develop it for “high priority tumor indications,” such as non-small cell lung cancer. Though the deal will put AGEN1777’s future in BMS’s hands, Agenus could still play a role in its development. The biotech keeps options to conduct clinical studies, as well as combination studies with unspecified assets in its pipeline. If the drug reaches the market, the biotech also has the option to co-promote it in the U.S. In the near term, the BMS deal will infuse Agenus with cash for its wholly owned programs, including AGEN1181. Agenus designed that antibody to block a protein called CTLA-4 and has advanced it to mid-stage testing. Armen said that the company plans to advance clinical development of that molecule for applications in indications such as colon cancer, where patients have been unresponsive to other immunotherapies. Photo by Flickr user Bristol-Myers Squibb via a Creative Commons license