Bristol-Myers Squibb International Corp.

The Librexia program evaluating milvexian is unrivaled as the most comprehensive factor XIa inhibitor clinical development program to date and will provide extensive data from nearly 50,000 patients, with all three studies underway RARITAN, N.J., May 25, 2023 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that all three prospective indications for milvexian, an investigational oral factor XIa (FXIa) inhibitor (being developed in collaboration with Bristol Myers Squibb), have now been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). The designations cover all three indication-seeking studies within the Phase 3 Librexia development program (Librexia STROKE, Librexia ACS and Librexia AF), which are all dosing patients. The Librexia program is unrivaled as the most comprehensive FXIa clinical development program to date and will provide extensive data from nearly 50,000 patients. "Despite major advances in cardiovascular and stroke treatment over the past two decades, millions of patients currently remain untreated or undertreated due to the risk of bleeding, but for whom thrombotic events could be prevented," said Robert Harrington, M.D., Arthur L. Bloomfield professor of medicine and chair of the Department of Medicine, Stanford University, Librexia program chair.i "If successful, milvexian could open the door to treat an entirely new set of patients who are currently overlooked due to bleeding risk." All three indications being studied in the Phase 3 Librexia program were granted Fast Track Designation from the FDA. Fast Track Designation is intended to expedite development and review timelines when preliminary nonclinical and clinical evidence indicates the drug may demonstrate substantial improvement over available therapies to address unmet medical need for serious or life-threatening conditions. Fast Track Designation encourages close communication between the FDA and sponsor to improve the efficiency of product development, with the aim of getting new therapeutics to patients faster. "For milvexian to receive Fast Track Designation from the FDA for all three indications demonstrates the enormous unmet need that still exists for the treatment of thrombotic events, like heart attack and stroke," said James F. List, M.D., Ph.D., Global Therapeutic Area Head, whose team oversees a portfolio of programs, including milvexian, at Janssen Research & Development, LLC. "We are now focused on enrolling patients to these trials with urgency, bringing us one step closer to potentially improving outcomes in a wide range of patients with thrombotic diseases." Phase 2 AXIOMATIC-TKR and AXIOMATIC-SSP proof-of-concept data for milvexian demonstrated a differentiated antithrombotic profile as both a monotherapy and in combination with antiplatelet therapy. These data also suggest a positive efficacy and bleeding profile in stroke patients where FXa inhibitors are not indicated. About Milvexian* Milvexian is an investigational, oral factor XIa (FXIa) inhibitor (antithrombotic) being studied for the prevention and treatment of major thrombotic conditions as part of the Librexia program, the most comprehensive FXIa clinical development program to date. *Milvexian is an investigational agent and has not been approved for use in any country, for any indication. About the Librexia Program The Librexia program is unrivaled as the most comprehensive FXIa clinical development program to date, studying nearly 50,000 patients across three parallel clinical trials (Librexia STROKE, Librexia ACS and Librexia AF). Grounded in positive Phase 2 efficacy and safety data, the Librexia program aims to investigate whether milvexian can enhance the benefit-risk profile associated with treating patients with these three conditions by delivering reduced thrombotic events with no increased risk of bleeding. The program is designed to potentially advance beyond the standard of care and help improve outcomes in a wide range of patients with thrombotic diseases. Each indication under evaluation in the Librexia program has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). Librexia STROKE, Librexia ACS and Librexia AF are dosing patients. About Librexia STROKE Librexia STROKE is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study to demonstrate the efficacy and safety of milvexian in addition to single or dual antiplatelet therapy for stroke prevention after an acute ischemic stroke or high-risk transient ischemic attack (TIA). More information can be found on (NCT05702034). About Librexia ACS Librexia ACS is a randomized, double-blind, placebo-controlled, event-driven study to demonstrate the efficacy and safety of milvexian after a recent acute coronary syndrome. More information can be found on (NCT05754957). About Librexia AF Librexia AF is a randomized, double-blind, double-dummy, parallel group, active-controlled study to evaluate the efficacy and safety of milvexian versus apixaban in participants with atrial fibrillation. More information can be found on (NCT05757869). About the Bristol Myers Squibb/Janssen Collaboration Bristol Myers Squibb and the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), two unsurpassed leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today's treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific heritage and world-class commercial capabilities of each company, all in service of improved patient outcomes. The alliance is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to ensure cutting-edge safe and effective treatment options are available for patients. About the Janssen Pharmaceutical Companies of Johnson & Johnson At Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension. Learn more at . Follow us at . Cautions Concerning Forward-Looking Statements This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding milvexian. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at , or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments. i Dr. Harrington is affiliated with Stanford University and was provided payment for his participation in the Phase 3 Librexia program. Media contact: Jennifer Silvent Phone: +1 (973) 479-9845 [email protected] Investor Relations: Raychel Kruper [email protected] SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson

The Librexia program evaluating milvexian is unrivaled as the most comprehensive factor XIa inhibitor clinical development program to date and will provide extensive data from nearly 50,000 patients, with all three studies underway PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) in collaboration with Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson and Johnson (Janssen), today announced that all three prospective indications for milvexian, an investigational oral factor XIa (FXIa) inhibitor, have now been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). The designations cover all three indication-seeking studies within the Phase 3 Librexia development program (Librexia STROKE, Librexia ACS and Librexia AF), which are all dosing patients. The Librexia program is unrivaled as the most comprehensive FXIa clinical development program to date and will provide extensive data from nearly 50,000 patients. “Despite major advances in cardiovascular and stroke treatment over the past two decades, millions of patients currently remain untreated or undertreated due to the risk of bleeding, but for whom thrombotic events could be prevented,” said Robert Harrington, MD, Arthur L. Bloomfield professor of medicine and chair of the Department of Medicine, Stanford University, Librexia program chair. i “If successful, milvexian could open the door to treat an entirely new set of patients who are currently overlooked due to bleeding risk.” All three indications being studied in the Phase 3 Librexia program were granted Fast Track Designation from the FDA. Fast Track Designation is intended to expedite development and review timelines when preliminary nonclinical and clinical evidence indicates the drug may demonstrate substantial improvement over available therapies to address unmet medical need for serious or life-threatening conditions. Fast Track Designation encourages close communication between the FDA and sponsor to improve the efficiency of product development, with the aim of getting new therapeutics to patients faster. “This Fast Track Designation underscores the unmet need that exists in the treatment of thromboembolic conditions,” said Puneet Mohan, MBBS, MD, PhD, vice president, Global Program Lead, Milvexian, Bristol Myers Squibb. “The goal of milvexian and the Librexia program is to enhance the benefit-risk profile in the treatment of these conditions by delivering reduced thrombotic events and less bleeding in at-risk patients than the current standard of care.” Phase 2 AXIOMATIC-TKR and AXIOMATIC-SSP proof-of-concept data for milvexian demonstrated a differentiated antithrombotic profile as both a monotherapy and in combination with antiplatelet therapy. These data also suggest a positive efficacy and bleeding profile in stroke patients where FXa inhibitors are not indicated. About Milvexian* Milvexian is an investigational, oral factor XIa (FXIa) inhibitor (antithrombotic) being studied for the prevention and treatment of major thrombotic conditions as part of the Librexia program, the most comprehensive FXIa clinical development program to date. *Milvexian is an investigational agent and has not been approved for use in any country, for any indication. About the Librexia Program The Librexia program is unrivaled as the most comprehensive FXIa clinical development program to date, studying nearly 50,000 patients across three parallel clinical trials (Librexia STROKE, Librexia ACS and Librexia AF). Grounded in positive Phase 2 efficacy and safety data, the Librexia program aims to investigate whether milvexian can enhance the benefit-risk profile associated with treating patients with these three conditions by delivering reduced thrombotic events with no increased risk of bleeding. The program is designed to potentially advance beyond the standard of care and help improve outcomes in a wide range of patients with thrombotic diseases. Each indication under evaluation in the Librexia program has received Fast Track Designation from the U.S. Food and Drug Administration (FDA). Librexia STROKE, Librexia ACS and Librexia AF are dosing patients. About Librexia STROKE Librexia STROKE is a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study to demonstrate the efficacy and safety of milvexian in addition to single or dual antiplatelet therapy for stroke prevention after an acute ischemic stroke or high-risk transient ischemic attack (TIA). More information can be found on http://www.clinicaltrials.gov (NCT05702034). About Librexia ACS Librexia ACS is a randomized, double-blind, placebo-controlled, event-driven study to demonstrate the efficacy and safety of milvexian after a recent acute coronary syndrome. More information can be found on http://www.clinicaltrials.gov (NCT05754957). About Librexia AF Librexia AF is a randomized, double-blind, double-dummy, parallel group, active-controlled study to evaluate the efficacy and safety of milvexian versus apixaban in participants with atrial fibrillation. More information can be found on http://www.clinicaltrials.gov (NCT05757869). About the Bristol Myers Squibb/Janssen Collaboration Bristol Myers Squibb and the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), two unsurpassed leaders in cardiovascular care, are determined to close the gap in unmet needs in thrombosis management by overcoming the limits of today’s treatments. The collaboration to develop and commercialize milvexian aims to leverage the combined scientific heritage and world-class commercial capabilities of each company, all in service of improved patient outcomes. The alliance is uniquely equipped to deliver on the promise of FXIa inhibitors and is working diligently to ensure cutting-edge safe and effective treatment options are available for patients. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , Twitter , YouTube , Facebook and Instagram . Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that future study results may not be consistent with the results to date, that milvexian may not achieve its primary study endpoints or receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all, that any marketing approvals, if granted, may have significant limitations on their use, and, if approved, whether such product candidate for such indications described in this release will be commercially successful. No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2022, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. i Dr. Harrington is affiliated with Stanford University, and was provided payment for his participation in the Phase 3 Librexia program. corporatefinancial-news Bristol Myers Squibb Media Inquiries: media@bms.com Investors: investor.relations@bms.com Source: Bristol Myers Squibb

Jeremy Moeller/Getty Images In July 2017, BeiGene inked a deal with Celgene Logistics Sarl, which is now a subsidiary of Bristol Myers Squibb. The deal was a license and supply agreement giving BeiGene exclusive right to distribute and market Abraxane, Revlimid and Vidaza in China, excepting Hong Kong, Macau and Taiwan. Then, in March 2020, the Chinese National Medical Products Administration (NMPA) suspended importation, sales and use of Abraxane in China under the deal. BMS then initiated a recall of Abraxane in China. The entire suspension and recall were related to inspection findings at Bristol Myers Squibb-Celgene’s contract manufacturing plant in the U.S. On October 6, 2021, Bristol Myers Squibb and Celgene terminated the original deal related to Abraxane and gave BeiGene 180 days of notice that it was withdrawing Abraxane from the deal. The Notice stated: “Indeed, as you are aware, due to the National Medical Products Association decision to suspend the importation, sale, or use of Abraxane in China on March 25, 2020, Celgene has been unable to manufacture Abraxane for China and, thus, has been unable to manufacture Abraxane on a global basis…” The notice went on to say that after the NMPA suspended manufacturing at the facility in Illinois, the company shifted production to a facility in Phoenix, Arizona. In July 2021, there was a failure in media fill testing at that facility. After a root cause investigation and corrective actions, there was still rejection of additional vials. Celgene is working on the issue, but currently all manufacturing of Abraxane at the Phoenix facility has halted, and they have notified the U.S. Food and Drug Administration. The Illinois site was run by contract drug manufacturing (CDMO) company Fresenius Kabi and the Phoenix site is owned by BMS. BeiGene indicates they believe the “reasons stated in the Notice do not provide a valid basis for terminating the Agreement with respect to Abraxane, and that the Notice is a tactical maneuver on the part of BMS-Celgene to reduce its damages in the on-going arbitration proceedings described above. The Company intends to contest the purported termination vigorously.” On a little less threatening note, BeiGene also said that BMS and Celgene had not told them how long the manufacturing delays in Phoenix would last, but “would be happy to work with BMS-Celgene to help get the Phoenix manufacturing facility or another facility qualified to restore the supply of Abraxane for patients in China as soon as possible.” Abraxane is approved for use in advanced non-small cell lung cancer with carboplatin, in advanced pancreatic cancer with gemcitabine, and for advanced breast cancer. The other drugs are Revlimid, which with dexamethasone is used to treat multiple myeloma, and Vidaza, a chemotherapy used to treat myelodysplastic syndrome (MDS). They do not appear to be part of the dispute. At least one analyst, Andrew Berens, with SVB Leerink, suggests that the real issue is competition between BMS’s checkpoint inhibitor Opdivo and BeiGene and Novartis’s tislelizumab. Berns projected BeiGene would rake in $100 million in Abraxane sales in China next year once the marketing hold is resolved. Berns is taking that figure out of the equation, but believes that the BeiGene-BMS deal isn’t as important as it used to be, particularly now that BeiGene and Amgen have a strategic collaboration that initiated in January 2020. That deal is to accelerate Amgen’s oncology presence in China. Amgen also has a 20.5% stake in BeiGene, which it paid $2.8 billion in cash for. Under that deal, BeiGene is commercializing Amgen’s XGEVA (denosumab), Kyprolis (carfilzomib) and Blincyto (blinatumomab) in China. Two of the drugs will revert to Amgen, one after five years and one after seven. After the commercialization period, BeiGene will keep the rights to one of the drugs and be eligible for royalties on sales in China for another five years on the drugs returned to Amgen. XGEVA was launched in China in September 2019. The two companies are also collaborating on 20 drugs from Amgen’s oncology pipeline in China and globally. Another hit against Abraxane occurred in August 2021. Roche had an accelerated approval for its Tecentriq (atezolizumab) in combination with Abraxane for adults with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) whose tumors express PD-L1. After consulting with the FDA, Roche withdrew the accelerated approval. It only affected the mTNBC indication in the U.S. for that indication. It was granted accelerated approval in March 2019, the first immunotherapy to be approved for that setting. It was based on progression-free survival (PFS) in the Phase III IMpassion 130 study, but continued approval was contingent on the results of IMpassion131. That trial failed to hit its primary endpoint.