Sanford Burnham Prebys Medical Discovery Institute

Members of an FDA advisory committee were not asked to vote Thursday on AstraZeneca’s anticoagulant reversal drug Andexxa, but they did raise several safety and efficacy concerns. Last year, AstraZeneca began plans to shift Andexxa to a full approval from its accelerated approval after halting its confirmatory trial early due to positive efficacy. But the FDA explained in briefing documents and at the meeting that the confirmatory trial, known as ANNEXA-I, revealed “major safety findings,” including a “doubling of the rate of thromboses and thrombosis related deaths at Day 30 in the andexanet arm compared with” a standard of care clotting agent known as a prothrombin complex concentrate (PCC). While several hematologists on the adcomm explained how Andexxa does work at stopping serious bleeds, adcomm chair Taby Ahsan, VP of cell and gene therapy operations at City of Hope, said the committee generally indicated that there needs to be a better understanding of risks like thrombotic events. Committee members also questioned if the dose and the indicated population were understood well enough. While Andexxa demonstrated a statistically significant improvement in hemostasis in the confirmatory trial, the agency said that the “observed treatment difference between arms appears to be primarily driven by hematoma volume.” Panelist Rajiv Ratan, associate dean at Weill Cornell Medicine, said in the final discussion that “it doesn’t seem like the change in hematoma volume — especially because it was relatively large for patients who are untreated — is enough as a primary endpoint.” Others seemed to suggest that if the goal is the immediate reversal of the anti-coagulation drug, rather than long-term outcomes, then perhaps the drug should be converted to a full approval. “As a clinician this is a difficult decision,” said panelist Evan Snyder of Sanford Burnham Prebys Medical Discovery Institute. He stressed that other clinicians may want this drug in their toolbox, and potentially they would know that if a person is at high-risk for a thrombotic event they should not receive this drug. “We can be more nuanced with the indication,” Snyder said. Adcomm member Sanjay Ahuja of the Indiana Hemophilia and Thrombosis Center said that if a patient is bleeding on an anticoagulant, “the first thing you need to do is reverse that effect,” and Andexxa “does that. Looks like pretty well.” But thrombotic risk needs to be assessed before you place people at risk, panelist Thomas Ortel of Duke University Medical Center said. “There is no alternative here,” Ahuja said. “People use PCCs without any approval in that category and that actually complicates matters because a lot of physicians will use PCCs the way they want to use PCCs.”

Industry leader Barry Quart, Pharm.D. appointed as Chief Executive Officer succeeding Zheng Wei, Ph.D., who will remain on the Board of Directors and serve as an advisor to assist with the transitionExperienced life science executive David Szekeres appointed as PresidentKleanthis G. Xanthopoulos, Ph.D. appointed as Chair of the Board of Directors SAN DIEGO, CA and TAICANG, China, June 12, 2024 (GLOBE NEWSWIRE) -- Connect Biopharma Holdings Limited (Nasdaq: CNTB) (Connect or the Company), a U.S.-headquartered, global clinical-stage biopharmaceutical company dedicated to improving the lives of patients with chronic inflammatory diseases through the development of therapies derived from T cell-driven research, announced today the appointments of Barry Quart, Pharm.D., as Chief Executive Officer (CEO) and Director, David Szekeres as President, and Kleanthis G. Xanthopoulos, Ph.D., as the new Chair of the Board of Directors (Board). Dr. Xanthopoulos, currently the lead independent member of the Board since 2022, has been appointed Chair of the Board. Dr. Xanthopoulos succeeds Wubin (Bill) Pan, Ph.D., M.B.A., who will remain on the Board and serve as an advisor to the Company during the transition. “On behalf of the board and the Connect team I would like to thank Drs. Zheng Wei and Wubin (Bill) Pan, who co-founded Connect with the vision to bring next-generation therapeutics to patients with inflammatory diseases and improve their lives. We are grateful for their contributions and unwavering commitment to the Connect mission by building an outstanding organization with Phase 3-ready programs and a robust pipeline,” said Kleanthis G. Xanthopoulos, Ph.D., Chair of the Board of Directors of Connect. “The highly differentiated data generated from positive readouts in both asthma and atopic dermatitis for the lead asset, rademikibart, establishes Connect now as a U.S.-driven late-stage company entering its pre-commercial phase. I am thrilled to welcome the new leadership team with such an impressive track record and eager to leverage Barry’s and David’s operational expertise and wealth of experience to unlock the maximum potential/value of rademikibart and the rest of the pipeline.” "Founding and leading Connect with Bill and working with many talented colleagues who are passionate about discovery and development of life-changing medicines in the past 12 years has been a true honor and privilege," said Dr. Zheng Wei. "As Connect evolved to focus on advancing rademikibart, Bill and I look forward to supporting Barry and David as Connect enters an exciting new phase." Dr. Barry Quart, the Company’s newly appointed CEO, brings over 30 years of extensive experience serving in leadership positions in biotechnology and pharmaceutical companies and developing innovative pharmaceutical products. He has personally led several early-stage biotech companies through late-stage clinical development and regulatory strategy, highlighted by nine U.S. Food and Drug Administration (FDA) approved drugs. “I am honored to assume the CEO role for Connect and to join the Board. I am incredibly excited about the potential of the Company going forward with rademikibart, which I believe to be a best-in-class competitor to dupilumab,” said Barry Quart, Pharm.D., CEO and Director of Connect. “With the multiple innovative therapies in our pipeline, a cash runway into at least 2026, and an expanded management team with proven experience in the U.S., I believe we have all the elements in place to achieve significant shareholder returns in the future.” Dr. Quart was most recently CEO at Heron Therapeutics. He first served as CEO and Director starting in 2012, transitioned to President and CEO in 2019 and was named Chair of the Board in October 2020. At Heron, Dr. Quart oversaw the development and approval of four drugs: two drugs for CINV (CINVANTI® and SUSTOL®) and two acute care drugs (ZYNRELEF® and APONVIE®). Prior to Heron, Dr. Quart co-founded Ardea Biosciences, Inc. in 2006 and served as its President and Chief Executive Officer and Director from its inception through its acquisition by AstraZeneca PLC in 2012. At Ardea, Dr. Quart invented and oversaw the development of a drug for gout (ZURAMPIC®), as well as the design and development of a series of MEK inhibitors for cancer that were licensed to Bayer AG. Dr. Quart currently serves on the Board of Directors of Kiniksa Pharmaceuticals. He is an inventor on 18 U.S. patents and an author on 75 publications and abstracts. Dr. Quart received his Pharm.D. from the University of California, San Francisco. David Szekeres is an experienced life science executive with a proven track record of creating value with deep operational, commercial, corporate development/strategy, and legal expertise. Mr. Szekeres was most recently Executive Vice President and Chief Operating Officer of Heron Therapeutics. Prior to Heron, he was the Chief Business Officer and General Counsel of Regulus Therapeutics, a clinical-stage biotech company focused on RNA therapeutics and the Head of Mergers & Acquisitions at Life Technologies Corporation. Mr. Szekeres also holds positions as the Chair of the Board of GRI Bio, Inc. (Nasdaq: GRI) and is a member of the Board of Directors of CureMatch, Colossal Biosciences, and the Sanford Burnham Prebys Medical Discovery Institute. He received his J.D. from Duke University School of Law and earned his B.A. at the University of California, Irvine. About Connect Biopharma Holdings Limited Connect Biopharma is a global, clinical-stage biopharmaceutical company applying its expertise in T cell biology and deep knowledge of the drug discovery industry to develop innovative therapies to treat chronic inflammatory diseases with the goal of improving the lives of millions of those affected around the world. The Company is building a rich pipeline of proprietary small molecules and antibodies, using functional T cell assays, to screen and discover potent product candidates against validated immune targets. The Company’s lead product candidate, rademikibart (formerly known as CBP-201), is an antibody designed to target interleukin-4 receptor alpha (IL-4Rα) in development for the treatment of atopic dermatitis and asthma. The Company’s second product candidate, icanbelimod (formerly known as CBP-307), is a modulator of S1P1 T cell receptors and is in development for the treatment of ulcerative colitis (UC). For more information, please visit: https://www.connectbiopharm.com/ Forward-Looking Statements Connect Biopharma cautions that statements included in this press release that are not a description of historical facts are forward-looking statements. Words such as “may”, “could”, “will”, “would”, “should”, “expect”, “plan”, “anticipate”, “believe”, “estimate”, “intend”, “predict”, “seek”, “contemplate”, “look forward”, “potential”, “continue” or “project” or the negative of these terms or other comparable terminology are intended to identify forward-looking statements. These statements include the Company’s plans to advance the development of its product candidates, the timing of achieving any development, regulatory or commercial milestones or reporting data or whether such milestones or data will be achieved or generated, including whether any new drug application will be submitted or accepted and the timing thereof, and the potential of such product candidates, including to achieve any benefit, improvement, differentiation, trend or profile or any product approval or be effective, and the sufficiency of the Company’s cash and investments to support planned operations. The inclusion of forward-looking statements should not be regarded as a representation by Connect Biopharma that any of its plans will be achieved. Actual data may differ materially from those set forth in this release due to the risks and uncertainties inherent in the Company’s business and other risks described in the Company’s filings with the Securities and Exchange Commission (SEC), including the Company’s Annual Report on Form 20-F filed with the SEC on April 16, 2024, and its other reports. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Connect Biopharma undertakes no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included in Connect Biopharma’s filings with the SEC which are available from the SEC’s website (www.sec.gov) and on Connect Biopharma’s website (www.connectbiopharm.com) under the heading “Investors.” All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. INVESTOR CONTACT:Tim McCarthyLifeSci Advisorstim@lifesciadvisors.com

Most cancer patients do not benefit from early targeted therapies. Scientists now describe a new computational pipeline to systematically predict patient response to cancer drugs at single-cell resolution. With more than 200 types of cancer and every cancer individually unique, ongoing efforts to develop precision oncology treatments remain daunting. Most of the focus has been on developing genetic sequencing assays or analyses to identify mutations in cancer driver genes, then trying to match treatments that may work against those mutations. But many, if not most, cancer patients do not benefit from these early targeted therapies. In a new study published on April 18, 2024, in the journal Nature Cancer, first author Sanju Sinha, Ph.D., assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, with senior authors Eytan Ruppin, M.D., Ph.D., and Alejandro Schaffer, Ph.D., at the National Cancer Institute, part of the National Institutes of Health (NIH) -- and colleagues -- describe a first-of-its-kind computational pipeline to systematically predict patient response to cancer drugs at single-cell resolution. Dubbed PERsonalized Single-Cell Expression-Based Planning for Treatments in Oncology, or PERCEPTION, the new artificial intelligence-based approach dives deeper into the utility of transcriptomics -- the study of transcription factors, the messenger RNA molecules expressed by genes that carry and convert DNA information into action. "A tumor is a complex and evolving beast. Using single-cell resolution can allow us to tackle both of these challenges," says Sinha. "PERCEPTION allows for the use of rich information within single-cell omics to understand the clonal architecture of the tumor and monitor the emergence of resistance." (In biology, omics refers to the sum of constituents within a cell.) Sinha says, "The ability to monitor the emergence of resistance is the most exciting part for me. It has the potential to allow us to adapt to the evolution of cancer cells and even modify our treatment strategy." Sinha and colleagues used transfer learning -- a branch of AI -- to build PERCEPTION. "Limited single-cell data from clinics was our biggest challenge. An AI model needs large amounts of data to understand a disease, not unlike how ChatGPT needs huge amounts of text data scraped from the internet." PERCEPTION uses published bulk-gene expression from tumors to pre-train its models. Then, single-cell data from cell lines and patients, even though limited, was used to tune the models. PERCEPTION was successfully validated by predicting the response to monotherapy and combination treatment in three independent, recently published clinical trials for multiple myeloma, breast and lung cancer. In each case, PERCEPTION correctly stratified patients into responder and non-responder categories. In lung cancer, it even captured the development of drug resistance as the disease progressed, a notable discovery with great potential. Sinha says that PERCEPTION is not ready for clinics, but the approach shows that single-cell information can be used to guide treatment. He hopes to encourage the adoption of this technology in clinics to generate more data, which can be used to further develop and refine the technology for clinical use. "The quality of the prediction rises with the quality and quantity of the data serving as its foundation," says Sinha. "Our goal is to create a clinical tool that can predict the treatment response of individual cancer patients in a systematic, data-driven manner. We hope these findings spur more data and more such studies, sooner rather than later." Additional authors on the study include Rahulsimham Vegesna, Sumit Mukherjee, Ashwin V. Kammula, Saugato Rahman Dhruba, Nishanth Ulhas Nair, Peng Jiang, Alejandro Schäffer, Kenneth D. Aldape and Eytan Ruppin, National Cancer Institute (NCI); Wei Wu, Lucas Kerr, Collin M. Blakely and Trever G. Biovona, University of California, San Francisco; Mathew G. Jones and Nir Yosef, University of California, Berkeley; Oleg Stroganov and Ivan Grishagin, Rancho BioSciences; Craig J. Thomas, National Institutes of Health; and Cyril H. Benes, Harvard University. This research was supported in part by the Intramural Research Program of the NIH; NCI; and NIH grants R01CA231300, R01CA204302, R01CA211052, R01CA169338 and U54CA224081.