Vividion Therapeutics, Inc.

CHICAGO — A new type of targeted cancer drug that blocks a “DNA caretaker” protein called Werner helicase has captured the attention of several big pharma companies in recent years, and the first data appear to reinforce its potential. Cells are typically equipped with critical redundancies for important proteins, but when they mutate in cancer patients, a single protein can become the key to a cell’s life or death. By finding the proteins that aberrant cancer cells need to function and then blocking them, drug developers are building the next generation of targeted cancer treatments. Roche now has the first data for its experimental drug, which takes advantage of what’s known as synthetic lethality, in gynecologic and colon cancers. It was shared this week at the American Association for Cancer Research’s annual meeting in Chicago. In the span of six years, scientists and physicians took a promising drug target identified via CRISPR screening and created a handful of experimental treatments for cancer patients. There are now four different Werner helicase-targeting agents in early-stage clinical trials from Roche, Novartis, GSK and Nimbus Therapeutics — a private drug developer with a track record of doing big deals. “Werner helicase really and truly represents a synthetic lethal vulnerability and therefore a therapeutic opportunity in MSI cancers,” said Timothy Yap, a physician-scientist with the University of Texas MD Anderson Cancer Center, referring to cancers with a specific DNA signature. “That’s really the crux of it and why it was so exciting.” Synthetic lethality is a phenomenon that scientists are exploiting to develop new targeted cancer treatments. Their inspiration is PARP inhibitors (such as AstraZeneca’s Lynparza), a class of drugs used to treat a wide range of cancers including breast and ovarian. PARP inhibitors are a synthetic lethal therapy for cancers with BRCA mutations. In the Phase 1 study, Roche’s experimental drug led to four confirmed responses — two in endometrial cancer, one in colorectal cancer, and one in ovarian cancer — in 35 patients. There was also a fifth unconfirmed response in endometrial cancer. Yap presented the data Sunday at the AACR meeting. The responses mean the drug, which came from Roche’s partnership with Vividion Therapeutics in 2020, shrank the tumors in these patients at least 30%. It’s the first time that researchers have shown the effect of a Werner helicase blocker in people. Many of the patients in the study had gone through several previous treatment regimens. While their cancers were found in a wide range of locations, most of the tumors were considered microsatellite instable, which is a sign of DNA misrepair that physicians frequently look for in cancer diagnoses. The initial science that identified Werner helicase as a potential target showed that knocking it out was lethal to the microsatellite instable cells, and this piqued the interest of drug developers. Microsatellite instability-high cancers make up around 3% of all cancer cases, according to some estimates. The responses to Roche’s drug occurred at a range of doses, from 150 mg a day to 1,000 mg twice a day. In an interview, Ryan Corcoran, director of the gastrointestinal cancer center program at the Massachusetts General Hospital Cancer Center, said there’s not a clear correlation between the responses and dose levels. Researchers typically look for dose dependency (more drug equals better efficacy) in clinical studies as a green flag the treatment is working as intended. Corcoran, who chaired the session where Roche’s clinical trial results were presented, consults for Roche but not on the Werner helicase project. The primary side effects related to the drug were nausea, vomiting and diarrhea. There were no dose-limiting toxicities. Like Novartis had already reported, both GSK and Nimbus disclosed at the meeting that their molecules were non-covalent, meaning they do not permanently bind Werner helicase. This leaves Roche as the lone company developing a covalent, or permanently binding, agent in clinical trials. GSK suggested in its presentation that its drug could work in tumors that acquired resistance to Roche or Novartis’ compounds, but that’s based on animal model data and has not been shown in humans. GSK’s drug comes from a partnership with Ideaya Biosciences, a biotech company that’s focused on developing drugs against synthetic lethalities. In 2019, four papers were published showing Werner helicase could be a promising target for treating microsatellite instable cancers. These cancers tend to respond well to immunotherapy, but patients have few other options beyond those treatments. Of the two studies published in Nature on the same day, one was from Mathew Garnett’s lab at the Wellcome Sanger Institute, while the other was led by Adam Bass, who at the time was at the Dana-Farber Cancer Institute and now leads translational cancer research at Novartis. Using CRISPR screening, researchers from both groups found that Werner helicase was needed in microsatellite instable cancer models but dispensable in models that were microsatellite stable. “When you knock out Werner helicase, in 48 hours, the cells are dead,” Garnett said. “All their DNA is just shattered, and it’s really phenomenal. You had this sense when you saw this genome shattering, that there was something really profound happening to these cells.” There are several other synthetic lethality programs in early-stage trials. Corcoran said he has yet to see results from another class of synthetic lethal drugs that matches the success of PARP inhibitors, though many of these efforts are still early and have yet to report clinical data. One closely-watched effort to leverage synthetic lethality is targeting a protein called PRMT5 in cancers with mutations known as MTAP deletions. This is an area in which Bristol Myers Squibb, Amgen, Ideaya and others are all working on early-stage programs, though readouts so far have been mixed . Eli Lilly and Foghorn Therapeutics last year began a Phase 1 trial for a SMARCA2 inhibitor, which they are studying in patients with SMARCA4-mutated cancers. “Imagine you’re riding a bicycle — it’s a bicycle with two wheels — and one of the wheels is lost, and now you’re riding a unicycle,” Foghorn CEO Adrian Gottschalk said. And so giving a SMARCA2 inhibitor to one of these patients is like taking a stick to the cancer cell’s remaining wheel, he said.

SAN DIEGO, CA, USA & BERLIN, Germany I April 03, 2025 I Vividion Therapeutics, Inc. (Vividion) today announced that the first patient has been dosed in a Phase I clinical trial evaluating VVD-159642, an investigational oral inhibitor designed to target RAS-driven cancers. Vividion is a clinical-stage biopharmaceutical company, and a wholly owned and independently operated subsidiary of Bayer AG, utilizing innovative discovery technologies to unlock targets with strong disease-link, yet traditionally undruggable and develop small molecule precision therapeutics for devastating cancers and immune disorders. The new Phase I study ( NCT06804824 ) will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of VVD-159642 as a single agent and in combination with either sotorasib or trametinib in patients with advanced solid tumors. “Despite being a major driver in approximately 20% of cancers, the RAS gene has proven exceptionally difficult to target with drugs, largely due to its essential role in the RAS-PI3Kα signaling pathway, which is vital for healthy cell function,” said Jenna Goldberg, M.D., Chief Medical Officer of Vividion. “VVD-159642 is designed and being studied to selectively prevent RAS activation of the PI3Kα pathway, thus blocking oncogenic signaling without disrupting normal cellular function. Preclinical studies of VVD-159642 give us confidence in its potential to inhibit tumor growth while avoiding the on-target toxicities that have limited prior attempts to drug this important target. In addition to providing a more tolerable alternative to current therapies, we believe that VVD-159642 has potential to treat a broad patient population, including in both RAS-mutant and HER2-overexpressed tumors, and may deliver increased efficacy in combination with other RAS/MAPK pathway inhibitors.” “We’re excited to bring our fourth innovative oncology asset into the clinic, which not only represents continued validation of Vividion’s covalent-first chemoproteomics platform but also provides a potential new treatment option for patients with RAS-driven cancers,” said Aleksandra Rizo M.D., Ph.D., Chief Executive Officer of Vividion. “The team at Vividion is rapidly advancing scientific innovations into clinical development that have the potential to address multiple devastating diseases not reachable by current therapies,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “The initiation of this clinical trial marks a significant step forward in leveraging Vividion’s innovative drug discovery approach to target a highly relevant signaling pathway and bring a potential new treatment option to people suffering from difficult-to-treat cancers.” Vividion also has ongoing Phase I trials evaluating an oral KEAP1 activator in solid tumors and oral STAT3 inhibitor in solid and hematologic malignancies. The company is advancing multiple innovative drug discovery programs toward the clinic and has a rich pipeline of opportunities emerging in early discovery in the fields of oncology and immunology. About Vividion Vividion Therapeutics, Inc., a wholly owned and independently operated subsidiary of Bayer AG, is a clinical stage biopharmaceutical company utilizing novel discovery technologies to unlock high value, traditionally undruggable targets with precision therapeutics for devastating cancers and immune disorders. The company’s platform has enabled it to identify hundreds of previously unknown functional pockets on well-validated protein targets implicated in a wide range of diseases, while simultaneously identifying compounds from its proprietary covalent chemistry library that interact in a highly selective manner with those pockets. The company is leveraging its proprietary chemoproteomic platform to advance a diversified pipeline of highly selective small molecule therapeutics targeting high value, traditionally undruggable targets in oncology and immunology. For more information, please visit www.vividion.com . About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2024, the Group employed around 93,000 people and had sales of 46.6 billion euros. R&D expenses amounted to 6.2 billion euros. For more information, go to www.bayer.com . Find more information at https://pharma.bayer.com/ Follow us on Facebook: http://www.facebook.com/bayer SOURCE: Bayer

SAN DIEGO--(BUSINESS WIRE)--Mar. 17, 2025-- Contineum Therapeutics, Inc. (NASDAQ: CTNM) (Contineum or the Company), a clinical-stage biopharmaceutical company pioneering differentiated therapies for the treatment of neuroscience, inflammation and immunology (NI&I) indications, today announced the appointment of Diego Miralles, M.D. as a member of its board of directors, effective March 14, 2025. “We are excited to welcome Diego to our board,” commented Eef Schimmelpennink, Contineum’s Chairperson. “He has successfully led the development of novel therapies throughout his distinguished career and has an extensive track record in both early stage research and all stages of clinical development. During his time at Janssen Research, Dr. Miralles was engaged in the development and approval of several important medicines. He is an accomplished life sciences executive and his perspective in guiding life sciences companies will provide our board with valuable insights as we look ahead to key clinical development and operating milestones.” Dr. Miralles has served as Chief Executive Officer at AZURNA Therapeutics, Inc., a private pharmaceutical development company, since January 2024. From December 2020 to September 2022, Dr. Miralles was Chief Executive Officer at Laronde Inc., an early-stage biotechnology company. From August 2017 to September 2020, Dr. Miralles served as Chief Executive Officer at Vividion Therapeutics, Inc., a private biopharmaceutical company. From October 2007 to March 2016, Dr. Miralles held executive positions of increasing responsibility leading various research and clinical development programs at Johnson & Johnson. Dr. Miralles has served on the board of directors of Artiva Biotherapeutics, Inc., a publicly traded biotechnology company, since May 2024 and in January 2025, he was appointed as chair of the Clinical Strategy Committee. Dr. Miralles has also been a member of the board of directors at Rady Children’s Institute for Genomic Medicine since 2008 and served as a member of the board of directors at NeuBase Therapeutics, Inc., a public biopharmaceutical company, from April 2019 to April 2021. Dr. Miralles received his M.D. degree from the University of Buenos Aires, his residency in Internal Medicine at the Mayo Clinic and fellowship in Infectious Diseases at The New York Hospital/Cornell University and was on the faculty at Duke University. “I am impressed with Contineum’s progress as it works to meet the significant unmet needs in several NI&I indications,” stated Dr. Miralles. “The Company’s robust pipeline enables multiple opportunities with de-risked, clinically-validated targets. I am thrilled to join a passionate board of directors with a unified vision to help guide the Company as it initiates multiple proof-of-concept clinical trials.” About Contineum Therapeutics Contineum Therapeutics (Nasdaq: CTNM) is a clinical-stage biopharmaceutical company pioneering novel, oral small molecule therapies for NI&I indications with significant unmet need. Contineum is advancing a pipeline of internally-developed programs with multiple drug candidates now in clinical trials. PIPE-791 is an LPA1 receptor antagonist in clinical development for idiopathic pulmonary fibrosis, progressive multiple sclerosis and chronic pain, and PIPE-307 is a selective inhibitor of the M1 receptor in clinical development for relapsing-remitting multiple sclerosis and major depressive disorder. For more information, please visit www.contineum-tx.com. Forward-Looking Statements Certain statements contained in this press release, other than historical information, constitute forward-looking statements within the meaning of the federal securities laws. Forward-looking statements include, but are not limited to, statements regarding the Company’s plans for, and the anticipated benefits of, and market opportunities for its drug candidates, including PIPE-791 and PIPE-307; its business strategies and plans; and the quotations of the Company’s management and board members. These statements involve known and unknown risks, uncertainties and other important factors that are in some cases beyond the Company’s control and may cause its actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties, include, but are not limited to, the following: the Company is heavily dependent on the success of PIPE-791 and PIPE-307, both of which are in the early stages of clinical development, and neither of these drug candidates may progress through clinical development or receive regulatory approval; the results of earlier preclinical studies and clinical trials, including those conducted by third parties, may not be predictive of future results and unexpected adverse side effects or inadequate efficacy of the Company’s drug candidates may limit their development, regulatory approval and/or commercialization; the timing and outcome of research, development and regulatory review is uncertain; clinical trials and preclinical studies may not proceed at the time or in the manner expected, or at all; the potential for our programs and prospects to be negatively impacted by developments relating to our competitors, including the results of studies or regulatory determinations relating to our competitors; risks associated with reliance on third parties to successfully conduct clinical trials and, in the case of PIPE-307, the Company’s reliance, pursuant to a global license and development agreement, upon Janssen Pharmaceutica NV, a Johnson & Johnson company, to develop PIPE-307 for any other indication other than RRMS and, after completion of the Company’s PIPE-307 Phase 2 VISTA trial, Janssen Pharmaceutica NV’s decision, in its sole discretion, whether or not to further develop PIPE-307 for RRMS; the Company has incurred significant operating expenses since inception and it expects that its operating expenses will continue to significantly increase for the foreseeable future; the Company’s license agreement with Janssen Pharmaceutica NV may not result in the successful development of PIPE-307; the Company may be unable to obtain, maintain and enforce intellectual property protection for its technology and drug candidates; and unstable market and economic conditions and military conflict may adversely affect our business and financial condition and the broader economy and biotechnology industry. Additional risks and uncertainties that could affect the Company’s business, operations and results are included under the captions, “Risk Factors” and "Management’s Discussion and Analysis of Financial Condition and Results of Operations” in its most recent filing on Form 10-K and in other filings that it makes with the SEC from time to time. These documents are available on the Company’s website at www.contineum-tx.com under the Investor section and on the SEC’s website at www.sec.gov. Accordingly, readers should not rely upon forward-looking statements as predictions of future events. Except as required by applicable law, the Company undertakes no obligation to update publicly or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. View source version on businesswire.com: https://www.businesswire.com/news/home/20250317917183/en/ Steve Kunszabo Contineum Therapeutics Senior Director, Investor Relations & Corporate Communications 858-649-1158 skunszabo@contineum-tx.com Source: Contineum Therapeutics, Inc.