CID-078

SOUTH SAN FRANCISCO, CA, USA I October 15, 2024 I Circle Pharma, Inc., a clinical-stage biopharmaceutical company dedicated to discovering and developing a new generation of macrocycle therapies, announced today that the first patient cohort has been dosed in the phase 1 trial of CID-078, the company’s first-in-class oral cyclin A/B RxL inhibitor. The trial will evaluate CID-078 in patients with advanced solid tumors, including tumors with elevated E2F transcription factor activity, such as small cell lung cancer, triple negative breast cancer and ER+ HER-2- breast cancer following CDK 4/6-inhibitor therapy. “We are thrilled that the IND for CID-078 was cleared at the end of the 30-day regulatory review period and that CID-078 has now moved into human dosing at a consortium of world class cancer centers. This will allow our investigators to generate clinical proof-of-concept data which will inform CID-078’s potential impact in settings of high unmet medical need as well as validate Circle Pharma’s proprietary MXMO™ macrocycle platform for difficult-to-drug targets in cancer and other serious diseases,” said David J. Earp, JD, Ph.D., CEO of Circle Pharma. CID-078 is designed to selectively inhibit key protein-to-protein interactions involving cyclins A and B, both of which have been implicated in the proliferation and survival of cancer cells. The research program builds on work performed in the laboratory of Nobel Laureate and Circle Pharma’s Scientific Advisory Board Chair, William G. Kaelin Jr., MD, who demonstrated synthetic lethality through the disruption of these cyclins in settings of dysregulated cell cycle control and elevated E2F activity. Geoffrey Shapiro, MD, Ph.D., senior vice president, Development Therapeutics at Dana-Farber Cancer Institute and professor of medicine at Harvard University, stated, “Disrupting the ability of E2F-driven cancer cells to turn off E2F at the appropriate time in the cell cycle has been shown to selectively induce apoptosis. Until now there hasn’t been a selective therapeutic agent to exploit this observation and so I am extremely excited to see Circle Pharma’s cyclin A/B RxL inhibitor move into the clinic.” All patients in the cohort are enrolled at The START Center for Cancer Research, Midwest, Grand Rapids, MI. Other clinical sites currently open include The START Center for Cancer Research, West Valley City, UT, and NEXT Oncology in San Antonio, TX. Additional clinical sites are planned to open soon. Circle Pharma’s Phase 1 clinical trial (NCT06577987) is an open label, multi-center dose escalation and expansion study that is expected to enroll up to 100 patients. The study will evaluate the safety, pharmacokinetics and pharmacodynamics of CID-078 as well as preliminary anti-tumor activity in solid tumors. Circle Pharma anticipates reporting preliminary safety and anti-tumor data from the Phase 1 study in 2025. About CID-078, Circle Pharma’s Cyclin A/B RxL Inhibitor Program CID-078 is an investigational orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation. In biochemical and cellular studies, Circle Pharma’s investigational cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and Myt1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple xenograft models. Based on these findings CID-078 has progressed to a Phase 1 clinical study (NCT06577987). About Circle Pharma, Inc. South San Francisco-based Circle Pharma is advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle Pharma’s MXMO™ platform combines structure-based rational drug design and advanced synthetic chemistry to develop a new generation of macrocycle therapies for challenging targets to address unmet clinical needs. Circle Pharma is focusing its development efforts on cyclins, which are master regulators of the machinery that controls the progression of cells through the cell cycle and are key drivers in many cancers. To learn more about Circle Pharma, please visit www.circlepharma.com . SOURCE: Circle Pharma

INGELHEIM, Germany and SOUTH SAN FRANCISCO, CA, USA I October 09, 2024 I Boehringer Ingelheim and Circle Pharma (Circle) announce a new research collaboration and license agreement with the shared goal to develop a first-in-class cyclin inhibitor that can halt the growth of cancer cells potentially offering hope to those living with hard-to-treat cancers. Uncontrolled cell growth is a common feature in most tumor types and is a driving force in the formation of tumors. Genetic alterations like mutations or amplifications in the genes encoding the regulatory machinery of cell division contribute to malignant growth in a significant fraction of all solid tumors. That is why Boehringer Ingelheim is targeting the proteins involved in this process, a promising strategy for new cancer treatments. Current methods targeting cyclin-dependent kinases can be limited by low selectivity and toxicity. Circle has developed a possible solution to these challenges by creating macrocycle therapies that directly inhibit cyclins, the proteins that regulate cell division. “We’re delighted to be joining forces with Circle’s scientists to develop an innovative cancer treatment based on their proprietary macrocycle platform molecules to achieve our goal of transforming the lives of people living with cancer,” said Clive R. Wood, Ph.D., Senior Vice President and Global Head of Discovery Research at Boehringer Ingelheim. “This new collaboration complements our oncology research portfolio, and further reinforces our commitment to tackling intractable targets.” David Earp, Ph.D., JD, chief executive officer, Circle Pharma said, “With our lead program, CID-078, a Cyclin A/B RxL inhibitor, we have demonstrated the capability of our MXMO TM platform to deliver oral macrocycles against a target that was previously considered to be undruggable. We’re excited to partner with Boehringer Ingelheim to leverage the platform against another challenging cyclin target that offers the potential to address high unmet need cancer indications.” This partnership is a significant step toward Boehringer Ingelheim’s goal of transforming cancer care. It bolsters the already robust oncology pipeline of cancer cell-directed and immuno-oncology investigational therapies for smart combinations that may offer the greatest benefit for people living with cancer. As part of the agreement, Circle Pharma will receive an upfront payment and potential development, regulatory, and sales milestone payments of up to USD 607 million. About Boehringer Ingelheim in oncology We have a clear aspiration – to transform the lives of people with cancer by delivering meaningful advances, with the ultimate goal of curing a range of cancers. Boehringer Ingelheim’s generational commitment to driving scientific innovation is reflected by the company’s robust pipeline of cancer cell-directed and immuno-oncology investigational therapies, as well as the smart combination of these approaches. Boehringer’s ambition in oncology is to take a diligent and broad approach, creating a collaborative research network to tap into a diversity of minds, which is vital in addressing some of the most challenging, but potentially most impactful, areas of cancer research. Simply put, for Boehringer Ingelheim, cancer care is personal, today and for generations. About Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com/uk (UK) or https://www.boehringer-ingelheim.com (rest of world). About Circle Pharma South San Francisco-based Circle Pharma is advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle Pharma’s MXMO™ platform combines structure-based rational drug design and advanced synthetic chemistry to develop a new generation of macrocycle therapies for challenging targets to address unmet clinical needs. Circle Pharma is focusing its development efforts on cyclins, which are master regulators of the machinery that controls the progression of cells through the cell cycle and are key drivers in many cancers. The company’s lead candidate, CID-078 , is currently in clinical trials as part of a growing pipeline of novel macrocycle therapeutics. To learn more about Circle Pharma, please visit www.circlepharma.com . SOURCE: Boehringer Ingelheim