Circle Pharma, Inc.

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Circle Pharma, a clinical-stage biopharmaceutical company dedicated to discovering and developing a new generation of macrocycle therapies, today announced a poster for preclinical data on CID-078, a first-in-class oral macrocycle cyclin A/B RxL inhibitor, will be presented at the San Antonio Breast Cancer Symposium 2024. The event, which runs from December 10-13, brings together global leaders in breast cancer research and treatment. Poster presentation details are below: Author: Molina et al Title: CID-078, a first-in-class oral cyclin A/B-RxL inhibitor, elicits anti-tumor activity in breast cancer patient-derived xenograft models Poster Number: P2-05-29 Date and Time: December 11, 2024, from 5:30-7:00 PM CST The digital poster can be viewed here. The pre-clinical data showed CID-078 demonstrated single agent antitumor activity with CID-078 in preclinical models of triple-negative breast cancer (TNBC) and estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer following CDK4/6 inhibitor (CDK4/6i) therapy. In vivo activity was correlated with E2F1 and separase (ESPL1) expression and consistent with the proposed mechanism of action. Further, treatment with CID-078 increased phosphorylation of separase in sensitive breast cancer patient-derived xenograft (PDX) models. These findings suggest that CID-078 may offer a novel treatment option for patients with Triple Negative Breast Cancer or patients with ER+/HER2- breast cancer following CDK4/6i therapy. Circle Pharma is evaluating CID-078 in a multi-center Phase 1 clinical trial ( NCT06577987 ), which aims to assess safety, tolerability, and preliminary efficacy in patients with advanced cancers, including TNBC and ER+/HER2- breast cancer. About CID-078, Circle Pharma’s Cyclin A/B RxL Inhibitor Program CID-078 is an 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 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 in vivo models. A multi-center phase 1 clinical trial ( NCT06577987 ) is currently enrolling patients. 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 .

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- #BreastCancer --Circle Pharma, a clinical-stage biopharmaceutical company dedicated to discovering and developing a new generation of macrocycle therapies, today announced that preclinical data from its lead candidate, CID-078, a first-in-class oral macrocycle cyclin A/B RxL inhibitor, has been selected for a late-breaking poster presentation at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, also known as the Triple Meeting. The symposium is taking place from October 23-25, 2024, in Barcelona, Spain. Poster presentation details are below: Author: Wang et al. Title: CID-078, a First-in-Class Oral Macrocycle Cyclin A/B RxL Inhibitor, Demonstrates Anti-Tumor Activity in ESF-driven Cancers Abstract Number: PB-515 Session Title: Late breaking posters Date and Time: October 23, 2024 (6 a.m. EST/12 p.m. CEST) to October 25, 2024 (11 a.m. EST/5 p.m. CEST) The digital poster can be viewed here. The pre-clinical data shows CID-078 demonstrated single-agent tumor activity across tumor cell line and in vivo models with dysregulated cell cycle (CDK-RB-E2F) function. Notably, tumor regressions were observed in small-cell lung cancer (SCLC), non-small-cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC) preclinical models. Within specific indications, CID-078 single agent activity was correlated with RB1 mutation, high E2F target, or G2M checkpoint hallmark pathway scores. The cumulative pre-clinical data suggests that CID-078 holds promise as a monotherapy for patients with these cancers. A multi-center phase 1 clinical trial (NCT06577987) is currently enrolling patients. About CID-078 CID-078 is an 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 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 in vivo models. A multi-center phase 1 clinical trial ( NCT06577987 ) is currently enrolling patients. 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 . Contacts Media Contact: Roslyn Patterson 650.825.4099 roslyn.patterson@circlepharma.com

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