MYT1

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 .

New preclinical data on PRMT5-MTA inhibitor program will also be presented NEW YORK, NY, USA I October 23, 2024 I Schrödinger (Nasdaq: SDGR) today announced new preclinical data on SGR-3515, its investigational Wee1/Myt1 inhibitor, during a poster session at the 36th EORTC-NCI-AACR Symposium (ENA 2024). The data demonstrate that in preclinical models, treatment with SGR-3515 results in synergistic anti-tumor activity that leads to deeper and more durable responses compared to inhibitors that target only Wee1 or Myt1. The preclinical data also show that SGR-3515 has a favorable pharmacological profile and dosing schedule that supports evaluating intermittent dosing in patients. Wee1 and Myt1 kinases regulate the cell cycle and DNA damage response, allowing time for DNA repair before cell division takes place. Concurrent loss of function or inhibition of Wee1 and Myt1 confers selective vulnerability in cancer cells, a mechanism referred to as synthetic lethality, which has become an emerging therapeutic strategy for a range of cancers. A Phase 1 dose-escalation study of SGR-3515 in patients with advanced solid tumors is ongoing in the U.S. and Canada, and initial data from the clinical study is expected in the second half of 2025. Schrödinger will also present preclinical data from its PRMT5-MTA program during a poster session on October 25. Schrödinger scientists have identified a novel series of selective, potent PRMT5-MTA inhibitors and are optimizing lead compounds for use in peripheral and brain tumors. “We are pleased to share these encouraging preclinical data on SGR-3515, a potential best-in-class treatment for patients with a broad range of solid tumors, including uterine and ovarian cancers, two patient populations with high unmet need,” stated Karen Akinsanya, Ph.D., president of R&D therapeutics at Schrödinger. “We also look forward to presenting preclinical data on the discovery of a novel series of compounds for our PRMT5-MTA inhibitor program. These programs highlight how we are deploying our computational platform at scale to discover highly optimized molecules to address diseases with significant medical need, and we believe the future of our therapeutics portfolio is very promising.” SGR-3515 Data at ENA 2024 The presentation (Abstract # 147), “Discovery of SGR-3515, a first-in-class Wee1/Myt1 inhibitor with differentiated pharmacological properties in xenograft tumor models,” includes preclinical data demonstrating superior anti-tumor activity of SGR-3515 compared to inhibitors of Wee1 or Myt1 alone due to strong target engagement of both Wee1 and Myt1. The data show that SGR-3515 is a more potent co-inhibitor of both Wee1 and Myt1 than previously disclosed inhibitors of either target. These data are consistent with prior preclinical observations demonstrating that SGR-3515 has a unique and differentiated pharmacological profile that supports evaluating an intermittent dosing schedule of three days on and 11 days off, as well as five days on and nine days off, which maintained anti-tumor activity while allowing recovery from any mechanism-based hematological toxicity in preclinical models. The preclinical data also demonstrate superior kinase selectivity and in vitro cell potency of SGR-3515 across a broad cell line panel compared to other known Wee1 and Myt1 inhibitors. These new data suggest that SGR-3515 is significantly more selective than existing compounds with low potential for drug-drug interaction. PRMT5-MTA Data at ENA 2024 Additionally, Schrödinger will present new preclinical data on its PRMT5-MTA inhibitor program at a poster session during the meeting on October 25 from 9:00 a.m. – 3:00 p.m. CEST. The presentation (Abstract # 372), “Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology,” will include preclinical data on the discovery of highly selective PRMT5-MTA inhibitors. The poster will describe how Schrödinger’s virtual screening platform facilitated the identification of structurally distinct chemical matter with a high degree of MTA-synergy for compounds within a novel chemical series in vitro and in cellular contexts. Schrödinger has identified a novel series of selective, potent PRMT5-MTA inhibitors that did not show major off-target liabilities such as hERG inhibition in preclinical studies and may be suitable for use in combinations across tumor types. About Schrödinger Schrödinger is transforming the way therapeutics and materials are discovered. Schrödinger has pioneered a physics-based computational platform that enables discovery of high-quality, novel molecules for drug development and materials applications more rapidly and at lower cost compared to traditional methods. The computational platform is licensed by biopharmaceutical and industrial companies, academic institutions, and government laboratories around the world. Schrödinger’s multidisciplinary drug discovery team also leverages the software platform to advance a portfolio of collaborative and proprietary programs to address unmet medical needs. Founded in 1990, Schrödinger has approximately 850 employees and is engaged with customers and collaborators in more than 70 countries. To learn more, visit www.schrodinger.com , follow us on LinkedIn , or visit our blog, Extrapolations.com . SOURCE: Schrödinger

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