Circle Pharma Reveals Promising Preclinical Data on CID-078 at 2024 Breast Cancer Symposium

Circle Pharma, based in South San Francisco, is progressing in its mission to discover and advance new macrocycle therapies. At the San Antonio Breast Cancer Symposium 2024, which takes place from December 10-13, Circle Pharma will present a poster detailing preclinical data on CID-078. This compound is a pioneering oral macrocycle cyclin A/B RxL inhibitor and shows promise in breast cancer treatment.

The presentation, authored by Molina et al, is titled "CID-078, a first-in-class oral cyclin A/B-RxL inhibitor, elicits anti-tumor activity in breast cancer patient-derived xenograft models." This poster, numbered P2-05-29, will be available for viewing on December 11, 2024, from 5:30-7:00 PM CST.

Preclinical studies of CID-078 have revealed significant single-agent antitumor activity in models of triple-negative breast cancer (TNBC) and estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, especially following CDK4/6 inhibitor (CDK4/6i) therapy. The efficacy of CID-078 was associated with the expression of E2F1 and separase (ESPL1), aligning with the hypothesized mechanism of action. Additionally, treatment with CID-078 led to increased phosphorylation of separase in sensitive breast cancer patient-derived xenograft (PDX) models. These results indicate that CID-078 could serve as a novel therapeutic option for patients with TNBC or ER+/HER2- breast cancer post-CDK4/6i therapy.

Circle Pharma is currently assessing CID-078 in a multi-center Phase 1 clinical trial (NCT06577987), which aims to evaluate the drug's safety, tolerability, and preliminary efficacy in patients with advanced cancers, including TNBC and ER+/HER2- breast cancer.

CID-078 is part of Circle Pharma’s Cyclin A/B RxL Inhibitor Program. This orally bioavailable macrocycle possesses dual inhibitory activity against cyclins A and B RxL, specifically targeting tumor cells with cell cycle dysregulation due to oncogenic changes. Circle Pharma's cyclin A/B RxL inhibitors have been shown in biochemical and cellular studies to effectively and selectively disrupt interactions between cyclins A and B and their substrates and modulators, such as E2F and Myt1. Preclinical studies have demonstrated these inhibitors' ability to induce single-agent tumor regressions in multiple in vivo models. The compound is undergoing a multi-center phase 1 clinical trial (NCT06577987) with current patient enrollment.

Circle Pharma, headquartered in South San Francisco, is dedicated to developing intrinsically cell-permeable macrocycles that offer versatility in administration routes, including oral delivery. The company's MXMO™ platform integrates structure-based drug design and advanced synthetic chemistry to create a new generation of macrocycle therapies aimed at challenging targets to fulfill unmet clinical needs. Circle Pharma’s primary focus is on cyclins, which play a crucial role in regulating cell cycle progression and are pivotal in many cancers.