CID-078 / Circle Pharma - LARVOL DELTA

Circle Pharma Announces Poster Presentation Highlighting the Potential of CID-078, a First-in-class Oral Cyclin A/B RxL Inhibitor, at the American Association for Cancer Research Special Conference on Discovery and Innovation in Pediatric Cancer (Businesswire) - "The presentation...will focus on the novel mechanism of action of CID-078 for cancers driven by high E2F activity including those with alterations in the tumor suppressor genes RB1 or CDKN2A/B, as well as the prevalence of these biomarkers across a diverse range of pediatric cancer types. In addition, the presentation will outline new preclinical data on the correlation between CID-078 sensitivity and RB1 and E2F biomarker status..."

Biomarker • Preclinical • Oncology

Circle Pharma Receives FDA Orphan Drug Designation for CID-078 for the Treatment of Small Cell Lung Cancer (Businesswire) - "Circle Pharma...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to CID-078 for the treatment of small cell lung cancer (SCLC)....Circle Pharma has initiated a Phase 1 clinical trial (NCT06577987) of CID-078 to evaluate its safety, tolerability, pharmacokinetics, and early signs of anti-tumor activity in patients with advanced solid tumors, including SCLC."

Orphan drug • Small Cell Lung Cancer

A phase 1 study to evaluate the safety, pharmacokinetics, and efficacy of the first-in-class cyclin A/B RxL inhibitor CID-078, an orally bioavailable, cell-permeable macrocycle. (ASCO 2025) - P1 | "Based on preclinical data generated to date, the study plans to include patients with SCLC, TNBC, and RB1-mutated tumors with additional tumor types expanded based on observed efficacy. Dose escalation is ongoing with no DLT reported in the initial 3 dose cohorts evaluated."

Clinical • P1 data • PK/PD data • Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CCNA2 • CCNB1 • CDK1 • CDK2 • E2F1 • PKMYT1 • RB1

Preclinical Data on Circle Pharma’s CID-078 Featured in Poster Presentation at Advances in Neuroblastoma Research Meeting (Businesswire) - "Key Findings Presented: Potent Single agent CID-078 activity was observed across multiple neuroblastoma cell line models. Mechanism of action studies confirmed induction of DNA damage, G2/M arrest and the activation of the spindle assembly checkpoint (SAC). Deletion of CDKN2A sensitized cells to CID-078 suggesting CDKN2A status maybe be used as a potential patient stratification strategy."

Preclinical • Neuroblastoma

Safety/Efficacy Study of CID-078 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: Circle Pharma | N=100 ➔ 220

Enrollment change • Breast Cancer • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Triple Negative Breast Cancer

Anti-cancer effect of Cyclin A/B RxL inhibitors is mediated in part by disruption of the ATR/Chk1 DNA repair pathway (AACR 2025) - P1 | "The combined effect of Cyclin A/B RxLi on E2F and Treslin, together with the activation of mitotic CDK by displacement of Myt1 from Cyclin B, drives the anticancer activity in E2F high SCLCs. Circle's Cyclin A/B RxLi, CID-078, has recently entered a multi-center phase 1 clinical trial (NCT06577987) for patients with solid tumors, including SCLC."

Late-breaking abstract • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CCNA2 • CHEK1 • CHEK2 • PKMYT1 • TOPBP1

Orally bioavailable cyclin A/B-RxL inhibitors elicit antitumor activity in breast cancer patient-derived xenograft models (SABCS 2024) - "PDXs were treated with either vehicle or active therapy, including standard of care (cisplatin for TNBC and ERlow, and cisplatin alone or palbociclib in combination with the oral SERD elacestrant for ER+/HER2- models) or oral formulation of CID-078 at 100 mg/kg QD, BID or TID for at least 28 days. CID-078 exhibits potent anti-tumor activity in the TNBC, ERlow and ER+ preclinical models tested, consistent with the proposed mechanism of action and correlating well with E2F1 and ESPL1 expression. Given these compelling results, CID-078 may be a new treatment option for TNBC, ERlow/HER2-, or ER+/HER2- breast cancer. This hypothesis and the correlation of anti-cancer activity with biomarkers will be explored in the CID-078 first-in-human clinical trial CID-AB1-24001."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CCNA2 • CCNB1 • CDK1 • CDK2 • E2F1 • ER • HER-2 • PKMYT1

Circle Pharma Presents Promising Preclinical Data on First-in-Class Oral Macrocycle Cyclin A/B RxL Inhibitor CID-078 at the San Antonio Breast Cancer Symposium 2024 (Businesswire) - "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."

Preclinical • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Triple Negative Breast Cancer

Circle Pharma’s First-in-Class Oral Macrocycle Cyclin A/B RxL Inhibitor, CID-078, Preclinical Data Highlighted at the 36th EORTC-NCI-AACR Symposium (Businesswire) - "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."

Preclinical • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer

CID-078, a first-in-class oral macrocycle cyclin A/B-RxL inhibitor, demonstrates anti-tumor activity in E2F-driven cancers (EORTC-NCI-AACR 2024) - P1 | "The pre-clinical data for CID-078 provide compelling proof of concept for CID-078's potential as a novel and differentiated treatment for E2F-driven cancers. These data, along with suitable physical and pharmacokinetic properties and established nonclinical safety margins, supported progression of CID-078 into clinical studies. A multi-center phase 1 clinical trial (NCT06577987) recently commenced enrollment of patients."

Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CCNA2 • E2F1 • HER-2 • RB1

Circle Pharma Announces First Patients Dosed in Phase 1 Clinical Trial of First-in-Class Oral Cyclin A/B RxL Inhibitor CID-078 for Advanced Solid Tumors (Businesswire) - "Circle Pharma, Inc...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....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....Circle Pharma anticipates reporting preliminary safety and anti-tumor data from the Phase 1 study in 2025."

P1 data • Trial status • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer

Orally Bioavailable Cyclin A/B Rxl Macrocycle has Antitumor Effect in SCLC & NSCLC Cell Line Derived (CDX) & Patient Derived Xenograft (PDX) Models (IASLC-WCLC 2024) - "Interfering with RxL-mediated interactions between cyclins A and B with their substrates and modulators, including E2F1 and Myt1 by CID-078 may be a new treatment option for patients with SCLC, NSCLC, or TNBC. This hypothesis will be explored in the CID-078 first-in-human trial CID-AB1-24001 beginning later this year."

Preclinical • Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CCNA2 • CCNB1 • CDK1 • CDK2 • E2F1 • PKMYT1 • RB1

Circle Pharma Announces Preclinical Data Poster Presentation of CID-078, a First-and-Only-in-Class Cyclin A/B RxL Inhibitor at the 2024 World Conference on Lung Cancer (Businesswire) - "Circle Pharma...announced that it presented a digital poster at the 2024 World Conference on Lung Cancer. CID-078, Circle Pharma’s first-and-only-in-class cyclin A/B RxL inhibitor, demonstrated single-agent tumor regressions in both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) preclinical models. Tumor models with high E2F targets and G2M checkpoint hallmark pathways scores and elevated levels of E2F1, cyclin B1 and ESPL1 demonstrate tumor growth inhibition and/or regression when treated with CID-078 dosed at clinically achievable doses. CID-078 activity correlated with E2F1 and ESPL1 expression and was consistent with the proposed mechanism of action of cyclin A/B RxL inhibition leading to DNA damage."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Circle Pharma Closes $90 Million Series D Financing to Advance Innovative Oral Macrocycle Therapies (Businesswire) - "ircle Pharma...announced the successful closing of a $90 million Series D financing round, which includes the conversion of a convertible note. The financing was led by The Column Group with participation from new and existing investors, including Nextech Invest and Euclidean Capital. The proceeds from the financing will be used to fund the clinical development of CID-078, Circle Pharma’s first-and-only-in-class cyclin A/B RxL inhibitor, and to support the development of the company’s portfolio of discovery programs built with its MXMO macrocycle platform."

Financing • Oncology

Safety/Efficacy Study of CID-078 in Patients With Advanced Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Circle Pharma

New P1 trial • Breast Cancer • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Solid Tumor • Triple Negative Breast Cancer

Circle Pharma files first Investigational New Drug application for first-in-class oral cyclin A/B RxL inhibitor for treatment of advanced solid tumors (Businesswire) - "Circle Pharma...announced the submission of its first Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for CID-078, a first-and-only-in-class cyclin A/B RxL inhibitor....CID-078 is an orally bioavailable macrocycle that has shown preclinical efficacy across multiple tumor types characterized by high E2F expression, including small cell lung cancer, triple negative breast cancer, ER-low breast cancer, and HR-positive breast cancer following a CDK 4/6-inhibitor. The IND submission includes comprehensive data from preclinical studies which have demonstrated a safety, efficacy, and pharmacokinetic profile of CID-078 to support the proposed phase 1 trial."

IND • New P1 trial • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer

Compelling Data in Breast Cancer Treatment with First-In-Class Cyclin A/B Inhibitor Presented at 2023 AACR-NCI-EORTC International Conference (Businesswire) - "Circle Pharma...recently unveiled preclinical data demonstrating the efficacy of Circle’s oral Cyclin A/B inhibitor macrocycles in patient-derived breast cancer tumor models. This significant development was presented at the 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....Most notably, multiple triple-negative breast cancer (TNBC) cell lines and luminal B breast cancer cell lines displayed sensitivity to Cyclin A/B inhibition. These findings were instrumental in selecting TNBC and luminal breast cancer patient-derived tumor models for subsequent in vivo efficacy studies....Circle Pharma plans to file an investigational new drug (IND) application for its Cyclin A/B inhibitor clinical candidate, CID-078, with the U.S. Food and Drug Administration (FDA) and initiate clinical development in 2024."

IND • Preclinical • Triple Negative Breast Cancer

Circle Pharma Announces Upcoming Presentation at 2023 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "Circle Pharma...announced an upcoming poster presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, taking place from October 11-15, 2023, in Boston, MA."

Preclinical • Breast Cancer • Oncology