Oral macrocyclic cyclin D1 RxL inhibition demonstrates potent and selective disruption of cyclin D1–Rb interaction with robust anti-tumor activity in multiple cancer models
Nomination of development candidate expected by year-end 2025
SOUTH SAN FRANCISCO, CA, October 23, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, today presented preclinical data related to the company’s cyclin D1 development program at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. The data highlight the therapeutic potential of Circle Pharma’s first-in-class oral macrocyclic inhibitors to preserve retinoblastoma protein (Rb) tumor-suppressor activity by selectively blocking its interaction with cyclin D1, a key driver of cell cycle progression and proliferation in multiple hematological and solid tumor cancer types.
“Cyclin D1 has long been recognized as a key driver in many cancers, but it has remained an elusive direct therapeutic target,” said Marie Evangelista, Ph.D., senior vice president and head of cancer biology at Circle Pharma. “Using our MXMO™ platform, we have engineered orally bioavailable, cell-permeable macrocycles that selectively inhibit cyclin D1-Rb binding while sparing related isoforms such as cyclin D3—an approach aimed at reducing hematologic toxicities commonly observed with dual CDK4/6 inhibitors. These data mark a significant step forward in developing novel, macrocycle-based therapies for patients with cyclin D1-driven cancers.”
“We are excited by the strong selectivity and anti-tumor activity we’re seeing across multiple cyclin D1-driven cancer models including mantle cell lymphoma and ER-positive breast cancer,” said David J. Earp, J.D., Ph.D., president and chief executive officer of Circle Pharma. “Our approach has the potential to open a new class of therapeutics for patients, including for use in combination with other therapies, and we are on track to declare a development candidate for our cyclin D1 program by end of 2025.”
Presentation Highlights:
In cyclin D1-dependent preclinical tumor models, Circle’s oral macrocyclic cyclin D1 RxL inhibitors:
The poster presentation will be made available on the Circle Pharma website at https://circlepharma.com/publications.
About Circle Pharma’s Oral Cyclin D1 RxL Inhibitor Program
Cyclin D1 is a regulatory protein that plays a crucial role in cell cycle progression and is overexpressed in many solid tumors and hematologic malignancies. In these cancers, the cyclin D1/CDK4 complex drives cell proliferation by binding to the tumor suppressor retinoblastoma protein (Rb) and promoting its phosphorylation and inactivation. Using its MXMO™ platform, Circle Pharma has developed oral macrocyclic inhibitors that potently and selectively disrupt the cyclin D1-Rb interaction, demonstrating robust anti-tumor activity in cyclin D1-driven cancers.
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB
SOUTH SAN FRANCISCO, CA, October 14, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, today announced an upcoming poster presentation highlighting the preclinical anti-tumor potential of cyclin D1 RxL inhibition at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, being held from October 22 – 26, 2025, in Boston, MA.
Details of the presentation are as follows:
Title: First-in-class Oral Macrocyclic Cyclin D1-selective Inhibitors Demonstrate Anti-Tumor Activity in Cyclin D1-dependent Tumors
Session: Poster Session A
Date & Time: Thursday, October 23, 12:30-4:00 p.m. ET
About Circle Pharma’s Oral Cyclin D1 RxL Inhibitor Program
Cyclin D1 is overexpressed in certain solid tumors and hematologic malignancies. In these cancers, the cyclin D1/CDK4 complex drives cell proliferation by binding to the tumor suppressor retinoblastoma protein (Rb) and promoting its phosphorylation and inactivation. Using its MXMO™ platform, Circle Pharma has developed oral macrocyclic inhibitors that potently and selectively disrupt the cyclin D1-Rb interaction, demonstrating robust anti-tumor activity in cyclin D1-driven cancers.
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB
AACR25_CMayoh_Poster_CirclePharma_final
SOUTH SAN FRANCISCO, CA, September 25, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, today announced an upcoming poster presentation highlighting the potential of CID-078 as a novel therapeutic option in pediatric cancers at the American Association for Cancer Research (AACR) Special Conference on Pediatric Cancer, taking place from September 25-28 in Boston, MA. CID-078 is a first-in-class, orally bioavailable macrocyclic cyclin A/B RxL inhibitor that is currently being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors.
The presentation, based on a collaboration between Circle Pharma and Children’s Cancer Institute (Sydney, Australia), 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 in a database of pediatric tumor samples from The ZERO Childhood Cancer Precision Medicine Program.
“We believe CID-078 may represent a promising new therapeutic option for pediatric cancers with certain defined molecular drivers,” said Michael C. Cox, PharmD, MHSc, BCOP, senior vice president and head of early development at Circle Pharma. “These findings may inform strategies for real-time patient identification and stratification in potential future pediatric studies of CID-078. Presenting these data generated in collaboration with Children’s Cancer Institute during Childhood Cancer Awareness Month reinforces our commitment to advancing the development of our therapies for patients who urgently need new options.”
Details of the presentation are as follows:
Title: Investigating the Cyclin A/B RxL Inhibitor CID-078 in Pediatric Cancers with RB1 Loss and High E2F1
Abstract Number: B021
Session: Poster Session B
Date & Time: Friday, September 26, 5:00-7:00 p.m. ET
Presenting Author: Chelsea Mayoh, Children’s Cancer Institute, Lowy Cancer Centre, UNSW Sydney, Kensington, Australia
About CID-078, Circle Pharma’s Oral Cyclin A/B RxL Inhibitor Program
CID-078 is an orally bioavailable macrocycle with dual activity blocking protein-protein interactions between both cyclins A and B and key substrates that bind to them via conserved RxL motifs. CID-078 selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation, including alterations in the tumor suppressor RB1. In pre-clinical 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 with advanced solid tumors harboring RB1 alterations.
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB
SOUTH SAN FRANCISCO, CA, September 9, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for difficult-to-treat cancers, today announced an agreement with Eli Lilly and Company (Lilly) that enables the company to use Lilly TuneLab, a pioneering artificial intelligence and machine learning (AI/ML) platform designed to accelerate the development of new medicines by providing biotech companies access to powerful drug discovery models that have been trained on Lilly’s proprietary research data.
Circle Pharma will leverage Lilly TuneLab to further strengthen its AI/ML capabilities and proprietary MXMO™ platform, which is designed to overcome key challenges in macrocycle drug development to enable the creation of intrinsically cell-permeable and orally bioavailable macrocycle therapies, including for historically undruggable targets. Circle Pharma’s lead program, CID-078, is a first-in-class, orally bioavailable cyclin A/B RxL inhibitor that is being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors.
“We are thrilled to partner with Lilly and gain access to TuneLab,” said Constantine Kreatsoulas, Ph.D., senior vice president, head of discovery technology sciences at Circle Pharma. “This collaboration will further enhance our MXMO™ platform, which enables us to better predict how various types of macrocycles may be able to penetrate cells, show oral bioavailability, exhibit desirable drug-like properties, and be manufactured at scale. This collaboration comes at an important time of growth at Circle Pharma with our lead program, CID-078, now in clinical development and our preclinical pipeline advancing rapidly to address cyclins and other historically undruggable targets in oncology.”
This agreement is part of the Lilly Catalyze360 model, a comprehensive approach to empower early-stage biotechs to advance groundbreaking science by providing access to capital, cutting-edge lab space and technology, and drug development talent and resources.
About Circle Pharma’s MXMO™ platform
Circle Pharma’s proprietary MXMO™ platform combines computationally driven drug design along with advanced, fully synthetic macrocycle chemistry. Through this platform, Circle Pharma’s scientists screen vast permeability-biased physical and virtual macrocycle libraries to identify early hit compounds. Artificial Intelligence (AI), Machine Learning (ML), and rigorous physics-based simulations are used to assess many designs simultaneously and to rapidly explore structure-activity relationships for hit-to-lead progression. These diverse compounds are then synthesized in the lab, utilizing both natural and unnatural chemical building blocks, many of which are custom and proprietary to Circle Pharma, to evaluate them as lead investigational macrocycles.
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB
SOUTH SAN FRANCISCO, CA, September 2, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for difficult-to-treat cancers, today announced that management will participate in two upcoming investor conferences:
Morgan Stanley 23rd Annual Healthcare Conference
1X1 Meetings: Monday, September 8, 2025
Location: New York, NY
Oppenheimer Life Sciences Private Company Showcase
1X1 Meetings: Thursday, September 25, 2025
Location: Virtual
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB
https://www.nature.com/articles/s41586-025-09433-w
Research uncovers how inhibiting interactions between cyclin A and cyclin B and their key binding partners, E2F and MYT1, selectively kills E2F-high tumor cells
Circle Pharma’s oral first-in-class cyclin A/B RxL inhibitor program, CID-078, is advancing in Phase 1 clinical development for patients with advanced solid tumors
Publication underscores potential of Circle Pharma’s MXMO™ platform to enable creation of oral, cell-permeable macrocycle therapies, including for historically undruggable targets such as cyclins, with applicability across significant cancer patient populations
SOUTH SAN FRANCISCO, CA, August 20, 2025 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for difficult-to-treat cancers, today announced a Nature publication describing robust pre-clinical tumor suppression and novel mechanistic insights from inhibiting the binding of certain protein substrates (that bind via RxL motifs) to cyclins A and B in E2F-high tumor cells. Circle Pharma’s oral cyclin A/B RxL inhibitor, CID-078, is a first-in-class, orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that is being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors.
Cyclins (including cyclins A and B) are a family of proteins that function as master regulators of the cell cycle by binding to and activating their catalytic partners, the cyclin-dependent kinases (CDKs). Cancers driven by high E2F activity, such as small cell lung cancer (SCLC) and other tumors with RB1 alterations, have an overactive cell cycle that leads to uncontrolled tumor cell proliferation. In preclinical models, cyclin A/B RxL inhibitors:
The publication, which was co-authored by scientists from Circle Pharma and the Dana-Farber Cancer Institute, Harvard Medical School, the University of Texas Southwestern Medical Center, and the University of Oxford, can be accessed here (doi: 10.1038/s41586-025-09433-w).
“We are excited to have the novel biology and compelling anti-cancer effects of the cyclin A/B RxL inhibitors developed at Circle recognized within the broader scientific community through this publication in Nature,” said David J. Earp, J.D., Ph.D., president and chief executive officer of Circle Pharma. “This work underscores the capabilities of our MXMO™ platform to generate oral, cell-permeable macrocycle therapies, such as CID-078, including for historically undruggable targets such as cyclins. With our first-in-human Phase 1 study of CID-078 well underway, we are eager to see the innovative research outlined in this publication translate into new, high-impact therapeutic options for people living with cancer.”
“These findings build upon previous work and reveal additional gain-of-function mechanisms through which cyclin A/B RxL inhibition triggers apoptosis in cancer cells, further supporting this approach for E2F-driven cancers, such as cancers with RB1 alterations, which includes nearly all SCLCs, up to half of triple-negative breast cancers, and subsets of other solid tumors,” said Matthew G. Oser, M.D., Ph.D., senior author of the publication and associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School. “Circle Pharma’s cell-permeable, oral macrocycles are designed to overcome the limitations of other therapeutic modalities and are ideally positioned to access cyclins and other historically undruggable targets, offering exciting potential for patients with cancer.”
About CID-078, Circle Pharma’s Oral Cyclin A/B RxL Inhibitor Program
CID-078 is an orally bioavailable macrocycle with dual activity blocking protein-protein interactions between both cyclins A and B and key substrates that bind to them via conserved RxL motifs. CID-078 selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation, including alterations in the tumor suppressor RB1. In pre-clinical 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 with advanced solid tumors harboring RB1 alterations.
About Circle Pharma
Circle Pharma is a clinical-stage biopharmaceutical company harnessing the power of macrocycles to develop next-generation targeted therapies for cancer and other serious illnesses. The company’s proprietary MXMO™ platform overcomes key challenges in macrocycle drug development, enabling the creation of intrinsically cell-permeable and orally bioavailable therapies, including for historically undruggable targets. Circle Pharma’s pipeline is focused on targeting cyclins, key regulators of the cell cycle that drive many cancers. The company’s lead program, CID-078, is a cyclin A/B RxL inhibitor in Phase 1 clinical development for patients with advanced solid tumors. Circle Pharma is based in South San Francisco, CA. For additional information, please visit us at circlepharma.com and follow us on LinkedIn and X.
Contacts:
Media:
Josie Butler
1AB
Investors:
Steve Klass
1AB