Circle Pharma files first Investigational New Drug application for first-in-class oral cyclin A/B RxL inhibitor for treatment of advanced solid tumors

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Circle Pharma, a leader in macrocycle drug discovery and development, 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. This milestone marks a significant advancement in the development of novel drug candidates generated by Circle’s proprietary MXMO™ platform for difficult-to-drug targets in oncology and other serious illnesses.

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.

CID-078 is designed to selectively inhibit key protein-to-protein interactions involving cyclins A and B, which are implicated in the proliferation and survival of cancer cells. Cyclins are a family of proteins that function as master regulators of the cell cycle. Early work in the laboratory of Nobel Laureate and Circle Pharma’s Scientific Advisory Board Chair William G. Kaelin Jr., MD, showed that disrupting the function of cyclins in certain types of cancer cells that had dysregulated cell cycle control was synthetic lethal – meaning that these cancer cells were selectively killed while the viability of normal cells was unaffected.¹ The mechanism of action of CID-078 offers a novel therapeutic approach to potentially address unmet medical needs in patients with advanced solid tumors who currently have limited therapeutic choices.

“I am proud that we have reached this critical milestone in the development of CID-078,” said David J. Earp, CEO of Circle Pharma. “Our team has worked diligently to advance this promising candidate from discovery through preclinical development. The IND filing represents a major step forward in our mission to harness the power of macrocycle therapies to create effective treatments for cancer and other serious illnesses.”

“We believe, based on our preclinical data package, that CID-078 has the potential to provide a transformative therapeutic option for patients with cancer,” said Michael Cox, PharmD, MHSc, BCOP, head of Early Development and senior vice president. “We are excited to advance CID-078 into clinical studies. This step underscores our commitment to develop innovative therapeutics that target challenging and previously undruggable proteins.”

Pending regulatory approval, Circle Pharma plans to initiate a phase 1 clinical trial of CID-078 in patients with advanced solid tumor malignancies. The dose escalation and dose expansion portions of the trial will evaluate safety, tolerability, and pharmacokinetics, as well as anti-tumor activity as assessed by objective response rate and duration of response.

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’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 xenograft models.

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.

¹ Chen et al., PNAS 96, 4235 (1999)​