SOUTH SAN FRANCISCO, Calif. – September 16, 2024 – Circle Pharma, Inc., a clinical-stage biopharmaceutical company dedicated to discovering and developing cell-permeable macrocycles as a new class of therapies, today announced two executive appointments as it continues to advance its MXMO macrocycle discovery platform and its oncology pipeline. Marie Evangelista, Ph.D., has been appointed Senior Vice President and Head of Cancer Biology, while Constantine Kreatsoulas, Ph.D., has been promoted to Senior Vice President and Head of Discovery Technology Sciences. These appointments align with Circle’s investments in its pipeline of macrocycle therapies, including its lead program, CID-078, currently being evaluated in a Phase 1 clinical trial in solid tumors.
“These two senior executive appointments deepen Circle’s drug discovery expertise and scientific leadership” said David J. Earp, JD, Ph.D., Circle’s president and CEO. “With Circle’s first oral macrocycle, CID-078, now in the clinic, we are keen to deploy our MXMO platform against a wide range of new targets as we drive to expand our pipeline. I look forward to working closely with Marie and Constantine as they lead our discovery teams to bring more first-in-class medicines to the clinic.”
Dr. Evangelista has more than 18 years of experience in translational oncology and small molecule drug discovery, having successfully led programs from early discovery to clinical development. Prior to joining Circle, she spent 15 years at Genentech where her leadership was instrumental in advancing Genentech’s KRAS-targeting programs. Following Genentech, Dr. Evangelista held senior leadership roles at Frontier Medicines and most recently at Recursion. Dr. Evangelista holds a Ph.D. in cell and molecular biology from Queen’s University in Ontario, Canada.
“I’m excited to join Circle at this important juncture, where its innovative macrocycle platform is translating into clinical progress,” said Dr. Evangelista. “I look forward to contributing to the development of transformative therapies for patients.”
Dr. Kreatsoulas has played a pivotal role at Circle Pharma since joining in 2021, overseeing the development of the MXMO platform and contributing to the advancement of CID-078 into the clinic. Before joining Circle Pharma, he held leadership roles at GlaxoSmithKline (GSK), Merck & Co., and Bristol-Myers Squibb, with expertise in molecular design, machine learning, and computational toxicology. He earned his Ph.D. in Chemistry from Princeton University and a master’s degree in Regulatory Affairs and Quality Assurance from Temple University.
“Being a part of Circle’s evolution to a clinical-stage company has been incredibly rewarding,” said Dr. Kreatsoulas. “I am very excited to step into the role of Head of Discovery Technology Sciences as we continue to advance our ground-breaking macrocycle technologies.”
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. The company’s lead candidate, CID-078, is currently in clinical trials as part of a growing pipeline of novel macrocycle therapeutics.
To learn more about Circle Pharma, please visit www.circlepharma.com.
Media Contact:
Roslyn Patterson
Director of Corporate Communications
Phone: 650.825.4099
Email: roslyn.patterson@circlepharma.com
SOUTH SAN FRANCISCO, Calif. – (BUSINESS WIRE) – Circle Pharma, a clinical-stage biopharmaceutical company dedicated to discovering and developing cell-permeable macrocycle therapies, today 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. The data suggest that CID-078 holds promise as a monotherapy for patients with these cancers, which will be evaluated in a phase 1 clinical trial.
The digital poster can be viewed here.
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 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.
Media Contact:
Roslyn Patterson
650.825.4099
roslyn.patterson@circlepharma.com
SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Circle Pharma, a clinical-stage biopharmaceutical company dedicated to discovering and developing cell-permeable macrocycles as a new class of therapies, today 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.
“We are grateful for the continued support of such a strong syndicate of investors as we advance our pioneering work in macrocycle therapeutics,” said David Earp, JD, Ph.D., CEO of Circle Pharma. “This financing not only enables us to progress CID-078 through critical stages of clinical development but also allows us to further advance our pipeline of innovative therapies targeting cancer and other serious diseases.”
With this latest round of funding, Circle Pharma is well positioned to advance its mission of creating effective treatments for cancer and other serious illnesses.
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.
Contacts
Roslyn Patterson
650.825.4099
roslyn.patterson@circlepharma.com
Read original article at Business Wire
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)
Contacts
Roslyn Patterson
650.825.4099
roslyn.patterson@circlepharma.com
Read original article at Business Wire
SAN FRANCISCO–(BUSINESS WIRE)–Circle Pharma, in collaboration with the laboratory of Violeta Serra, Ph.D., at Vall d’Hebron Institute of Oncology (VHIO) in Barcelona, Spain, 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.
The study in 40 breast cancer cell lines identified an association between hallmark pathway scores in E2F, G2/M, and mitotic spindle pathways and sensitivity to Cyclin A/B inhibition. 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. In these in vivo studies, oral administration of Circle’s Cyclin A/B inhibitor led to substantial tumor regression in both TNBC and luminal breast cancer models, with complete response observed in a luminal B breast cancer model derived from a patient whose tumor had previously progressed following multiple treatments, including with a CDK4/6 inhibitor.
Breast cancer is the second leading cause of cancer-related deaths in women globally. Triple negative breast cancer, which accounts for 10-20% of all breast cancer cases, is an aggressive and challenging subtype of breast cancer, associated with poor prognosis and high risk of relapse1. Because TNBC lacks specific receptors (estrogen, progesterone, or HER2) that some other breast cancers have, many newer therapies used to target these receptors in other forms of breast cancer are not effective. Luminal breast cancers are hormone receptor-positive and generally less aggressive than TNBC. Luminal breast cancers can be further divided into two subtypes: luminal A (HR+/ER+/HER2+) and luminal B (HR+/PR+/HER2-). These two subtypes make up about 70% of all breast cancer cases2.
Dr. Serra expressed optimism about the results, stating, “The responses in both TNBC and luminal breast cancer models are very compelling, and we look forward to evaluating the effects of these first-in-class Cyclin A/B inhibitors in additional models in future studies.”
“October is breast cancer awareness month; at Circle our mission is to bring new therapies and new hope to patients who have limited treatment options, and this new research indicates that we may have an opportunity to do just that for patients with breast cancer. We will work assiduously to bring this first-in-class therapy to patients,” said David J. Earp, JD, PhD, Circle Pharma’s chief executive officer.
Building on the success demonstrated in small cell lung cancer and ovarian cancer models, 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.
ABOUT CIRCLE PHARMA’S CYCLIN A/B INHIBITOR PROGRAM
Circle Pharma has developed an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types. In biochemical and cellular studies, Circle’s Cyclin A/B inhibitor has been shown to potently and selectively disrupt the protein-protein interaction between Cyclins A and B and their key substrates, including E2F (a substrate of Cyclin A) and Myt1 (a substrate of Cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B inhibitors to cause pronounced tumor regression in multiple xenograft models. Circle Pharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for its clinical candidate, CID-078, and initiate clinical development in 2024.
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 first-in-class macrocycle therapeutics 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 American Society of Clinical Oncology. (2017 May) Triple-Negative Breast Cancer: Current Practice and Future Directions. Ricardo L.B. Costa and William J. Gradishar.
2 Nature. (2000; 406) Molecular portraits of human breast tumours. Perou CM, Sorlie T, Eisen MB, et al.
Contacts
About Circle Pharma
Media Contact:
Roslyn Patterson
650.825.4099
Info@povconsultantgroup.com
Read original article at Business Wire
SAN FRANCISCO–(BUSINESS WIRE)– Circle Pharma, a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles, today 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.
Details of the presentation are as follows:
Title: Novel orally bioavailable macrocycles that target cyclin A and B elicit antitumor activity in breast cancer patient-derived xenograft models
Presenter: Mariana Paes Dias, Vall d’Hebron Institute of Oncology, Barcelona, Spain
Abstract Number: LB_C04
Session: Poster Session C
Date/Time: Saturday, Oct 14 12:30-4:00pm
ABOUT CIRCLE PHARMA’S CYCLIN A/B INHIBITOR PROGRAM
Circle Pharma has developed an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types. In biochemical and cellular studies, Circle’s cyclin A/B inhibitor has been shown to potently and selectively disrupt the protein-protein interaction between Cyclins A and B and their key substrates, including E2F (a substrate of Cyclin A) and Myt1 (a substrate of Cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B inhibitors to cause pronounced tumor regression in multiple xenograft models. Circle Pharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for its clinical candidate, CID-078, and initiate clinical development in 2024.
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 first-in-class macrocycle therapeutics 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 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.
Circle Pharma Media Contact:
Roslyn Patterson
650.825.4099
info@povconsultantgroup.com
Read original article at Business Wire
SAN FRANCISCO–(BUSINESS WIRE)–Circle Pharma, a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles, announced today the appointments of Michael Cox, PharmD., MHSc, BCOP as senior vice president, head of Early Development, and Edward Garmey, M.D., as its new consulting chief medical officer. These additions to the leadership team further bolster Circle Pharma’s capabilities in oncology drug development as it advances its Cyclin A/B inhibitor program into clinical studies.
“We are thrilled to welcome Michael and Edward to Circle Pharma. Their exceptional backgrounds and deep expertise in clinical development and medical affairs will be instrumental in accelerating our efforts to develop groundbreaking oncology therapeutics. We look forward to their contributions as we advance our lead program into the clinic and continue to drive innovation in cancer treatment,” said David Earp, president and CEO of Circle Pharma. “We are in a period of dynamic growth as we prepare to advance our Cyclin A/B inhibitor into clinical studies. With the leadership and expertise of Michael and Edward, the company is well-positioned to bring its transformative macrocycle therapeutics to patients.”
Dr. Michael Cox will play a crucial role in driving the company’s clinical development mission, providing strategic leadership, and overseeing the execution of early-stage clinical programs. He has held key leadership positions in oncology drug development, including serving as vice president, Clinical Development at Day One Biopharmaceuticals, Inc., where he successfully led global oncology programs across all stages of development, including leading the development and regulatory strategy for tovorafinib, an investigational pan-RAF kinase inhibitor that has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration. Previously, Dr. Cox was the executive director of Pediatric Clinical Development and Medical Affairs at Loxo Oncology Inc. (acquired by Eli Lilly and Co.) and contributed to the development of multiple oncology assets including larotrectinib, selitrectinib and selpercatinib. Earlier in his career, he held roles at Bayer Healthcare AG, Merck KGaA, and Amgen.
Dr. Cox holds a Master’s of Health Science in Clinical Research from Duke University, a Doctorate of Pharmacy from Ohio Northern University, and completed post-graduate training at the National Cancer Institute, the University of Pittsburgh Medical Center, and Mission Hospital in Asheville, North Carolina.
In addition to Dr. Cox’s appointment, Circle Pharma is pleased to welcome Edward Garmey, M.D., as the new consulting Chief Medical Officer. Dr. Garmey will provide clinical strategy leadership and medical expertise, guiding the clinical development of the company’s pipeline programs and fostering strong partnerships with key stakeholders. He is a highly regarded former academic hematologist-oncologist with over 17 years of experience in the biopharmaceutical industry. Dr. Garmey has served as Chief Medical Officer and Senior Vice President at Cerulean Pharma, where he led the initiation of multi-national clinical trials for multiple drug programs and played a key role in the company’s successful IPO. Earlier in his career, he was the Vice President of Clinical Development at ArQule.
Dr. Garmey is an alumnus of Harvard and New York Universities and completed medical training at Mount Sinai Medical Center, the Children’s Hospital of Los Angeles and Memorial Sloan-Kettering Cancer Center. He also undertook research fellowships at the National Institutes of Health and the Botswana-Harvard Partnership for H.I.V. Research.
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 first-in-class macrocycle therapeutics 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 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.
Contacts
Circle Pharma Media Contact:
Roslyn Patterson
650.825.4099
info@povconsultantgroup.com
Read original article at Business Wire
SAN FRANCISCO, Calif., July 19, 2023— Circle Pharma, a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles, announced today the selection of CID-078 for its first clinical development program. CID-078 is the first-and-only-in-class dual inhibitor of Cyclins A and B, which play essential roles in regulating cell cycle progression. Inhibiting Cyclins A and B selectively induces synthetic lethality in certain cancers exhibiting cell cycle dysregulation while sparing healthy cells.
Circle Pharma recently presented pre-clinical data for its dual Cyclin A/B inhibitors at this year’s American Association for Cancer Research (AACR) Annual Meeting. The data demonstrated activity across a wide range of human tumor cell lines including tumor regression in xenograft models of small cell lung carcinoma (SCLC) and ovarian cancer. SCLC has a five-year survival rate of 3.5%, and its treatment has seen minimal progress in the last 30 years. Ovarian cancer patients commonly face poor outcomes and resistance to the current standard of care. In advance of human clinical trials for CID-078, further preclinical studies using patient-derived models (PDX) are underway in breast cancer (including triple negative breast cancer), non-small cell lung cancer, gastric cancer, pancreatic cancer, and other tumor types.
“The selection of CID-078 represents a major milestone for our team; we are excited to advance this molecule into clinical development and to realize its potential to bring new hope for the many cancer patients who currently have woefully inadequate treatment options,” said David Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma. “This achievement is also a reflection of the capabilities of our macrocycle discovery platform as the cyclins have until now been considered undruggable.”
ABOUT CID-078
CID-078 is an orally bioavailable macrocycle with dual cyclin A and B inhibitory activity that drives synthetic lethality in multiple tumor types. In biochemical and cellular studies, CID-078 has been shown to potently and selectively disrupt the protein-protein interaction between Cyclins A and B and their key substrates, including E2F (a substrate of Cyclin A) and Myt1 (a substrate of Cyclin B). Preclinical studies have demonstrated the ability of CID-078 to cause pronounced tumor regression in multiple xenograft models. Circle Pharma plans to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) for CID-078 and initiate clinical development in 2024.
ABOUT CIRCLE PHARMA’S MACROCYCLE THERAPEUTICS
Macrocycles are a class of molecules that have properties outside of the conventional “rule of five” for oral small molecule drugs. They have the potential to address important therapeutic targets, such as protein-protein interactions, that are refractory to other drug classes, but their larger size and chemical complexity present additional challenges to drug developers. Circle Pharma’s proprietary technology platform, MXMO™, introduces a highly differentiated ability to develop precision macrocycle therapeutics that are passively cell-permeable and orally bioavailable. Circle Pharma’s macrocycles also have desirable pharmacokinetics, are exquisitely selective, and can be directed to both intra- and extra-cellular therapeutic targets.
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 first-in-class macrocycle therapeutics 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 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.
Circle Pharma Media Contact:
Roslyn Patterson
650.825.4099
info@povconsultantgroup.com
Read original article at Business Wire
SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Circle Pharma announced today that two poster presentations at the American Association for Cancer Research (AACR) Annual Meeting held April 14-19, in Orlando, Florida, highlight promising pre-clinical data of its first-in-class orally bioavailable macrocyclic cyclin A/B inhibitors targeting intractable cancers. Circle expects to advance its cyclin A/B inhibitor program into IND-enabling studies later this year and subsequently into clinical development for testing in a range of cancer types, including SCLC.
The data presented by Circle Pharma shows activity across a wide range of human tumor cell lines and tumor regression in xenograft models of small cell lung carcinoma (SCLC) and ovarian cancer. Pre-clinical development of orally bioavailable macrocycles with dual cyclin A and B inhibitory activity drive synthetic lethality in multiple tumor types. The compounds are shown to be well-tolerated in mice with no observed body weight loss, neutropenia, or depletion of bone marrow across all dose regimens. In vitro studies showed that target engagement in cells leads to displacement of E2F1 from Cyclin A:CDK2 and Myt1 from Cyclin B:CDK1, and the compounds induce DNA damage, G2/M arrest, and apoptosis. The presentation further showed that sensitivity in SCLC cell lines is correlated with RB dysfunction and E2F1 target gene expression.
In addition, studies conducted by the laboratory of Matthew Oser at Dana Farber Cancer Institute (DFCI) validate that cyclin A/B inhibitors induce mitotic arrest and apoptosis in SCLC cell lines. The researchers deployed a genome wide CRISPR/Cas9 positive selection screen to identify that activation of the mitotic spindle assembly checkpoint (SAC) complex by the kinase MSP1 is a dominant mechanism for selective cancer cell killing by the cyclin A/B inhibitors. Dr. Oser’s laboratory at DFCI was sponsored by Circle Pharma.
| Program | Presentation Details |
|---|---|
| Cyclin A/B | Abstract Number: 1559 Abstract Title: Mechanisms responsible for hypersensitivity of small cell lung cancers to novel cyclin A/B RxL macrocyclic peptide inhibitors Session Title: Experimental and Molecular Therapeutics Session Type: Poster |
| Cyclin A/B | Abstract Number: 1560 Abstract Title: Orally bioavailable macrocycles that target cyclins A and B RxL motifs cause tumor regression in xenograft models and in vitro show activity across multiple cancer types Session Title: Experimental and Molecular Therapeutics Session Type: Poster |
About Circle Pharma, Inc.
Circle is a biopharmaceutical company advancing the discovery and development of intrinsically cell-permeable macrocycles that can be delivered by multiple routes, including oral administration. Circle’s MXMO™ platform combines structure-based rational drug design and advanced synthetic chemistry to develop first-in-class macrocycle therapeutics for challenging targets to address unmet clinical needs. Circle’s macrocycle can address both intra- and extra-cellular therapeutic targets and is applicable across a wide range of serious diseases; the company is initially focusing its development efforts on intracellular protein-protein interactions that are key drivers in cancer but have remained elusive to other treatment modalities. Circle is headquartered in South San Francisco and has raised $160 million to date from leading life sciences investors including The Column Group, Nextech, Pfizer and Eli Lilly.
To learn more about Circle Pharma please visit www.circlepharma.com.
Contacts
Circle Pharma Media Contact:
Eleanor Lim
650.825.4099
info@circlepharma.com
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