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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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SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Circle Pharma, a company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, has appointed Stephen Kelsey as an independent member of its Board of Directors. Dr. Kelsey has extensive experience in oncology clinical development. He currently serves as president, head of research and development and chief medical officer at Revolution Medicines (NASDAQ:RVMD), and previously held roles including president of Onkaido Therapeutics, the oncology-focused unit of Moderna (NASDAQ:MRNA), senior vice president of new products at Medivation (acquired by Pfizer (NYSE:PFE)), executive vice president and chief medical officer at Geron Corporation (NASDAQ:GERN), vice president of oncology at Genentech (part of the Roche Group) and medical director at Pharmacia / SUGEN (acquired by Pfizer). Dr. Kelsey has had key roles in the development of many oncology therapeutics including Sutent®, Perjeta®, Kadcycla®, Erivedge® and imetelstat.
“I’m delighted to welcome Steve to our Board,” said David J. Earp, JD, PhD, Circle’s president and CEO. “We expect to initiate IND-enabling studies in our lead program, an orally bioavailable cyclin A inhibitor, in 2023, and are building the clinical team that will support this program as it enters clinical development. In parallel, we are progressing our pipeline of other targeted oncology therapeutics. Steve has extensive experience in early oncology clinical development, including building successful development teams, and I look forward to working with him closely as Circle progresses to become a clinical-stage company.”
“Circle’s macrocycle platform offers a new approach to important oncology targets that have proven refractory to other modalities, and I have been impressed by the quality of the pre-clinical work and the broad clinical potential of the company’s lead cyclin A program,” noted Dr. Kelsey. “I’m excited to join Circle’s Board and to help the company bring its promising therapies to cancer patients.”
Dr. Kelsey received his medical degrees from the University of Birmingham in the UK and trained as a hematologic oncologist at Barts and The London Hospital where he was a clinician-scientist focused in leukemias and lymphomas.
About Circle Pharma, Inc.
Circle is a pre-clinical stage company deploying a platform that 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 technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform 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. Its pipeline targets include cyclin proteins, including cyclins A and E, which are part of the regulatory machinery that controls progression of cells through the cell cycle. Inhibition of cyclin A has been reported to be synthetic lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.
Contacts
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Circle Pharma, a company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, has appointed Paul Park, MBA, as its Chief Business Officer. Mr. Park has extensive business development experience in life sciences in prior roles including vice president of business development at Ionis Pharmaceuticals, head of strategic partnerships at Aetion and various roles in international licensing, strategy and corporate development at Amgen. He joins the leadership team at Circle as the company is advancing its lead program, an orally bioavailable Cyclin A inhibitor, towards the clinic and applying its macrocycle platform to expand its pipeline which includes other targeted oncology therapeutics.
“Paul has a strong record of leading deals including large pharma partnerships, major M&A transactions, licensing and financings, as well as strategic corporate development experience,” noted David J. Earp, JD, PhD, Circle’s president and CEO. “We’re delighted to welcome him at an exciting time: our lead program is moving towards the clinic in a target space – cyclins and cyclin dependent kinases – that is generating a lot of interest, and we are growing our pipeline.”
“I’ve been impressed by the capabilities of Circle’s macrocycle platform to address key challenges that have stymied macrocycle drug developers, including achieving robust cell permeability and oral bioavailability, as exemplified by the company’s Cyclin A program,” noted Mr. Park. “I am looking forward to helping the Circle team to harness the platform against other challenging targets that will hopefully yield new treatment options for patients with unmet medical needs.”
Mr. Park led the Ionis team that orchestrated numerous significant transactions including most recently the co-development and co-commercialization deal with AstraZeneca for eplontersen, the spin-out of Ionis’ oncology portfolio to Flamingo Therapeutics, and in-licensing transactions with Bicycle Therapeutics and Genuity Sciences. Earlier in his career at Amgen he played key roles in the acquisitions of Tularik and Immunex. He obtained an AB in health and society from Brown University and an MBA in healthcare management from The Wharton School.
About Circle Pharma, Inc.
Circle is a pre-clinical stage company deploying a platform that 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 technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform 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. Its pipeline targets include cyclin proteins, including cyclins A and E, which are part of the regulatory machinery that controls progression of cells through the cell cycle. Inhibition of cyclin A has been reported to be synthetic lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.
Contacts
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
The Company’s presentation provided details of its progress towards structure-guided macrocycles that inhibit the protein-protein interaction between the cyclin A:CDK2 complex and key substrates that are phosphorylated by this complex. Inhibition of Cyclin A substrate binding has been postulated to be synthetic lethal in Rb mutated cancers. The data presented included evidence that macrocycle inhibitors of cyclin A induce G2/M arrest and apoptosis in small cell lung cancer (SCLC) cell lines and have anti-tumor efficacy in SCLC xenograft animal models. Circle plans to advance its cyclin A inhibitor program to the clinic for testing in a range of cancer types, including SCLC where Rb mutations are highly prevalent.
The presentation was made as part of the Mechanisms of Drug Action / Experimental and Molecular Therapeutics session at the AACR meeting, Abstract No. 5379.
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SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Circle Pharma, a pre-clinical stage company focused on developing macrocycle therapeutics against targets previously considered to be undruggable, will present a poster at the American Association for Cancer Research (AACR) Annual Meeting being held April 8-13, in New Orleans, Louisiana.
The Company’s presentation will provide details of its progress towards structure-guided macrocycles that inhibit the protein-protein interaction between the cyclin A:CDK2 complex and key substrates that are phosphorylated by this complex. Inhibition of Cyclin A substrate binding has been postulated to be synthetic lethal in Rb mutated cancers. The data presented include evidence that macrocycle inhibitors of cyclin A induce G2/M arrest and apoptosis in small cell lung cancer (SCLC) cell lines and have anti-tumor efficacy in SCLC xenograft animal models. Circle plans to advance its cyclin A inhibitor program to the clinic for testing in a range of cancer types, including SCLC where Rb mutations are highly prevalent.
The presentation will be made as part of the Mechanisms of Drug Action / Experimental and Molecular Therapeutics session at the AACR meeting, Abstract No. 5379.
About Circle Pharma, Inc.
Circle is a pre-clinical stage company deploying a platform that 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 technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform 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. Its lead programs target cyclin proteins, including cyclins A and E, which are part of the regulatory machinery that controls progression of cells through the cell cycle. Inhibition of cyclin A has been reported to be synthetic lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.
Contacts
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
South San Francisco, CA, July 12, 2021, — Evelyn Wang, PhD has joined Circle Pharma as its Vice President of Translational Medicine and will lead Circle’s translational team in its development of macrocycle therapeutics against intractable cancer targets.
Dr. Wang has over 20 years of experience developing and applying advanced techniques in translational biology. She most recently served as the Executive Director of Translational Medicine at Exelixis, where she was responsible for leading all translational medicine from pre-IND through development across multiple programs and was a member of the clinical development team. Earlier in her career, Dr. Wang was the Director of Translational Research at BioMarin Pharmaceutical, Inc., where she was the translational research lead for the Poly ADP-ribose polymerase (PARP) inhibitor Talazoparib, which is now marketed by Pfizer for BRCA-mutated HER2-negative breast cancer. Prior to her role at BioMarin, she held leadership positions in Translation Medicine for several pipeline candidate programs in an earlier engagement at Exelixis and was the Founding Director of the Stanford Proteomics and Integrative Research Facility. Dr. Wang was awarded a doctorate in biochemistry and pathology from New York University Medical Center and was a postdoctoral fellow at MIT / Harvard Medical School where she conducted research in the laboratory of Dr. Hidde Ploegh.
“We are delighted to have Evelyn join the Circle team” said Raj Singh, PhD, Circle’s Chief Scientific Officer. “Evelyn brings a wealth of translational medicine experience to Circle having successfully led teams advancing multiple oncology programs into the clinic in her prior roles. She is joining us as our work against the cyclin targets is generating exciting data and we are excited to have Evelyn to help us drive these and other programs to the clinic.”
About Circle Pharma, Inc.
Circle is developing a new paradigm for macrocycle drug discovery deploying structure-based rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform 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. Its lead programs target cyclin proteins, which are part of the regulatory machinery that controls progression of cells through the growth and division cycle. Inhibition of cyclin A is synthetically lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
South San Francisco, CA, June 16, 2021, — Circle Pharma, Inc., a macrocycle drug discovery and development company focused on intractable cancer targets, today announced that it has raised $66 million in an oversubscribed Series C financing.
The financing was co-led by The Column Group and Nextech Invest. All investors from the prior round participated in the Series C, including Pandect Bioventures, together with new investors including Euclidean Capital, Pavillion Capital, Hartford HealthCare Endowment and Eli Lilly and Company.
Proceeds from the financing will be used to advance the Company’s wholly-owned cyclin-targeted programs towards the clinic, with potential applications in Rb-dysregulated cancers such as small cell lung cancer and cyclin E dependent malignancies, including ovarian cancer. In addition, the Company will apply its macrocycle platform to other precision oncology targets that have a clear therapeutic rationale but are considered undruggable with small molecules.
“Circle has made excellent progress since its Series B financing last year and we are very pleased to have co-led this round with Nextech Invest,” said Peter Svennilson, managing partner at The Column Group. “We look forward to seeing Circle’s pioneering macrocycle platform bring highly innovative, first-in-class therapies to patients.”
“We are deeply appreciative of the continuing support of our existing investors and welcome the support of a strong group of new investors in this financing,” said David J. Earp, J.D., Ph.D., Circle’s President and CEO. “The funding will help drive our progress to the clinic and support the addition of new pipeline programs.”
About Circle Pharma, Inc.
Circle is developing a new paradigm for macrocycle drug discovery deploying structure-based rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by multiple routes, including oral administration. Circle’s macrocycle drug discovery & development platform 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. Its lead programs target cyclin proteins, which are part of the regulatory machinery that controls progression of cells through the growth and division cycle. Inhibition of cyclin A is synthetically lethal to cancer cells that carry mutations causing dysregulation of the Rb pathway – such mutations are frequently found in small cell lung cancer. Cyclin E upregulation is found in many tumor types including uterine and ovarian cancer, and is often associated with resistance to widely used cancer therapies, including trastuzumab and cdk4/6 inhibitors.
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
February 1st, 2021 4:00 AM Pacific Standard Time
SOUTH SAN FRANCISCO, Calif. — (Business Wire) — Constantine Kreatsoulas, PhD has joined Circle Pharma as its Vice President of Research Informatics and Computational Chemistry.
Dr. Kreatsoulas joins Circle from GlaxoSmithKline (GSK) where he was the Head of US Molecular Design and Interim Head of Computational Toxicology. His responsibilities at GSK included leading structure-based drug design (SBDD) teams and the development of informatics tools for quantitative experimental data analytics and drug hazard identification. Previously he was a Research Fellow at Merck & Co., Inc., where he focused on SBDD, molecular modeling, machine learning, and small molecule safety assessment and a postdoctoral fellow at Bristol-Meyers Squibb focused on machine learning in predictive toxicology. Dr. Kreatsoulas was awarded a doctorate in chemistry from Princeton University, holds a master’s degree in regulatory affairs and quality assurance from Temple University and received a BA in mathematics and chemistry from New York University.
“We are delighted to welcome Constantine to the Circle team” said Raj Singh, PhD, Circle’s Chief Scientific Officer. “Constantine brings over two decades of experience spanning molecular modeling and design for early drug discovery through development, high performance scientific computing, and toxicology modeling. We are excited to add Constantine’s experience to our team as we add new targets to our discovery pipeline and advance our cyclin programs towards the clinic.”
About Circle Pharma, Inc.
Circle is developing a new paradigm for macrocycle drug discovery based on rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by oral administration. Circle’s macrocycle development platform 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. Its lead programs target cyclins A and E, which are part of the regulatory machinery that controls the progression of cells through the cell growth and division cycle. Inhibition of Cyclin A has been shown to be synthetically lethal in cancers driven by mutations in the Rb pathway. Cyclin E upregulation is associated with resistance to drugs that target cdk4/6 activity and is also found across several cancer types.
More information: www.circlepharma.com
Contact: info@circlepharma.com
Eleonor Lim: 650.825.4099
Read original article at Business Wire
October 26, 2020 5:00 AM Pacific Daylight Time
SOUTH SAN FRANCISCO, Calif. — (Business Wire) — James Aggen, PhD has joined Circle Pharma as its Vice President of Medicinal Chemistry and will lead Circle’s chemistry team in its discovery and development of macrocycle therapeutics against intractable cancer targets.
Dr. Aggen has over 20 years of experience in medicinal chemistry. He most recently served as the Senior Director of Medicinal Chemistry at Revolution Medicines and earlier in his career held positions at Oligiasis, Achaogen, Chemocentryx, Gilead Sciences and Theravance. In addition, Jim held the role of Associate Professor of Medicinal and Natural Products Chemistry at Northeastern University. He also served in the US Marine Corps Reserves. Dr. Aggen was awarded a doctorate in synthetic organic chemistry from the University of California, Irvine, where he studied under Prof. Richard Chamberlin.
“We are delighted to have Jim join the Circle team,” said Raj Singh, PhD, Circle’s Chief Scientific Offer. “Jim brings deep medicinal chemistry experience and has successfully led teams engaged in targeted drug discovery against multiple oncology targets including mTORC1 and KRAS. Notably, Jim also has experience in the medicinal chemistry of larger molecules, having been the project lead from inception to IND submission for the novel aminoglycoside antibiotic plazomicin which is now marketed as Zemdri. We are excited to add Jim’s experience to our team as we work to bring Circle’s cancer therapies to patients.”
About Circle Pharma, Inc.
Circle is developing a new paradigm for macrocycle drug discovery based on rational design and synthetic chemistry. Circle’s technology facilitates the design and synthesis of intrinsically cell-permeable macrocycles that can address both intra- and extra-cellular therapeutic targets, and can be delivered by oral administration. Circle’s macrocycle development platform 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. Its lead programs target cyclins A and E, which are part of the regulatory machinery that controls the progression of cells through the cell growth and division cycle. Inhibition of Cyclin A has been shown to be synthetically lethal in cancers driven by mutations in the Rb pathway. Cyclin E upregulation is associated with resistance to drugs that target cdk4/6 activity and is also found across several cancer types.
More information: www.circlepharma.com
Contacts
Eleonor Lim: 650.825.4099
info@circlepharma.com
Source: Circle Pharma, Inc.
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