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LifeArc announces seed fund investment in start-up GyreOx

On March 17, 2020 LifeArc has joined leading UK venture capital firm UK Innovation & Science Seed Fund (UKI2S) in investing into GyreOx Therapeutics (GyreOx). The funding will support a two-year programme to develop and automate GyreOx’s proprietary drug discovery platform, MACRO (Press release, LifeArc, MAR 17, 2020, View Source [SID1234555736]).

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The MACRO platform generates a range of highly modified macrocyclic peptide molecules, known as gyrocycles, which can penetrate cells and be targeted to tackle the protein-protein interactions (PPI) within. These intracellular processes are potentially implicated in many health conditions including cancer, inflammation and autoimmune diseases and are difficult to reach with currently available medicine classes. Automation of the MACRO platform will enhance the generation process further to allow a greater number of novel macrocycles to be generated more quickly and more cheaply.

Dr Bill Primrose, Founder and CEO of GyreOx said: "It’s a strong endorsement of our technology that we have been able to attract support from such quality investors. We have an ambitious plan to develop the platform and to deploy it on a number of internal programmes, including one targeting an epigenetic cancer target. It is our ambition to make GyreOx into a clinical stage company with a strong drug pipeline and a number of discovery alliances with major players in the pharmaceutical industry."

Common medicines classes include small molecules and biologics. While small molecules can enter cells to modulate intracellular process, they have difficulty in addressing complex targets, including PPIs. Biologics, such as humanised antibodies, are unable to enter the cell and are therefore only suitable for addressing drug targets on the cell surface. GyreOx’s Gyrocycle highly modified macrocyclic peptides combine the targeting ability of biologics with the cell-entry ability of small molecules; these molecules present an attractive, novel therapeutic modality as they can also be engineered to further improve their pharmacokinetic profile and ability to penetrate cells to reach previously "undruggable" targets.

Dr David Holbrook, Head of Seed Fund, LifeArc said: "The LifeArc Seed Fund is delighted to be supporting GyreOx on its work on the macrocycles platform and helping translate the science on the next step towards the patient. GyreOx is a great example of the type of company we are trying to support—great science, great scientists, strong start up management all addressing a significant unmet health need."

ShangPharma Innovation portfolio company Circle Pharma raises $45 Million in Series B Financing

On March 17, 2020 Circle Pharma, Inc., a macrocycle drug discovery and development company focused on intractable cancer targets, reported that it has raised $45 million in a Series B financing (Press release, ShangPharma Innovation, MAR 17, 2020, View Source [SID1234555735]).

The financing was led by The Column Group, with participation by Nextech Invest. All investors from the prior round – ShangPharma, LifeForce Capital, and the Berkeley Catalyst Fund – joined the financing.

In conjunction with the financing, Peter Svennilson, founder and managing partner of The Column Group, and Thilo Schroeder, Ph.D., partner at Nextech Invest were appointed to the board. John Josey, Ph.D., formerly President and CEO of Peloton Therapeutics, was appointed to the board as Chairman.

Proceeds from the investment will be used to advance Circle’s work to develop inhibitors of Cyclin A and Cyclin E, and to expand the company’s pipeline.

"We are delighted to have these premier life science investors supporting our Series B financing," said David J. Earp, J.D., Ph.D., Circle’s President and CEO. "With this strong backing, we will expand our team, drive our cyclin targeted programs towards the clinic, and apply our macrocycle platform to additional intractable targets."

Circle’s new board appointments:

Peter Svennilson is the founder and managing partner of The Column Group. He was the chairman of Aragon Pharmaceuticals (acquired by Johnson & Johnson) and Seragon Pharmaceuticals (acquired by Roche / Genentech) and was a board director of Gritstone Oncology, NGM Biopharmaceuticals, Immune Design and Constellation Pharmaceuticals. He is currently a board director of ORIC Pharmaceuticals, Ribon Therapeutics and Carmot Therapeutics.

Thilo Schroeder, Ph.D., is a partner at Nextech Invest, a Zurich-based oncology-focused investment firm. He previously served on the board of Peloton Therapeutics (acquired by Merck) and Blueprint Medicines. He is currently a board director at IDEAYA Biosciences, Revolution Medicines, PMV Pharma, Silverback Therapeutics and a board observer at Black Diamond Therapeutics.

John Josey, Ph.D., served as the President, Chief Executive Officer, and member of the Board of Directors at Peloton Therapeutics from 2013 until its acquisition by Merck in 2019. From 2011 to 2013, he was President and Chief Scientific Officer at Peloton, and from 1998 to 2011, Vice President of Discovery Chemistry at Array Pharma.

The continuing members of Circle’s board of directors are Walter H. Moos, Ph.D., CEO of ShangPharma Innovation and Managing Director of Pandect Bioventures, Matthew P. Jacobson, Ph.D., Circle Pharma co-founder, chair of the department of pharmaceutical chemistry at U.C. San Francisco and also co-founder of Global Blood Therapeutics, Relay Therapeutics and Cedilla Therapeutics, and David J. Earp, J.D., Ph.D., President and Chief Executive Officer of Circle Pharma.

Oncotarget | Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss

On march 17, 2020 Oncotarget reported the cover for issue 11 of Oncotarget features Figure 6, "Effects of AZD8186 in combination with anti-PD1 on syngeneic models," by Owusu-Brackett, et al.

In vitro cell viability assay and immunoblotting demonstrated that PTEN loss was significantly correlated with AZD8186 sensitivity in triple-negative breast cancer cell lines.

AZD8186 in combination with paclitaxel, eribulin had synergistic effects on growth inhibition in PTEN loss cells.

AZD8186 significantly enhanced the antitumor efficacy of anti-PD1 antibodies in the PTEN-deficient BP murine melanoma xenograft model, but not in the PTEN-wild-type CT26 xenograft model.

In vitro, cell proliferation and colony formation assays were performed to determine cell sensitivity to AZD8186.

AZD8186 has single-agent efficacy in PTEN-deficient TNBC cell lines in vitro but has limited single-agent efficacy in vivo.

Dr. Funda Meric-Bernstam from the Department of Surgical Oncology, the Department of Investigational Cancer Therapeutics, the Department of Breast Surgical Oncology, as well as The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy at The University of Texas MD Anderson Cancer Center, in Houston, Texas, USA said, "Phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is an important regulator of many physiological cellular processes that promote differentiation, proliferation and survival of a normal cell."

"Phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway is an important regulator of many physiological cellular processes that promote differentiation, proliferation and survival of a normal cell."

– DR. FUNDA MERIC-BERNSTAM, DEPARTMENT OF INVESTIGATIONAL CANCER THERAPEUTICS, THE DEPARTMENT OF BREAST SURGICAL ONCOLOGY & THE SHEIKH KHALIFA BIN ZAYED AL NAHYAN INSTITUTE FOR PERSONALIZED CANCER THERAPY

Mutations, loss of copy number, epigenetic silencing and downregulation of PTEN protein by mi RNA can result in PTEN function inactivation, leading to activation of PI3K/AKT/mTOR pathway, which subsequently increases tumor growth, invasion and metastasis across a diverse set of solid tumors including breast, endometrial, prostate, renal cell, hepatocellular, glioblastoma, and colorectal cancers.

Loss of PTEN and increased PI3K signaling are associated with resistance to trastuzumab and endocrine therapy in hormone receptor-positive breast cancer and with poor prognosis in triple-negative breast cancers.

In vitro, they revealed significant growth inhibition of PTEN-deficient tumors by depleting PIK3CB which encodes PI3K, while no such growth inhibition effect was shown in corresponding PTEN-deficient tumors with downregulation of PIK3CA or PIK3CD encoding PI3K and PI3K, respectively.

Thus, PI3K isoform is the driver of abnormal proliferation in PTEN-null cancers, and as such, PI3K is a promising target for therapy in PTEN-deficient TNBC. AZD8186 is a selective and potent small-molecule inhibitor of PI3K, with additional activity against PI3K isoform.

The Meric-Bernstam Research Team concluded in their Oncotarget Research Paper, "these results provide preclinical evidence of antitumor efficacy of AZD8186 in PTEN-deficient solid tumors. AZD8186 has single-agent efficacy in PTEN-deficient TNBC cell lines in vitro, with modest single-agent efficacy in vivo. Furthermore, AZD8186 enhanced the antitumor efficacy of paclitaxel but stable and progressive disease were noted with this combination in immunosuppressed models. In immunocompetent models, AZD8186 in combination with anti-PD1 resulted in tumor regression in PTEN-deficient BP tumor. We realize that while there appears to be an association of AZD8186 sensitivity to PTEN loss, a cause-effect relationship can only be speculated on. In summary, although further insights are needed into the mechanisms of activity of these combinations, the combination of AZD8186 with taxanes and with anti-PD1 agents hold promise for the treatment of PTEN-deficient solid tumors."

MORPHIC ANNOUNCES APPOINTMENT OF PETER G. LINDE, M.D., AS CHIEF MEDICAL OFFICER

On March 17, 2020 Morphic Therapeutic (NASDAQ: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, reported the appointment of Peter G. Linde, M.D., as chief medical officer (Press release, Morphic Therapeutic, MAR 17, 2020, View Source [SID1234555665]). Dr. Linde was previously vice president of medical research at Acceleron Pharma, Inc., where he was responsible for the design and execution of clinical trials with positive outcomes in both pulmonary and hematologic diseases. Dr. Linde will oversee the development of Morphic’s small molecule integrin inhibitors as the company advances its oral integrin inhibitors toward clinical trials.

"Dr. Linde has an extensive track record of driving clinical advancement across multiple therapeutic areas including inflammatory, pulmonary and hematologic disease. Notably, his experience includes clinical studies in inflammatory bowel disease, the therapeutic target of MORF-057, our lead oral integrin inhibitor anticipated to enter the clinic this year," commented Praveen Tipirneni, M.D., president and chief executive officer of Morphic Therapeutic. "On behalf of everyone at Morphic, I welcome Dr. Linde to the team. We look forward to his leadership in developing the processes, partners and resources to guide MORF-057 and our portfolio of additional product candidates through development."

Dr. Linde brings more than 15 years of experience in pharmaceutical clinical development and research. Most recently he served as vice president of medical research at Acceleron Pharma, Inc., where he led study design and development for clinical trials in pulmonary and hematologic diseases. These studies included the recently successful Phase 2 study of sotatercept in pulmonary arterial hypertension as well as late-stage development work on luspatercept, which in 2019 obtained FDA approval for treatment of transfusion-dependent patients with beta-thalassemia. Prior to this role, Dr. Linde was a project leader in clinical asset development at AbbVie, Inc., where he guided the global development of renal and immunology products. Dr. Linde also served as a senior director of clinical development at FibroGen, Inc., developing trial protocols and leading clinical studies to treat anemia in hemodialysis patients. Dr. Linde began his pharmaceutical career developing new indications for the decompensated heart failure treatment NATRECOR (nesiritide) as a director of clinical research at Johnson & Johnson, Inc.

"Morphic is built on world-class insight into integrin biology, outstanding medicinal chemistry and a growing body of impressive preclinical data. It has also established itself as the leader in the discovery of small molecule drug candidates that specifically target this important receptor class. Oral integrin therapy has the potential to transform treatments for patients suffering from diseases spanning autoimmunity, fibrosis and cancer," said Dr. Linde. "I am very much looking forward to guiding the clinical development of Morphic’s pipeline."

Dr. Linde completed medical school at Stanford University and a residency at the University of Pennsylvania Medical Center in internal medicine. He then went on to complete two fellowships at Massachusetts General Hospital/Harvard Medical School in nephrology and transplantation. Following the completion of his core medical training, Dr. Linde spent approximately 10 years as a practicing clinician, clinical instructor and mentor at several institutions including Allegheny University, Massachusetts General Hospital, Brigham & Women’s Hospital and San Francisco General Hospital. Dr. Linde earned his bachelor’s degrees from the Massachusetts Institute of Technology in both chemical engineering as well as applied biology. He is also an inventor on multiple issued patents relating to stem cell and extracorporeal organ support technologies.

NATRECOR is a registered trademark of Johnson & Johnson.

InnoCare (Beijing) Prices Hong Kong IPO at Top of Range, Raises $288 Million

On March 17, 2020 InnoCare Pharma reported that Beijing priced its Hong Kong IPO at the top end of its proposed range to raise $288 million at a $1 billion valuation, according to insiders (Press release, InnoCare Pharma, MAR 17, 2020, View Source [SID1234555664]). The company develops immunotherapies for cancer and autoimmune diseases. It has three molecules in clinical trials, including its lead product, a BTK inhibitor under NDA review in China for leukemia and lymphoma. The company discovers candidates through its own research and in-licenses products from other biopharmas. Hong Kong has not completed an IPO since January because of the coronavirus outbreak.