On March 16, 2021 PEP-Therapy, a biotechnology company developing cell penetrating peptides as targeted therapies in oncology, and Institut Curie, France’s leading cancer center, reported that they have been granted approval from the French National Agency for Medicines and Health Products (ANSM) to proceed with the first-in-human clinical trial of PEP-Therapy’s lead drug candidate, PEP-010 (Press release, PEP-Therapy, MAR 16, 2021, View Source [SID1234576754]).

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PEP-010 is a first-in-class therapeutic peptide based on PEP-Therapy’s innovative Cell Penetrating and Interfering Peptides (CP&IP) technology. These innovative molecules penetrate cells and specifically block relevant intracellular protein-protein interactions, leading to the inhibition of key pathological mechanisms, without altering physiological mechanisms. PEP-010 is a pro-apoptotic agent which has demonstrated anti-tumor efficacy in a number of pre-clinical models and a good safety profile.

The clinical trial, named ‘CleverPeptide’, is an open-label, non-controlled, multicenter, dose escalation, Phase I clinical trial with an expansion Phase. This Phase Ia/b study has been designed to evaluate the safety, tolerability, pharmacokinetics and preliminary antitumor activity of intravenous PEP-010, administered as a single agent and in combination with paclitaxel in patients with recurrent and/or metastatic solid tumors, and in particular in Triple Negative Breast Cancer (TNBC) and Ovarian Cancer (OC).

This study is sponsored by Institut Curie and led by Pr. Christophe Le Tourneau, Medical Oncologist at Institut Curie and Head of Department of Drug Development and Innovation (D3i), and Principal Investigator of the trial.

Antoine Prestat, CEO and co-founder of PEP-Therapy said: "We are pleased to have been granted approval by ANSM to start this first-in-human clinical trial of PEP-010. This is a major milestone for PEP-Therapy and our partners, amongst which Institut Curie and Sorbonne University where our technology originated from. PEP-010 aims to fight cancers with poor prognosis for which there are only few or no therapeutic alternatives. We look forward to starting this trial in the coming weeks and to generating results that we hope will confirm the promising results seen in preclinical studies."

"This exciting step has been achieved through a strong collaboration between PEP-Therapy and Institut Curie since its inception, demonstrating the ability to develop innovative therapeutics emerging from French institutional research. I am very pleased to involve the D3i – Department of Drug Development and Innovation – in this clinical trial", says Pr Christophe Le Tourneau.

The study will be conducted in three clinical centers in France: Institut Curie, Gustave Roussy and the François Baclesse Center.

On March 16, 2021 Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported topline data from the Phase II INTR@PID BTC 047 study evaluating bintrafusp alfa as a monotherapy in the second-line treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) who have failed or are intolerant of first-line platinum-based chemotherapy (Press release, Merck KGaA, MAR 16, 2021, View Source [SID1234576753]).

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In the study of 159 patients, bintrafusp alfa demonstrated single-agent efficacy and durability with a manageable safety profile after more than nine months of follow-up, with an Independent Review Committee (IRC)-adjudicated objective response rate (ORR) of 10.1% (95% CI: 5.9% to 15.8%) per RECIST 1.1. Though single-agent activity was observed, the study did not meet the pre-defined threshold that would have enabled regulatory filing for BTC in the second line setting. The results will be submitted for presentation at an upcoming medical meeting or publication.

"Given the high unmet treatment need in BTC, where single agent immunotherapy in PD-L1 all comers has shown an ORR of 5.8%, we are encouraged by the single agent clinical activity of bintrafusp alfa in this study as a second-line treatment," said Milind Javle, MD, professor of GI medical oncology, MD Anderson Cancer Center, and an investigator for the INTR@PID BTC 047 study. "The bintrafusp alfa 047 study is one of the most important clinical investigations conducted for chemo-refractory biliary cancers, and I would like to thank the patients, families, and study team for their valuable participation."

"This study demonstrates single-agent activity with bintrafusp alfa in locally advanced or metastatic BTC, a disease that has been historically difficult to treat," said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business sector of Merck KGaA, Darmstadt, Germany. "The data will contribute to our understanding of addressing both TGF-β and PD-L1 inhibition in the tumor microenvironment."

A Phase II/III study of bintrafusp alfa in combination with chemotherapy as a first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different hypothesis than the second-line monotherapy study, has completed enrollment in the Phase II portion and is currently ongoing.

*Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.

About Biliary Tract Cancer (BTC)

BTCs are a group of rare, aggressive gastrointestinal cancers associated with poor outcomes and limited treatment options. There is currently no globally accepted standard of care in the second-line setting and chemotherapy as well as immunotherapies have demonstrated low response rates in BTC. Epithelial-to-mesenchymal transition (EMT), a hallmark of tumor progression and drug resistance, plays an important role in BTC, and has been shown to be triggered by TGF-β signaling.

About Bintrafusp Alfa

Bintrafusp alfa (M7824), discovered in-house at Merck KGaA, Darmstadt, Germany, and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

About the INTR@PID Clinical Trial Program

INTR@PID is a global clinical trial program investigating the potential co-localized, dual inhibition of TGF-β and PD-L1 with bintrafusp alfa (M7824) in multiple tumor types. Current clinical trial information can be found on the INTR@PID website at www.intrapidclinicaltrials.com. To date, globally more than 1,300 patients with various types of solid tumors have received bintrafusp alfa in the INTR@PID clinical development program.

The INTR@PID clinical development strategy is comprehensive and is pursuing non-redundant hypotheses grounded in preclinical and early clinical data findings that continue to be explored and may yield clinically meaningful insights to patients in need, including exploring settings where simultaneous, synchronized targeting of TGF-β and PD-L1 may offer the key to expanding the potential of immunotherapy; focusing on opportunities where PD-1/PD-L1 has suboptimal clinical activities and pathogenesis linked to TGF-β biology; and targeting specific tumors with biomarkers with a strong link to TGF-β signaling pathway.

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On March 16, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the fourth quarter ended December 31, 2020 and provided several corporate updates (Press release, Cogent Biosciences, MAR 16, 2021, View Source [SID1234576752]).

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"Cogent Biosciences was formed in July 2020, and we are extremely proud of the progress our team has made in such a short amount of time," said Andrew Robbins, President and CEO of Cogent Biosciences. "We remain on track and plan to initiate clinical trials of CGT9486 in advanced systemic mastocytosis in the first half of this year, and will follow in non-advanced systemic mastocytosis and GIST in the second half of this year. We are excited to demonstrate the role of this novel, potent, selective KIT-mutant inhibitor for these patient populations with significant remaining unmet medical need."

Recent Program and Corporate Highlights

Encouraging data from CGT9486 + sunitinib in Phase 1/2 combination study in heavily pre-treated patients with GIST support a randomized trial in 2H21
Data presented at the Connective Tissue Oncology Society (CTOS) 2020 virtual meeting demonstrated that treatment with a combination of CGT9486, a KIT inhibitor with activity against exon 17 mutations, and sunitinib, a KIT inhibitor with activity against exon 13 mutations, is associated with encouraging clinical activity in heavily pre-treated patients with GIST.
Data showed median progression free survival (PFS) of 12 months in a heavily pre-treated population of advanced GIST patients and an objective response rate (ORR) of 20%.
The combination was well-tolerated across three dose levels with no maximum tolerated dose level reached. The most common minor adverse events were anemia, hypophosphatemia, diarrhea, and lymphopenia.
Based on these encouraging data, Cogent plans to initiate a randomized trial in patients with imatinib-resistant GIST during the second half of 2021.
Upsized Public Offering with gross proceeds of approximately $115 million support advancement of CGT9486 into three clinical trials in 2021
On December 4, 2020, Cogent Biosciences announced the closing of its upsized underwritten public offering; net proceeds from which will be used for the continued clinical development of CGT9486 to treat patients with systemic mastocytosis and GIST.
Appointed new individuals to several key leadership positions
Todd E. Shegog to Board of Directors
Mr. Shegog currently serves as the Chief Financial Officer for Forma Therapeutics and brings more than 25 years of financial, operations, corporate strategy, and compliance expertise in the biotechnology and pharmaceutical industries to Cogent Biosciences’ Board. Todd has past experience as CFO at Synlogic, FORUM, and Millennium and received degrees in electrical engineering from Lafayette College and an MBA from the Tepper School of Management at Carnegie Mellon University.
Sara Saltzman as Senior Vice President, Regulatory Affairs
Ms. Saltzman has built extensive experience in Regulatory Affairs working for top-tier life sciences companies such as Genzyme, Takeda, and Alexion; most recently serving as the Vice President of Regulatory Affairs for Unum Therapeutics. Sara holds a degree in Biology from Colby College.
Ben Exter as Vice President, Pharmacovigilance and Risk Management
Dr. Exter spent several years in clinical development at Biogen and Takeda, culminating with his role as Global Head of Risk Management at Takeda. Most recently he was VP of Pharmacovigilance at Unum Therapeutics. Ben received his Doctorate of Pharmacy degree from Northeastern University.
Mark Lohman as Vice President, CGT9486 Program Team Leader
Mr. Lohman has spent over 20 years in program and alliance management and leadership roles at Array BioPharma and most recently at Pfizer as Executive Director, Alliance and Program Management for Oncology. Mark holds a degree in Chemistry from Kent State University and an MBA from the University of Colorado Denver.
Fourth Quarter and Year End 2020 Summarized Financial Results

R&D Expenses: Research and development expenses were $6.1 million for the fourth quarter of 2020 and $25.7 million for the year ended December 31, 2020, as compared to $10.4 million for the fourth quarter of 2019 and $43.7 million for the year ended December 31, 2019. This decrease is primarily related to the reduction in clinical activity of legacy cell therapy clinical trials.
G&A Expenses: General and administrative expenses were $5.3 million for the fourth quarter of 2020 and $17.4 million for the year ended December 31, 2020, as compared to $2.7 million for the fourth quarter of 2019 and $11.0 million for the year ended December 31, 2019. The increase is primarily related to higher professional fees and stock compensation.
Net Loss: Net loss was $11.3 million for the fourth quarter of 2020 and $74.8 million for the year ended December 31, 2020 as compared to a net income of $2.3 million for the fourth quarter of 2019 and a net loss of $31.8 million for the year ended December 31, 2019.
Cash and Cash Equivalents: As of December 31, 2020, Cogent Biosciences had cash and cash equivalents of $242.2 million. We believe our cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements into 2024.

On March 16, 2021 Vesigen Therapeutics, Inc., a biotechnology company pioneering a novel extracellular vesicle delivery technology to develop transformative therapeutics, reported that the United States Patent and Trademark Office has issued U.S. Patent No. 10,945,954 entitled "ARRDC1-Mediated Microvesicles (ARMMs) and Uses Thereof (Press release, Vesigen Therapeutics, MAR 16, 2021, View Source [SID1234576751])". This patent, exclusively licensed to Vesigen from Harvard University, broadly covers many of the drug delivery features of any ARRDC1-mediated microvesicles (ARMMs).

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This patent covers ARMMs compositions containing an enzymatic payload. Important enzymes include those needed in enzyme replacement therapy as well as those intended to create a therapeutic function.

"The issuance of this patent has strengthened Vesigen’s intellectual property estate and provided us with a vast therapeutic blueprint to enable a robust pipeline of agents for use in CNS, oncology, ocular applications and beyond," said Robert Millman, Co-Founder and CEO of Vesigen Therapeutics.

ARMMs particles are a unique class of extracellular vesicles that are naturally produced by cells and serve as a vehicle to package and deliver communication signals, including transcription complexes, between cells and tissues. ARMMs show enhanced functionality in packaging and transferring payloads, by fusing directly with the cell membrane of a target cell. The cellular ARRDC1 system is a pathway co-opted by enveloped viruses, such as HIV, using a functional homolog, Gag. Like ARMMs particles, enveloped virus particles avoid immune clearance and deliver their viral genome payload specifically to target cells in a fusogenic delivery. Vesigen is engineering ARMMs particles to improve this natural mechanism for more effective targeted delivery of therapeutic agents.

On March 16, 2021 COTA, Inc., an oncology real-world data and analytics company, reported a collaboration with Kite, a Gilead company, through which COTA’s real-world data will be used to accelerate Kite’s drug development pipeline (Press release, COTA, MAR 16, 2021, View Source [SID1234576750]). This approach will help inform decisions about future therapeutic applications for blood cancers while inspiring new ways of thinking about how clinical trials are designed.

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The use of real-world data (RWD) is expanding as it is increasingly used in a complementary role to support, clarify, or accelerate randomized clinical trials. Kite will work closely with oncologists, data scientists, and researchers at COTA to develop and validate real-world endpoints and accelerate the clinical development timeline for patient benefit.

"COTA’s real-world data will be used to accelerate Kite’s drug development pipeline." – COTA CEO Mike Doyle

"At COTA, we pride ourselves not just on the high quality of the data we deliver to our partners, but also on our ability to collaborate with sponsors to inform clinical research and get the best drugs to patients more efficiently," said Mike Doyle, CEO of COTA. "With the support of the FDA, Kite and many others, COTA is helping to pioneer the use of RWD in clinical research with the ultimate goal of accelerating clinical development, reducing healthcare costs, and helping cancer patients live longer, healthier lives."

COTA provides comprehensive and diverse cancer RWD to leading life sciences and healthcare provider organizations that are caring and developing treatments for patients living with a wide range of cancers. COTA uniquely combines its oncology expertise with technology-enabled human data abstraction to curate meaningful, longitudinal, and de-identified patient data. As RWD is increasingly applied in clinical development, COTA’s customized data sets can help increase patient diversity in clinical trials; expand indications of already approved drugs; replace the traditional standard-of-care or placebo group via a RWD-powered synthetic control arm; and empower life sciences companies to make faster decisions on their pipeline.