On March 16, 2021 Merck, a leading science and technology company, reported that 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 & Co, MAR 16, 2021, View Source [SID1234576709]).

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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. "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, 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.

All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.

On March 16, 2021 Elevation Oncology, a clinical stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, and NeoGenomics, Inc. (NASDAQ:NEO), a leading provider of cancer-focused genetic testing services and global oncology contract research services, reported a collaboration to enhance identification of patients with any solid tumor harboring an NRG1 fusion who may be eligible for enrollment in the Phase 2 CRESTONE study (Press release, Elevation Oncology, MAR 16, 2021, View Source;utm_medium=rss&utm_campaign=elevation-oncology-and-neogenomics-announce-collaboration-to-expand-genomic-testing-for-nrg1-fusions-across-solid-tumors-in-support-of-the-phase-2-crestone-study [SID1234576708]). NeoGenomics is a leading provider of next-generation sequencing (NGS) performing more than 50,000 NGS tests per year.

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NRG1 gene fusions are oncogenic driver alterations that have recently been identified in over 10 solid tumor types, with an overall estimated incidence of 0.2% in all solid tumors.1 Though rare, gene fusions are a proven target for precision oncology therapeutics, with over a dozen FDA-approved therapies now available for both hematologic and solid tumors driven by various gene fusions.2

"Our collaboration with Elevation Oncology reflects our shared pursuit of matching cancer patients to clinical trials and therapies that are precisely targeted to their unique tumor types and genomic biomarkers," said Douglas M. VanOort, Chairman and Chief Executive Officer of NeoGenomics. "Through cross-industry collaborations, we enable greater efficiency in the development and delivery of the latest advancements in both diagnostics and targeted therapies. Together, we work towards a future where every patient living with cancer has the opportunity to benefit from precision medicine."

As part of its comprehensive oncology test menu, NeoGenomics offers a variety of gene fusion panels that leverage RNA-based NGS to detect translocations and fusions with known and novel fusion partners across all solid tumors, including actionable gene fusions such as in ALK, BRAF, FGFR, NRG1, NTRK, PDGF, RET, and ROS1. In addition to all solid tumor panels, targeted panels are available in tumor types where gene fusions are commonly enriched:

Lung NGS Fusion Panel (Complete or Limited)
Cholangio/Pancreatic Carcinoma NGS Fusion Panel
Prostate NGS Fusion Panel
Thyroid NGS Fusion Panel
Targeted Solid Tumor NGS Fusion Panel
Universal Solid Tumor NGS Fusion Panel
RNA-based sequencing is the most sensitive detection method for structural variants that span large intronic regions, such as those leading to NRG1 gene fusions, which may not be detectable by most DNA-based sequencing techniques reliant on short-read methods. In addition, the use of RNA-based NGS furthers the scientific understanding of gene fusions by enabling full characterization of gene fusion partners and nucleotide-level resolution of fusion junctions.

"Accurate and widespread identification of gene fusions is critical to ensure patients can be matched to the growing number of approved and investigational precision therapies for these key oncogenic drivers," said Shawn Leland, PharmD, RPh, Founder and CEO of Elevation Oncology. "We are pleased to partner with NeoGenomics to ensure that across any solid tumor, each positive NRG1 fusion test result has the potential to be met with an actionable therapeutic opportunity in our Phase 2 CRESTONE study."

Patients and physicians can learn more about the CRESTONE study at www.nrg1fusion.com or on www.ClinicalTrials.gov under the NCT number NCT04383210.

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 [SID1234576707]).

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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 Advaxis, Inc. (Nasdaq: ADXS), a clinical-stage biotechnology company focused on the development and commercialization of immunotherapy products reported its financial results for the first quarter ended January 31, 2021 and provides a business update (Press release, Advaxis, MAR 16, 2021, View Source [SID1234576706]).

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First Quarter Ended January 31, 2021 Financial Results and Recent Key Accomplishments:

Presented updated clinical data from the ongoing Phase 1/2 trial of ADXS-503 as a monotherapy and in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in non-small cell lung cancer (NSCLC) at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting
° Disease control rate of 67% and overall response rate of 17% in first six evaluable patients with immediate prior progression on KEYTRUDA. The first two patients treated in Part B combination arm that had achieved stable disease (SD) and partial response (PR) remain on treatment for 10 and 8 months, respectively
° Biomarker data across 9 patients across trial arms confirmed on-mechanism activation of innate and adaptive immune responses to ADXS-503 with transient elevation of immune-modulatory cytokines, activation of cytotoxic -and/or memory CD8+ T cells as well as 100% efficient priming by ADXS-503
° Across trial arms, ADXS-503 appeared safe and well tolerated as a monotherapy and in combination with KEYTRUDA with no added toxicities from combination therapy
Announced upcoming presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2021 Annual meeting, in collaboration with Precision for Medicine, on the development of a novel immunophenotyping assay to accurately evaluate PD-1 expression as a pharmacodynamic marker during PD-1 blockade treatment with pembrolizumab, and the correlation of changes in T cell populations with observed clinical activity in the ongoing ADXS-503 clinical trial
Announced receipt of funding milestone payment under ADXS-HER2 licensing agreement with OS Therapies
Announced closing of $9.2 million public offering of common stock and warrants, with proceeds being used to fund continued development and expansion of our product pipeline
Management Commentary

"We are encouraged by the growing body of evidence that suggest ADXS-503 has the potential to synergistically enhance and/or restore sensitivity to checkpoint inhibitors," said Kenneth A. Berlin, President and Chief Executive Officer of Advaxis. "Based on our encouraging data, we are prioritizing the ongoing and recently expanded ADXS-503 trial in diverse treatment settings for NSCLC, and will remain focused on continued clinical execution. We look forward to our presentation at AACR (Free AACR Whitepaper), which will further expand upon the previously reported on-mechanism innate and adaptive immune stimulation which we believe are driving meaningful and durable clinical benefit for patients treated with ADXS-503. Our strengthened balance sheet leaves us well positioned to continue progress with our off-the-shelf neoantigen immunotherapy ADXS-HOT program, including our planned expansion into prostate cancer with ADXS-504, and we look forward to providing study updates in the coming months."

First Quarter Ended January 31, 2021 Financial Results

Research and development expenses for the first quarter of fiscal year 2021 were $2.6 million, compared with $4.9 million for the first quarter of fiscal year 2020. The reduction of $2.3 million was primarily attributable to the substantial reduction in costs associated with the winding down of clinical studies that have been discontinued.

General and administrative expenses for the three months ended January 31, 2021 were approximately unchanged at $3 million, compared to $3 million in the same three-month period in 2020.

As of January 31, 2021, the Company had approximately $33.3 million in cash and cash equivalents. The Company believes this is sufficient capital to fund its obligations, as they become due, in the ordinary course of business until May 2022.

On March 16, 2021 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported it has signed an exclusive distribution agreement with Switzerland-based Ewopharma for Piclidenoson in the treatment of psoriasis and Namodenoson in the treatment of liver diseases namely, hepatocellular carcinoma (HCC) the most common form of liver cancer and nonalcoholic steatohepatitis (NASH) (Press release, Can-Fite BioPharma, MAR 16, 2021, View Source [SID1234576703]). Under the terms of the distribution agreement, Ewopharma will pay to Can-Fite $2.25 million upfront with up to an additional $40.45 million payable upon the achievement of regulatory and sales milestones plus 17.5% royalties on net sales. In exchange, Ewopharma will have the exclusive right to market and sell Piclidenoson in Central Eastern European (CEE) countries and Namodenoson in CEE countries and Switzerland. Ewopharma has the right to extend the distribution agreement to new indications that Can-Fite may identify for its drug candidates.

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Ewopharma is a pharmaceutical marketing organization that helps pharma companies access markets in CEE and Switzerland. In addition to Can-Fite, Ewopharma has distribution agreements with many leading healthcare companies worldwide.

"We are very pleased to enter into this distribution agreement with Ewopharma, a leader in pharmaceutical distribution in Eastern Europe. This is a high-value deal that brings Can-Fite non-dilutive funding, and upon regulatory approval, it gives our products immediate access and distribution in the European market," stated Can-Fite VP Business Development Dr. Sari Fishman.

Dr. Shila Schneider, Business Development Manager Ewopharma Group, added, "We are honored to partner with Can-Fite and help bring their innovative and much needed new treatments to patients in our market in Central Eastern Europe and Switzerland. This is a key strategic deal with therapies complementing our portfolio in gastroenterology, oncology and immunology and reinforcing Ewopharma’s long-standing commitment to its entire region."

About Piclidenoson

Piclidenoson is a novel, first-in-class, A3 adenosine receptor agonist (A3AR) small molecule, orally bioavailable drug with a favorable therapeutic index demonstrated in Phase II clinical studies. It is currently being evaluated in a multinational Phase III study as a treatment for moderate to severe psoriasis and a Phase II U.S. study for the treatment of moderate to severe COVID-19.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.