On April 14, 2021 GlaxoSmithKline plc reported, following a recommendation by the Independent Data Monitoring Committee, that it has taken the decision to stop enrolling patients in the phase II INDUCE-3 trial, including discontinuing treatment with feladilimab (Press release, GlaxoSmithKline, APR 14, 2021, View Source [SID1234578032]).

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The INDUCE-3 study is investigating feladilimab in combination with pembrolizumab versus placebo in combination with pembrolizumab in patients with PD-L1 positive recurrent locally advanced or metastatic head and neck squamous cell carcinoma.

GSK has also made the decision to stop the INDUCE-4 phase II trial, a study investigating feladilimab versus placebo in combination with pembrolizumab and chemotherapy.

The totality of the data will be evaluated to assess the impact on the overall clinical development programme for feladilimab.

The INDUCE-3 and INDUCE-4 studies are conducted pursuant to an agreement between GSK and Merck & Co, Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the US and Canada).

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline of oncology assets in development is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On April 14, 2021 BioAge Labs, Inc. a biotechnology company developing medications that target the molecular causes of aging to extend healthy human life, reported that it has entered into an exclusive worldwide license agreement with Amgen, Inc. [Head Office: Thousand Oaks; CEO: Robert Bradway] to develop and commercialize Amgen’s clinical-stage APJ agonist, BGE-105 (named AMG 986 by Amgen) to ameliorate muscle aging (Press release, BioAge Labs, APR 14, 2021, View Source [SID1234578031]). In older people, muscle aging causes loss of strength, mobility, and function, driving mortality and multiple age-related diseases and decreasing overall quality of life.

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APJ and its natural agonist apelin are components of a signaling pathway that regulates multiple aspects of muscle metabolism, growth, and repair.

BGE-105 is a potent APJ agonist that can be administered orally or intravenously. Phase 1 clinical trials completed in 2019 in 198 subjects who received the drug for up to 21 days showed that BGE-105 had a tolerable safety profile, with acceptable pharmacokinetics (PK) supporting once-daily administration. BioAge’s first clinical trial of BGE-105, planned for initiation in the first quarter of 2022 under the existing IND, will be a Phase 1 study comparing the pharmacodynamic (PD) effects of BGE-105 in humans with those seen in previous trials examining the effects of the apelin peptide.

"BioAge’s advanced proprietary platform comprehensively analyzes longitudinal human data to identify key molecular drivers of aging, which we then validate in preclinical experiments," said Kristen Fortney, PhD, BioAge’s Chief Executive Officer. "Using this robust approach, we found that higher levels of apelin signalling in older people are associated with increased lifespan and reduced symptoms of frailty. Our human-first analysis suggests that the apelin-mimicking drug BGE-105 could recapitulate these positive effects in older patients."

In mice, deficiency in apelin or APJ accelerates loss of muscle function. Consistent with the key roles of apelin–APJ signaling in muscle physiology, BioAge showed in preclinical experiments that BGE-105 increases running wheel activity and other measures of frailty, improves regeneration, and decreases muscle atrophy due to immobilization in old mice.

"Maintaining muscle mass and strength is key to maintaining physical function in the elderly," said Dr. Cedric Dray, an Associate Professor and BioAge collaborator. In 2018, Dr. Dray’s research group discovered that apelin reverses age-associated sarcopenia, and since then has collaborated with BioAge to evaluate BGE-105 in murine models of muscle regeneration. "It is tremendously exciting to trial in humans an oral APJ agonist that recapitulates the positive effects of apelin peptide."

"As with all of BioAge’s clinical assets, BGE-105 is de-risked in two key ways," Fortney said. "First, data from a previous clinical trial show that the molecule was well tolerated in human patients. Second, our human-centric approach reveals that the drug target is physiologically relevant to human aging — in this case, showing that enhancing apelin signaling is compatible with a long and healthy lifespan. This approach maximizes our potential for success and our ability to efficiently deliver solutions to patients for broader, more impactful outcomes."

Under the terms of the license agreement, which covers all indications, BioAge will make an upfront payment to Amgen, who is entitled to receive development and regulatory milestone payments plus royalties based on annual net sales. Amgen will also receive BioAge shares. BioAge will be responsible for all development, manufacturing, and commercialization of BGE-105 worldwide.

"Because it targets a fundamental mechanism of muscle aging, BGE-105 could be used to treat multiple acute and chronic indications, potentially improving muscle strength in frail elderly people, shortening rehabilitation time after hip fracture, or increasing mobility after extended bed rest," Fortney said. "The licensing agreement represents a major milestone toward our vision of developing a pipeline of treatments that separate growing older from disability and disease, dramatically improving the quality of life as we age."

On April 14, 2021 Wugen Inc., a clinical stage biotechnology company developing a pipeline of allogeneic, off-the-shelf cell therapies, reported the appointment of Daniel M. Kemp Ph.D., as the company’s Chief Executive Officer (Press release, Wugen, APR 14, 2021, View Source [SID1234578030]). Dr. Kemp is an accomplished researcher with over 30 publications and built his career at Novartis, Merck and Takeda over 20 years leading pipeline initiatives from early discovery through to the clinic. More recently, he was responsible for transacting Takeda’s key strategic partnerships in the CAR-NK and CAR-T cell therapy space.

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As CEO of Wugen, Kemp will initially focus on propelling the company’s allogeneic memory NK and CAR-T cell therapy platforms through mid-stage clinical development and continue to build on Wugen’s current strategic partnerships. Dr. John McKearn, the founding Chief Executive Officer of Wugen and a managing director at RiverVest Venture Partners, will remain as Chairman of the Board of Directors.

"We welcome Dan as an experienced strategist with invaluable knowledge of cell therapy development and strong research background. We look forward to him leading the company’s rapid growth and innovative pipeline of cell therapies to treat both hematologic and solid organ malignancies," said John McKearn. "His leadership experience and ability to make good strategic business decisions will be critical to Wugen’s path forward."

Dr. Kemp added, "I am thrilled to be joining such an exceptional team at Wugen. I’m incredibly impressed with how rapidly the company has leveraged its foundational partnerships with Washington University, HCW Biologics and Alpha Biopharma to advance its lead Memory NK cell therapy through clinical proof of concept for relapsed/refractory AML, in addition to advancing its "off-the-shelf" fratricide-resistant CAR-T cell therapy for clinical testing later this year to treat T-cell cancers. I thank John for his trust in me and in the strong foundation that he has created for Wugen."

During his tenure at Takeda, Dr. Kemp was a formative member of the company’s oncology cell therapy leadership team where he transacted a series of cornerstone collaborations that established a pipeline of CAR-NK, CAR-T and gdT cell programs. Notably, Dan spearheaded the in-licensing of Takeda’s flagship allogeneic NK cell program from MD Anderson Cancer Center in late 2019, which consolidated the emergence of NK cell therapies as an important therapeutic platform in the immuno-oncology space. He served on the Boards of GammaDelta Therapeutics and Adaptate Biotherapeutics, both companies that he was instrumental in creating in 2017 and 2019, respectively. Previously, Dr. Kemp was Senior Vice President at Beryllium (acquired by UCB) where he was responsible for directing drug discovery partnerships, and prior to that he directed drug discovery programs at Merck Research Labs ranging from target validation to clinical proof of concept. At Novartis Institutes for BioMedical Research, he led an early discovery team in diabetes and metabolic diseases.

Dr. Kemp received his BSc and Ph.D. in molecular pharmacology from the University of Kent at Canterbury, UK. He was awarded an HHMI Fellowship at Harvard Medical School and carried out his postdoc research on pancreatic beta-cell biology at Massachusetts General Hospital.

On April 14, 2021 Boehringer Ingelheim and The University of Texas MD Anderson Cancer Center reported the extension and expansion of their joint Virtual Research and Development Center (VRDC) to explore new molecules from Boehringer Ingelheim’s KRAS (Kirsten rat sarcoma) and TRAILR2 (TNF-related apoptosis-inducing ligand receptor 2) portfolios for the potential treatment of lung cancer, particularly non-small cell lung cancer (Press release, Boehringer Ingelheim, APR 14, 2021, View Source [SID1234578023]).

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The collaboration, launched in 2019, has successfully combined MD Anderson’s innovative clinical research infrastructure and the patient-driven drug development capabilities of the Therapeutics Discovery division with Boehringer Ingelheim’s pipeline of innovative cancer medicines and expertise in advancing breakthrough therapies. Under the new agreement, joint research will continue for five additional years.

"Our collaboration with MD Anderson strengthens our determination to find solutions for the most difficult-to-treat cancers, and this latest commitment marks an important step forward, especially in our holistic KRAS program," said Norbert Kraut, Ph.D., Head of Global Cancer Research at Boehringer Ingelheim. "We are delighted to extend our collaboration with MD Anderson. With our shared dedication to patients and like-minded approach to innovation, we have the potential to bring the medicines to lung and gastrointestinal cancer patients that they so much need."

The flexible nature of the VRDC agreement allows the teams to expand their lung cancer indication programs targeting KRAS and TRAILR2, including Boehringer Ingelheim’s first-in-class SOS1::pan-KRAS inhibitor (BI 1701963), inhibitors of KRAS G12C (BI 1823911) and MEK (BI 3011441), as well as a novel undisclosed bi-specific TRAILR2 agonist.

The collaboration already has resulted in a number of joint publications1, conference presentations (including at the 2021 AACR (Free AACR Whitepaper) Annual Meeting2) and clinical trial activities. Boehringer Ingelheim is pursuing a comprehensive mutant KRAS-directed effort with multiple programs expected to enter the VRDC with MD Anderson.

"We are proud to expand our work with Boehringer Ingelheim in a very exciting drug-development space – advancing novel targeted therapies against KRAS and TRAILR2," said Timothy Heffernan, Ph.D., Head of Oncology Research in Therapeutics Discovery at MD Anderson. "Our collaboration is built upon a strong working relationship and complementary expertise, highlighting how an academic center and a pharmaceutical company can strategically work together to advance innovative therapies for patients with cancer."
MD Anderson’s Therapeutics Discovery division is anchored by an experienced team of drug development experts working to advance the next generation of cancer therapies. The Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform, led by Heffernan, performs cutting-edge translational research to rapidly advance new therapies to the patients most likely to benefit.

KRAS is the most frequently mutated cancer-causing oncogene. One in seven of all human metastatic cancers expresses KRAS mutations, with mutation rates of more than 30 percent in lung adenocarcinomas, more than 40 percent in colorectal cancers and more than 90 percent in pancreatic cancers. No approved treatments for KRAS-driven cancers exist currently, further underscoring the need for continued investment in research and development. Tumor cell-selective activation of TRAILR2 can trigger cancer cell death in indications of high medical need, including lung and gastrointestinal malignancies.

Intended Audiences
This press release is issued from our corporate headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

Disclosures
MD Anderson has an institutional financial conflict of interest with Boehringer Ingelheim related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan.

On April 14, 2021 Aura Biosciences, a clinical-stage oncology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the online publication of data in the peer-reviewed medical journal Cancer Immunology Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), that supports the broad application of the Company’s proprietary VDC technology platform for treating cancer (Press release, Aura Biosciences, APR 14, 2021, View Source [SID1234578022]). The manuscript, titled, "Virus-like Particle-drug Conjugates Induce Protective, Long-lasting Adaptive Anti-Tumor Immunity in the Absence of Specifically Targeted Tumor Antigens," describes promising long term anti-tumor activity of AU-011, the Company’s lead VDC candidate, as a monotherapy and in combination with checkpoint inhibitor antibodies in preclinical studies conducted in collaboration with the Center for Cancer Research at the National Cancer Institute of the National Institutes of Health.

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"Collectively, these promising results confirm treatment of AU-011 resulted in targeted tumor cytotoxicity with hallmarks of immunogenic cell death that may promote a durable anti-tumor immune response," said Cadmus C. Rich, MD, MBA, Chief Medical Officer and Head of R&D for Aura. "Additionally, the additive activity of AU-011 in combination with checkpoint inhibitors has shown a high level of durable complete responses and prevention of tumor recurrence, warranting continued research into its potential clinical utility to effectively treat multiple types of tumors like non-muscle invasive bladder cancer as a primary treatment and further prevent metastatic disease."

Key findings from the manuscript include:

In vitro and in vivo studies in immunocompetent murine tumor models demonstrated a dose-dependent cytotoxic response of AU-011 with an upregulation of the markers of immunogenic cell death like caspase-1 and calreticulin surface expression demonstrating that AU-011 mediated cell death was able to generate potent immune stimulatory conditions within the tumor microenvironment.

A single in vivo dose administration of AU-011 caused rapid cell death leading to long term complete responses in 50% of all animals. Combination with immune checkpoint inhibitor antibodies improved therapeutic efficacy resulting in 70-100% complete response rate that was durable 100 days post-treatment with 50-80% of those animals displaying protection from secondary tumor re-challenge.

Depletion studies of CD4+ or CD8+ T-cells at the time of AU-011 treatment or tumor re-challenge confirmed the involvement of both cell populations in the mechanism of action of AU-011 and the promotion of long-lasting anti-tumor protection.

"These promising findings further reinforce the therapeutic advantages of VDCs in treating cancer compared to other available treatments, which include the broad tumor selectivity and multivalent binding of the virus-like particles compared to antibodies, the ability to deliver hundreds of cytotoxic molecules and the generation of long-lasting anti-tumor immunity," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura. "While our initial clinical focus has been in ocular oncology, our VDC approach has wide application as a single agent and as a combination therapy in a variety of solid tumors, including non-muscle invasive bladder cancer, which is expected to enter the clinic in 2022 We remain focused on advancing our novel VDC approach to transform the treatment of tumors and improve outcomes for patients with cancer."

About AU-011 (belzupacap sarotalocan)

AU-011 is a first-in-class virus-like drug conjugate (VDC) therapy in development for the first line treatment of choroidal melanoma. The virus-like component of the VDC selectively binds unique heparan sulphate proteoglycans (HSPGs) that are modified and overexpressed on the tumor cell surface of choroidal melanoma (and other tumor types) and delivers a potent cytotoxic drug that is activated with infrared light. Upon activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant melanoma cells with a pro-immunogenic cell death that can activate the immune system generating long term anti-tumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. The possibility of early treatment intervention and the activation of the immune system could lead to a reduction in the metastases rate for patients with this life-threatening disease. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration and is currently in Phase 2 clinical development.