On June 28, 2022 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported that selection of a potential first-in-class Pol Theta Helicase development candidate (DC) (Press release, Ideaya Biosciences, JUN 28, 2022, View Source [SID1234616348]).

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The Pol Theta Helicase DC is a potential first-in-class small molecule inhibitor of the helicase domain of DNA Polymerase Theta. IDEAYA is collaborating with GSK on IND-enabling studies to support the evaluation of the Pol Theta Helicase DC in combination with niraparib, GSK’s PARP inhibitor, for patients having tumors with BRCA or other homologous recombination (HR) mutations or homologous recombination deficiency (HRD).

"We are excited about potential clinical development opportunities for this potential first-in-class Pol Theta Helicase inhibitor. Pol Theta promotes DNA repair by Microhomology-Mediated End-Joining (MMEJ), an error-prone mutagenic DNA repair pathway, which is active in BRCA mutant and other HRD cancer cells. PARP1 is also involved in MMEJ DNA repair, supporting a hypothesis for synergistic combination of our Pol Theta Helicase DC with niraparib," said Michael White, Senior Vice President and Chief Scientific Officer of IDEAYA Biosciences.

"The development candidate has demonstrated robust in vivo efficacy in combination with niraparib, with significant tumor regressions and durable responses in multiple cancer models. We believe the Pol Theta helicase and niraparib combination has the opportunity to deliver meaningful patient benefit," said Benjamin Schwartz, Ph.D., Vice President, Head of Oncology Synthetic Lethality Research Unit at GSK.

IDEAYA and GSK are targeting an IND submission for the Pol Theta Helicase DC, subject to satisfactory completion of ongoing preclinical and IND-enabling studies, to enable first-in-human studies in the first half of 2023.

IDEAYA and GSK are collaborating on the ongoing IND-enabling studies, and GSK will lead clinical development for the Pol Theta program. GSK holds a global, exclusive license to develop and commercialize the Pol Theta Helicase DC and is responsible for all research and development costs for the program, including those incurred by IDEAYA. IDEAYA is eligible to receive future development and regulatory milestones of up to $485 million aggregate, inclusive of preclinical and clinical milestones of up to $10 million aggregate for advancing this asset through IND effectiveness.

Upon potential commercialization, IDEAYA will be eligible to receive up to $475 million of commercial milestones and tiered royalties on global net sales by GSK, its affiliates and their sublicensees ranging from high single digit to sub-teen double digit percentages, subject to certain customary reductions.

On June 28, 2022 Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immuno-modulatory antibodies for cancer immunotherapy, reported a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ., USA, to evaluate the oncolytic virus BT-001 in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a Phase I/IIa clinical trial for the treatment of patients with solid tumors (Press release, Transgene, JUN 28, 2022, View Source [SID1234616332]).

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Under the terms of the supply agreement, MSD will provide pembrolizumab to be used in combination with BT-001 in the ongoing Phase I/IIa clinical trial.

"By combining BT-001 with the anti-PD-1 drug KEYTRUDA we expect to optimize the patient’s immune response to induce a strong and effective anti-tumor response. This agreement will allow us to move further on the clinical development of our promising co-developed oncolytic candidate BT-001" said Hedi Ben Brahim, CEO of Transgene.

"We are very pleased to be signing another collaboration with MSD, supporting the expansion of the clinical trial program of BT-001, the oncolytic virus expressing our proprietary anti-CTLA-4 antibody, jointly developed by Transgene and BioInvent. It marks a further validation of our expanding and promising clinical pipeline of anti-cancer treatments, which currently encompasses three compounds in four ongoing clinical trials" added Martin Welschof, CEO of BioInvent.

Recruitment in the clinical study (NCT04725331) is ongoing. The trial is a Phase I/IIa of BT-001, which is being co-developed as part of a 50/50 collaboration between Transgene and BioInvent, as a single agent and in combination with KEYTRUDA for the treatment of solid tumors.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the trial

The ongoing Phase I/IIa (NCT04725331) study is a multicenter, open label, dose-escalation trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment). Patient inclusions are ongoing in Europe (France, Belgium) and the trial has been authorized in the US.

This Phase I is divided into two parts. In part A, patients with metastatic/advanced tumors receive single agent, intra-tumoral administrations of BT-001. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab. The Phase IIa will evaluate the combination regimen in several patient cohorts with different tumor types. These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment.

About BT-001

BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody will be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.

On July 28, 2022 QIMR Berghofer reported that it has signed an exclusive worldwide licence agreement with Proteomics International Laboratories Ltd allowing the company to develop and commercialise a simple blood test for early detection of the most common form of oesophageal cancer (Press release, QIMR Berghofer Medical Research Institute, JUN 28, 2022, View Source [SID1234616313]).

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Oesophageal adenocarcinoma affects the section of the digestive tract just above the stomach and is potentially fatal when diagnosed late. Unfortunately, early symptoms are vague and often masked by chronic acid reflux which means patients don’t realise something is wrong until the disease is at a late stage and symptoms become more severe and obvious. Currently, oesophageal cancer diagnosis involves the invasive and expensive specialist medical procedure of upper endoscopy.

Proteomics International will use blood biomarkers discovered by QIMR Berghofer scientists to develop and commercialise the simple blood test, after a joint study of more than 300 patients earlier this year validated research findings.

The blood test will target patients with Barrett’s oesophagus which is a non-cancerous condition that increases the risk of developing oesophageal cancer.

Associate Professor Michelle Hill, the head of QIMR Berghofer’s Precision and Systems Biomedicine Laboratory, who led the discovery of the biomarkers, said the agreement could lead to better screening for oesophageal cancer.

"It is incredibly rewarding to see our research work in the laboratory lead to an agreement like this with Proteomics International that could make such a difference for patients and the health system," Associate Professor Hill said.

"We envisaged that blood test-based screening will allow better use of health resources by identifying the right patients for endoscopy while reducing unnecessary procedures. Most importantly, once found, the pre-cancerous cells and early-stage oesophageal adenocarcinoma can be effectively treated, thereby improving survival from this deadly cancer."

Proteomics International managing director Dr Richard Lipscombe said oesophageal cancer is an area of significant unmet medical need.

"At-risk patients are currently screened with invasive and costly endoscopy procedures. Instead, this panel of biomarkers—or protein ‘fingerprints’ in the blood—can detect the early stages of oesophageal adenocarcinoma which we hope to do using a simple blood test," Dr Lipscombe said.

The licence agreement comes after the two organisations signed a Memorandum of Understanding in 2020 to improve detection of oesophageal adenocarcinoma.

Proteomics International will now undertake additional studies to confirm the diagnostic performance of the potential new blood test, which will take approximately six months.

QIMR Berghofer’s Director and CEO Professor Fabienne Mackay said the signing of the licence agreement with Proteomics International was a great example of scientists and companies working together to improve health outcomes.

"At QIMR Berghofer we actively encourage and highly value our collaborations with our commercial partners such as Proteomics International, because we know this can help take our impactful medical research from the bench to the bedside to achieve better health for patients," Professor Mackay said.

On June 28, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that the U.S. Food and Drug Administration (FDA) cleared its investigational new drug (IND) application for its MALT1 inhibitor, SGR-1505. Schrödinger expects to initiate a Phase 1 clinical trial of SGR-1505 in patients with relapsed or refractory B-cell lymphoma in the second half of 2022 (Press release, Schrodinger, JUN 28, 2022, View Source [SID1234616334]).

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"Based on the preclinical data for SGR-1505, we believe we have an opportunity to advance a potential best-in-class MALT1 inhibitor into the clinic," stated Karen Akinsanya, Ph.D., president of R&D, therapeutics at Schrödinger. "There is a significant medical need for patients with relapsed or refractory B-cell lymphoma who have exhausted currently approved treatment options, and we look forward to initiating our Phase 1 clinical study of SGR-1505 later this year."

The planned multi-center, dose-escalation study will be conducted in patients with relapsed or refractory B-cell malignancies to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary signals of therapeutic activity of SGR-1505 as a monotherapy. Once the recommended dose is determined, an expansion cohort is planned to evaluate SGR-1505 in combination with other anti-cancer agents, such as BTK and BCL-2 inhibitors, in patients with specific B-cell malignancies.

"Our platform, which combines physics and machine learning, enabled us to accurately assess 8.2 billion compounds computationally and to synthesize only 78 molecules over a 10-month period of iterative "design, make, test" optimization cycles, ultimately selecting SGR-1505 as our development candidate," said Robert Abel, Ph.D., chief computational scientist at Schrödinger. "FDA clearance of the IND for SGR-1505 marks an important milestone for our MALT1 program and underscores the impact of incorporating a digital chemistry strategy into research programs."

About SGR-1505
SGR-1505 is a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor that was discovered using Schrödinger’s proprietary physics-based computational platform. MALT1 is a protease that is downstream of Bruton’s tyrosine kinase (BTK), in the NF-kB signaling pathway. Constant activation of NF-kB is a hallmark of several subtypes of lymphoma. MALT1 is considered a potential therapeutic target for several non-Hodgkin’s B-cell lymphomas. Data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting showed that inhibiting MALT1 may provide additional therapeutic options for patients with certain subtypes of non-Hodgkin’s B-cell lymphomas such as ABC-DLBCL, with the possibility of expanding into other B-cell lymphomas such as mantle cell lymphoma. Furthermore, the data showed that Schrödinger’s MALT1 inhibitors demonstrated strong anti-tumor activity alone and in combination with BTK inhibitors and overcame drug-induced resistance in samples derived from patients with relapsed and resistant B-cell lymphomas. SGR-1505 is initially being developed for the treatment of non-Hodgkin’s B-cell lymphomas.

On June 28, 2022 Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported the hiring of Jan M. Van Tornout, M.D., MSc., as chief medical officer, and Gordon Schooley, Ph.D., as chief regulatory officer (Press release, Elevar Therapeutics, JUN 28, 2022, View Source [SID1234616351]).

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Van Tornout, an accomplished hematologist-oncologist, genetic epidemiologist and pharma-biotech executive, joins Elevar after serving as acting chief medical officer of biotechnology company Tyme Technologies, Inc. since March 2021. He brings more than 25 years’ experience in the medical industry and related academia, including over 15 years successfully developing drugs across the full spectrum of hematological, oncological and immuno-oncological indications from pre-investigational new drug (IND) meeting through Phase 4.

"Jan Van Tornout’s broad experience and demonstrated leadership in every phase of the clinical development process, and his interest in the potential of drugs that address gaps in critical medical treatments, make him an ideal addition to the Elevar team," said Dr. Saeho Chong, chief executive officer of Elevar. "We are pleased to add him to our leadership team."

Van Tornout’s clinical management and development experience includes work for Moleculin Biotech, Inc., Bright Peak Therapeutics, Cyclacel Pharmaceuticals, GlaxoSmithKline, Puma Biotherapeutics, Maverick Therapeutics, ERT Inc., HUYA Bioscience Int’l, Gradalis Inc., Inovio Pharmaceuticals, Natera Inc., Bristol-Myers Squibb and Amgen. He played an instrumental role in two successful NDAs, led several INDs and has expertise in all phases of clinical trials.

Van Tornout previously held academic appointments at the University of Southern California (USC), with a clinical appointment as attending pediatric hematologist-oncologist at Children’s Hospital Los Angeles. He earned his Doctor of Medicine from the Katholieke Universiteit Leuven (KUL), Leuven, Belgium, a Master of Science in classical philosophy from KUL and a Bachelor of Science from the Faculté Notre-Dame de la Paix, Namur, Belgium. He obtained his certification as a pediatrician from the Gasthuisberg University Hospitals, KUL, and completed his training as a pediatric hematologist-oncologist at Children’s Hospital. Van Tornout earned a Master of Science in applied biometry from USC and completed a post-doctoral fellowship in molecular epidemiology at USC.

Schooley, a global regulatory leader with more than 30 years of drug development experience, joins Elevar after nine years as chief regulatory officer for BeyondSpring Pharmaceuticals Inc., a global, clinical-stage biopharmaceutical company that develops immuno-oncology cancer therapies.

"Careful navigation of the road to regulatory approval is so critical to the clinical development process and Gordon Schooley has demonstrated his leadership in this discipline throughout his distinguished career," said Chong. "His addition to the Elevar team adds valuable perspective with respect to both regulatory strategy and execution, and will bolster our efforts to fulfill the unmet needs of patients awaiting new therapeutic options."

Schooley has spent more than a quarter century at the vice president level or higher, working in both startup and large company environments. He’s led global development teams through every clinical development milestone; worked closely with regulatory bodies in several different countries; overseen successful breakthrough designations and accelerated approvals; and managed complex label negotiations for initial product approvals.

Prior to BeyondSpring, Schooley spent seven years as a consultant for drug development activities related to clinical development, biostatistics and regulatory affairs. He previously worked at SkyePharma PLC/Pacira Pharma, Alliance Pharmaceuticals and Allergan/Herbert Labs.

Schooley holds a doctorate in biostatistics from the University of Michigan School of Public Health. He earned a Master of Science in statistics and Bachelor of Science in business management at Brigham Young University.