On April 12, 2021 Schrödinger (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, reported that new preclinical data from its CDC7 inhibitor program in a poster session on April 10, 2021, during the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Virtual Meeting (Press release, Schrodinger, APR 12, 2021, View Source [SID1234577928]). The data showed that Schrödinger’s picomolar CDC7 inhibitors were highly selective and inhibited tumor cell growth alone and in combination with several approved and investigational cancer treatments.

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CDC7 is a protein kinase that is required for DNA replication initiation and is involved in DNA replication stress response. CDC7 is thought to be linked to cancer cells’ proliferative capacity and ability to bypass normal DNA damage responses. Targeting proteins that play important roles in DNA replication and replication stress is gaining momentum as a new therapeutic approach based on the proliferative capacity of cancer cells to bypass DNA damage responses.

"Based on our preclinical data, we believe we have identified the most potent CDC7 inhibitors reported to date, capable of inhibiting cell growth and causing programmed cell death in both blood and solid tumors, while sparing healthy cells," said Karen Akinsanya, Ph.D, executive vice president, chief biomedical scientist and head of discovery R&D at Schrödinger. "We’re excited by the rapid progress in our internal pipeline. We look forward to selecting development candidates and moving multiple oncology programs into IND-enabling studies this year."

Additional Details About the Data Presented at AACR (Free AACR Whitepaper)

The presentation, "Discovery of novel CDC7 inhibitors that disrupt cell cycle dynamics and show anti-proliferative effects in cancer cells," highlighted preclinical data with multiple lead molecules discovered by Schrödinger scientists. The company’s CDC7 inhibitor compounds demonstrated dose-dependent picomolar potency as measured by in vitro inhibition of CDC7 enzymatic activity. The compounds were highly selective, inducing apoptosis in cancer cells but not in normal fibroblasts. They also showed synergy with several approved and investigational cancer therapies that modulate apoptosis, DNA repair mechanisms and DNA checkpoints, including venetoclax, olaparib, ceralasertib and adavosertib. Additionally, Schrödinger’s compounds significantly inhibited tumor growth in mouse models of both acute myeloid leukemia and colorectal cancer. Taken together, these data provide further rationale for developing CDC7 inhibitors as a potential therapeutic approach, particularly in combination with existing therapies.

Schrödinger’s MALT1 and Wee1 Programs

Schrödinger is continuing to advance its MALT1 and Wee1 inhibitor programs. Targeting MALT1 is emerging as a potential therapeutic strategy to treat certain relapsed or resistant B-cell lymphomas and chronic lymphocytic leukemia. In December 2020, Schrödinger scientists presented preclinical data at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting highlighting that its MALT1 inhibitors demonstrated anti-tumor activity alone and in combination with approved anti-cancer therapies in models of B-cell lymphoma.

Similar to CDC7, Wee1 targets cancer through replication stress and DNA repair mechanisms. The company has identified highly selective, potent Wee1 inhibitors with optimized drug-like properties, including no observable inactivation of CYP3A4, a key liver enzyme. Lead compounds exhibited favorable pharmacokinetic properties and strong anti-tumor activity in preclinical models.

Based on the strong data generated to date, Schrödinger is on track to move forward with IND-enabling studies for its MALT1, CDC7 and Wee1 programs. Subject to completion of the preclinical data packages, the company expects to submit up to three IND applications in 2022, with the first submission expected in the first half of next year.

Webcast Information

Today at 10:00 a.m. ET, Schrödinger will host a webcast to review the preclinical data presented from its CDC7 program at the virtual AACR (Free AACR Whitepaper) Annual Meeting. The company will also provide an overview of two other internal programs, MALT1 and Wee1, as well as highlight the role of its computational platform in accelerating the discovery of its novel molecules. The webcast will be available under "News & Events" in the investors section of Schrödinger’s website, View Source and will be archived for approximately 7 days.

On April 12, 2021 FairJourney Biologics S.A (FJB) and IONTAS Limited (IONTAS), leaders in the discovery and optimisation of VHH fully human antibodies, reported a collaboration with global immunology company, argenx to harness IONTAS’ proprietary mammalian display technology (Press release, FairJourney Biologics, APR 12, 2021, View Source [SID1234577927]). The goal of the collaboration is to explore diverse panels of novel antibody candidates, with the potential to advance select candidates into the argenx discovery pipeline.

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Under the terms of the agreement, FJB and IONTAS will provide argenx with access to IONTAS’ novel mammalian display technology, which can generate abundant therapeutic antibody leads, selecting for key attributes that may address the novel targets or pathways that argenx is exploring. The agreement will also provide a dedicated full-time FJB/IONTAS team assigned to the project.

FJB/IONTAS and argenx have highly complementary capabilities for identification of potential next-generation antibody candidates, including argenx’s pipeline of investigational immunology therapies aimed at improving the lives of people living with severe autoimmune diseases and cancer. Through its Immunology Innovation Program, argenx collaborates with leading researchers to translate immunology breakthroughs in disease biology into differentiated therapeutic antibodies.

Dr António Parada, CEO at FairJourney Biologics and IONTAS commented: "We have gained considerable experience in antibody discovery through mammalian display for use in generating therapeutics with specific properties.

Additionally, we continue to make improvements to the technology that will allow more diverse applications. We look forward to growing our relationship with argenx and applying our deep knowledge and experience to generate a diverse set of antibodies for potential immunological application."

For further information on mammalian display technology, please visit: fjb.pt/_mammalian-display/

On April 12, 2021 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the presentation of a scientific poster detailing additional promising preclinical results for its LYT-210 antibody at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Virtual Meeting (Press release, PureTech Health, APR 12, 2021, View Source [SID1234577926]).

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LYT-210 is a novel, fully human monoclonal antibody (mAb) directed against T cells bearing γδ1 receptors, which are known to suppress the anti-tumor immune response. The new research shared at AACR (Free AACR Whitepaper) demonstrates that LYT-210 is both highly specific and highly potent, rapidly inducing cell death of immune-suppressive γδ1 T cells, while sparing other T cells that play important roles in a healthy immune response. The research was conducted in vitro using both patient blood and cancer tissue. LYT-210 has potential as either a single agent or in combination with checkpoint inhibitors and other anti-cancer treatments.

"The role of γδ1 T cells in cancer immune suppression has come into sharp focus in recent years. We now know that these cells deploy multiple immunosuppressive signals to dampen the anti-tumor response and enable the cancer to grow and spread," said Aleksandra Filipovic, M.D. Ph.D., Head of Oncology at PureTech. "We are excited by these new data demonstrating that our LYT-210 therapeutic candidate can precisely target and swiftly deplete pathogenic γδ1 T cells. We believe that removing these culprits from the tumor microenvironment systemically may have the potential to reawaken the immune system and contribute to a strong anti-tumor response. Moreover, both we and others in the field have established that a heightened presence of pathogenic γδ1 T cells in tumor tissue and blood is correlated with more aggressive disease, poorer response to some therapies and a lower chance of survival. Given those links, we believe that the biomarker-centric approach we are developing as part of our γδ1 T cell program may have the potential to identify and select the patients who are most likely to benefit from LYT-210 in the clinic and beyond."

γδ1 T cells are upregulated in multiple solid tumors including breast cancer, glioblastoma, melanoma and pancreatic cancer. They suppress the immune response through multiple mechanisms, including blocking effector T cells, hindering antigen-presenting dendritic cells, restricting the anti-tumoral activity of γδ2 T cells and attracting tumor-associated macrophages and myeloid-derived suppressor cells to the tumor microenvironment. Pathogenic γδ1 T cells are distinct from cytotoxic γδ T cells, which are being used for adoptive T cell transfer or therapeutic engagement with bispecific antibodies. Depleting pathogenic γδ1 T cells has the capacity to modulate both innate and adaptive immunity, and their distinct phenotypic and functional properties make them excellent potential therapeutic targets.

On April 12, 2021 Seneca Therapeutics, Inc. ("STI"), a clinical-stage biopharmaceutical company dedicated to the development of targeted oncolytic immunotherapeutics based on Seneca Valley Virus (SVV-001), reported the poster presentation of Seneca Therapeutics’ abstract titled "Oncolytic Seneca Valley Virus (SVV) overcomes resistance to checkpoint inhibitor therapies in neuroendocrine and melanoma murine models expressing the receptor for SVV" (Press release, Seneca Therapeutics, APR 12, 2021, View Source [SID1234577925]). Key points from the presentation:

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SVV-001 demonstrates the ability to turn cold tumors hot;
Intratumoral administration of SVV-001 in combination with a checkpoint inhibitor demonstrates up to six fold increase in anti-tumor response over SVV-001 alone or check point inhibitor therapy alone;
SVV-001 specifically targets, infects and kills TEM8 positive cancer cells. No cell killing was observed in normal cells;
RNA seq data confirm up regulation of genes known to stimulate an immune response;
A randomized Phase III clinical study comparing SVV-001 administered IT in combination with Opdivo and Yervoy compared to Opdivo and Yervoy alone in TEM8 positive neuroendocrine tumors and neuroendocrine carcinomas is planned to begin later in 2021. STI is also developing SVV-001 for intravenous use in TEM8 positive tumors as well as developing SVV-001 to deliver armed viruses to TEM8 positive tumor cells.

On April 12, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported initiation of its Phase 1/2 FORGE-1 study of TPX-0131, a potent inhibitor of the anaplastic lymphoma kinase (ALK) and multiple resistant mutations of ALK (Press release, Turning Point Therapeutics, APR 12, 2021, View Source [SID1234577924]).

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The investigational new drug (IND) application for TPX-0131 is Turning Point’s third IND to be cleared by the FDA in less than 2 years, and FORGE-1 is the company’s fourth clinical study to initiate during the same period of time.

The study was initiated in Australia, with U.S. site activations now planned.

"With a lack of available therapies to address a broad spectrum of ALK resistant mutations, we are encouraged by the preclinical potency for TPX-0131, particularly against the G1202R solvent front mutation which is reported to occur in more than 40% of biopsies with resistance mutations," said Ben Solomon, M.D., principal investigator for the FORGE-1 study, a medical oncologist and group leader of the Molecular Therapeutics and Biomarkers Laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia. "In addition, TPX-0131 has been shown preclinically to penetrate the central nervous system, which is important in the treatment of patients with ALK-positive non-small cell lung cancer as the disease often progresses in the brain."

ALK alterations are estimated to be responsible for 3% to 5% of non-small cell lung cancer (NSCLC) cases annually in the U.S. and EU5 countries. In preclinical studies, TPX-0131 potently inhibits wildtype ALK and is more potent in comparison to approved ALK inhibitors against many clinically observed resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and multiple compound mutations. In addition, TPX-0131 has shown brain tissue penetration after repeat oral dosing.

"Our clinical study of TPX-0131 will begin with a Phase 1 dose finding portion in patients previously treated with up to 2 prior ALK tyrosine kinase inhibitors, a population we believe is underserved today by available therapies that are less potent against known resistant mutations of ALK," said Mohammad Hirmand, M.D., chief medical officer of Turning Point Therapeutics.

The Phase 1 dose finding portion of the FORGE-1 study will enroll patients with locally advanced or metastatic TKI-pretreated ALK-positive NSCLC. Patients with up to 2 prior ALK TKIs and 1 prior platinum-based chemotherapy will be enrolled. The study endpoints include safety and tolerability, determination of the maximum tolerated dose and/or the recommended Phase 2 dose, and objective response rate by RECIST 1.1.