PACT Reports New Data on First-of-its-Kind Personalized Neoantigen Platform for Adoptive T Cell Therapies at American Association for Cancer Research (AACR) Annual Meeting 2022

On April 11, 2022 PACT Pharma, Inc., a clinical-stage company developing transformational personalized neoantigen-specific T cell receptor (neoTCR) T cell therapies for the eradication of solid tumors, reported that new data highlighting several aspects of its first-of-its-kind personalized neoantigen platform for adoptive cell therapies were presented in five separate poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, PACT Pharma, APR 11, 2022, View Source [SID1234612018]). The breadth of presented data reflects the expansive collection of pioneering insights into patient-specific TCR repertoires against solid tumors that the company has been able to accumulate through analysis of research samples, as well as patient samples from its ongoing first-in-human Phase 1 trial. The AACR (Free AACR Whitepaper) conference is being held April 8-13, 2022, in New Orleans, Louisiana.

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"The scope of presented findings at AACR (Free AACR Whitepaper) highlights the significant progress that we have made across all aspects of our unique neoTCR T cell therapy platform, spanning identification and verification of patient-specific tumor driving mutations, gene editing, cell manufacturing, machine learning and bioinformatics," said Stefanie Mandl, Ph.D., senior vice president, head of research at PACT Pharma. "This continued progress speaks to the dynamic research and development approach that we are undertaking at PACT, as we aggressively advance our clinical-stage assets in human studies while using the evolving data set and learnings from our Phase 1 trial to continue to enhance various aspects of our technology platforms. This constellation of activities is focused on the single goal of bringing much needed, first-of-its kind neoTCR T cell therapies to patients battling solid tumors."

PACT is currently conducting a Phase 1 clinical trial evaluating the safety, tolerability and feasibility of adoptive cell therapy with its non-viral PACT^NV gene-edited autologous neoTCR T cells in advanced and metastatic solid tumors. This trial, in combination with extensive preclinical studies, has provided the company with unique data sets and insights derived from the core technologies that comprise its personalized adoptive T cell therapy platform for the treatment of solid tumors.

Key presented findings at AACR (Free AACR Whitepaper) included:

imPACT Isolation Technology Platform for TCR Discovery and Validation: Identifies TCRs to Patient-Specific Tumor Driver Mutations

By applying its imPACT Isolation Technology platform to peripheral blood samples of more than 170 patients with solid tumors, PACT generated key findings on the relative distribution of patient-private mutations versus mutations in known cancer driver genes. Data demonstrated that tumor-specific T cells preferentially recognize patient-private mutations. However, TCRs that target known cancer driver mutations were shown to constitute > 5% of the functionally characterized TCRs, highlighting a high-value opportunity for "off-the-shelf" TCR therapies. Based on these findings, PACT is expanding its platform to develop such "off-the-shelf" treatments, and anticipates filing an investigational new drug (IND) application in the second half of 2022.

Proprietary Machine Learning and Bioinformatics Optimize Personalized Treatment Strategies

In two separate AACR (Free AACR Whitepaper) posters, PACT highlighted its continued work building and utilizing its PACTImmune Database with extensive pre-, on- and post-treatment data from its ongoing Phase 1 trial. Analysis of this maturing data set with proprietary machine learning and bioinformatics produced new insights into patient-specific tumor immunogenicity in solid cancers, providing opportunities to optimize personalized neoTCR T cell treatment. The company’s application of its proprietary PACT-ESCAPE technology provided key learnings regarding neoepitope presentation escape mechanisms, which is a critical aspect of personalized TCR-based immunotherapy.

PACT^NV: Efficiently Enabling Single-Step Precision Gene Editing

In two separate poster presentations, PACT reported continued progress with PACT^NV, the company’s non-viral precision gene editing approach for generating clinical-grade TCR T cells for adoptive cell therapy. Importantly, the company has demonstrated the ability to execute precise, time-efficient, single-step gene editing to simultaneously knock-out TCR genes and insert neoantigen-specific TCRs isolated from a patient’s own blood. Furthermore, the company described its success incorporating additional complex modifications, which are intended to address challenges presented by the immunosuppressive nature of some tumor microenvironments, into the single-step gene editing process.

Copies of the posters presented at the AACR (Free AACR Whitepaper) conference are available on the "Events" page of the PACT Pharma website at: View Source

Vivace Therapeutics Presents New Preclinical Data Highlighting Strong Synergistic Activity for Combination of VT3989 and Osimertinib at American Association for Cancer Research (AACR) Annual Meeting 2022

On April 11, 2022 Vivace Therapeutics, Inc., a small molecule discovery and development company developing first-in-class therapies targeting the Hippo pathway, reported that new preclinical data on the company’s transcriptional enhanced associate domain (TEAD) autopalmitoylation inhibitor, VT3989, were reported at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Vivace Therapeurtics, APR 11, 2022, View Source [SID1234612016]). Presented findings demonstrated that the combination of VT3989 and osimertinib (Tagrisso), an epidermal growth factor receptor (EGFR) inhibitor, possessed enhanced anti-tumor activity and delayed tumor growth as compared to osimertinib alone in preclinical EGFR mutant tumor models. The AACR (Free AACR Whitepaper) conference is being held April 8-13, 2022, in New Orleans, Louisiana.

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Data reported in the poster presentation demonstrated that VT3989 exhibits strong synergistic activity with osimertinib. This was highlighted by the ability of the combination to enhance the blocking of tumor growth in EGFR mutant, non-small cell lung cancer (NSCLC) cell-line derived xenograft models, including the HCC827 model that is already known to be particularly sensitive to osimertinib. Furthermore, the combination of VT3989 and osimertinib significantly increased the life span of mice in an NCI-H1975 NSCLC CDX model as compared to osimertinib monotherapy.

Additionally, researchers showed similar synergistic activity in blocking tumor regrowth in human patient-derived xenograft models of EGFR mutant NSCLC. Of note, data demonstrated that TEAD inhibition achieved with VT3989 significantly delayed the re-emergence of tumor mass after osimertinib treatment resulted in non-palpable tumors. This finding offers evidence that EGFR mutant NSCLC relies upon dysfunction in the Hippo pathway to survive treatment with osimertinib, and can thus be targeted with TEAD inhibition.

"The exciting new data presented at AACR (Free AACR Whitepaper) not only support previous research highlighting the potency and selectivity of VT3989 as a TEAD inhibitor and its single agent anti-tumor activity in mesothelioma models, the findings also begin to build a compelling strategy around a synergistic combination treatment approach featuring VT3989 and EGFR inhibitors such as osimertinib," said Tracy Tang, Ph.D., vice president of biology at Vivace Therapeutics and lead author on the AACR (Free AACR Whitepaper) poster presentation. "We are eager to continue our pioneering research into the Hippo pathway and how addressing dysfunction in that pathway may pave the way for first-in-class cancer therapies capable of addressing the unmet needs of patients."

Vivace’s proprietary compounds inhibit palmitoylation of members of the TEAD protein family, including both covalent and non-covalent inhibitors. The company’s clinical candidate, VT3989, is currently in Phase 1 clinical trials. Pre-clinical research and development activities have demonstrated that the clinical candidate is active as a monotherapy against tumors that rely upon dysfunction of the Hippo pathway, and in combination with other anti-cancer therapies in additional tumor types.

The poster presented is available at the company’s website www.vivacetherapeutics.com.

Glenmark Specialty S.A. receives approval for conducting Phase 1 Clinical Trial of its Novel Molecule GRC 54276 in patients with Advanced Solid Tumors and Hodgkin’s Lymphoma

On April 11, 2022 Glenmark Pharmaceuticals Limited, an innovation-driven, global pharmaceutical company, reported that its subsidiary Glenmark Specialty S.A. (Glenmark) received approval from the Indian drug regulator, Drug Controller General of India (DCGI), to conduct a Phase 1 clinical trial of its novel small-molecule, GRC 54276, a hematopoietic progenitor kinase 1 (HPK1) inhibitor (Press release, Glenmark, APR 11, 2022, View Source [SID1234612015]). GRC 54276 is one of the many novel molecules from Glenmark’s resident, Innovative Medicines Group, headed by Dr. Nikhil Amin, Chief Scientific Officer, specializing in the development of novel molecular entities for critical unmet medical needs. HPK1 is a key regulator of T cell, B cell and dendritic cell-mediated immune responses, which improves antitumor immunity by activating and priming T cells. GRC 54276 has shown tumor cell killing ability in preclinical studies as a single agent and as well in combination with checkpoint inhibitors, making it a high-priority target in immuno-oncology.

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The study will evaluate the safety and tolerability of GRC 54276 as a monotherapy, and also in combination with checkpoint inhibitors in patients with advanced solid tumors and Hodgkin’s lymphoma. Glenmark will initiate Phase 1 clinical trial in India by June 2022, and also plans to file an IND in the US and Clinical Trial Applications in Europe to kick-off a fully global clinical study program.

"Glenmark’s endeavor has been to provide innovative treatment solutions in its core therapeutic areas. We are delighted that our first novel molecule from the newly formed ‘Innovative Medicines Group’ within Glenmark has received approval from India’s drug regulator to initiate a Phase 1 clinical trial. This reinforces Glenmark’s growing capabilities of innovative clinical research and is a step closer in providing holistic solutions for cancer treatment," said Glenn Saldanha, Chairman & Managing Director, Glenmark Pharmaceuticals Limited.

Obsidian Therapeutics to Present Preclinical Data from cytoTIL15™ Program at the American Associate of Cancer Research (AACR) Annual Meeting 2022

On April 11, 2022 Obsidian Therapeutics, Inc., a biotechnology company pioneering engineered cell and gene therapies, reported it will present preclinical data highlighting its cytoTIL15 program during a poster session at the upcoming AACR (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Obsidian Therapeutics, APR 11, 2022, View Source [SID1234612014]). The abstract title has been posted to the AACR (Free AACR Whitepaper) Online Itinerary Planner, will be published in the online Proceedings of the AACR (Free AACR Whitepaper), and is detailed below.

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The data to be presented demonstrate significantly greater anti-tumor activity of cytoTIL15 therapy in vivo compared to conventional TIL + IL2 therapy in a human leukocyte antigen (HLA)-matched, allogeneic patient-derived xenograft (PDX) melanoma model, including greater persistence of cytoTIL15 cells in blood and lymphoid organs, superior tumor growth inhibition including complete responses, and increased infiltration of tumors with cytoTIL15 cells.

"We look forward to presenting these new data at AACR (Free AACR Whitepaper), which continue to validate the exciting potential of our cytoTIL15 therapy to improve the treatment of patients with solid tumors," said Jan ter Meulen, M.D., Ph.D., Chief Scientific Officer at Obsidian Therapeutics. "We are encouraged by the data demonstrating superior anti-tumor activity of cytoTIL15 cells in the absence of IL2 in a novel PDX tumor model. These data deliver preclinical proof of concept for the potential of cytoTIL15 therapy as a treatment for metastatic melanoma and will support the planned filing of an IND for our lead program, OBX-115, later this year."

Details of the poster presentation are as follows:

Abstract Number: 7994
Title: Allogeneic, IL-2-independent tumor-infiltrating lymphocytes expressing membrane-bound IL-15 (cytoTIL15) eradicate tumors in a melanoma PDX model through recognition of shared tumor antigens
Presenter: Dr. Jeremy Tchaicha, Director, Head of In Vivo Pharmacology, Obsidian Therapeutics
Date and Time: Section 18, April 13, 2022, 9:00 a.m.-12:30 p.m. CT
Abstract Summary: Current TIL therapy requires systemic administration of IL2 to promote TIL survival, and IL2-associated toxicities greatly limit patient eligibility and reduce the long-term clinical benefit of TIL therapy. Obsidian designed genetically engineered IL2-free TILs (cytoTIL15) to express a regulated form of membrane-bound IL15 for tunable long-term persistence, leading to enhanced persistence and efficacy in vitro and in PDX tumor models. Obsidian previously demonstrated cytoTIL15 exhibited enhanced potency and persistence over conventional TILs in vitro, and persisted without IL2 at greater frequencies compared to conventional TILs + IL2 in a 10-day antigen-independent in vitro assay. Additionally, cytoTIL15 adoptively transferred into naïve NSG mice demonstrated long-term persistence without antigen or exogenous IL-2.

About OBX-115
OBX-115 is Obsidian’s lead cytoTIL15 program, currently in preclinical development for the treatment of patients with metastatic melanoma and other solid tumors. OBX-115 is a novel engineered tumor infiltrating lymphocyte therapy armed with regulated membrane-bound IL15 that is designed to remove the need for concomitant IL2 therapy, a toxic and costly requirement for conventional TILs. The Company expects to submit an IND for OBX-115 in 2022.

Ryvu Therapeutics Announces Presentations at the AACR 2022 Annual Meeting

On April 11, 2022 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, reported presentations from its most advanced oncology program RVU120 and MTA-cooperative PRMT5 inhibitor program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 8-13 in New Orleans, U.S (Press release, Ryvu Therapeutics, APR 11, 2022, View Source [SID1234612012]).

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Poster presentation details:

Title: RVU120, a selective CDK8/CDK19 inhibitor, demonstrates efficacy against hormone-independent breast cancer cells in vitro and in vivo
Session Title: Novel Targets and Pathways
Abstract Number: 2647
Date and Time: Tuesday, Apr 12, 2022, 9:00 AM – 12:30 PM
Location: Poster Section 24

Title: Discovery of novel MTA-cooperative PRMT5 inhibitors as a targeted therapeutic for MTAP deleted cancers
Session Title: Drug Targets
Abstract Number: 1117
Date and Time: Monday, Apr 11, 2022, 1:30 PM – 5:00 PM
Location: Poster Section 23

Title: Trials in Progress – RVU120 SOL-021: An open-label, single agent, Phase I/II trial of RVU120 (SEL120) in patients with relapsed/refractory metastatic or advanced solid tumors
Session Title: Phase II Trials in Progress
Abstract Number: 8023
Date and Time: Monday Apr 11, 2022 9:00 PM – 12:30 PM
Location: Poster Section 34

About RVU120 (SEL120)

RVU120 (also known as SEL120) is a clinical stage, highly specific and orally bioavailable dual inhibitor of CDK8/CDK19 kinases, which has demonstrated efficacy in a number of solid tumor in vitro and in vivo models as well as in hematologic malignancies.

At present, Ryvu is conducting two clinical studies with RVU120: (i) Phase Ib in patients with AML/HR-MDS (NCT04021368) and (ii) Phase I/II in relapsed/refractory metastatic or advanced solid tumors (NCT05052255). Additionally, multiple translational research activities are underway.
On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with AML.

RVU120 has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers.

About PRMT5

Deletion of the metabolic gene MTAP occurs in 10 to 15% of all human tumors. Targeting PRMT5 in MTAP-deleted tumors in a synthetic lethal approach represents a promising antitumor strategy across many tumor types. Ryvu has identified a series of MTA-cooperative PRMT5 inhibitors which have good drug-like physicochemical properties and block methyltransferase activity of PRMT5 with nanomolar IC50 values. Ryvu’s compounds selectively inhibit growth of MTAP deleted cancer cells in prolonged 3D culture, which strongly correlates with inhibition of PRMT5-dependent protein symmetric demethylation in those cells.