On March 8, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported that it will publish financial results for the fourth quarter and fiscal year 2021 and provide a business update on March 15, 2022 (Press release, Precision Biosciences, MAR 8, 2022, View Source [SID1234609680]).

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On March 8, 2022 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical-stage, precision oncology biopharmaceutical company, reported that it will present the first data from its preclinical synthetic lethality pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting, being held April 8-13, 2022, in New Orleans, LA (Press release, Calithera Biosciences, MAR 8, 2022, View Source [SID1234609679]).

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The accepted poster will detail Calithera’s discovery of a novel series of vacuolar protein sorting-associated protein 4A (VPS4A) inhibitors that are currently advancing through lead optimization. VPS4A and VPS4B are paralog ATPases essential for remodelling intracellular organelle membranes. Membrane remodelling is an essential cellular function and loss of function of both VPS4 paralogs is lethal to cells. The preclinical data demonstrate that VPS4A genetic inhibition in cell lines with loss of VPS4B preferentially showed profound death in cancer cells.

"The data being shared at the AACR (Free AACR Whitepaper) annual meeting suggest that inhibition of VPS4A is a promising approach to treat cancers across a wide variety of cancer types that harbor VPS4B deletions. We believe the discovery of this series of VPS4A inhibitors is a significant step forward in our efforts to expand our pipeline of targeted therapies to ultimately treat patients with high unmet need," said Susan Molineaux, chief executive officer of Calithera. "Additionally, we are excited about the progress we have made in advancing these discoveries as we focus on lead optimization. Synthetic lethal cancer therapies are highly promising, and we look forward to contributing to this rapidly advancing field with this novel mechanism."

Calithera is building a robust preclinical pipeline of additional synthetic lethality targets with a continuing focus on paralog genes. Gene paralog pairs represent a promising class of synthetic lethal cancer targets. When a tumor cell loses one paralog, the cell is dependent on the second paralog to carry out an essential cellular process, since loss of both paralogs leads to tumor cell death. Calithera researchers have confirmed VPS4A and VPS4B as synthetic lethal paralog pairs, noting that both homozygous and heterozygous loss of VPS4B in cancer cells makes them vulnerable to VPS4A inhibition. VPS4B is lost in a heterozygous fashion in the majority of colorectal cancer, pancreatic ductal adenocarcinoma, ovarian, esophageal and head & neck cancers and is deleted in large numbers of other tumor types. At AACR (Free AACR Whitepaper) 2022, Calithera will report the discovery of a series of novel, small-molecule VPS4A inhibitors which have potential in the treatment of VPS4B-deleted tumors.

Details of the abstract accepted for presentation at AACR (Free AACR Whitepaper) 2022 (#1816) are as follows:

Title: Identification of novel VPS4A inhibitors for the treatment of VPS4B-deleted cancers
Session Category: Experimental and Molecular Therapeutics/Drug Targets
Session Title: Drug Targets
Date and Time: Monday Apr 11, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 23
Poster Board Number: 14
Permanent Abstract Number: 1816
Presenter: Meredith Kuo, Ph.D.
This abstract is currently available on the AACR (Free AACR Whitepaper) website, and the poster will be available on Calithera’s website on April 8, 2022.

On March 8, 2022 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that four abstracts have been accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held in New Orleans from April 8-13, 2022 (Press release, Kura Oncology, MAR 8, 2022, View Source [SID1234609678]).

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"We look forward to showcasing the four abstracts for tipifarnib, including a late-breaking presentation highlighting the opportunity for our next-generation farnesyl transferase inhibitor program," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "We are excited about this emerging opportunity, focused on delaying the onset of drug resistance and look forward to sharing more detailed information at AACR (Free AACR Whitepaper) next month. In the meantime, we intend to perform initial clinical evaluation with tipifarnib in non-small cell lung cancer while in parallel advancing KO-2806, the lead development candidate in our next-generation farnesyl transferase inhibitor program, through IND-enabling studies."

Session titles and information for the four abstracts are listed below and are now available on the AACR (Free AACR Whitepaper) online itinerary planner.

Tipifarnib prevents emergence of resistance to osimertinib in EGFR-mutant NSCLC
Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 1 / Chemistry
Session Date and Time: Monday Apr 11, 2022; 1:30 PM – 5:00 PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 16
Abstract / Poster: LB080 / 5

A Phase 1/2 trial to evaluate the safety and antitumor activity of tipifarnib and alpelisib for patients with HRAS-overexpressing and/or PIK3CA mutated/amplified recurrent/metastatic head and neck squamous cell carcinoma (The KURRENT trial)
Session Title: Phase I Trials in Progress 2
Session Date and Time: Wednesday Apr 13, 2022; 9:00 AM – 12:30 PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 35
Abstract / Poster: CT253 / 14

Tipifarnib potentiates the antitumor effects of PI3Ka blockade in HNSCC via convergent inhibition of mTOR activity
Session Title: Experimental and Molecular Therapeutics – Mechanisms of Drug Action 3
Session Date and Time: Monday Apr 11, 2022; 9:00 AM – 12:30 PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 24
Abstract / Poster: 1120 / 10

Translating genotype to immunophenotype in HRAS mutated head and neck squamous cell carcinoma (HNSCC) to identify effective Tipifarnib partners for optimal patient outcomes
Session Title: Tumor Biology – Models and Technical Approaches to Analyze and Examine the Tumor Microenvironment
Session Date and Time: Wednesday Apr 13, 2022; 9:00 AM – 12:30 PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 14
Abstract / Poster: 3882 / 27

Copies of the presentations will be available on Kura’s website at www.kuraoncology.com/pipeline/publications/ following presentation at the meeting.

On March 8, 2022 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, reported three abstracts have been accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place April 8-13, 2022, in New Orleans, Louisiana (Press release, Gritstone Oncology, MAR 8, 2022, View Source [SID1234609677]). In the poster presentations, Gritstone representatives will review data from individualized neoantigen program, GRANITE, and the "off-the-shelf" neoantigen vaccine program, SLATE. In the oral presentation, Christine D Palmer, PhD will discuss how immunodominant human T cell responses to tumor specific neoantigens presented by the same HLA in a first-generation construct informed development of a second-generation candidate that exhibits immunogenic superiority over version 1 in preclinical models within SLATE. This optimized candidate, SLATE-KRAS, exclusively includes KRASmut epitopes and is now in Phase 2 testing in solid tumor patients.

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Abstracts associated with these presentations are now available on the conference website. Details of the presentations are as follows:

Oral Presentation Details

Abstract 3578: Optimization of shared neoantigen vaccine design to increase vaccine potency: From bench to bedside and back
Date/Time: Tuesday Apr 12, 2022, 2:30 PM – 4:30 PM ET
Session: Clinical Research Excluding Trials; Resistance Mechanisms & New Advances in Immunotherapeutics
Presenter: Christine D Palmer, PhD
Location: New Orleans Convention Center, Theater B
Poster Presentation Details

Abstract 4149: Lower doses of self-amplifying mRNA drive superior neoantigen-specific CD8+ T cell responses in cancer patients versus high doses
Date/Time: Wednesday Apr 13, 2022, 9:00 AM – 12:30 PM ET
Session: Clinical Research Excluding Trials; Vaccines/Immunomodulatory Agents & Interventions
Presenter: Amy Rappaport, PhD
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 34, Poster Board 13
Abstract 1238: Comprehensive ctDNA monitoring provides early signal of clinical benefit with a novel personalized neoantigen directed immunotherapy for late-stage cancer patients
Date/Time: Monday Apr 11, 2022, 9:00 AM – 12:30 PM ET
Session: Clinical Research Excluding Trials; Biomarkers Predictive of Therapeutic Benefit 1
Presenter: Matthew Davis, PhD
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 30, Poster Board 10

On March 8, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported the publication of two abstracts for its upcoming poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Cogent Biosciences, MAR 8, 2022, View Source [SID1234609676]). The meeting will be hosted April 8-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana.

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The first poster presentation will highlight new nonclinical data on the unique properties of bezuclastinib that differentiate it from other KIT inhibitors. Bezuclastinib is currently under clinical investigation in Advanced Systemic Mastocytosis (NCT04996875), Nonadvanced Systemic Mastocytosis (NCT05186753), and imatinib-resistant Gastrointestinal Stromal Tumors (GIST) (NCT05208047). A second poster presentation will reveal in vitro and in vivo characteristics of a novel series of FGFR inhibitors with potency against clinically relevant mutations.

Details for the poster presentations are as follows:

Abstract Number: 147
Title: Bezuclastinib is a differentiated KIT inhibitor that exhibits unique selectivity to KIT A-loop mutations, minimal brain penetration, and favorable pharmacokinetic properties in preclinical models
Session Category: Molecular/Cellular Biology and Genetics
Session Title: Kinases and Phosphatases
Session Date and Time: Sunday, April 10, 2022, 1:30 – 5:00PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 8

Abstract Number: 167
Title: Pre-clinical characterization of a novel series of FGFR2 selective inhibitors with potency against clinically relevant mutations
Session Category: Molecular/Cellular Biology and Genetics
Session Title: Kinases and Phosphatases
Session Date and Time: Sunday, April 10, 2022, 1:30 – 5:00PM CT
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 8