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

On March 8, 2022 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that preclinical, translational, and clinical biomarker data from its oncology pipeline have been selected for four poster presentations at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (AACR) (Free AACR Whitepaper), taking place April 8-13 (Press release, Hookipa Pharma, MAR 8, 2022, View Source [SID1234609675]).

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"We’re thrilled to have four poster presentations accepted at AACR (Free AACR Whitepaper) as they provide further evidence of the broad potential of our arenaviral platform to address unmet needs in various types of cancer, either alone or in combination with other modalities," said Joern Aldag, Chief Executive Officer at HOOKIPA. "New translational data from our ongoing Phase 1/2 trial in head and neck cancers continue to show strong T cell responses, and new preclinical data further support our early-stage prostate cancer program, as well as highlight new potential combination approaches."

The AACR (Free AACR Whitepaper) posters provide a broad preclinical, translational, and clinical biomarker dataset highlighting the versatility and therapeutic utility of replicating arenavirus vectors to activate and augment tumor-specific CD8+ T cell responses for tumor killing. Specifically, the data support the potential of arenaviral vectors to target self and non-self tumor antigens and be used as monotherapy or in combination with other modalities. The abstracts are available on the AACR (Free AACR Whitepaper) website.

Abstract # 2038: In vitro and in vivo characterization of non-oncolytic engineered arenavirus for cancer immunotherapy

This detailed preclinical and translational characterization of arenavirus vectors based on Lymphocytic choriomeningitis virus and Pichinde virus shows anti-tumor effects in preclinical models, as well as infection and activation of human professional antigen-presenting cells key for eliciting a robust tumor specific CD8+ T cell response.
In person poster presentation
Monday, April 11, 1:30pm – 5:00pm CT
Presenter: Henning Lauterbach, HOOKIPA

Abstract # 3284: HB-201 and HB-202, an arenavirus-based immunotherapy, induces tumor T cell infiltration in patients with HNSCC and other HPV16+ tumors

These data demonstrate that HB-201 and HB-202/HB-201 rapidly induce unprecedented levels of systemic, tumor-specific CD8+ T cells in patients with Human Papilloma Virus 16-positive (HPV16+) head and neck squamous cell carcinoma (HNSCC) after one dose. In addition, the data show a sustained polyfunctional profile of these cells during treatment, infiltration of CD8+ T cells into tumors and decrease of HPV16+ DNA in tumor tissue, in line with the proposed mode of action of the therapy.
In person poster presentation
Tuesday, April 12, 1:30pm – 5:00pm CT
Presenter: Henning Lauterbach, HOOKIPA

Abstract # 3298: Propagation competence of a self-antigen-targeting arenavirus vector-based cancer therapy determines antitumor efficacy in mouse melanoma

These data highlight the crucial role of replication competence of arenavirus-based vectors for: overcoming immune tolerance; robust induction of CD8+ T cell responses against tumor self-antigens; and activation and amplification of adoptively transferred TCR transgenic CD8+ T cells in a combination therapy which proved able to induce complete tumor remission in mice.
In person poster presentation
Tuesday, April 12, 1:30pm – 5:00pm CT
Presenter: Klaus Orlinger, HOOKIPA

Abstract # 4198: Evaluation of a cancer immunotherapy with engineered arenavirus vectors and 4-1BB agonists in a preclinical tumor model

The data demonstrate one strategy to unlock the potential of arenavirus vector-induced CD8+ T cell responses for tumor killing in a combination therapy with 4-1BB agonists.
In person poster presentation
Wednesday, April 13, 9:00am – 12:30pm CT
Presenter: Judith Strauss, HOOKIPA

About HB-202/HB-201
HB-201 and HB-202 are HOOKIPA’s lead oncology candidates engineered with the company’s proprietary replicating arenaviral vector platform. Each single-vector compound uses a different arenavirus backbone (Lymphocytic Choriomeningitis Virus for HB-201 and Pichinde Virus for HB-202), while expressing the same antigen, an E7E6 fusion protein derived from HPV16. In pre-clinical studies, alternating administration of HB-201 and HB-202 resulted in a ten-fold increase in immune response and better disease control than either compound alone.

About the HB-200 trial (NCT04180215)
This Phase 1/2 clinical trial is an open-label trial exploring different dose levels and dosing schedules in individuals with treatment-refractory HPV16+ head and neck cancers who progressed on standard of care, including check point inhibitors. The trial is evaluating HB-201 as a monotherapy, as an alternating 2-vector therapy with HB-202, and in combination with a PD-1 inhibitor. The primary endpoint of Phase 1 is a recommended Phase 2 dose. Secondary endpoints include safety and tolerability, as well as preliminary efficacy defined by RECIST 1.1. The study also includes exploratory objectives on immunogenicity and pharmacodynamic biomarkers.

On March 8, 2022 NuCana plc (NASDAQ: NCNA) reported the release of two abstracts to be presented as posters at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held from April 8 to 13, 2022 (Press release, Nucana BioPharmaceuticals, MAR 8, 2022, View Source [SID1234609674]).

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Abstract 4992: NUC-3373 Potentiates Immune-Mediated Cytotoxicity of CRC Cells

NUC-3373 causes colorectal cancer (CRC) cell lines to release damage associated molecular patterns (DAMPs), molecular signals that can activate immune cells leading to immunogenic cell death (ICD). The addition of nivolumab, an anti-PD-1 antibody, to NUC-3373 enhanced tumor cell death in a model where cancer cells were incubated alongside human-derived immune cells, highlighting NUC-3373’s potential as an attractive combination partner for checkpoint inhibitors.

Abstract 1835: NUC-3373 Targets the DNA-Directed Pathway More Effectively than 5-FU

NUC-3373 and 5-FU exert their anti-cancer effects through the metabolite, FUDR-MP (or FdUMP), which inhibits thymidylate synthase (TS), a critical enzyme for cancer cell growth and survival. Pre-clinical and clinical data show that NUC-3373 generates far higher levels of FUDR-MP than 5-FU and is more effective at inhibiting TS activity. Data indicate that NUC-3373 also induces anti-cancer activity via the DNA-targeting metabolite, FdUTP. Furthermore, NUC-3373 avoids the RNA damage associated with 5-FU’s dose-limiting toxicities of diarrhea, myelosuppression and mucositis.

Through a more targeted, DNA-directed pathway, NUC-3373 may provide, if approved, a potentially more effective, safer and convenient therapeutic option than 5-FU for patients with cancer.

Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer said: "We believe these data demonstrate NUC-3373’s advantages over 5-FU and are highly supportive of our clinical development strategy. Our Phase 1/2 study of NUC-3373 in patients with colorectal cancer (NuTide:302) continues to generate data which will support our Phase 3 study for NUC-3373 in second-line colorectal cancer patients. In addition, NUC-3373 is entering a Phase 1/2 study (NuTide:303) in patients with solid tumors to identify additional indications for development, including in combination with checkpoint inhibitors."

On March 8, 2022 Nkarta, Inc. (Nasdaq: NKTX), a biopharmaceutical company developing engineered natural killer (NK) cell therapies to treat cancer, reported that it will present four posters at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held April 8 to 13, 2022 (Press release, Nkarta, MAR 8, 2022, View Source [SID1234609673]).

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Abstracts are now available on the AACR (Free AACR Whitepaper) website, www.aacr.org. Posters will be made available electronically on April 8, 2022 at 1:00 p.m. ET on the AACR (Free AACR Whitepaper) e-poster website.

Presented jointly with CRISPR Therapeutics:

Title: CBLB, CISH and CD70 multiplexed gene knockout with CRISPR/Cas9 enhances cytotoxicity of CD70-CAR NK cells and provides greater resistance to TGF-β for cancer immunotherapy
Session Category: Immunology
Session Title: Preclinical Immunotherapy
Abstract Number: 5512

Nkarta presentations:

Title: Surveying surface antigen expression in multiple myeloma preclinical models
Session Category: Tumor Biology
Session Title: Nonclinical Models of Cancer
Abstract Number: 6004

Title: Development of multiomics approaches to evaluate NKG2D ligand dynamics and anti-tumor immune responses during CAR-NK treatment
Session Category: Clinical Research Excluding Trials
Session Title: Immuno-oncology
Abstract Number: 5187

Title: Immune masking strategies to extend the pharmacokinetics of allogeneic cell therapies
Session Category: Immunology
Session Title: Preclinical Immunotherapy
Abstract Number: 5511