On March 8, 2022 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported it will present preclinical data on two novel XmAb cytokine programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 8-13, 2022 at the New Orleans Ernest N. Morial Convention Center in New Orleans (Press release, Xencor, MAR 8, 2022, View Source [SID1234609667]).

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"Cytokines evolved to be highly active and short acting immune signaling molecules, which makes them difficult to repurpose for therapeutic use. We have applied our protein engineering expertise and Fc technologies to create a broad set of XmAb cytokine drug candidates, designed to be long acting and drug-like," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "We look forward to sharing our first preclinical data from two additional wholly owned cytokine programs, a decoy-resistant and potency-reduced IL18-Fc fusion protein, and a LAG-3 targeted IL15/IL15α-Fc fusion protein, which is biased toward binding and activating checkpoint-upregulated lymphocytes that are more likely to be tumor-reactive."

Poster Presentation Details

Abstract 2080, "LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion"
Session: Immunomodulatory Agents and Interventions 1
Date and Time: Monday, April 11, 2022, 1:30 – 5:00 p.m. CDT
Location: Exhibit Halls D-H, Section 38, Board 18
Abstract 3515, "Engineered IL18 heterodimeric Fc-fusions featuring improved stability, reduced potency, and insensitivity to IL18BP"
Session: Immunomodulatory Agents and Interventions 2
Date and Time: Tuesday, April 12, 2022, 1:30 – 5:00 p.m. CDT
Location: Exhibit Halls D-H, Section 37, Board 17
Abstracts are now available on AACR (Free AACR Whitepaper)’s website located at www.aacr.org. E-posters will be available to registrants of the AACR (Free AACR Whitepaper) Annual Meeting at 1:00 p.m. EDT on Friday, April 8. Posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

On March 08, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported the acceptance of two abstracts for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2022 Annual Meeting April 8-13, 2022 in New Orleans, Louisiana and virtual (Press release, Iovance Biotherapeutics, MAR 8, 2022, View Source [SID1234609666]). Details for the abstracts are as follows:

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Abstract Title: Preclinical activity and manufacturing feasibility of genetically modified PDCD-1 knockout (KO) tumor infiltrating lymphocyte (TIL) cell therapy
Presenting Author: Arvind Natarajan, Ph.D., Iovance Biotherapeutics, Inc.
Abstract Number: 2746
Poster Session: Tuesday, April 12, 2022, 9:00 a.m. – 12:30 p.m. ET, New Orleans Convention Center, Exhibit Halls D-H, Poster Section 30
Abstract Title: Trial in progress: A phase 2 multicenter study (IOV-LUN-202) of autologous tumor-infiltrating lymphocyte (TIL) cell therapy (LN-145) in patients with metastatic non-small cell lung cancer (mNSCLC)
Presenting Author: Jason Alan Chesney, M.D., Ph.D., Director, James Graham Brown Cancer Center, University of Louisville
Abstract Number: CT130
Poster Session: Monday, April 11, 2022, 9:00 a.m. – 12:30 p.m. ET, New Orleans Convention Center, Exhibit Halls D-H, Poster Section 34
Posters will also be available starting at 1:00 p.m. ET on Friday, April 8, in the Virtual ePoster Hall at www.aacr.org.

On March 8, 2022 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported three poster presentations and one oral presentation at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 8-13, 2022, in New Orleans, LA (Press release, ORIC Pharmaceuticals, MAR 8, 2022, View Source [SID1234609665]). The presentations will highlight preclinical data regarding two Phase 1 programs, including ORIC-533, a highly potent, orally bioavailable CD73 inhibitor, and ORIC-114, a brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations. The presentations will also introduce a new program targeting a synthetic lethality pathway in breast cancer.

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Details of the presentations are as follows:

Title: ORIC-533, a small molecule CD73 inhibitor with best-in-class properties, reverses immunosuppression and has potential as an immunomodulatory therapy in patients with multiple myeloma
Session Title: Immunomodulatory Agents and Interventions 1
Date and Time: April 11, 2022, 1:30 p.m. – 5:00 p.m.
Abstract Number: 2074

Abstract Highlights
Using an autologous ex vivo assay, bone marrow aspirates from patients with multiple myeloma were evaluated to assess the impact of CD73 inhibition. The results showed that CD73 inhibition stimulated the activation of plasmacytoid dendritic cells and T cell activation. Moreover, the ORIC CD73 inhibitor as a single agent overcame immune suppression and triggered significant lysis and cell death of multiple myeloma cells by autologous T-cells in the bone marrow microenvironment. Taken together, these results demonstrate that the ORIC small molecule CD73 inhibitor potently inhibits the adenosine pathway, which restores anti-tumor immunity and therefore holds potential for patients with multiple myeloma.

Oral Presentation Title: Optimizations leading to ORIC-533: A potent orally bioavailable CD73 inhibitor that restores anti-tumor immunity in high AMP environments
Session Title: Chemistry to the Clinic, Part 2 of 3: Progress in Small Molecule Cancer Immunology Therapy
Date and Time: April 9, 2022, 11:00 a.m. – 11:30 a.m.

Title: ORIC-114, an orally bioavailable, irreversible kinase inhibitor, has superior brain
penetration and antitumor activity in subcutaneous and intracranial NSCLC models
Session Title: Tyrosine Kinase and Phosphatase Inhibitors
Date and Time: April 12, 2022, 1:30 p.m. – 5:00 p.m.
Abstract Number: 3335

Abstract Highlights
Oral administration of ORIC-114 resulted in tumor regressions in an EGFR exon 20 NSCLC model, with superior efficacy relative to CLN-081 and BDTX-189. Additional studies confirmed the brain-penetrance and free unbound exposure in the CNS, which translated to greater anti-tumor activity compared to TAK-788 in an intracranial NSCLC model. Taken together, these data confirm ORIC-114 as a potent, selective, irreversible, brain penetrant EGFR exon 20 inhibitor, and a promising therapeutic candidate, including for patients with CNS metastases.

Title: Discovery of novel, highly selective inhibitors of PLK4 that demonstrate in vivo regressions in TRIM37 high xenografts
Session Title: Novel Targets and Pathways
Date and Time: April 12, 2022, 9:00 a.m. – 12:30 p.m.
Abstract Number: 2633

Abstract Highlights
ORIC discovered novel, potent, orally bioavailable small molecule inhibitors of PLK4 that are highly selective, including against the closely related aurora kinases and PLK1-3. Cell viability assessment across a cancer cell line panel revealed that the highly selective ORIC PLK4 inhibitors showed greater potency in TRIM37 high cancer cell lines as compared to TRIM37 low cell lines. In contrast, less selective compounds, including from the clinical literature, did not display differential potency in TRIM37 high versus low cancer cell lines. Importantly, cell potency in TRIM37 high cancer cells was rescued with knockdown of TRIM37, illustrating that selective PLK4 inhibitors are synthetic lethal with TRIM37 amplification. Oral administration of ORIC PLK4 inhibitors resulted in strong anti-tumor activity of TRIM37 high xenograft tumors, with corresponding pharmacodynamic effects and no body weight loss.

Abstracts are available for viewing in the AACR (Free AACR Whitepaper) Online Itinerary Planner located here, View Source!/10517.

On March 8, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported two poster presentations at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) virtual annual meeting taking place April 8-13, 2022 (Press release, Tempest Therapeutics, MAR 8, 2022, View Source [SID1234609664]). The presentations contain new preclinical data for two of Tempest’s small molecule programs, TPST-1495 (clinical-stage dual EP2/4 antagonist) and TREX1 (preclinical STING agonist).

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Details:

Title: Dual Blockade of the EP2 and EP4 PGE2 Receptors with TPST-1495 is an Optimal Approach for Drugging the Prostaglandin Pathway

Session Title: Inflammation, Tumor Intitiation and Progression
Session Date and Time: Monday April 11, 2022 9:00 a.m. – 12:30 p.m. CST
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 36
Abstract Number: 1333

Title: Systemic Small Molecule TREX1 Inhibitors to Selectively Activicate STING in the TME of Metastatic Disease

Session Title: Immunomodulatory Agents and Interventions 1
Session Date and Time: Monday April 11, 2022 1:30 p.m. – 5:00 p.m. CST
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 38
Abstract Number: 2075

Full abstracts are available for viewing in the AACR (Free AACR Whitepaper) Online Itinerary Planner located here, View Source!/10517.

On March 8, 2022 OnKure, Inc., a clinical-stage biopharmaceutical company discovering and developing the next generation of oncology precision medicines, reported that preclinical data demonstrating synergy between OKI-179, the Company’s oral Class I histone deacetylase (HDAC) inhibitor, and the MEK inhibitor, binimetinib, in NRAS melanoma models has been accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, OnKure, MAR 8, 2022, View Source;utm_medium=rss&utm_campaign=onkure-therapeutics-to-present-late-breaking-preclinical-data-on-oki-179-at-the-aacr-annual-meeting-2022 [SID1234609663]). The meeting will be held in New Orleans, Louisiana from April 8, 2022 to April 13, 2022.

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Late-Breaker Poster Presentation:

Title: The class I selective, oral HDAC inhibitor OKI-179 increases tumor regressions when combined with the MEK inhibitor binimetinib in models of NRAS melanoma

Session: Late-Breaking Research: Experimental and Molecular Therapeutics 2

Abstract ID: LB204

Date/Time: Wednesday, April 13, 2022; 9:00 a.m. – 12:30 p.m. CT

The e-poster and abstract will be available starting Friday, April 8, 2022 at 1 p.m. ET on the AACR (Free AACR Whitepaper) Annual Meeting 2022 website(opens in a new tab).