On November 3, 2023 Verismo Therapeutics, a clinical-stage CAR-T company developing novel KIR-CAR platform technology reported that it will be presenting at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting (SITC 2023), to be held in San Diego and virtually November 1-5, 2023 (Press release, Verismo Therapeutics, NOV 3, 2023, View Source [SID1234636926]).

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Presentation Details

Title: Preclinical potency assessment of SynKIR-110, a mesothelin-specific KIR-CAR T cell therapy for mesothelioma
Abstract Number: 321
Date and Time: Friday, November 3rd: 12:00-1:30 p.m. and 5:10-6:40 p.m.
Presenting Authors: Dr. Jun Xu, PhD & Dr. Laura Johnson, PhD
Description: We conducted in vivo potency studies to assess the impact of the engineered T cell dose of the first mesothelin (MSLN)-specific KIR-CAR T cell therapy (SynKIRTM-110) in an NSG mouse xenograft model of human mesothelioma. Our data demonstrate for the first time that anti-tumor efficacy of SynKIRTM-110 is dose-dependent with greater potency compared with MSLN-41BBz CAR T cells previously evaluated in the clinic. This enhanced potency of SynKIRTM-110 was observed both at the primary tumor site and metastatic sites as demonstrated by histopathologic analysis. This increased potency did not impact any serum markers of toxicity, which remained the same regardless of CAR/KIR-CAR treatments. This data supports further clinical development of SynKIRTM-110 in patients with advanced solid tumors. SynKIRTM-110 is currently being investigated in a Phase I clinical trial STAR-101 (NCT05568680).

About the KIR-CAR Platform
The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acts as a novel costimulatory molecule for T cells using additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell functional persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with additional emerging technologies.

On November 3, 2023 Actym Therapeutics, pioneering a new drug modality to treat solid tumors, reported that it will present preclinical data of its lead asset, ACTM-838, in a poster presentation at the 2023 38th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in San Diego, California (Press release, Actym Therapeutics, NOV 3, 2023, View Source [SID1234636925]). The presentation will feature data examining the tumor-specific enrichment and payload delivery of ACTM-838 in multiple tumor models.

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"Utilizing genetically modified bacteria to elicit a potent and comprehensive immune response has the potential to bring a new level of therapeutic impact to cancer patients across multiple solid tumor types," said Dr. Christopher D. Thanos, President, CEO, and Co-founder of Actym. "The data presented at this year’s SITC (Free SITC Whitepaper) Meeting highlights ACTM-838’s ability to specifically accumulate in the tumor microenvironment and deliver two potent engineered payloads. We believe that these results further validate our scientific approach and provide a strong rationale to advance our candidate into the clinic."

ACTM-838 is a novel immunotherapy designed to locally deliver engineered IL-15 (IL-15plex) and engineered STING (eSTING) payloads to phagocytic tumor-resident myeloid cells to induce a durable anti-tumor immune response, following intravenous administration. The data that will be presented demonstrates specific uptake by tumor-resident myeloid cells in a mouse model of breast cancer, leading to the expression of IL-15plex and eSTING in the tumor microenvironment (TME), with no evidence of payload expression in other tissues. TME-specific payload delivery and efficacy was also observed in a mouse breast cancer model of metastatic disease. Actym will also show that treatment with ACTM-838 induces tumor-antigen-specific cytolytic T cells and effector T cells. Furthermore, Actym will show that in healthy human donor cells, ACTM-838 treatment results in significantly lowered inflammatory cytokines than a control strain lacking ACTM-838’s genetic modifications. Patient tumor database analysis revealed numerous tumor types that have both an adenosine pathway signature for tumor-specific enrichment, and a tumor-associated myeloid cell signature for payload delivery, by ACTM-838. In addition to demonstrating compelling efficacy characteristics, intravenously administered ACTM-838 exhibits a strong safety profile in mice and non-human primates with a first-in-human clinical trial planned in Australian cancer patients in early 2024.

SITC Poster Presentation details:

Abstract Title: PK/PD biomarker analysis to assess tumor-specific enrichment and payload delivery of ACTM-838, a microbial-based immunotherapy
Abstract number: 408
Presenter: Dr. Akshata Udyavar
Location: Ground Level – Exhibit Halls A and B1 – San Diego Convention Center
Date/Time: Saturday, November 4, 11:55 AM – 1:25 PM and 7:00 PM – 8:30 PM (PST)

On November 3, 2023 NKILT Therapeutics, Inc., a preclinical-stage cell therapy biotech company developing proprietary Chimeric ILT-Receptor (CIR)–engineered natural killer (NK) cell therapies, reported that preclinical data of the CIRNK cells have been selected for an oral presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held December 9-12, 2023, and for poster presentation at the 38th Society of Immunotherapy for Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held November 1-5, 2023 (Press release, NKILT Therapeutics, NOV 3, 2023, View Source [SID1234636924]). Both events are taking place at the San Diego Convention Center in San Diego, California.

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The SITC (Free SITC Whitepaper) 2023 presentation will highlight the latest updates on NKILT Therapeutics’ engineered CIRNK cells proof-of-concept in vitro data against leukemia cells expressing human leukocyte antigen G (HLA-G).

The ASH (Free ASH Whitepaper) 2023 oral presentation will feature details of the proprietary activation domains that enhance activity of the CIRNK engineered cells against HLA-G-positive acute myeloid leukemia (AML) cells. This presentation will expand preclinical data with a specific focus on these novel activation domains and will characterize the serial killing activity against AML cells. These data illustrate the potential of the CIR technology, associated with proprietary activation domains, to enhance engineered NK cells’ direct and innate killing activity against leukemia cells.

"Today’s poster presentation at SITC (Free SITC Whitepaper) 2023 and the oral presentation at the upcoming ASH (Free ASH Whitepaper) 2023 Annual Meeting confirm the great progress we have made in the development of our unique engineered CIRNK cells, which allows us to remain on track to name our lead assets to launch our IND process later this year," emphasized Raphaël G. Ognar, President & CEO, Co-founder of NKILT Therapeutics, Inc.

Details of the presentations:

Poster presentation – 38th SITC (Free SITC Whitepaper) Annual Meeting, San Diego, November 2-5, 2023
Title: Targeting HLA-G positive tumors with engineered Natural Killer cells expressing a Chimeric ILT Receptor (CIR)
Presenter: MyLinh Duong, PhD
Poster Display Date & Time: Friday, November 3, 2023, 9:00 am-7:00 pm PDT
Abstract Number: 251
Location: San Diego Convention Center, Ground Level, Exhibit Halls A and B1

Oral presentation – 65th ASH (Free ASH Whitepaper) Annual Meeting & Exposition, San Diego, December 9-12, 2023
Title: Engineered Natural Killer Cells Expressing Chimeric ILT Receptors (CIR) Effectively Target HLA-G-Positive AML Tumor Cells.
Presenter: J. Henri Bayle, PhD
Presentation Date & Time: Sunday, December 10, 2023, 10:30 am PDT
Session Name: 703. Cellular Immunotherapies: Basic and Translational: Novel Approaches for Next Generation Cellular Immunotherapies
Session Time: 9:30-11:00 am PDT
Abstract Number: 467
Location: San Diego Convention Center, Room 6A

"We are very pleased to present our findings on the development of CIRNK cells targeting HLA-G at SITC (Free SITC Whitepaper) and the further augmentation of CIRNK cell anti-AML efficacy at ASH (Free ASH Whitepaper). We are very proud of the work delivered by our team," said J. Henri Bayle, PhD, CTO/CDO & Co-founder of NKILT Therapeutics, Inc.

About Chimeric ILT-Receptor (CIR) Technology

Chimeric ILT Receptor, or CIR, technology utilizes engineered proteins designed to provide activating signals to immune cells in response to engagement of the tumor-enriched immunosuppressing protein human leukocyte antigen G (HLA-G) with extracellular binding domains derived from ILT2 or ILT4, the natural inhibitory receptors of HLA-G. This technique converts HLA-G from an agent for tumor immune evasion into a target protein for immunotherapy. The use of a CIR engager permits targeting of the several isoforms of HLA-G that can be expressed by tumors.

On November 3, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization approval for KRAZATI (adagrasib) as a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy (Press release, Mirati, NOV 3, 2023, View Source [SID1234636923]).

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"KRAZATI offers a compelling therapeutic option for patients with previously treated locally advanced NSCLC with a KRASG12C mutation. MHRA’s authorization is a significant step towards improving the options available for patients and clinicians in Great Britain," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We are encouraged by the opportunity to bring KRAZATI, a potential best-in-class treatment to qualified patients."

"Fourteen percent of people living with NSCLC harbour the KRASG12C mutation yet there are limited targeted treatment options for patients with this devastating disease1,2," said Dr Shobhit Baijal (Consultant Medical Oncologist of The University Hospital Birmingham). "The expansion of treatment options for NSCLC benefits patients and clinicians alike. As someone intensively involved in the management of lung cancer patients, I look forward to KRAZATI being available for use in clinical practice."

For more information, visit KRAZATI.com.

About KRAZATI (adagrasib)

Mirati has risen to meet one of the most challenging mutations in cancer research by developing KRAZATI, a highly selective and potent oral small-molecule inhibitor of KRASG12C.

Intentionally designed to meet the challenge of KRASG12C, adagrasib is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours.1 Adagrasib has shown clinically to be a CNS penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis.2,3,4

KRAZATI (adagrasib) GB Indication

KRAZATI as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.

Important Safety Information

The full Summary of Product Characteristics (SPC/SmPC) for KRAZATI (adagrasib) will be available on the MHRA website at View Source

About the KRYSTAL-1 Study

KRYSTAL-1 is an open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.

About KRASG12C in NSCLC

Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020.5 Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases.6 KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.

On November 3, 2023 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a commercial stage biotechnology company, reported the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization approval for KRAZATI (adagrasib) as a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy (Press release, Mirati, NOV 3, 2023, View Source [SID1234636923]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"KRAZATI offers a compelling therapeutic option for patients with previously treated locally advanced NSCLC with a KRASG12C mutation. MHRA’s authorization is a significant step towards improving the options available for patients and clinicians in Great Britain," said Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We are encouraged by the opportunity to bring KRAZATI, a potential best-in-class treatment to qualified patients."

"Fourteen percent of people living with NSCLC harbour the KRASG12C mutation yet there are limited targeted treatment options for patients with this devastating disease1,2," said Dr Shobhit Baijal (Consultant Medical Oncologist of The University Hospital Birmingham). "The expansion of treatment options for NSCLC benefits patients and clinicians alike. As someone intensively involved in the management of lung cancer patients, I look forward to KRAZATI being available for use in clinical practice."

For more information, visit KRAZATI.com.

About KRAZATI (adagrasib)

Mirati has risen to meet one of the most challenging mutations in cancer research by developing KRAZATI, a highly selective and potent oral small-molecule inhibitor of KRASG12C.

Intentionally designed to meet the challenge of KRASG12C, adagrasib is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours.1 Adagrasib has shown clinically to be a CNS penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis.2,3,4

KRAZATI (adagrasib) GB Indication

KRAZATI as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.

Important Safety Information

The full Summary of Product Characteristics (SPC/SmPC) for KRAZATI (adagrasib) will be available on the MHRA website at View Source

About the KRYSTAL-1 Study

KRYSTAL-1 is an open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.

About KRASG12C in NSCLC

Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020.5 Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases.6 KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.