On September 27, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical stage immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported that the first patient has been dosed in the combination therapy arm of the Phase 1/2 clinical trial for SNS-101, a conditionally active, human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation) (Press release, Sensei Biotherapeutics, SEP 27, 2023, View Source [SID1234635458]). This initial cohort of patients will receive a dose of 3 mg/kg of SNS-101 and a flat dose of Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) at 350 mg. Additionally, the Company announced that the fourth cohort of the monotherapy arm at a dose of 10 mg/kg has been fully enrolled.

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The multi-center Phase 1/2 clinical trial is a dose escalation study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of SNS-101 as both a monotherapy and in combination with Libtayo in patients with advanced solid tumors. To date 10 patients have been treated in the monotherapy arm, consisting of four cohorts receiving SNS-101 treatment at 0.3, 1, 3, or 10 mg/kg. Sensei expects to report initial pharmacokinetic and safety monotherapy data in the fourth quarter of 2023, and topline monotherapy data in 2024.

"We are pleased with the rapid enrollment of our clinical trial and are excited to evaluate SNS-101 as a combination therapy earlier than anticipated," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "Sensei is now treating patients at a dose significantly higher than any VISTA antibody for which clinical data have been reported, while dosing less frequently at a rate of once every three weeks. We believe these important differentiators underscore the vast potential of SNS-101 to treat patients with solid tumors."

As a result of faster enrollment than anticipated, Sensei now expects to report initial combination pharmacokinetic and safety data in Q1 2024 with preliminary anti-tumor activity data in 2024.

On September 27, 2023 Pathios Therapeutics Limited ("Pathios"), a biotech company focused on the development of first-in-class therapies for cancer, reported that the company has been awarded a £567K (~US$727K) grant from Innovate UK, the UK government’s innovation agency (Press release, Pathios Therapeutics, SEP 27, 2023, View Source [SID1234635457]). The grant funding will enable the company to expand its development of novel small molecule GPR65 inhibitors into the area of a possible treatment of malignant brain tumors. The project is being conducted in collaboration with researchers from the University of Nottingham and is focused on optimizing small molecule GPR65 inhibitors to penetrate the central nervous system (CNS) and evaluate those optimized compounds in preclinical models of brain cancer.

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The treatment of patients with malignant brain tumors remains a high unmet medical need. While chemotherapy has modestly improved survival rates among these patients, the need for truly impactful treatments remains. Immunotherapy has demonstrated some promise in this area, though overcoming the immunosuppressive tumor microenvironment (TME) remains a key challenge.

Pathios is pursuing a novel immuno-oncology approach to the treatment of cancer focused on counteracting the immunosuppressive polarization of immune cells, including tumor associated macrophages (TAMs), that is triggered by an acidic TME. This is achieved by the design and development of inhibitors of GPR65, an acid sensing G protein-coupled receptor that is exclusively expressed on immune cells and is associated with driving the immunosuppressive immune cell phenotype in the TME that prevents immune-mediated killing of cancer cells. Pathios’ internal human genetic analysis demonstrates that reductions in GPR65 function are associated with significantly improved survival across a range of solid tumor types, positioning it as a unique immuno-oncology target for therapeutic intervention.

With this grant, Pathios is utilizing an extensively developed proprietary assay platform to optimize CNS penetration of small molecule GPR65 inhibitors for the treatment of human malignant gliomas. Optimized GPR65 inhibitors are being tested in a human ex vivo co-culture system model of human glioblastoma in collaboration with University of Nottingham researchers, followed by in vivo efficacy evaluation in mouse models.

"Recent research suggests that a portion of glioblastoma patients do not respond to approved immuno-oncology drugs due to the immunosuppression of immune cells in the TME by the acidic microenvironment inherent to all solid tumors, including brain cancers." said Stuart Hughes, Ph.D., chief executive officer of Pathios. "We believe there is promise in applying our novel immuno-oncology approach to cancers of the brain with a CNS-penetrating small molecule GPR65 inhibitor. We are excited to be working alongside the talented team at the University of Nottingham on this important preclinical research, which we hope will pave the way for future clinical studies."

"We are excited to be supporting the research and development of this novel therapy for malignant brain tumours. By working with Pathios we aim to support their preclinical development and

expedite the progress of their inhibitors into the clinic," said Alan McIntyre, Associate Professor of Faculty of Medicine & Health Sciences, at the University of Nottingham. "This is important as malignant brain tumours are difficult to treat. In addition, this approach offers a new avenue to overcome the therapy resistance caused by the acidic microenvironment, frequently found in malignant brain tumours."

About Acidity in the Tumor Microenvironment
The acidic tumor microenvironment, inherent to many cancers, causes a profound immunosuppression of infiltrating immune cells. This environment disarms the anti-cancer immune response and negates the effectiveness of current immunotherapies. This is particularly evident in tumor associated macrophages (TAM), where acidity is sensed by the cell-surface receptor GPR65, leading to an induction of the transcriptional repressor ICER (inducible cAMP early repressor) and the widespread suppression of a host of pro-inflammatory mediators and anti-tumorigenic genes.

On September 27, 2023 Onchilles Pharma, a private biotech company developing new pan-cancer therapeutics that leverage a novel mechanism of action, reported the presentation of preclinical data for the N17350 program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting, to be held virtually and at the San Diego Convention Center from November 1-5, 2023 (Press release, Onchilles Pharma, SEP 27, 2023, View Source [SID1234635456]).

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N17350, is a first-in-class biologic therapeutic inspired by the immunobiology of neutrophils, with the potential to be effective against a wide range of cancer types. The company is targeting to start first-in-human clinical trials in skin cancers, head and neck cancer, and triple-negative breast cancer in 2024.

Presentation Details
Poster Title: N17350 combines selective cancer killing with adaptive immune activation to eradicate tumors
Abstract Number: 1344
Date and Time: Saturday, November 4, 9:00 a.m. to 8:30 p.m. PT
Location: San Diego Convention Center, Hall A and B1 or online at View Source

About N17350 and its Novel Mechanism of Action
First described in research published in Cell from the lab of Onchilles’ Co-Founder Lev Becker, human neutrophils release catalytically active neutrophil elastase (called ELANE), which selectively and potently kills cancer cells independent of their genetics and anatomical origin, mobilizes adaptive immunity, and avoids resistance mechanisms. The team at Onchilles translated this ground-breaking discovery into a proprietary set of molecules, including N17350, with the potential to treat a wide variety of tumor types with an optimal efficacy and safety profile.

On September 27, 2023 MaaT Pharma (EURONEXT: MAAT – the "Company"), a clinical-stage biotech company and a leader in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported that two abstracts have been accepted for poster presentations at the 38th Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, the world-leading event in immunotherapy, scheduled to be held from November 1-5, 2023, in San Diego, California, U.S.A (Press release, MaaT Pharma, SEP 27, 2023, View Source [SID1234635455]). This is the first time that the Company will present non-clinical data in immuno-oncology which include its Artificial Intelligence (AI) screening approach and in vitro results for the first member of the new generation MaaT03X range of products dedicated to improving responses in immunotherapy for patients with solid tumors.

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Immune checkpoint inhibitor (ICI) therapies have become the standard of care for treating solid tumors. However, only around 25% to 35% of patients respond to the treatment. Simultaneously, numerous studies have indicated that immune homeostasis and the diversity and richness of gut microbiota could improve the response to ICI treatment[1]. This research opens promising new possibilities for enhancing cancer treatment. The Company has chosen to pursue this avenue, focusing on the potential of the gut microbiome’s diversity, richness, and its key functional networks, which could be a game-changer in the field of immuno-oncology in the coming years. In this context, the company has developed an AI-driven program to select the most effective tailor-made microbiome for specific indications in multiple areas, with a first focus on ICI.

SITC Poster Presentations details:

Title: Evaluation of a new co-cultured microbiome ecosystem therapy candidate (MaaT03X) for clinical testing as adjuvant/neoadjuvant to immune checkpoint inhibitors in solid tumors
Abstract Number: 1321

Title: Robust Machine Learning (ML) approach for Screening Microbiome Ecosystem Therapies (MET) Drug Candidates in combination with Immune Checkpoint Inhibitors
Abstract Number: 1304

In line with the embargo policy of the congress, additional details on data scheduled to be presented at the 2023 edition of SITC (Free SITC Whitepaper) will be released on October 31st, 2023.

On September 27, 2023 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, reported that six abstracts highlighting its broad pipeline of clinical and preclinical product candidates as well as a shortened TIL manufacturing process have been accepted for presentation at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place in San Diego, Nov. 1-5, 2023 (Press release, Lyell Immunopharma, SEP 27, 2023, View Source [SID1234635454]).

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"Our presentations at SITC (Free SITC Whitepaper) highlight the progress we are making on several fronts to advance new product candidates and technologies designed to generate potent and durable cell therapies for patients with solid tumors," stated Dr. Gary Lee, chief scientific officer at Lyell. "At SITC (Free SITC Whitepaper), we look forward to sharing new preclinical findings on product candidates and emerging technologies, data on our Epi-R P2 manufacturing process which is designed to shorten TIL product delivery time to patients, and highlighting the design of our two ongoing Phase 1 clinical trials in progress."

Four presentations highlight new nonclinical data from pipeline product candidates and research programs, including a new technology being advanced through a collaboration with Outpace to enable context-dependent, localized IL-12 activity to enhance solid tumor T cell therapies; and Lyell’s novel Epi-R P2 manufacturing process to shorten manufacturing time for tumor infiltrating lymphocyte (TIL) therapy.

Two additional presentations highlight the design of Lyell’s ongoing Phase 1 clinical trials in progress: LYL797, a ROR1-targeted CAR T-cell therapy being evaluated in a Phase 1 trial in patients with relapsed refractory triple-negative breast cancer and non-small cell lung cancer, and LYL845, a tumor infiltrating lymphocyte (TIL) therapy being evaluated in a Phase 1 trial in advanced solid tumors.

Details on the six poster presentations are below:

Epi-R P2 protocol produces a scalable polyclonal TIL product with a greater expansion success rate across hot and cold tumors in shorter culture time

Presentation Date & Time: Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
Abstract Number: 379
Preclinical development of LYL119, a ROR1-targeted CAR T-cell product incorporating four novel T-cell reprogramming technologies to overcome barriers to effective cell therapy for solid tumors

Presentation Date & Time: Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
Abstract No.: 278
Protein design and inducible expression allow context-dependent, localized IL-12 activity to enhance solid tumor T cell therapies

Presentation Date & Time: Friday, Nov. 3, 12–1:30 p.m. and 5:10–6:40 p.m.
Abstract No.: 1047
Rejuvenation of tumor-infiltrating lymphocytes (TIL) through Partial Reprogramming

Presentation Date & Time: Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.
Abstract No.: 393
Phase 1 trial of LYL797, a ROR1-targeted CAR T-cell therapy enhanced with genetic and epigenetic reprogramming, in advanced triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC)

Presentation Date & Time: Saturday, Nov. 4, 2023, 11:55–1:25 p.m. and 7–8:30 p.m.
Abstract Number: 754
Phase 1 trial of LYL845, an autologous tumor-infiltrating lymphocyte (TIL) therapy enhanced with epigenetic reprogramming, for the treatment of advanced solid tumors

Presentation Date & Time: Friday, Nov. 3, 2023, 12–1:30 p.m. and 5:10–6:40 p.m.
Abstract No.: 747