On September 27, 2023 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease (NDD) through the inhibition of SEMA4D, reported that it will present data on a new ActivMAb application on September 28th and an update on the Phase 1b/2 pepinemab study in patients with PDAC on September 29th (Press release, Vaccinex, SEP 27, 2023, View Source [SID1234635460]).

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Vaccinex will provide an overview of the design and enrollment for the pancreatic ductal adenocarcinoma (PDAC) study (NCT05102721). Currently, seven patients are enrolled. Treatment has been well-tolerated by these patients to date and a mixed response with some lesions showing radiologic partial and even complete response has been observed in one patient. The trial, which employs a Bayesian Optimal Interval (BOIN) Design in the Phase 1b segment and a Simon two stage assessment in the Phase 2 segment, is expected to enroll up to 40 patients. The study rationale builds on safety and efficacy data from the CLASSICAL-Lung study of pepinemab and avelumab and the observation that pepinemab appears to modulate the tumor microenvironment by increasing effector cell infiltration and reducing immune suppression, rendering "cold" tumors such as PDAC to become "hot". The study is being conducted with grant support from the Gateway Discovery Award (Conquer Cancer Foundation / ASCO (Free ASCO Whitepaper)).

Update on Phase 1b/2 Pepinemab/PDAC Study (NCT05102721)
Meeting AACR SPECIAL CONFERENCE IN CANCER RESEARCH: PANCREATIC CANCER
Date:
September 29, 2023
Poster Time: 4:40 p.m. to 6:40 p.m.
Session Title: A Phase 1b/2 trial of pepinemab and avelumab as second line immunotherapy for patients with chemotherapy refractory metastatic pancreatic adenocarcinoma
Presenter Luis Ruffolo, MD, University of Rochester Cancer Center & Wilmot Cancer Institute, Rochester, NY, USA
Presentation will be available here

New ActivMAb "Antigen Virus" Application
Meeting CHI’s 20th Annual DOT Conf: Antibodies Against Membrane Proteins
Date:
September 28, 2023
Time: 8:35 a.m. ET: GPCR Sessio
Session Title: Discovery of High-Affinity Functional Antibodies Specific for CXCR5 and Other Multi-Pass Membrane Proteins
Presenter Ernest Smith, Ph.D., Senior Vice President, Research
Presentation will be available here

Vaccinex will describe use of the new "Antigen Virus" application, a potential tool to improve antibody development for high complexity, hard-to-drug targets, such as G-protein coupled receptors (GPCRs) and ion channels. This technology, a powerful complement to the existing ActivMAb platform, allows the direct incorporation of properly folded, complex multi-pass membrane proteins into specially designed poxviruses. We believe based on our rigorous evaluation that the ActivMab system can readily generate functional and properly folded complex proteins that can be used for selection of novel, high value, antibody therapeutics. A new manuscript describing this technology was recently published in mAbs, a leading biotech journal.

About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can trigger collapse of the actin cytoskeleton and loss of homeostatic functions of astrocytes and glial cells in the brain and dendritic cells in immune tissue. Pepinemab has been administered to more than 400 patients and appears to be well-tolerated and to have a favorable safety profile.

Vaccinex has global commercial and development rights to pepinemab and is the sponsor of the NCT05102721 PDAC trial. BAVENCIO/avelumab is provided by Merck KGaA, Darmstadt, Germany, previously as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer.

About ActivMAb
ActivMAb is a proprietary mammalian cell-based antibody discovery platform developed by Vaccinex with unique capabilities for multi-pass membrane targets such as G-protein-coupled receptors (GPCRs). The ActivMAb technology has multiple applications including: complex membrane antigen presentation and expression, antibody and antigen discovery, directed evolution and protein optimization.

The first clinical candidate selected through use of this technology (SRF114, a fully human monoclonal antibody targeting CCR8 for the potential treatment of solid tumors), entered development in a Phase 1/2 study sponsored by our licensee, Surface Oncology, recently acquired by Coherus Biosciences, Inc. The technology and its potential applications for drug discovery against complex membrane protein targets have been described in several publications and is the focus of collaborations with leading biopharmaceutical companies.

On September 27, 2023 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported the acceptance of two abstracts (related to TAC-001 and TAC-003) at the SITC (Free SITC Whitepaper) 38th Annual Meeting in San Diego, CA, from November 3-5, 2023 (Press release, Tallac Therapeutics, SEP 27, 2023, View Source [SID1234635459])b.

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Additionally, Tallac announced that President and CEO, Hong Wan and Chief Business Officer, Curtis Hecht will participate and host investor meetings at the Truist Securities BioPharma Symposium on November 8-9, 2023 in New York, NY.

Details of the SITC (Free SITC Whitepaper) poster presentations are as follows:

Title: INCLINE-101: Preliminary Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAC-001 (TLR9 agonist conjugated to a CD22 mAb) in Patients with Advanced or Metastatic Solid Tumors
Abstract/Poster #: 743
Session Date: Friday, Nov. 3, 2023
Title: TAC-003, a TLR9 agonist antibody conjugate for targeted immunotherapy of Nectin-4 expressing tumors
Abstract/Poster #: 1121
Session Date: Friday, Nov. 3, 2023
Both abstracts will be available for viewing on October 31, 2023 at 9:00 am EDT on the Journal for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (JITC) website.

About TAC-001 (CD22 TRAAC)
TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent toll-like receptor 9 agonist (T-CpG) conjugated to an antibody against CD22, a receptor restricted to B cells, including tumor-infiltrating B cells. TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 leads to potent anti-tumor activity. TAC-001 is being developed for the potential treatment of solid tumors and is currently in a Phase 1/2 Study in cancer patients (NCT05399654)

About TAC-003 (anti-Nectin-4 TRAAC)
TAC-003 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a T-CpG conjugated to a novel Nectin-4-targeting antibody for systemic administration and TME delivery of a potent TLR9 agonist. Nectin-4 is a cancer associated antigen over-expressed in many solid tumor types with limited expression in normal tissues. Additionally, Nectin-4 over-expression correlates with poor prognosis. Preclinical data demonstrate that TAC-003 triggers TLR9 signaling, induces myeloid and dendritic cell activation, phagocytosis, cytokine production and lymphocyte activation, resulting in potent anti-tumor efficacy.

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.