On November 7, 2024 BPGbio, Inc., a leading biology-first, AI-powered clinical-stage biopharma company focused on mitochondrial biology and protein homeostasis, reported that it will present three scientific posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting, taking place November 6-10, 2024, in Houston, Texas (Press release, BPGbio, NOV 7, 2024, View Source [SID1234647992]). The posters will highlight the latest research on the company’s drug candidates BPM31510 and BRG399 in the immuno-oncology space, providing further validation and paving the way for new potential therapeutic strategies in cancer treatment.

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In the first study, titled "The Anti-tumor Response of BPM31510 is Associated with Immune Cell Regulation in the Tumor Microenvironment," researchers showed that BPM31510 significantly increases reactive oxygen species (ROS) levels in cancer cells, leading to cell death across multiple cancer types. They also identified that, BPM31510 can boost the activity of cytotoxic tumor-infiltrating lymphocytes and reduce markers of T cell exhaustion. This dual action gives it the potential to be especially effective in treating "immunologically cold" tumors, such as glioblastoma and pancreatic cancer.

The second study, titled "BRG399, a Novel Oral Microtubule Binding Agent, Induces Tumor Regression and Immune Memory in an Orthotopic Glioblastoma Rat Model," found that BRG399 treatment leads to glioblastoma tumor regression, with 100% survival in treated rats. BRG399 also induces an immune memory response, preventing the recurrence of tumors when surviving rats are re-challenged with glioma cancer cells.

The third study, titled, "BRG399, a Novel Oral Microtubule Binding Agent, Exhibits Immune-Modulatory Properties Enhancing Anti-Tumor Responses," showed that BRG399 alters the immune cell composition within the tumor microenvironment and blood. BRG399 also reduced markers of T cell exhaustion, suggesting that it can reinvigorate immune responses against tumors. These findings suggest that BRG399 should be further investigated as a potential component of cancer therapy, particularly when combined with immunotherapies, as it can both kill cancer cells and enhance immune activity.

"These compounds – BPM31510 and BRG399 – push the boundaries of what’s possible in cancer therapy, showing that we can not only attack the tumor but also empower the body’s immune system to keep fighting long after the treatment ends," said Stephane Gesta, Ph.D., VP, Discovery and Translational Biology at BPGbio. "As we advance BRG399 through preclinical trials and approach the completion of BPM31510’s Phase 2b study, we will continue leveraging our NAi Interrogative Biology Platform to gain additional insight for exploring new therapeutic opportunities for other diseases."

Poster Presentation Details:

The Anti-Tumor Response of BPM31510 Is Associated with Immune Cell Regulation in the Tumor Microenvironment
Date and Time: November 8, 2024, 1:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Maria-Dorothea Nastke, Ph.D.
Abstract Number: 1312

BRG399, a Novel Oral Microtubule Binding Agent, Induces Tumor Regression and Immune Memory in an Orthotopic Glioblastoma Rat Model
Date and Time: November 9, 2024, 2:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Maria-Dorothea Nastke, Ph.D.
Abstract Number: 1313

BRG399, a Novel Oral Microtubule-Binding Agent, Exhibits Immune-Modulatory Properties Enhancing Anti-Tumor Responses
Date and Time: November 9, 2024, 3:00 p.m. CST
Location: Exhibit Halls A B, George R. Brown Convention Center, Houston, Texas
Presenter: Kaila Bennett, Ph.D.
Abstract Number: 1284
About BPM31510

BPM31510 is BPGbio’s lead candidate in late-stage development for glioblastoma multiforme (GBM) and pancreatic cancer. The compound has demonstrated a tolerable safety profile and shown potential clinical benefit in both populations. The mechanism of action of BPM31510 was first validated by data from BPGbio’s NAi Interrogative Biology platform, which suggested that there is a hallmark shift in the tumor microenvironment (TME) induced by BPM31510 which modulates mitochondrial oxidative phosphorylation in highly aggressive tumors. BPGbio has received FDA’s Rare Pediatric Disease Designation for BPM31510IV for primary CoQ10 deficiency and BPM31510T for Epidermolysis Bullosa (EB) .

About BRG399

BRG399 is a BPGbio-developed candidate being studied for its therapeutic potential as a treatment for solid and liquid tumor cancers as well as diseases associated with neutrophil-driven inflammation. This experimental drug, a first-in-class, anti-tubulin agent with broad-spectrum anti-cancer activity and favorable pharmacological properties including oral bioavailability for clinical testing. BRG399 is leading the new oncology drug pipeline for BPGbio among other drug candidates which uniquely target the colchicine binding pocket in tubulin.

On November 7, 2024 Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation TCEs, reported new data validating the potential of its lead program, CLSP-1025 (Press release, Clasp Therapeutics, NOV 7, 2024, View Source [SID1234647991]). CLSP-1025 is a half-life extended TCE targeting cancer cells expressing the p53R175H mutant peptide presented by HLA-A*02:01. Data demonstrating the therapeutic potential of CLSP-1025 will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 39th Annual Meeting on November 8, 2024.

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Clasp’s innovative approach focuses on developing TCEs with absolute tumor specificity (i.e., no anticipated off-tumor binding) by targeting shared cancer neoantigens derived from oncogenic driver mutations presented by human leukocyte antigen (HLA) on cancer cells. The company’s proprietary pHLAre platform mimics the natural immune synapse by bridging cancer cells and T cells through CD3 binding. This engagement activates T cells, resulting in potent targeting and destruction of cancer cells. CLSP-1025 targets the p53R175H mutation, which is prevalent in a range of solid tumors such as colorectal, esophageal, gastric, gynecological, lung, pancreatic and prostate cancers.

Together, Clasp’s data support advancing CLSP-1025 into clinical trials. CLSP-1025 is expected to be the first TCE targeting a shared cancer neoantigen to reach the clinic, with the first-in-human trial anticipated to begin in early 2025.

"Clasp was built to bring absolute precision to the power of immunotherapies, thereby improving and extending the lives of people with cancer," said Chief Executive Officer Rob Ross, M.D. "Building on this promising preclinical data, we look forward to advancing CLSP-1025 into the clinic. Today’s presentation marks a significant milestone in our mission to deliver a new class of precision TCEs that expand the reach of immunotherapy."

Data Highlights:

Selectivity: CLSP-1025 demonstrates high selectivity for p53R175H presented on HLA-A*02:01
Specifically binds the R175H mutant peptide and spares wildtype p53;
No reactivity with any other human peptides presented on HLA-A*02:01;
Sensitivity: CLSP-1025 activates T cells and effectively kills patient-derived organoids, demonstrating activity at endogenous target expression levels;
Activity: CLSP-1025 induces the regression of established tumors in vivo.

On November 7, 2024 AbCellera (Nasdaq: ABCL) reported new data on its T-cell engager (TCE) platform, to be presented as a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting at the George R. Brown Convention Center in Houston, Texas (Press release, AbCellera, NOV 7, 2024, View Source [SID1234647990]).

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AbCellera’s presentation, which is available for viewing here, describes:

Strategies to address key challenges in TCE development:

CD3-binding antibodies to widen the therapeutic window by generating TCEs with potent tumor-cell killing and optimal cytokine release
Molecules to enhance efficacy for solid tumor indications by increasing T-cell activation and proliferation through costimulation of CD28 and 4-1BB
Application of the platform to two of AbCellera’s TCE programs:

Preclinical characterization of TCEs against solid tumor targets B7-H4 and PSMA show tumor-cell killing and cytokine release profiles that are differentiated from clinical benchmarks

On November 7, 2024 Indapta Therapeutics, Inc., a privately held clinical stage biotechnology company developing next-generation differentiated cell therapies for the treatment of cancer and autoimmune diseases, reported the presentation of clinical and preclinical data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting in Houston, TX (Press release, Indapta Therapeutics, NOV 7, 2024, View Source [SID1234647989]).

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The clinical presentation (Abstract #1483), entitled "Activity of IDP-023 Allogeneic g-NK Cells Without Antibody Targeting in First-in-Human Phase 1/2 Study in Patients with Advanced Multiple Myeloma or Non-Hodgkin Lymphoma," summarized the data from the safety run-in of the Phase 1 trial. Patients received one to three doses of IDP-023, with or without interleukin-2 (IL-2). The treatment was generally well-tolerated, with no dose limiting toxicities. The most common adverse events were cytopenias related to the conditioning chemotherapy. Objective responses were observed in five of nine patients treated. Of the five patients treated with IDP-023 and IL-2, four achieved an objective response (one very good partial response, two partial responses, one minimal response). Of the eight relapsed/refractory myeloma patients, the mean maximum decrease in serum M-protein or light chain was 73%, with three patients achieving a reduction of 84% or greater.

"We are encouraged to observe this degree of clinical activity during the safety run-in, at the lowest cell dose and without the addition of a targeting antibody," said Dr. Robert Sikorski, Chief Medical Officer of Indapta. "We look forward to the enrollment in the antibody cohorts, in which multiple myeloma patients will receive IDP-023 in combination with a CD38-targeting monoclonal antibody, and non-Hodgkin’s lymphoma patients will receive IDP-023 in combination with a CD20-targeting monoclonal antibody. In our preclinical models, the addition of a targeting monoclonal antibody markedly increases efficacy."

In Abstract #365, entitled, "Artificial Intelligence-Based Dynamic Single-Cell Imaging Reveals Enhanced Migration and Immune Synapse Formation by IDP-023, an Allogeneic g-NK Cell Product," researchers demonstrated that the enhanced antibody-dependent cellular cytotoxicity (ADCC) of g-NK cells is driven in part by faster cell migration and a higher frequency of synapse formation with target cells compared to conventional NK cells. Faster migration correlates with enhanced expression of CD2 (LFA-2), a protein involved in leukocyte adhesion, as a potential factor in the increased migration and cytotoxic functions of IDP-023.

In Abstract #1285, entitled, "IDP-023 has superior single agent and antibody-dependent cytotoxicity against solid tumor cell lines compared to conventional NK cells," data presented demonstrate potent activity of g-NK cells against HER2 and EGFR positive cells lines, both without and with tumor targeting antibodies. Furthermore, the analysis of publicly available datasets of patients treated with trastuzumab, a monoclonal antibody used to treat HER2-positive breast and other cancers, show that patients with increased levels of naturally occurring g-NK cells had a higher rate of pathological complete response in a neoadjuvant study and improved distant disease-free survival in an adjuvant study.

"These data demonstrate both the differentiated mechanism of g-NK cells, as well as their potential efficacy in solid tumors," said Stefanie Mandl-Cashman, Chief Scientific Officer of Indapta Therapeutics. "In addition, analyses of clinical outcomes in patients treated with trastuzumab highlight the powerful effect of naturally occurring g-NK cells on the outcome of patients undergoing therapy with monoclonal antibodies, demonstrating the strong antibody-dependent cellular toxicity of g-NK cells."

Indapta’s Proprietary g-NK Cell Therapy

Indapta’s universal, allogeneic NK cell therapy platform consists of a potent subset of naturally occurring NK cells, known as "g minus" NK cells, or "g-NK" cells. g‑NK cells arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). To generate IDP-023, Indapta preferentially expands g-NK cells from healthy donors, with low donor to donor variability. IDP-023 has several differentiated mechanisms of killing target cells without the need for genetic engineering, including highly robust antibody-dependent cell mediated cytotoxicity (ADCC), the targeting of HLA-E expressing cells via the NKG2C receptor, and the inherent anti-viral activity of g-NK cells.

Indapta’s g-NK can release dramatically more immune activating cytokines and cell-killing compounds than conventional NK cells. In preclinical studies, IDP-023 has demonstrated more potent and durable antitumor activity when combined with cancer targeting monoclonal antibodies as compared to conventional NK cells. (Bigley et al., Blood Advances 2021, View Source). g-NK cells in combination with a B cell targeting antibody can also deplete normal B cells from healthy donors or patients with autoimmune disease.

On November 7, 2024 Brenus Pharma reported the publication of a scientific article describing its new "off-the-shelf" cancer treatment in "Frontiers in Oncology" Section Cancer Immunity and Immunotherapy (Press release, Brenus Pharma, NOV 7, 2024, View Source [SID1234647988]).

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Brenus’ platform mimics patients’ relapsing conditions in lab, to educate the immune system against tumors evolution with the largest panel of multi-specific targets available. Its lead candidate is a proteomic-guided immunotherapy, designed to treat patients with advanced or metastatic CRC.

Results show that the murine surrogate treatment inhibits tumor growth and improves survival of treated mice bearing tumors. It has also shown efficacy in a PD1-resistant model, with an increased infiltration of CD8+T cells in cold tumors, associated with strong safety data.

Indeed, the treatment’s in vitro exposition to standards of care induces the expression of cancer-related proteins linked to therapeutic pressure, which were then safely rendered immunogenic by haptenation (in vitro chemical tagging). The final product thus obtained reinforces the recognition of tumor antigens by the immune system, allowing its activation against patient’s tumor cells after intradermal injection.

The findings, published in collaboration with renowned academic institutions and scientific partners, emphasize the potential of Brenus Pharma’s platform to overcome challenges faced in CRC, particularly in cases where standard immunotherapies like anti-PD1 have proven ineffective.

"These studies demonstrate that we can produce an immunotherapeutic approach inducing a safe anti-tumor response to target cancer cells in a proof-of-concept syngeneic mouse model. The technology has now been adapted with the human first candidate. This is providing solid foundations for the first-in-human study, moving us closer to offering therapeutic solutions for patients. We extend our gratitude to all co-authors for their invaluable contributions," said Dr. George Alzeeb, Innovation Manager at Brenus Pharma.