On November 7, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported the presentation of new data on two of its promising investigational immunotherapy candidates, botensilimab and AGEN1721, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting in Houston, Texas (Press release, Agenus, NOV 7, 2024, View Source [SID1234647994]). The data, showcasing potential breakthroughs in treating immune-resistant tumors, will be presented by Dhan Chand, Ph.D., Vice President of Research at Agenus.

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The first two presentations will spotlight botensilimab, an innovative, investigational, Fc-enhanced anti-CTLA-4 antibody that has shown remarkable efficacy in overcoming immune barriers across several treatment-resistant cancers, including glioblastoma, melanoma, colorectal, pancreatic, and breast cancers. Botensilimab’s unique mechanism of action enhances both innate and adaptive immunity to promote optimal T-cell priming, stimulate antigen-presenting cells, and deplete immune suppressing regulatory T cells in the tumor microenvironment, creating a multi-pronged attack on cold and refractory tumors.

"These findings represent a significant milestone in understanding how botensilimab can be optimally combined with both established and emerging therapies," said Dr. Chand. "What’s particularly compelling is the profound efficacy we’re seeing in traditionally ‘cold’ tumors and treatment-resistant cancers—offering potential new options for patients with limited therapeutic choices."

Featured botensilimab presentations:

Preclinical dose-pharmacokinetic-efficacy modeling of botensilimab using a mouse surrogate of the Fc-enhanced anti-CTLA-4 antibody

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Location: Exhibit Halls A B George R. Brown Convention Center

Date: Friday, Nov. 8, 2024 – Odd Number Posters

Poster Hall Hours: 9 a.m.–7 p.m.

Fc-enhanced anti-CTLA-4 antibody, botensilimab, enhances the efficacy of multiple therapeutic modalities in immunotherapy-refractory tumor models

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Location: Exhibit Halls A B George R. Brown Convention Center

Date: Saturday, Nov. 9, 2024 – Even Number Posters

Poster Hall Hours: 9 a.m.–8:30 p.m.

An additional presentation will cover AGEN1721, a first-in-class, Fc-enhanced bifunctional antibody targeting FAP and TGFβ. AGEN1721 is engineered to remodel the tumor microenvironment by depleting cancer-associated fibroblasts (CAFs) and neutralizing TGFβ’s immunosuppressive effects. By facilitating T-cell infiltration and activation, AGEN1721 effectively transforms cold tumors into "hot," immune-responsive environments.

"AGEN1721 represents a breakthrough in addressing the challenges of immune-excluded tumors by targeting key elements that suppress immune activity within the tumor microenvironment," said Dr. Chand. "The data we’re presenting at SITC (Free SITC Whitepaper) 2024 highlight how AGEN1721’s dual-action approach can dismantle barriers to immune infiltration, offering renewed hope for more durable and effective responses against resistant cancers."

Featured AGEN1721 presentation:

AGEN1721, a first-in-class Fc-enhanced bifunctional antibody targeting FAP and TGFβ, remodels the tumor microenvironment to overcome cancer-associated fibroblast-mediated immune suppression

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Location: Exhibit Halls A B George R. Brown Convention Center

Date: Friday, Nov. 8, 2024 – Odd Number Posters

Poster Hall Hours: 9 a.m.–7 p.m.

About Botensilimab

Botensilimab is an investigational human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

On November 7, 2024 SOTIO Biotech, a clinical-stage immuno-oncology company owned by PPF Group, reported data supporting SOT201, its next-generation PD-1-targeting immunocytokine (Press release, SOTIO, NOV 7, 2024, View Source [SID1234647993]). The company also reported advancements in its BOXR cell therapy platform, introducing an innovative chimeric PGC-1α transgene to boost CAR T cell efficacy in patients with solid tumors. SOTIO will be presenting three posters highlighting these advancements at the 2024 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Meeting, taking place November 6–10 in Houston, TX, U.S.

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SOT201 is a PD-1-targeted and cis-acting attenuated IL-15 agonist designed to preferentially activate PD-1+CD8+ T cells, inducing superior anti-tumor effects and reinvigorating exhausted CD8+ T cells in PD-1 sensitive and resistant tumors. The VICTORIA-01 study is a Phase 1, open-label, dose escalation trial that aims to assess the safety, tolerability, and preliminary efficacy of SOT201 as a monotherapy for adults with advanced unresectable or metastatic solid tumors (NCT06163391). This trial is currently enrolling patients across six sites in the U.S., Belgium, Spain, and the Czech Republic. Four patients have been treated so far and the treatment was well tolerated.

SOTIO Chief Scientific Officer Martin Steegmaier, Ph.D., noted, "SOT201 demonstrates a superior ability to reinvigorate exhausted tumoral CD8+ T cells with a high cytotoxicity and minimal cellular exhaustion compared to the related cytokine PD1-IL2v. These data reinforce SOT201’s reduced off-target interactions and more durable anti-tumor efficacy in vivo, underscoring its potential to address current limitations in anti-PD-1 therapies, as we continue to enroll patients in the VICTORIA-01 study."

The third poster highlights a preclinical study of a chimeric PGC-1α transgene that enhances CAR T cell activity. Chimeric PGC-1α transduced cells displayed fewer dysfunctional mitochondria and improved glucose uptake compared to CAR T cell controls. "Furthermore, the chimeric PGC-1α enhanced CAR T anti-tumor efficacy with no overt signs of toxicity, suggesting that co-expression of CAR and the chimeric PGC-1α is a promising approach to improving CAR T cell efficacy in solid tumors," added Dr. Steegmaier.

Presentation materials will be available here on Sunday, November 10, after the conference concludes.

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