On November 7, 2024 Noetik, an AI-native biotech company leveraging self-supervised machine learning and high-throughput spatial data to develop next-generation cancer therapeutics, reported the first two presentations of its AI-enabled drug discovery platform at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting (Press release, Noetik AI, NOV 7, 2024, View Source [SID1234647997]). The posters showcase Noetik’s OCTO foundation model of cell and tissue biology and demonstrate for the first time the application of OCTO to therapeutics discovery.

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"Noetik’s platform brings together one of the largest multimodal spatial datasets of human tumor biology, generated in-house at Noetik labs, with custom-built self-supervised models that are trained at a scale to unlock the complexities of biology. The work at SITC (Free SITC Whitepaper) showcases, for the first time, how we can use these models as powerful engines for drug discovery," said Lacey Padron, Ph.D., Chief Technical Officer of Noetik and presenter.

SITC, a leading member-driven organization dedicated to improving cancer patient outcomes by advancing cancer immunotherapy, will host its 2024 Annual Meeting from November 6th to 10th at the George R. Brown Convention Center in Houston. The abstracts will be published in the Journal for ImmunoTherapy of Cancer (JITC).

Details on Noetik’s poster presentations at SITC (Free SITC Whitepaper) are as follows:

Title: Foundation Models of Cell and Tissue Biology Enabled by Custom Scaled Data Generation: Insights from 1000 Lung Tumor Samples
Abstract Number: 1231
Date: Friday, November 8
Location: Houston George R. Brown Convention Center – Level 1 – Exhibit Halls AB or online at View Source

Title: Multimodal foundation model of human lung tumors identifies tertiary lymphoid structures (TLS) and reveals novel therapeutic targets that promote anti-tumor immune response
Abstract Number: 861
Date: Friday, November 8
Location: Houston George R. Brown Convention Center – Level 1 – Exhibit Halls AB or online at View Source

To learn more about OCTO, visit View Source

To learn more about our comprehensive patient dataset, visit View Source

On November 7, 2024 NextPoint Therapeutics, a clinical-stage biotechnology company developing a new class of precision immuno-oncology and tumor-directed therapeutics targeting the novel B7-H7 axis, reported an upcoming poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting, being held from November 6-10, 2024 in Houston, Texas (Press release, , NOV 7, 2024, View Source [SID1234647996]).

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Building on its deep biological understanding of the B7-H7 axis, NextPoint has developed a series of B7-H7 targeted bispecific CD3 engaging antibodies (BsAbs). These BsAbs are designed to bind both B7-H7 expressed on the surface of tumors cells and CD3 on the surface of T cells to induce potent T cell-mediated cytotoxicity toward B7-H7+ tumors independent of existing ADC/IO approaches. NextPoint’s B7-H7xCD3 BsAb 2:1 bispecific antibody design provides optimized target:CD3 affinity ratio, inactivated Fc effector function and ability to fully evaluate safety preclinically. Due to very limited normal tissue expression, B7-H7xCD3 is safe to administer in a wide dose range. Efficacy data presented at SITC (Free SITC Whitepaper) demonstrates potent T cell-mediated cytotoxicity against multiple B7-H7+ tumor cell lines with sub-nanomolar EC50s in addition to induction of complete regressions in most of B7-H7+ tumor bearing mice.

"Targeting B7-H7, a novel tumor antigen highly upregulated in cancer cells with restricted normal tissue expression profile, is a new frontier in the treatment of solid tumors. B7-H7 directed T cell engagers have the potential to overcome the complex tumor microenvironment and drive durable anti-tumor responses," said Tatiana Novobrantseva, PhD, Chief Scientific Officer of NextPoint Therapeutics. "NextPoint’s T cell engagers’ precise activation of T cells in the proximity of B7-H7-positive cells combined with its potent anti-tumor activity in both in vitro and in vivo studies support our vision of developing effective and targeted B7-H7 immunotherapies. Complete regressions in vivo across multiple animal models is an impressive sign of efficacy showing that B7-H7 targeting BsAbs will push the boundaries of cancer treatments and become a powerful tool in our arsenal against a new group of B7-H7 biomarker defined patients with solid malignancies. Armed with tolerability data, NextPoint is rapidly advancing the Investigational New Drug (IND) application for our T cell engager, NPX372. We look forward to advancing this innovative approach into clinical development supported by the B7-H7 biomarker assay to enrich for responders."

Presentation Details:
Title: B7-H7-CD3 Bispecific T cell Engaging Antibodies Demonstrate Potent Anti-Tumor Activity In B7-H7+ Preclinical Tumor Models
Abstract Number: 1318
Date & Time: Saturday, November 9, 2024, 9:00 a.m.-7:00 p.m. CST
Presenters: Matthew Rausch PhD, Director, Molecular Biology R&D, Karishma Vekaria, Research Associate, R&D
Location: Exhibit Halls A B

On November 7, 2024 Pheast Therapeutics ("Pheast"), a biotech developing novel macrophage checkpoint therapies to defy cancer, reported the presentation of new preclinical data for PHST001, an anti-CD24 antibody drug candidate that is designed to block a key macrophage "don’t eat me" signal on cancer cells (Press release, Pheast Therapeutics, NOV 7, 2024, View Source [SID1234647995]). The data were presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place both virtually and at the George R. Brown Convention Center in Houston from November 6-10, 2024.

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The presented data show that PHST001, through potent CD24 binding, promotes macrophage-induced phagocytosis in a number of cancer cells and significantly shrinks tumors in vivo. In addition, PHST001 has a favorable PK profile in non-human primates and does not induce immune-mediated toxicity in vitro.

"These data build on the results we presented earlier this year at PEGS showing that PHST001 can powerfully induce an anti-cancer immune response and drive therapeutic efficacy in challenging mouse model systems," said Roy Maute, Ph.D., Cofounder and CEO, Pheast Therapeutics. "Macrophage checkpoint therapies such as PHST001 have the potential to expand clinical options for patients in high unmet need oncology indications where other immunotherapies have not yet been successful."

CD24 is highly expressed by many human cancers, including ovarian and triple negative breast cancer (TNBC), and high expression of CD24 is a negative prognostic factor in multiple cancer indications. CD24 interacts with the macrophage receptor Siglec-10, and shields cancer cells from attack by macrophages. Pheast has engineered PHST001 to bind CD24 on the surface of cancer cells with high affinity and specificity and to block Siglec-10 binding.

"The preclinical data demonstrate the potential of PHST001 to address multiple cancer types, and its differentiation as a novel macrophage checkpoint inhibitor with potent inhibition of CD24," said Suzana Kahn, Ph.D., Senior Director, Biology at Pheast Therapeutics. "PHST001 does not have a toxic preclinical profile, which, combined with its superior efficacy in our preclinical models, supports the initiation of first-in-human clinical trials."

Dr. Kahn presented these data in a poster presentation entitled, "PHST001, a humanized anti-CD24 antibody, induces phagocytosis of human tumor cells in vitro and tumor clearance in vivo."

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

527

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

720

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

1355

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.