On March 6, 2024 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in discovering and developing novel immunological agents to treat various cancers, reported that the first preclinical data from BMS-986442 (AGEN1777) will be presented in an oral presentation at the upcoming AACR (Free AACR Whitepaper) Meeting, to be held April 5 – 10, 2024 in San Diego, CA (Press release, Agenus, MAR 6, 2024, View Source [SID1234640893]).

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In non-clinical assays, BMS-986442 demonstrated superior immune activation both as monotherapy and in combination with PD-(L)1 blockade compared to conventional TIGIT antibodies. This novel, Fc-enhanced, bispecific antibody is differentiated from conventional TIGIT monoclonal antibodies by optimally targeting two critical immune checkpoint receptors in the same pathway, TIGIT and CD96. BMS-986442 (AGEN1777) leverages Agenus’ proprietary Fc-engineering platform to harness novel mechanisms of action that extend beyond the capabilities of conventional anti-TIGIT therapy. This innovative strategy could represent a promising approach to overcome the limitations of current anti-TIGIT therapies.

"Immune checkpoint blockade has emerged as a powerful strategy in enhancing anti-tumor immunity. However, conventional TIGIT antibodies have faced limitations with monotherapy activity in clinical settings," said Dhan Chand, Ph.D., Vice President of Research. "BMS-986442 has the potential to address these challenges through Fc modification and the targeting of complementary pathways."

Presentation Details:

Abstract Title: BMS-986442 (AGEN1777), a novel TIGIT/CD96 bispecific antibody, demonstrates superior monotherapy and combination activity versus conventional anti-TIGIT antibodies in preclinical models
Abstract Number: 3915
Presenting Author: Dhan Chand
Session: Immune Targets and Therapies
Presentation Session Date and Time: Monday April 8, 2024, 2:30 p.m. – 4:30 p.m. PST

Data presented at the conference will be available to view in the publications section of the Agenus website (View Source) following the AACR (Free AACR Whitepaper) Meeting.

About BMS-986442 (AGEN1777)

BMS-986442 (AGEN1777) is being developed in partnership between Agenus and Bristol Myers Squibb. The TIGIT and CD96 bispecific antibody is currently being investigated for the treatment of multiple solid tumors in clinical studies in combination with nivolumab and/or chemotherapy. TIGIT is expressed on T cells and NK cells, sharing ligands with the CD96 receptor, and generating co-stimulatory or co-inhibitory signals. Co-inhibition of TIGIT and CD96 is intended to restore effector cell function by blocking the inhibitory immune checkpoint signaling pathway.

On March 6, 2024 Sporos BioDiscovery, Inc. (a portfolio company of Sporos Bioventures, LLC.), a precision oncology company developing a diversified pipeline of small molecule therapeutic programs targeting cancer vulnerabilities in the tumor and tumor microenvironment, reported that it will present two posters highlighting preclinical data from the company’s novel TEAD1 / TEAD4 isoform selective inhibitor, SPR1, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, taking place April 5-10, 2024, in San Diego, CA (Press release, Sporos Bioventures, MAR 6, 2024, View Source [SID1234640892]).

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"We look forward to presenting two posters at this year’s AACR (Free AACR Whitepaper) meeting that highlight the significant preclinical work we have done to characterize SPR1 as a potential best-in-class TEAD inhibitor. In addition, our team’s expert biological analysis has uncovered a new therapeutic vulnerability that could broaden the potential use of SPR1, a TEAD1/4 inhibitor, to a new subset of cancers with certain homozygous deletions," said Stephen Rubino, Ph.D., President of Sporos BioDiscovery.

Presentation Details:

Title: TEAD1/4 inhibitors exhibit deeper biological impact and broader activity compared to TEAD1-only inhibitors in both monotherapy and combination without additional kidney toxicity
Session Category: Experimental and Molecular Therapeutics
Session Title: New Targets
Session Date and Time: Tuesday Apr 9, 2024, 1:30 p.m. – 5:00 p.m. PT
Abstract Number: 5913
Poster Number: 27

Title: VGLL4 is the target of the 3p25 homozygous deletion and presents a novel therapeutic vulnerability for TEAD1/4 but not TEAD1 inhibitors
Session Category: Experimental and Molecular Therapeutics
Session Title: YAP/TAZ/TEAD Modulators
Session Date and Time: Wednesday Apr 10, 2024, 9:00 a.m. – 12:30 p.m. PT
Abstract Number: 7266
Poster Number: 3

On March 6, 2024 Foundation Medicine, Inc., a genomics company dedicated to transforming cancer care, reported that research from its robust oncology diagnostics portfolio will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, California April 5-10, 2024 (Press release, Foundation Medicine, MAR 6, 2024, View Source [SID1234640891]).

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The presentations include new research from Foundation Medicine’s two circulating tumor DNA (ctDNA) monitoring tests – FoundationOneTracker and the research use version of FoundationOneMonitor – demonstrating the value of the company’s diverse portfolio of tissue-informed and tissue-naïve assays to support cancer treatment response monitoring. Highlights include:

In a retrospective study of 58 patients from the Genentech, a member of the Roche Group, MyPathway study (NCT02091141), tissue-informed early ctDNA monitoring using the clinically available FoundationOne Tracker test provided insight into treatment response and survival outcomes in patients across diverse HER2 amplified or mutated tumors receiving HER2 ​targeted​ therapy. ​Results suggest ​serial early ctDNA monitoring ​is a valuable complementary tool for real-time treatment response monitoring to targeted therapy. (Mini-symposium presented by Razelle Kurzrock, MD: Biomarkers Predictive of Therapeutic Benefit; Abstract #1209)
Leveraging plasma collected serially from patients in Genentech’s Prospective Clinico-Genomic (PCG) study (NCT04180176), the FoundationOne Monitor assay was used to investigate ctDNA tumor fraction for monitoring treatment response. The test’s highly specific algorithmic filtration of non-tumor signal (such as clonal hematopoiesis) enabled high confidence in ctDNA quantification and assessment of molecular response. These findings may enable personalized therapy approaches tailored to a patient’s risk of progression and downstream cancer treatment planning. (Poster #971)
Additional presentations focused on the value of genomic profiling in non-small cell lung cancer (NSCLC) include data on how tumor microenvironment (TME) impacts immunotherapy response and an ancestry-based genomic landscape study. Highlights include:

The composition of TME has been shown to influence response to immunotherapy. Using artificial intelligence, Foundation Medicine researchers investigated digital pathology TME features of immunotherapy outcomes among patients with non-squamous NSCLC within a real-world dataset from the Flatiron Health-Foundation Medicine Clinico-Genomic Database. These results indicate that the composition of the TME assessed via digital pathology may have utility in identifying NSCLC patients who will respond to first-line immune checkpoint inhibitors beyond the established immunotherapy biomarkers. (Poster #4969)
Racial and ethnic disparities are highly prevalent in cancer care and impact treatment outcomes. Foundation Medicine remains committed to studying how ancestral differences in genomic alterations may impact patient care. In this study, researchers conducted a comprehensive characterization of the ancestry-based genomic co-alteration landscape and patterns of immunotherapy-related biomarkers in KRAS and EGFR-altered non-squamous NSCLC tumors. (Poster #6120)
"We’re excited to present new data at AACR (Free AACR Whitepaper) reinforcing the diverse utility of our monitoring portfolio to help confirm that patients are on the right targeted therapies and immunotherapies for the right amount of time," says Mia Levy, MD, PhD, Chief Medical Officer at Foundation Medicine. "Additionally, we know that the impact of genetic ancestry on the genomic landscape of tumors remains understudied, and we are always proud to demonstrate our dedication to closing more gaps in these disparities in cancer care."

Additionally, Dr. Levy will be taking part in a plenary session on Wednesday, April 10 titled "AI at the Interface: Accelerating Evidence Generation, Advancing Disparities Research, and Improving Trial Design." The following is a list of the presentations, along with their viewing details. To access all abstracts being presented at AACR (Free AACR Whitepaper), please visit aacr.org.

Follow Foundation Medicine on LinkedIn and X for more updates from #AACR24 and visit us in person at booth #3117.

Abstract #

Title

Collaborator

Product

Mini Symposium

#1209

April 7

3:35 – 3:50 p.m.

Tumor-Informed Circulating Tumor DNA Monitoring for Early Treatment Response and Survival Outcomes on Trastuzumab + Pertuzumab

Genentech, Natera

MCW Cancer Center, University of Adelaide Sarah Cannon Research Institute, MD Anderson Cancer Center, Francis Crick Institute

FoundationOneTracker

Posters

#971

April 7

1:30 – 5:00 p.m.

Validation of a tumor-naïve circulating tumor DNA (ctDNA) response monitoring panel in advanced non-small cell lung cancer (aNSCLC)

Genentech, Yale School of Medicine,
Alabama Oncology,

New York Cancer and Blood Specialists

FoundationOneMonitor for research use

#4969

April 9

9:00 a.m. – 12:00 p.m.

Investigating digital pathology tumor microenvironment features for immunotherapy outcome in patients with advanced non-small cell lung cancer

Foundation Medicine & Flatiron Health’s Joint Clinico-Genomic Database

#6120

April 9

1:30 – 5:00 p.m.

Genomic profiling of KRAS and EGFR-altered non-squamous non-small cell lung cancer reveal ancestry-specific co-alterations with therapeutic implications

Genentech

FoundationOne

FoundationOneCDX

On March 6, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported that Dr. Rachid Drissi, Principal Investigator at the Center for Childhood Cancer Research, Nationwide Children’s Hospital, and Associate Professor at Ohio State University, will present an abstract detailing the potency of THIO, MAIA’s telomere-targeting agent, as treatment for pediatric brain cancers at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 5–10, 2024 in San Diego, California (Press release, MAIA Biotechnology, MAR 6, 2024, View Source [SID1234640890]).

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The research was conducted in collaboration with Nationwide Children’s Hospital and led by Dr. Drissi. The study explored the combination of THIO and ionizing radiation (IR) treatments to induce direct anticancer effects and stimulate anti-tumor immunity in diffuse intrinsic pontine glioma (DIPG).

DIPG, a very difficult-to-treat and high-risk childhood cancer, is a central nervous system (CNS) tumor that forms in the brainstem. Scientists from Nationwide Children’s Hospital and MAIA have shown that THIO synergistically sensitizes DIPG cells to ionizing radiation (IR), significantly decreasing cell proliferation.

"At the AACR (Free AACR Whitepaper) Annual Meeting, we will present study results demonstrating the potential for THIO and IR combinational treatments to stimulate anti-tumor immunity through activation of the STING pathway, one of the key regulators of immune responses in a DIPG model," said Sergei M. Gryaznov, PhD., MAIA’s Chief Scientific Officer. "Unfortunately, prognosis for DIPG is dismal with a survival rate of less than one year, and radiotherapy, the only standard of care for DIPG, extends survival by only a few months. Immunotherapy is emerging as a potential alternative. Novel therapies that activate the immune system while evading tumor immunosuppression are in high demand in the field of cancer research."

"MAIA is excited to see that the results of our scientific collaborative work with the Nationwide Children’s Hospital were accepted for presentation at the AACR (Free AACR Whitepaper) Annual Meeting, a gathering of many of the best minds in cancer research from institutions all over the world," added Vlad Vitoc, M.D., CEO of MAIA.

MAIA’s presentation at the 2024 AACR (Free AACR Whitepaper) Annual Meeting

Abstract #:
5108

Abstract title:
Immunomodulatory and Antitumor Effect of Radiation and Induced Telomere Damage to Treat Pediatric High-grade Gliomas

Authors:

Banlanjo Umaru, Shiva Senthil Kumar (Center for Childhood Cancer Research, Nationwide Children’s Hospital, Columbus, OH)
Sergei M. Gryaznov (MAIA Biotechnology, Inc., Chicago, IL)
Rachid Drissi (Center for Childhood Cancer Research, Nationwide Children’s Hospital, Columbus, OH; The Ohio State University College of Medicine, Columbus, OH)
Presenter:
Rachid Drissi

Session date and time:
Tuesday April 09, 2024, 09:00AM – 12:30PM (Section 43)

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleoside 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei activating both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About Nationwide Children’s Hospital

Named to the Top 10 Honor Roll on U.S. News & World Report’s 2023-24 list of "Best Children’s Hospitals," Nationwide Children’s Hospital is one of America’s largest not-for-profit free-standing pediatric health care systems providing unique expertise in pediatric population health, behavioral health, genomics and health equity as the next frontiers in pediatric medicine, leading to best outcomes for the health of the whole child. Integrated clinical and research programs, as well as prioritizing quality and safety, are part of what allows Nationwide Children’s to advance its unique model of care. NationwideChildrens.org

On March 6, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported positive efficacy data for third-line treatment in its Phase 2 THIO-101 clinical trial evaluating THIO sequenced with the immune checkpoint inhibitor (CPI) cemiplimab (Libtayo) in advanced non-small cell lung cancer (NSCLC) (Press release, MAIA Biotechnology, MAR 6, 2024, View Source [SID1234640889]).

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"As an impressive measure of efficacy, the strong response rate of 38% in third-line treatment supports our premise that THIO administration prior to cemiplimab can improve tumor responses to immunotherapy in advanced NSCLC patients resistant to CPIs and other standard treatments"

Post this
As of January 8, 2024, overall response rate (ORR), characterized as partial or complete response to therapy, was 38% (3 out of 8 patients) in the efficacy evaluable population for combination THIO 180mg + cemiplimab in third-line treatment for NSCLC patients who failed treatment with immune checkpoint inhibitors in prior lines of therapy, with or without chemotherapy.

"As an impressive measure of efficacy, the strong response rate of 38% in third-line treatment supports our premise that THIO administration prior to cemiplimab can improve tumor responses to immunotherapy in advanced NSCLC patients resistant to CPIs and other standard treatments," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "Around 60-70% of NSCLC patients do not have a targetable mutation and cannot benefit from a biomarker-targeted therapy, making it the greatest unmet medical need population in lung cancer. In currently available treatments for these patients in third-line, response rates range around 6%.1 We are encouraged by the excellent efficacy findings in THIO-101 to date, adding impressive ORR to unprecented disease control rates (DCR), and further demonstrating the potential of our first-in-class treatment to redefine the standard of care for NSCLC patients."

The efficacy evaluable population defined in the THIO-101 protocol considers all subjects who received at least one dose of THIO treatment and have at least one postbaseline tumor assessment (scans). Two third-line patients in the 180mg dose cohort did not have recorded scans at the data cutoff. Safety remained consistent with previous reports.

The Company recently announced early completion of enrollment in the THIO-101 trial. THIO-101 is expected to be the first completed clinical study of a telomere-targeting agent in the field of cancer drug discovery and treatment.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with cemiplimab (Libtayo) followed by THIO has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.