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.

On March 6, 2024 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported that the final overall survival (OS) data from the Phase 3 randomized, double-blind, placebo-controlled NORA study evaluating ZEJULA (niraparib) in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC) will be shared in oral presentations at the 2024 Congress of the European Society of Gynaecological Oncology (ESGO), March 7-10, 2024, in Barcelona, Spain, and the 2024 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, taking place March 16-18, 2024, in San Diego, CA (Press release, Zai Laboratory, MAR 6, 2024, View Source [SID1234640887]).

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"Previous progression-free survival and interim OS data from the NORA study demonstrated the benefit of niraparib maintenance therapy with an individualized starting dose among Chinese patients with PSROC," said Dr. Rafael Amado, President, Head of Global Oncology Research and Development, Zai Lab. "We look forward to sharing the final OS findings from this study at both the 2024 ESGO and SGO conferences. Based on these results, ZEJULA remains the only PARP inhibitor approved as maintenance monotherapy for ovarian cancer patients in both first-line and recurrent settings regardless of biomarker status."

In the NORA study, 265 patients with PSROC were randomized (2:1) to receive niraparib or placebo. The final OS analysis was conducted after ≥ 50% of OS events occurred in the intent-to-treat population. The ESGO presentation will feature data analyses showing that niraparib maintenance therapy with an individualised starting dose (ISD) based on patient weight and platelet count demonstrated a favorable OS trend versus placebo in this disease setting, regardless of BRCA-gene mutation status. No new safety signals were identified during the long-term follow up period subsequent to the primary analysis.

Details regarding the oral presentation at the 2024 ESGO Congress are as follows:

Title: Niraparib maintenance therapy using an individualised starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): Final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 trial
Presenter: Xiaohua Wu, M.D., PhD., Fudan University Shanghai Cancer Center, Shanghai, China
Date/Time: Saturday, March 9, 2024, 4:13 p.m. – 4:19 p.m. CET/Spain
Location: Session Hall III (112)

Details regarding the late-breaking oral presentation at the 2024 SGO Annual Meeting are as follows:

Title: Niraparib maintenance therapy using an individualized starting dose in patients with platinum-sensitive recurrent ovarian cancer (NORA): Final overall survival analysis of a randomized, double-blind, placebo-controlled phase 3 trial
Presenter: Xiaohua Wu, M.D., PhD., Fudan University Shanghai Cancer Center, Shanghai, China
Date/Time: Monday, March 18, 2024, 3:24 p.m. to 3:30 p.m. Pacific Time
Location: San Diego Convention Center, Hall F

About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic cancers in China with more than 55,000 newly diagnosed cases and 37,000 deaths each year. While platinum-based chemotherapy is effective at inducing an initial response in ovarian cancer, the disease will recur in the majority of women. New agents that prolong the duration of response following platinum-based treatment and delay the inevitable relapse of ovarian cancer will benefit patients with ovarian cancer in China.

About ZEJULA (niraparib)
ZEJULA (niraparib) is an oral, once-daily small-molecule poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor. A PARP inhibitor blocks the ability of cancer cells to repair themselves after they have been damaged by radiation and certain chemotherapies. This inhibition of DNA damage repair can result in the inability of cancer cells to replicate themselves and in programmed cell death. Tumors that are deficient in key DNA damage repair pathways, such as BRCA1 mutant tumors, are particularly sensitive to ZEJULA. As maintenance therapy, ZEJULA is for women who have had prior chemotherapy treatment but are at high risk of cancer recurrence. ZEJULA is intended to avoid or slow a recurrence of the cancer if it is in remission after prior treatment. In the maintenance setting, ZEJULA does not require the addition of radiation or chemotherapies to kill tumor cells.

As a first-line monotherapy maintenance treatment of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively, ovarian cancer) following a response to platinum-based chemotherapy, ZEJULA was approved by the NMPA in September 2020 and included in the NRDL in December 2021.

As a maintenance treatment of patients with platinum sensitive recurrent ovarian cancer, ZEJULA was approved by the NMPA in December 2019 and included in the NRDL in December 2020.

Zai Lab has an exclusive license from GSK to develop and commercialize ZEJULA in mainland China, Hong Kong, and Macau.

On March 6, 2024 Blacksmith Medicines, Inc. (Blacksmith), a leading biopharma dedicated to discovering and developing medicines targeting metalloenzymes, reported the company will present data on its oncology program targeting flap endonuclease 1 (FEN1), a structure-specific metallonuclease that cleaves 5′ DNA flaps during replication and repair, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024, taking place April 5-10 at the San Diego Convention Center, San Diego CA (Press release, Blacksmith Medicines, MAR 6, 2024, View Source [SID1234640886]).

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Details of the poster presentation are as follows:

Abstract Number: 7148
Title: "Small molecule inhibitor of FEN1 nuclease utilizing a novel metal binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR"
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Antitumor Agents 6
Session Date and Time: Wednesday April 10, 2024 9:00 AM – 12:30 PM
Location: Poster Section 23
Poster Board Number: 10

The abstract is now available on the conference website at AACR (Free AACR Whitepaper) Annual Meeting 2024.

About FEN1
Flap endonuclease 1 (FEN1) is a structure-specific di-magnesium metallonuclease that cleaves 5′ DNA flaps during replication and repair. FEN1 is an attractive target for development of anticancer therapeutics because it is overexpressed in many tumor types and has a large number of synthetic lethality partners including genes in Homologous Recombination (HR) pathway.

About metalloenzymes and the Blacksmith platform
Metalloenzymes utilize a metal ion cofactor in the enzyme active site to perform essential biological functions. This diverse class of targets has historically been difficult to drug due to small molecule chemistry limitations that have plagued the industry. The Blacksmith metalloenzyme platform has solved this problem by leveraging the following:

A large proprietary fragment library of metal-binding pharmacophores (MBPs);
A comprehensive database containing a full characterization of the metalloenzyme genome including functions, metal cofactors, and associations to disease;
A first-of-its-kind metallo-CRISPR library of custom single guide RNAs;
An industry-leading metalloenzyme computational toolkit for docking, modeling and structure-based drug design; and
A robust and blocking intellectual property estate covering bioinorganic, medicinal, and computational chemistry approaches for metalloenzyme-targeted medicines.