On March 28, 2024 Iambic Therapeutics reported it will highlight new preclinical data for IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers, in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10 in San Diego (Press release, Iambic Therapeutics, MAR 28, 2024, View Source [SID1234641597]).

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The poster presentation will showcase preclinical data illustrating how the unique binding mechanism and potent HER2 activity of IAM1363 overcomes multiple resistance mechanisms and how its strong EGFR avoidance widens the safety margin. IAM1363 potently inhibits both the wild type and mutant forms of HER2, showing over 1000-fold selectivity against EGFR due to a unique binding mode and tumor enhancement not seen with other HER2 inhibitors, leading to exceptional in vivo efficacy and tolerability in various HER2-driven cancer models, including those resistant to existing HER2-targeting agents. IAM1363 is now in a Phase 1 clinical study.

Poster Presentation Details:

Presentation Title: Validation of a novel Type II HER2 inhibitor through preclinical studies across various cancer models

Abstract Number: 1980/29

Session Title: Kinase and Phosphatase Inhibitors 2

Location: Poster Section 25

Date and Time: Monday, April 8th; 9:00 – 12:30 PT

Presenter: Lana Kulyk, PhD

On March 28, 2024 InnoCare Pharma (HKEX: 09969; SSE: 688428), a leading biopharmaceutical company reported that the first patient in China has been dosed in the Phase 1b clinical study of the combination of InnoCare’s novel SHP2 (Src Homology 2 domain containing protein tyrosine phosphatase) allosteric inhibitor, ICP-189, with ArriVent’s furmonertinib, a highly brain-penetrant, broadly active mutation-selective EGFR (epidermal growth factor receptor) inhibitor in patients with advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, InnoCare Pharma, MAR 28, 2024, View Source [SID1234641596]).

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NSCLC is the predominant subtype of lung cancer, accounting for approximately 85% of all cases. In July 2023, InnoCare and ArriVent BioPharma, Inc. (Nasdaq: AVBP) announced a clinical development collaboration, accelerating the clinical trial of ICP-189 in combination with furmonertinib in patients with advanced or metastatic NSCLC in China.

Furmonertinib is being advanced by ArriVent in global studies in patients with advanced or metastatic NSCLC with EGFR mutations, including exon 20 insertion mutations. It is approved in China as a first-line treatment for adults with locally advanced or metastatic NSCLC with EGFR exon 19 deletion (19DEL) or exon 21 (L858R) substitution mutations, where it is being further developed for additional indications with Allist Pharmaceuticals (SSE: 688578) who discovered furmonertinib. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for furmonertinib for the treatment of patients with previously untreated, locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Furmonertinib is also being evaluated for the treatment of NSCLC patients with EGFR P-loop alpha-c helix compressing (PACC) mutations.

ICP-189 is a potent and selective oral allosteric inhibitor of SHP2, developed by InnoCare for the treatment of solid tumors as a single agent and/or in combination with other antitumor agents. Preliminary efficacy was observed in ICP-189 monotherapy. In the dose escalation study, the dosage has been escalated up to 120 mg with no DLT observed and a favorable PK and safety profile have been demonstrated.

Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare, said: "We are excited to see the latest progress of our clinical collaboration with ArriVent. SHP2 inhibitors are ideal for the treatment of solid tumors by combination with various targeted drugs and immunotherapies and are expected to address the huge unmet medical needs. We will accelerate the clinical study and expect this innovative therapy to benefit more NSCLC patients early."

On March 28, 2024 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported that the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for NST-628 for the treatment of patients with advanced solid tumors harboring genetic alterations in the RAS-MAPK pathway (Press release, Nested Therapeutics, MAR 28, 2024, View Source [SID1234641595]). NST-628 is a mechanistically novel, fully brain penetrant non-degrading pan-RAF/MEK molecular glue that targets RAF and MEK nodes in the RAS-MAPK pathway.

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"The significant majority of KRAS-, NRAS-, and BRAF-mutant tumors are not addressable by currently approved therapies, creating a pressing need for new medicines that provide superior, durable efficacy and tolerability for people living with these hard-to-treat cancers," said Philip Komarnitsky, M.D., Ph.D., chief medical officer of Nested. "We believe that NST-628 has the potential to provide a differentiated clinical profile, including a superior therapeutic index and prevention of pathway reactivation, for patients with advanced solid tumors harboring RAS-MAPK pathway alterations. The IND clearance for NST-628 is an important step in the advancement of our first clinical-stage program, and with clinical trial sites already activated, we look forward to dosing the first patients in this trial in the first half of this year."

The Phase 1 open-label, single-arm, two-part study (NCT06326411) is intended to investigate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of single agent NST-628 in adult patients with RAS-MAPK pathway mutated/dependent advanced solid tumors who have exhausted standard treatment options. The study includes two parts: dose escalation (Part A) followed by dose expansion (Part B). The primary objectives for Part A are delineating NST-628’s safety profile and establishing the recommended dose for Part B. For more information, visit clinicaltrials.gov.

About NST-628
NST-628 is a fully brain-penetrant, mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway. NST-628 was developed based on Nested’s proprietary structural insights of how signaling complexes form and function in cancer and addresses common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of resistance via signaling pathway reactivation. Preclinical data evaluating all biomarkers relevant to RAS/MAPK-driven cell and patient-derived models collectively demonstrate superior anti-tumor activity, including in RAS and central nervous system-implanted tumor models, and tolerability of NST-628 compared to other MAPK-targeted compounds administered as either single agents or in combination. With a half-life and metabolic profile optimized to achieve a superior therapeutic index on a daily dosing schedule, as well as full intrinsic blood brain barrier penetrance, these data support NST-628’s potential as a best-in-class treatment for RAS and RAF-driven cancers.

On March 28, 2024 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported that preclinical data from its lead program, NST-628, will be featured in an oral presentation in the "New Drugs on the Horizon" series at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place in San Diego, California from April 5-10, 2024 (Press release, Nested Therapeutics, MAR 28, 2024, View Source [SID1234641594]).

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The preclinical data supports NST-628’s profile as a mechanistically novel, fully brain penetrant non-degrading pan-RAF/MEK molecular glue that targets RAF and MEK nodes in the RAS-MAPK pathway. Details for the presentation are listed below.

Title: NST-628 is a Novel, Potent, Fully Brain-Penetrant MAPK Pathway Molecular Glue that Inhibits RAS- and RAF-Driven Cancers
Session: New Drugs on the Horizon: Part 3
Session Date and Time: Monday, April 8, 10:15-11:45 a.m. PT
Presentation Date and Time: Monday, April 8, 10:40-10:55 a.m. PT
Location: Ballroom 20 CD, upper level, San Diego Convention Center
Presenter: Klaus Hoeflich, Ph.D., chief scientific officer and co-founder of Nested

About NST-628
NST-628 is a fully brain-penetrant, mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway. NST-628 was developed based on Nested’s proprietary structural insights of how signaling complexes form and function in cancer and addresses common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of resistance via signaling pathway reactivation. Preclinical data evaluating all biomarkers relevant to RAS/MAPK-driven cell and patient-derived models collectively demonstrate superior anti-tumor activity, including in RAS and central nervous system-implanted tumor models, and tolerability of NST-628 compared to other MAPK-targeted compounds administered as either single agents or in combination. With a half-life and metabolic profile optimized to achieve a superior therapeutic index on a daily dosing schedule, as well as full intrinsic blood brain barrier penetrance, these data support NST-628’s potential as a best-in-class treatment for RAS and RAF-driven cancers.

On March 28, 2024 Caris Life Sciences(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, reported that the company and collaborators within the Caris Precision Oncology Alliance (POA) will collectively present 10 studies across eight tumor types at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 5-10, 2024, in San Diego, CA, at Booth Number 1105 (Press release, Caris Life Sciences, MAR 28, 2024, View Source [SID1234641593]). Caris President, David Spetzler, MS, PhD, MBA, will lead an AACR (Free AACR Whitepaper) Scientist ↔ Survivor Program Special Session titled, "Very Early Cancer Detection Assays: The Future or Fantasy," on Tuesday, April 9, from 1:00 – 1:45 PM.

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"We are proud of the collaborative abstracts accepted for presentation at AACR (Free AACR Whitepaper), demonstrating the value of Caris’ comprehensive molecular profiling and the large-scale collaboration between the growing number of POA sites," said Caris EVP and Chief Medical Officer George W. Sledge, Jr., MD. "The findings represent important observations, particularly the power of large clinicogenomic datasets to enable the identification of new biomarkers with clinical implications across diverse tumor types, including lung, breast and prostate cancer. Moreover, we are excited to present validation data demonstrating the analytical and clinical utility of our AI-enabled whole exome and whole transcriptome liquid biopsy platform, Caris Assure, in early diagnosis, therapy selection and minimal residual disease monitoring for patients with cancer."

"Caris enables clinicians to make the best individualized treatment choices for their patients, researchers to discover new targets and the biopharmaceutical industry to develop the next breakthrough medicines," said Caris President David Spetzler, MS, PhD, MBA. "The findings illustrate how our physicians, scientists and collaborators in the POA are leveraging real-world evidence from over 593,000 lifetime clinical cases, including over 482,000 with matched molecular data and outcomes in Caris’ unique AI-driven platform, to deepen our understanding of the mechanisms of cancer pathogenesis and improve outcomes of all patients affected by cancer."

Mini symposium presentations include:

Tissue-specific thresholds and microenvironment correlates of tumor mutation burden associated with immunotherapy benefit and prognosis in microsatellite stable cancers. (Abstract Number: 1213)
April 7, 4:35 – 4:50 PM PST
Comprehensive molecular and immunological characterization of early onset esophagogastric cancer. (Abstract Number: 3890)
April 8, 3:35 – 3:50 PM PST
Poster presentations include:

Modulation of the MSS and MSI colorectal cancer immune microenvironment with FOLFOX and FOLFIRI -/+ anti-PD-1 immunotherapy. (Poster Number: 1189/23)
April 7, 1:30 – 5:00 PM PST
AI-enabled whole exome & transcriptome liquid biopsy addressing MCED, MRD, and therapy selection on a single platform. (Poster Number: 2300/11)
April 8, 9:00 AM – 12:30 PM PST
Surfaceome and cancer testis antigen profiling of lung adenocarcinoma by large-scale transcriptomic analysis. (Poster Number: 3361/18)
April 8, 1:30 – 5:00 PM PST
Describing the molecular landscape of cervical cancer metastases: Implications for future therapeutic targets. (Poster Number: 3362/19)
April 8, 1:30 – 5:00 PM PST
Characterization of PDLIM2 in non-small cell lung cancer. (Poster Number: 5201/9)
April 9, 9:00 AM – 12:30 PM PST
The genomic, transcriptomic, and immunologic landscape of TEM8 (ANTXR1) in neuroendocrine neoplasms (NENs). (Poster Number: 6851/28)
April 10, 9:00 AM – 12:30 PM PST
PIM kinases alter the prostate tumor immune microenvironment. (Poster Number: 6875/19)
April 10, 9:00 AM – 12:30 PM PST
Comprehensive molecular and immune profiling of triple-negative invasive lobular carcinoma. (Poster Number: 7037/4)
April 10, 9:00 AM – 12:30 PM PST
Poster and abstract summaries highlighting the Caris research presented at AACR (Free AACR Whitepaper) 2024 will be available onsite at Caris’ Booth (# 1105). The full abstracts will be available on the Caris website beginning on April 6.

The AACR (Free AACR Whitepaper) Scientist ↔ Survivor Program (SSP) is a unique program designed to build bridges and unity among the leaders of the scientific, cancer survivor and patient advocacy communities worldwide. By strengthening communications and forging partnerships between these important communities in the cancer field, the program enhances efforts to accelerate progress in the fight against cancer. Dr. David Spetzler will lead a special interest session at AACR (Free AACR Whitepaper)’s SSP, highlighting the current and future states of very early cancer detection assays.

The POA includes 91 cancer centers, academic institutions, research consortia and healthcare systems, including 43 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients.