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Clasp Therapeutics Doses First Patient in Phase 1 Clinical Trial With a First-in-Class T-Cell Engager Designed to Target Cancer Cells With Absolute Specificity

On April 28, 2025 Clasp Therapeutics, a biotechnology company bringing unparalleled precision to immuno-oncology using next-generation T-cell engagers (TCEs), reported dosing of the initial patient in the GUARDIAN-101 phase 1 trial of CLSP-1025, the first tumor-specific TCE to enter clinical development. CLSP-1025 exclusively targets cancer cells expressing the p53R175H mutation, a mutation associated with a wide range of solid tumors, including colorectal, pancreatic, lung, gastric, esophageal, gynecological, and prostate cancers (Press release, Clasp Therapeutics, APR 28, 2025, View Source [SID1234652285]).

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Unlike first-generation TCEs that target proteins present on both tumor and normal cells, Clasp’s TCEs target tumor-specific peptides derived from cancer driver mutations, ensuring absolute specificity and minimizing risk of toxicity to healthy tissues. Truncal mutations like p53R175H occur early in tumorigenesis and are present in every tumor cell, making them ideal targets for immune system attack. Moreover, these pHLAre molecules (precise HLA redirecting engagers) are designed to mimic the natural T cell receptor interface between a cancer cell and T cell, maximizing anti-cancer activity.

"Treating the first patient in the GUARDIAN-101 trial marks a pivotal milestone in Clasp’s mission to transform patient outcomes through precision immunotherapy," said Dr. Lauren Harshman, M.D., SVP of Clinical Development at Clasp Therapeutics. "Advancing CLSP-1025 into the clinic is an important step in validating the potential of our pHLAre platform to overcome the limitations of current T-cell engagers and offer a breakthrough treatment option for patients."

At the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting this week, Clasp also presented nonclinical data supporting the clinical development of CLSP-1025, including data supporting the therapeutic candidate’s selectivity, activity, pharmacokinetics and safety profile.

About GUARDIAN-101 and CLSP-1025

Clasp’s Phase 1 GUARDIAN-101 dose escalation study evaluates the safety and initial anti-tumor activity of CLSP-1025. CLSP-1025 is a bispecific antibody-like molecule that directs a patient’s T cells to the tumor, generating a precise immune response to selectively and potently eliminate cancer cells. CLSP-1025 is designed to target the p53R175H peptide in the context of HLA-A*02:01. Enrolled patients must be HLA-A*02:01 positive and have an advanced solid tumor that harbors the p53R175H mutation. This Phase 1 study will identify the dose of CLSP-1025 for use in future studies. Visit clinicaltrials.gov (NCT06778863) for more details.

Kairos Pharma, Ltd. Announces Data to be Presented at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting

On April 28, 2025 Kairos Pharma, Ltd. (NYSE American: KAPA), a clinical stage biopharmaceutical company, reported it will be presenting at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting to be held May 30-June 3, 2025 at McCormick Place, Chicago, Ill (Press release, Kairos Pharma, APR 28, 2025, View Source [SID1234652284]).

The poster is titled, "Effect of KROS 101, a small molecule GITR ligand agonist, on T effector cells, T reg cells and intratumoral CD8 T cell cytotoxicity," and will be presented on June 2.

John Yu, M.D., Kairos CEO commented, "We look forward to the opportunity to continue to share data regarding our platform assets at one of the most prestigious oncology meetings in the world. We believe that KROS 101 has the potential to help optimize cancer treatment and we look forward to discussing our findings with the medical and scientific communities."

Schrödinger Presents New Preclinical Data at AACR Annual Meeting

On April 28, 2025 Schrödinger, Inc. (Nasdaq: SDGR) reported preclinical data on SGR-3515, its investigational Wee1/Myt1 co-inhibitor today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 (Press release, Schrodinger, APR 28, 2025, View Source [SID1234652283]). The data demonstrated that SGR-3515 has improved anti-tumor activity in preclinical models compared to known Wee1 and Myt1 monotherapy inhibitors. The poster also described how the dosing schedule of SGR-3515 can be optimized to preserve efficacy and minimize target-related side effects. New data was also presented on the development of a computational method that predicts the response to Wee1-based drug combinations, including in novel cancer settings such as head and neck cancers. Schrödinger expects to report initial data from the ongoing Phase 1 clinical trial of SGR-3515 in patients with advanced solid tumors in the second half of 2025.

Additionally, Schrödinger presented its first preclinical data for SGR-4174, its SOS1 inhibitor that disrupts the interaction between SOS1 and KRAS, the most frequently mutated oncogene in human cancers. SGR-4171 demonstrated high selectivity for SOS1 over SOS2 as well as over other kinases. The data also demonstrated that SGR-4174 has strong tumor growth inhibition as a monotherapy as well as in combination with MEK or KRAS inhibitors, while maintaining a favorable safety profile. SOS1 development opportunities include cancers such as lung adenocarcinoma or RASopathies such as Neurofibromatosis Type 1.

"The preclinical data for SGR-3515 and SGR-4174 further demonstrate that molecules discovered and developed by Schrödinger have favorably differentiated molecular profiles compared to existing development-stage molecules," said Karen Akinsanya, Ph.D, president of R&D therapeutics at Schrödinger. "The preclinical profiles of these development candidates reinforce the power of our computationally-driven approach to designing molecules that meet challenging target product profiles and have the potential for meaningful benefit to patients."

SGR-3515 Data at AACR (Free AACR Whitepaper)

The poster (Abstract #3025), "Optimization of therapeutic index of SGR-3515, a first-in-class Wee1/Myt1 inhibitor through intermittent dosing for monotherapy and combination with chemotherapy in xenograft tumor models," includes preclinical data demonstrating that SGR-3515 monotherapy has superior anti-tumor activity compared to the Wee1 inhibitor ZN-c3 and the Myt1 inhibitor RP-6306 in multiple tumor models as well as synergistic efficacy when used in combination with chemotherapy. The poster also shares for the first time preclinical data demonstrating that the potential efficacy and tolerability of SGR-3515 can be optimized with three to five days of dosing, depending on the tumor type, in a two-week dosing cycle across multiple tumor settings. The optimized dosing schedule preserves efficacy while allowing for complete recovery from reversible on-target myelosuppression in preclinical tumor models.

A second poster (Abstract #3660), "Machine learning-based combination prediction for Wee1 inhibitor," presents data showing that a machine learning model, built on the integration of two large cell line combination screening studies of the Wee1 inhibitor AZD1775, successfully identified known and novel synergistic Wee1 drug combinations such as with tyrosine kinase inhibitors in ovarian and breast cancers, and with chemotherapy in head and neck or cancers. The data suggests potential for machine learning based approaches to make predictions with a high degree of confidence and gain novel insights beyond the data they are trained on.

SGR-4174 Data at AACR (Free AACR Whitepaper)

The poster (Abstract #4376), "Preclinical characterization of SGR-4174, a potent and selective SOS1 inhibitor for the treatment of pan KRAS mutant cancers in combination with KRAS pathway inhibitors," includes preclinical data demonstrating the superior binding, selectivity, and drug-like properties of SGR-4147 compared to MRTX0902 as assessed via comprehensive in vitro potency, ADME, and safety assays. The preclinical data for SGR-4174 also show robust suppression of the RAS signaling pathway and potent cell killing activity across multiple cancer types harboring diverse KRAS mutations as well as EGFR and SOS1 mutations. SGR-4174 monotherapy achieved dose-dependent target engagement and tumor growth inhibition and induced tumor shrinkage when used in combination with MEK or KRAS inhibitors in preclinical models of pancreatic and non-small cell lung cancer.

Vector Laboratories and Spatomics Present Novel Method for Multiplexed Spatial Profiling of Glycans and Proteins at AACR

On April 28, 2025 Vector Laboratories, a manufacturing partner of reagents and critical components for the development and production of life sciences tools, diagnostics, and clinical-stage biotherapeutics, in partnership with Spatomics, which specializes in developing spatial biology research tools, reported a poster at AACR (Free AACR Whitepaper) detailing a highly sensitive, multiplexed single-cell in situ analysis method that enables simultaneous detection of ten or more protein and glycan targets in the same biological sample (Press release, Vector Laboratories, APR 28, 2025, View Source [SID1234652282]).

The poster, "Multiplexed spatial profiling of protein and glycan expression using CFP fluor cleavable TSA fluorophores," was authored by scientists at Spatomics and Vector Laboratories. It describes a novel platform integrating off-the-shelf antibodies and lectins for sensitive multiplexed detection, opening up new insights into complex biological systems.

Spatomics employs a multiplexing strategy centered around its patented Cleavable Fluorescent Probe (CFP) fluorophores, which allows reiterative cycles of staining, imaging, and fluorophore cleaving. This enables sensitive, high-multiplex imaging without the use of highly complex or specialized detection systems.

"This partnership demonstrates our commitment to continue to improve the tools available for crucial basic research," said Lisa V. Sellers, PhD, CEO of Vector Laboratories. "We’re proud that this approach enables the multiplexed detection of in-situ glycosylation using Vector’s lectins, which have been validated over the years by the National Center for Functional Glycomics. We look forward to ultimately applying this approach to other research areas, including cancer biology, immunology, neuroscience, and infectious disease."

"We are excited to join with Vector Laboratories to bring this research to the attention of the scientific community," said Dr. Rui Zheng, CEO of Spatomics. "Our CFP Cleavable TSA fluorophore is the only commercially available fluorophore that leverages tyramide signal amplification and enables efficient removal of the fluorescent signal after staining."

The collaboration between Vector Laboratories and Spatomics will serve basic research in three key ways:

by making comprehensive multiplexing accessible to scientists;
by addressing biology questions in specific research areas where they are most effective;
by developing biomarker signatures that help in understanding disease state versus normal and could also facilitate target identification.
The poster will be presented at AACR (Free AACR Whitepaper) this afternoon, Central Time: Poster Section 52; Poster Board Number 17. The session title is "Late-Breaking Research: Chemistry." Authors of the poster are Nishinki Muthumuni, Jia Guo, Dana Ashworth, Rui Zheng, Jing Zhou, Shuhui Chen, Erika Leonard, Shamali Roy, and Xiaoshan Wang.

In 2024, Vector Laboratories merged with Absolute Biotech, expanding its manufacturing and distribution footprint from multiple manufacturing sites in the US to the UK and Europe. Absolute Biotech serves customers globally with antibody reagents, kits, and services to provide annotation, validation, sequencing, engineering, and recombinant manufacturing.

EpiBiologics Presents First Data on c-Met Degrading Bispecific Antibody

On April 28, 2025 EpiBiologics, a leader in tissue-selective extracellular protein degradation, reported the first preclinical data on its EpiTAC bispecific antibody degrader of c-Met, a potential first-in-class therapy for a range of cancers driven by mutated, amplified, or overexpressed c-Met signaling (Press release, EpiBiologics, APR 28, 2025, View Source [SID1234652281]). The data, which were presented in a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, show that c-Met degrading EpiTACs demonstrate strong anti-tumor activity in vivo and as ADCs, combining c-Met degradation with payload-dependent cell killing to broaden the clinical opportunity into tumors that are not solely dependent on c-Met signaling for survival.

c-Met is a receptor tyrosine kinase that acts as both a pathogenic driver and disease marker in multiple tumor types, including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer and renal cancer. While tyrosine kinase inhibitors are approved for tumors with c-Met mutations, targeted therapies for c-Met-amplified or -overexpressed tumors are lacking, hampered by the need for high levels of c-Met expression and variable dependency on c-Met for tumor cell survival and proliferation.

Key highlights of EpiBiologics’ data include:

c-Met EpiTACs degraded oncogenic mutant and wildtype forms of c-Met on tumor cells and demonstrated sustained tumor growth suppression in a patient-derived mouse model of NSCLC.
Degradation of c-Met resulted in deep anti-tumor activity, driven by the ability of EpiTACs to remove the oncogenic protein and associated scaffolding.
Combining targeted protein degradation of c-Met with a cytotoxic ADC payload suppressed tumor growth in c-Met-mutant, c-Met-amplified, and c-Met-overexpressed tumors, potentially broadening the clinical opportunity into tumors that have low c-Met expression and are not solely dependent on c-Met signaling for survival.
"We’re pleased to share data from our c-Met EpiTAC program, confirming our platform’s ability to drive deep and durable degradation with therapeutically relevant impact. These data underscore how we can flexibly tune EpiTACs to have specific characteristics that solve the limitations of current clinical therapies," said Shyra Gardai, Ph.D., Chief Scientific Officer of EpiBiologics. "Additionally, this dataset showed that there is exciting potential, in certain therapeutic settings, for augmenting our bispecific antibodies with a cytotoxic payload to drive even broader patient benefit."

"c-Met represents one of several important targets in our pipeline of EpiTAC bispecific antibodies," said Ann Lee-Karlon, Ph.D., Chief Executive Officer of EpiBiologics. "As our lead tissue-selective EGFR degrader moves rapidly toward the clinic, we are also advancing EpiTACs for membrane, soluble, and GPCR targets. We have demonstrated strong single-agent activity and can successfully combine with current standards-of-care, paving the way for future therapies."

The poster, entitled "Discovery of c-MET degrading bispecific antibodies (EpiTACs) for NSCLC and other c-MET driven tumors," will be available on the company’s website here when presentation concludes.