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.

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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.

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]).

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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.

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.

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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.

On April 28, 2025 Strand Therapeutics Inc., the programmable mRNA company developing curative therapies for cancer and beyond, reported that it will present preclinical data from its STX-003 program at the 2025 annual meetings of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago April 25-30 and the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in New Orleans May 13-17 (Press release, Strand Therapeutics, APR 28, 2025, View Source [SID1234652280]). The proof-of-concept studies demonstrate that Strand’s programmable mRNA genetic circuits can target the expression of interleukin-12 (IL-12) to cancerous tissue to help achieve the right therapeutic dose while reducing off target side effects. These groundbreaking findings underscore the potential of STX-003 and build on the promise of Strand’s platform and pipeline to address the critical challenges of solid tumor immunotherapy.

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Systemic delivery is an effective way to reach solid tumors that are not surface accessible. However, systemic delivery of potent cytokines such as recombinant IL-12 has been challenging due to toxicity from off-target side effects. STX-003 aims to overcome this limitation by restricting IL-12 expression to the tumor microenvironment.

STX-003 is a systemically delivered, self-replicating mRNA encoding IL-12. Its programmable mRNA genetic circuitry acts as a sophisticated control system, restricting the expression of the IL-12 payload to the tumor microenvironment and preserving its activity within the cancerous tissue. Through its genetic circuits, Strand engineers its mRNA to sense the unique molecular signatures of different cell types, ensuring that the therapeutic payload is primarily produced within the target tumor tissues, while its activity is significantly inhibited in healthy, off-target tissue areas. By precisely controlling the delivery of mRNA and its expression of IL-12, STX-003 offers a promising strategy to unlock the full therapeutic potential of this powerful cytokine in the fight against solid tumors. The early discovery work was supported by funding from Wellcome Leap, a nonprofit organization focused on accelerating breakthroughs in human health.

"The results from the Strand STX-003 preclinical studies are unprecedented. For the first time, systemically delivered programmable mRNA was used to safely target expression of IL-12 into cancerous tissue while inhibiting expression in healthy tissue," said Jacob Becraft, Ph.D., CEO & Co-Founder, Strand Therapeutics. "Our proprietary mRNA platform and genetic circuitry have the potential to make systemic delivery of mRNA and expression of powerful cytokines such as IL-12 safer and more effective for patients in a range of solid tumors, including hard to reach visceral tumors."

STX-003 presentations at AACR (Free AACR Whitepaper) and ASGCT (Free ASGCT Whitepaper) include key findings from preclinical studies regarding the functionality of its genetic circuitry and its impact on the efficacy and tolerability of systemically delivered mRNA expressing IL-12.

AACR
Abstract Title: STX-003: cancer immunotherapy with systemic delivery of mRNA utilizing programmable genetic circuits for precise regulation of IL-12 expression and reduced toxicity
Session Type: Poster
Session Title: PO.IM01.12 Local Treatments, Novel Tools, and Delivery Systems to Manipulate Tumor Immunity
Date and Time: April 28, 2:00-5:00 pm CT
Abstract Number: 3472/11
Location: Section 37

Full abstract is available on the AACR (Free AACR Whitepaper) Annual Meeting website.

ASGCT
Abstract Title: STX-003: A mRNA Cancer Immunotherapy Utilizing Cancer-Selective Programmable Genetic Circuits for Systemic Tumor Control
Session Type: Oral
Session Title: Targeted Gene and Cell Therapy for Cancer
Date and Time: May 17, 8:15-8:30 am CT
Abstract Number: 394
Location: Room 291-292

Full abstract is available on the ASGCT (Free ASGCT Whitepaper) Annual Meeting website.

Strand continues to demonstrate innovation in the field of programmable mRNA therapeutics, marked by significant preclinical and clinical progress for its mRNA platform for solid tumor treatment. In 2023, the company received U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application for STX-001, an investigational multi-mechanistic, synthetic self-replicating mRNA technology that expresses an IL-12 cytokine for an extended duration, directly into the tumor microenvironment via intratumoral delivery. Strand dosed their first patient in a Phase 1 clinical trial in 2024. STX-001 clinical development is ongoing and updates will be shared in the near future. These achievements reflect the company’s ability to translate its innovative mRNA technology from the laboratory into clinical development.

On April 28, 2025 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported new interim analysis results of the VICTORI study showing strong performance of its ultra-sensitive NeXT Personal assay in detecting early signs of residual or recurrent colorectal cancer (CRC) (Press release, Personalis, APR 28, 2025, View Source [SID1234652279]).

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The study, led by Dr. Jonathan Loree’s team at BC Cancer in Vancouver, Canada, utilized NeXT Personal to look for small traces of circulating tumor DNA (ctDNA) in blood samples from a cohort of 71 patients with resectable Stage I-IV CRC. The data was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois by Emma Titmuss at BC Cancer, in an oral presentation titled Detection of post-surgical minimal residual disease (MRD) in colorectal cancer; preliminary results from the VICTORI study.

"After surgery, ctDNA-based liquid biopsies may help identify patients who would benefit most from additional treatment," said Jonathan Loree, MD, MS, a medical oncologist at BC Cancer and the senior investigator of the study. "Alternatively, this may help patients with good prognosis avoid toxicities from unnecessary chemotherapy. By monitoring patients for recurrences, liquid biopsies can continue to support clinical care and allow more patients to undergo second curative intent surgeries to remove early recurrences."

Key findings presented from the interim analysis for VICTORI:

100% of patients who have recurred were detected as ctDNA positive by NeXT Personal prior to detection on imaging.
100% of patients who have been ctDNA negative throughout the study remain disease-free.
87% of clinical recurrences were detectable within the early "landmark window" 2 to 8 weeks after surgery, with 85% detectable by 4 weeks.
64% of detections within the landmark window were in the ultrasensitive range (under 100 ppm).
100% of distant metastatic recurrences were detected prior to imaging, including lung metastasis, an area which has traditionally been more challenging to detect by ctDNA testing.
70% of the first ctDNA detections were in the ultrasensitive range, with a median of 24.4PPM and as low as 2.45 PPM.
Median patient follow-up at the time of the interim analysis was 15.75 months, with the patients continuing to be followed clinically.

"The initial results from our study show the importance of using a highly sensitive MRD assay like NeXT Personal in colorectal cancer," said Dr. Loree.

"We are encouraged by the preliminary results from the VICTORI study, which show the ability of our ultrasensitive ctDNA assay NeXT Personal to detect residual and recurrent colorectal cancer at high rates in the early landmark window after surgery," said Dr. Richard Chen, Chief Medical Officer and Executive Vice President, R&D at Personalis. "We continue to expand this prospective study as we strive towards helping patients with colorectal cancer detect and treat recurrence earlier."