Mythic Therapeutics Presents Preclinical Data Demonstrating Potent Efficacy of MYTX-011 Across a Broad Range of Tumor Xenograft Models Harboring Clinically Relevant Mutations at the American Association for Cancer Research (AACR) Annual Meeting

On April 28, 2025 Mythic Therapeutics, a clinical-stage biotechnology company developing next-generation antibody-drug conjugate (ADC) therapies for the treatment of a wide range of cancers, reported preclinical data demonstrating the potential of MYTX-011 to treat multiple tumor types, regardless of mutation status or cMET expression level, in a poster session at the AACR (Free AACR Whitepaper) Annual Meeting in Chicago, Illinois (Press release, Mythic Therapeutics, APR 28, 2025, View Source;utm_medium=rss&utm_campaign=mythic-therapeutics-presents-preclinical-data-demonstrating-potent-efficacy-of-mytx-011-across-a-broad-range-of-tumor-xenograft-models-harboring-clinically-relevant-mutations-at-the-american-associati [SID1234652237]).

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"These findings highlight the broad therapeutic potential of MYTX-011 across a variety of cMET-expressing cancers and the opportunity to expand the treatable patient population to patients with EGFR, KRAS and MET mutations, which have shown reduced response rates in clinical studies of other anti-cMET ADCs in development," said Brian Fiske, Ph.D., chief scientific officer and co-founder of Mythic. "These preclinical data reinforce our confidence in the ongoing Phase 1 dose escalation trial of MYTX-011. Building on last year’s promising preliminary data, we remain highly optimistic and eagerly await additional readouts."

MYTX-011 is a novel cMET-targeted DAR 2 vcMMAE ADC with an antibody that has been engineered to have pH-dependent binding, which results in higher internalization and payload delivery to tumor cells with a range of cMET expression.

In the study, pH-dependent binding of MYTX-011 translated to potent efficacy in tumor xenografts regardless of mutation status, including models harboring MET exon 14 skipping, KRAS and EGFR mutations. Notably, MYTX-011 demonstrated anti-tumor activity in low or moderate cMET-expressing non-small cell lung cancer (NSCLC) KRAS G12C xenografts as well as tyrosine kinase inhibitor-resistant xenografts bearing EGFR T790M mutations. Additionally, live cell imaging studies demonstrated how FateControl technology drives increased uptake of MYTX-011 antibody in cMET-expressing tumor cells compared to a non-engineered parent antibody. In previous studies, a benchmark ADC was either inactive or had greatly reduced efficacy.

These findings support the continued clinical advancement of MYTX-011, which is currently being evaluated in the ongoing Phase 1 KisMET-01 trial in NSCLC.

The Company will present additional data from its Phase 1 KisMET-01 study at an upcoming major medical conference.

About MYTX-011

MYTX-011, an investigational cMET-targeting ADC, leverages Mythic’s innovative FateControl technology which is designed to allow ADCs to actively navigate inside of cells, potentially increasing delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase 1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose escalation and dose expansion study enrolling patients with locally advanced, recurrent or metastatic NSCLC (NCT05652868).

Actinium Presents Data Showing ATNM-400 is More Efficacious than Pluvicto and is Highly Efficacious after Pluvicto Resistance in Prostate Cancer Tumor Models at the American Association for Cancer Research Annual Meeting

On April 28, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported preclinical results with ATNM-400 in prostate cancer models presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, APR 28, 2025, View Source [SID1234652253]). ATNM-400 is a novel, non-PSMA targeting, first in class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that Actinium is evaluating in prostate cancer models prior to and following treatment with Pluvicto. Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed radiotherapy radiolabeled with the beta-particle emitter, Lutetitium-177 (Lu-177) is approved for patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024.

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In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Key Data and Highlights From the ATNM-400 AACR (Free AACR Whitepaper) Presentation

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.

Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working

ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option

ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400

Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver

ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo
Sandesh Seth, Actinium’s Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR (Free AACR Whitepaper), continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR (Free AACR Whitepaper) and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".

The ATNM-400 AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578

AVEO Oncology, an LG Chem company, Announces Three Poster Presentations at ASCO 2025 Annual Meeting

On April 28, 2025 AVEO Oncology, an LG Chem company ("AVEO"), a biopharmaceutical company committed to providing differentiated solutions to improve cancer patients lives, reported that three abstracts were accepted for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 annual meeting this May 30-June 3, 2025, in Chicago, IL (Press release, AVEO, APR 28, 2025, View Source [SID1234652269]).

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Presentation Details

Title: Efficacy of second line (2L) treatment with tivozanib (Tivo) as monotherapy or with nivolumab (Nivo) in patients (pts) with metastatic renal cell carcinoma (mRCC) previously treated with an immune checkpoint inhibitor (ICI) combination of ipilimumab (Ipi)/Nivo or vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)/ICI in the Phase 3 TiNivo-2 study
First Author: Alexander Chehrazi-Raffle, MD, City of Hope Cancer Center
Abstract Number: 4540
Poster Session: Genitourinary Cancer—Kidney and Bladder
Poster Board: 340
Date and Time: Monday, June 2, 2025, 9:00am – 12:00 PM CDT

Title: FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET Mab) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC)
First Author: Julie E. Bauman, MD, MPH, George Washington University Cancer Center
Abstract Number: TPS6115
Poster Session: Head and Neck Cancer
Poster Board: 520a
Date and Time: Monday, June 2, 2025, 9:00 AM – 12:00 PM CDT

Title: A phase1b dose escalation study of AV-380 (anti-GDF15 monoclonal antibody) in combination with standard-of-care therapy in cancer patients with cachexia
First Author: Eric Roeland, MD, FAAHPM, Oregon Health & Science University
Abstract Number: TPS12142
Poster Session: Symptom Science and Palliative Care
Poster Board: 159a
Date and Time: Monday, June 2, 2025, 1:30-4:30 PM CDT

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.

Financial Results for the Fiscal Year Ended March 31, 2025

On April 28, 2025 NEC reported Financial Results for the Fiscal Year Ended March 31, 2025 (Presentation, NEC, APR 28, 2025, View Source [SID1234654110]).

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