On April 28, 2025 SK Life Science Labs, a subsidiary of SK Biopharmaceuticals Co., Ltd., a global biotech focused on the research, development, and commercialization of treatments for disorders of the central nervous system (CNS) and cancer, presented late-breaking research at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2025 in Chicago (Press release, SK Life Science, APR 28, 2025, View Source [SID1234652265]). The research identified novel orally bioavailable p300-selective degraders that have therapeutic potential for difficult-to-treat prostate cancer and multiple cancers where the protein CBP is mutated or missing.

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"What is extremely promising about our research is that we have shown that selective p300 degraders are highly effective in rapidly shutting down tumor growth in hard-to-treat cancers while also reducing toxicity due to their precise targeting," said Ryan Kruger, Ph.D., Chief Scientific Officer at SK Life Science Labs. "This study offers great hope for the development of safer drug therapies that could effectively treat some of the most challenging types of cancers for patients who currently have few good treatment options."

The p300 protein is implicated in oncogenic processes that drive a variety of solid cancers. Targeted p300 degraders demonstrate superb selectivity and potency, inhibiting tumor cell growth across several indications including castrate-resistant prostate cancer and cancers where the related protein, CBP, is missing or mutated. Once daily oral administration of these potent p300-selective degraders in tumor-bearing mice results in rapid degradation of p300 and a significant reduction in tumor growth.

"There are two primary advantages of using a heterobifunctional degrader to target p300. First, using the power of ternary complex formation, we are for the first time able to generate molecules that can target p300 over CBP with exquisite selectivity. Second, p300 degraders eliminate this critical protein required for cancer cells instead of just suppressing its activity as other molecules in development do," continued Dr. Kruger. "This discovery underscores the potential for safer and more effective oncology therapies for some of the most difficult-to-treat cancers."

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 BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) ("BriaCell" or the "Company"), a clinical-stage biotechnology company that develops novel immunotherapies to transform cancer care, reported positive data from its Phase 2 study of lead product candidate, Bria-IMT, in metastatic breast cancer, and from its preclinical Bria-OTS+ platform at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place from April 25th – 30th at McCormick Place Convention Center, Chicago, IL (Press release, BriaCell Therapeutics, APR 28, 2025, View Source [SID1234652433]). In addition, Phase 3 early biomarker data will be presented as a late breaking abstract.

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The posters are summarized below and linked here: View Source

Title: Survival outcomes in a randomized phase 2 of Bria-IMT : An allogeneic whole cell cancer vaccine
Session Title: Phase II and Phase III Clinical Trials
Session Start: 4/28/2025 2:00 PM – 5:00 PM CST
Location: Poster Section 50
Poster Board Number: 18
Abstract Presentation Number: CT100

"The excellent survival responses reported in patients with different tumor types in the Phase 2 study is very exciting, and we look forward to seeing these promising data replicate in the pivotal Phase 3 study," stated Dr. William V. Williams, BriaCell’s President & CEO.

Of 54 metastatic breast cancer patients in the Phase 2 study, 37 patients received Bria-IMT formulation that is currently being used in BriaCell’s ongoing pivotal Phase 3 study (ClinicalTrials.gov as NCT06072612 ). Patients have been heavily pre-treated a median of 6 prior treatments — including Antibody-Drug Conjugates (ADCs) and check point inhibitors (CPIs).

Clinical benefit rates [CR, PR, SD] ranged from 45% to 100% based on subtype
Decrease in size or no change in all tumors noted in 83% of patients receiving Phase 3 formulation
Overall survival (OS) with the Phase 3 formulation was 17.3 months for HR+ patients and 11.44 months for patients with triple negative breast cancer (TNBC)
Overall response rate (ORR) for patients with intracranial metastases was 50% with a 75% clinical benefit rate
Safety profile: No unexpected adverse events, no treatment related discontinuation of therapy
Title: Bria-OTS+: A versatile therapeutic platform for inducing anti-cancer immunity
Session Category: Immunology
Session Title: Vaccines, In Situ Vaccines, and Vaccine Combinations
Session Date and Time: 4/28/2025 2:00 – 5:00 PM CST
Location: Poster Section 39
Poster Board Number: 29
Published Abstract Number: 3553

Miguel A. Lopez-Lago, PhD, BriaCell’s Chief Scientific Officer, commented, "We are very excited with the anti-cancer activity of Bria-OTS+ and expect the platform will enable the delivery of powerful and long-lasting immune activity against cancer."

"This data further validates the mechanism of action of our next-generation Bria-OTS+ platform. Additional immune activating factors are expected to enhance efficacy, and we look forward to replicating these results clinically as we advance our next generation Bria-BRES+ breast cancer and Bria-PROS+ prostate cancer programs," stated Dr. William V. Williams, BriaCell’s President and CEO.

Bria-OTS+ is an immunotherapy platform and enhanced version of Bria-OTS, BriaCell’s personalized pre-manufactured immunotherapy already demonstrating tremendous results as announced on April 24 2025 . Bria-OTS+ immunotherapy expresses multiple immune-activating cytokines and co-stimulatory molecules in addition to immune-boosting granulocyte-macrophage colony-stimulating factor (GM-CSF). Bria-BRES+ for breast cancer and Bria-PROS+ for prostate cancer are expected to be investigated in BriaCell’s upcoming Phase 1/2a clinical studies.

On April 28, 2025 Calidi Biotherapeutics Inc. (NYSE American: CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted antitumor virotherapies, reported the selection of IL15 superagonist (Il15-IL15Ra) as the first payload to be delivered into tumors using its systemic antitumor virotherapy platform, RTNova (Press release, Calidi Biotherapeutics, APR 28, 2025, View Source [SID1234653211]). New preclinical data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 27, 2025, in Chicago, IL.

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The first candidate developed using RTNova is a vaccinia virus (virotherapy) that is engineered to be tumor selective and produced in an enveloped form that allows the virus to survive bloodstream circulation and reach metastatic tumor sites where viral replication can destroy cancer cells while also activating an immune response. RTNova can be further engineered to deliver transgenes or gene medicines for expression in tumor cells. Data presented at AACR (Free AACR Whitepaper) demonstrates that the ability of the enveloped virotherapy to express IL15 superagonist specifically in the tumor microenvironment measurably increases the number of complete responses, or tumor eliminations, in preclinical models after a single systemic administration.

"IL15 superagonist is a potent cytokine capable of generating robust and durable immune responses against tumors but can induce severe toxicity when administered systemically" said Antonio F. Santidrian, PhD, Chief Scientific Officer at Calidi. "By using tumor-targeted virotherapies systemically delivered to express therapeutic proteins like IL-15 superagonist directly into the tumor microenvironment, we believe we can effectively boost immune response against the tumors precisely where it is needed while minimizing systemic toxicity".

"While intratumoral use of oncolytic viruses has shown positive clinical results, their applicability has been limited to injectable cancers," said Eric Poma, PhD, Chief Executive Officer at Calidi. "Our RTNova platform builds on the clinical success of current intratumoral oncolytic viruses but is designed for systemic administration, allowing us to target metastatic disease patients with high unmet need. RTNova also allows for the delivery of payloads like IL-15 superagonist to the tumor microenvironment, inducing a profound anti-tumor immune activation."

With the RTNova platform, Calidi Biotherapeutics is pioneering the systemic delivery of virotherapies, a major step forward in treating metastatic cancers. This adaptable platform can also deliver different therapeutic payloads, allowing a bespoke approach to candidate design determined by the intrinsic properties of different tumor types.

A copy of the poster presented at AACR (Free AACR Whitepaper) featuring data on delivering IL15 superagonist is available here.

On April 28, 2025 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported that the first patients have been dosed in KOMET-015, a Phase 1 clinical trial of ziftomenib, the Company’s potent and selective, oral investigational menin inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST) after imatinib failure (Press release, Kura Oncology, APR 28, 2025, View Source [SID1234652234]).

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"Building on compelling clinical activity of ziftomenib in patients with NPM1-mutant and KMT2A-rearranged AML, we are committed to evaluating the full therapeutic potential of menin inhibitors for the treatment of cancer," said Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology. "Approximately 4,000 to 6,000 new cases of GIST are diagnosed each year in the U.S., and advanced GIST patients have limited treatment options. Our preclinical data demonstrate the combination of ziftomenib and imatinib provides robust and durable antitumor activity in both imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST patient-derived xenograft models, and we look forward to seeing whether the combination offers potential to transform the treatment paradigm."

In preclinical studies, the data demonstrates the combination exerts antitumor activity via a synthetic lethal mechanism through which ziftomenib epigenetically targets a vulnerability of GIST tumors actively induced by even ineffective tyrosine kinase inhibitor (TKI) treatments. Sixty percent of patients develop resistance to imatinib, the frontline standard of care for GIST, within two years, and ziftomenib has the potential to delay the onset of or overcome that resistance in these patients.

"This study is an important step in developing new combination treatments to potentially improve outcomes for patients with advanced gastrointestinal stromal tumors, a disease indication for which new therapeutic options are needed," said Mrinal Gounder, M.D., Sarcoma Oncologist & Early Phase Drug Development Specialist at Memorial Sloan Kettering Cancer Center. "KOMET-015 builds upon the promising preclinical data observed with ziftomenib in combination with imatinib in GIST models and we look forward to evaluating the investigational drug candidate and its potential to transform the treatment landscape."

"Until now, most approaches to treating gastrointestinal stromal tumors rely on targeted KIT inhibition via tyrosine kinase inhibitors such as imatinib, however most patients eventually progress due to acquired secondary KIT mutations highlighting the need for new treatment options," said Shreyaskumar Patel, M.D., Center Medical Director, Sarcoma Center, at The University of Texas MD Anderson Cancer Center. "We are highly encouraged by the substantial preclinical data generated to date supporting the combination for ziftomenib in combination with KIT inhibitors in advanced GIST, and the dosing of the first patients marks an important milestone to address the meaningful unmet need for these patients."

The KOMET-015 Phase 1a/1b, open-label, dose-escalation trial is designed to evaluate the safety, tolerability, and preliminary antitumor activity of ziftomenib in combination with imatinib in adults with GIST who have documented disease progression while currently on or previously treated with imatinib. Upon completion of the dose-escalation portion of the trial, expansion cohorts are planned to further assess the safety, tolerability, and clinical activity of ziftomenib. The primary objectives include evaluation of safety and tolerability and determination of the recommended Phase 2 dose, and key secondary endpoints include clinical benefit, overall response rate (ORR), progression free survival (PFS), duration of response, and overall survival (OS).

Currently, there are no other clinical trials evaluating the combination of a menin inhibitor with standards of care for the treatment of GIST. For more information regarding the KOMET-015 trial, please visit www.clinicaltrials.gov (identifier: NCT06655246).

About GIST

Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, and are characterized as KIT-dependent solid tumors, with an estimated 4,000 to 6,000 new cases diagnosed in the U.S. each year. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed.

About Ziftomenib

Ziftomenib is a once daily, oral investigational menin inhibitor currently in development for the treatment of genetically defined AML and GIST patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) from the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant (NPM1-m) AML based on data from Kura’s KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at www.kuraoncology.com/clinical-trials/#ziftomenib.