On April 28, 2025 IN8bio, Inc. (Nasdaq: INAB), a clinical-stage biopharmaceutical company developing innovative gamma-delta (γδ) T cell therapies for cancer and autoimmune diseases, reported new preclinical data from its innovative γδ T cell engager (γδ-TCE) platform. The data will be presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 30, 2025 (Press release, In8bio, APR 28, 2025, View Source [SID1234652233]). The data showed that IN8bio’s new γδ-TCE platform demonstrated potent and consistent cancer-killing activity across targets in leukemia models, while avoiding the secretion of cytokines that drive the dangerous side effects seen with other TCE based immune therapies.

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Unlike traditional TCEs that rely on CD3 to activate all T cells in the body – often triggering excessive inflammatory responses, potential T cell exhaustion and other serious side effects – IN8bio’s next-gen platform is designed to specifically activate only γδ T cells, a small but powerful subset of immune cells. These cells can naturally detect, phagocytose (eat) and kill tumors cells without needing to be "trained" to recognize specific targets. The platform’s lead molecules, INB-619 (targeting CD19) and INB-633 (targeting CD33), were able to eliminate cancer cells in preclinical studies with minimal release of inflammatory cytokines. This potentially offers a lower risk of cytokine release syndrome (CRS) or the neurotoxicity that can impact 60-75% of patients treated with conventional CD3 TCEs.

William Ho, CEO and co-founder of IN8bio, commented, "Our INB-600 TCE platform combines the natural tumor-fighting abilities of γδ T cells with bispecific engagers to generate a more precise and powerful way to mobilize the immune system against cancer cells. These early results in leukemia models are exciting, and we believe this technology can eventually be applied to other hard-to-treat cancers, and even certain autoimmune diseases."

Key highlights from the in vitro studies:

INB-619 and INB-633 both triggered strong and specific, linear dose-related killing of leukemia cells (ALL and AML) at low picomolar concentrations.
Both molecules activated and expanded two key γδ T cell subsets (Vδ1+ and Vδ2+), which is critical since most cancer patients have reduced numbers of these cells.
Both molecules promoted activation and degranulation, with dose-related increases in the expression of cellular markers indicating a transition to a powerful cancer-cell killing phenotype.
Importantly, they did so with minimal, if any, changes in dangerous cytokines, such as IL-6, IL-10, and IL-17a – markers that are often linked to cytokine release syndrome (CRS) and other treatment-related toxicities.
Because this new off-the-shelf platform can drive γδ T cell expansion without the need for genetic engineering, it has the potential to offer a more scalable and flexible approach to building next-generation immunotherapies.

IN8bio continues to expand its γδ T cell therapeutic pipeline beyond genetically engineered and drug-resistant cellular therapies and is exploring various disease indications and any opportunities for partnership with the INB-600 platform. This preclinical data reinforces the company’s differentiated strategy to build modular and scalable therapeutic approaches to leverage the power of γδ T cells to target malignancies with increased precision and reduced toxicity.

The AACR (Free AACR Whitepaper) 2025 poster is available on the investor section of the company’s website at View Source

On April 28, 2025 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported that a presentation of new data supporting the immune component of amezalpat’s purported dual mechanism of action that reinforces its potential as a novel cancer treatment at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Tempest Therapeutics, APR 28, 2025, View Source [SID1234652248]).

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"The data presented at the AACR (Free AACR Whitepaper) Annual Meeting show that amezalpat reduced tumor promoting immunosuppression by M2 macrophages and T regulatory cells resulting in immune activation. These data support the immune-mediated anti-cancer activity of the proposed dual MOA of amezalpat," said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D at Tempest, "and are consistent with clinical data showing promising results in patients with HCC, RCC and CCA including in combination with approved immunotherapy. The results reinforce amezalpat’s novel and potentially first-in-class profile as a cancer therapy."

Amezalpat is an inhibitor of PPAR-alpha, the key regulator of fatty acid oxidation (FAO), which is a key metabolic pathway used by immunosuppressive macrophages and regulatory T cells (Tregs). Both cell populations are associated with poor prognosis in multiple cancer indications. Data presented demonstrated that amezalpat inhibits the development of these cells from precursor populations and is associated with reduced mitochondrial mass, the site of FAO, in immunosuppressive macrophages. Additionally, treatment of Tregs or immunosuppressive macrophages with amezalpat in the presence of tumor and cytotoxic T cells decreases anti-inflammatory cytokine production, indicating blockade of immune suppression that likely contributes to the efficacy of amezalpat observed in clinical trials.

About Amezalpat

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggests that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.

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 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.