On April 28, 2025 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that preclinical efficacy of SLS009 in TP53 mutated Acute Myeloid Leukemia (AML) cells are being presented in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place from April 25th – 30th at McCormick Place Convention Center, Chicago, IL (Press release, Sellas Life Sciences, APR 28, 2025, View Source [SID1234652247]).

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Patients with TP53–mutated AML continue to face extremely poor outcomes, even with intensive chemotherapy or the addition of stem cell transplantation. Preclinical data suggest that SLS009, a highly selective CDK9 inhibitor, can induce apoptosis downstream of p53 by targeting critical proteins such as MCL-1 and survivin, regardless of p53 status. Immunoblot analysis reveals near-complete removal of these proteins in treated cells within 8 hours of exposure to SLS009. Furthermore, the treatment reduced TP53-mutated leukemia cell populations by up to 97% in combination with azacitidine–venetoclax, and by up to 80% as monotherapy.

"These findings are an exciting step forward in addressing one of the most challenging subsets of AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The ability of SLS009 to overcome TP-53 driven resistance in preclinical models, combined with the positive data we have seen in our ongoing Phase 2 AML program, including a response in a patient with a TP53 mutation, gives us hope that we may one day offer an effective therapeutic option to patients with AML who have long been underserved."

SLS009 is currently in Phase 2 clinical trials in patients with relapsed or refractory (r/r) AML following venetoclax-based regimens, including patients with TP53-mutated leukemia. Recently announced data revealed that r/r AML patients receiving 30 mg of SLS009 BIW achieved a mOS of 8.8 months for all patients, while the mOS in AML myelodysplasia-related-changes (MRC) patients reached 8.9 months – far surpassing the historical benchmark of 2.5 months. Among patients with mutation ASXL1, 4/6 (67%) responded; among those with RUNX1 3/5 (60%) responded, and among those with TP53 1/3 (33%) responded. In addition, there were 3 patients with adverse karyotypes, and 1 responded.

"Over the past decade we’ve seen significant progress in the treatment of AML, particularly with the introduction of the venetoclax/azacitidine regimen, the use of targeted agents, and safer application of haploidentical stem cell transplants," said Dr Phillip Amrein, MD, Clinical Investigator, Massachusetts General Hospital, Assistant Professor of Medicine Harvard Medical School, the senior author of the study. "Yet, leukemias characterized by TP53 remain a major area of unmet need, with poor outcomes even with bone marrow transplantation. The preclinical findings suggest that CDK9 inhibition might have the potential to overcome this resistance and restore sensitivity to existing therapies, offering a promising new path forward for high-risk patient populations."

Poster presentation details:

Title: CDK9 inhibition enhances apoptosis of TP53 mutated AML when combined with standard chemotherapy

Session Date and Time: Monday, April 28, 20025, 9:00 AM to 12:00 noon

Session Title: CDK9 inhibition enhances apoptosis of TP53 mutated AML when combined with standard chemotherapy

Location: Poster Section 17

Poster Board #: 1626

The poster will be available on SELLAS websites following the session.

SLS009 is currently being investigated in a Phase 2 open-label, single-arm, multi-center study designed to evaluate the safety, tolerability, and efficacy of SLS009 in combination with venetoclax and azacitidine, including AML patients with ASXL1 mutations. Initial clinical safety and efficacy data are available. In addition, the study aims to identify biomarkers for the target patient population and enrichment for further trials. For more information on the study, visit clinicaltrial.gov identifier NCT04588922.

On April 28, 2025 Adela, Inc., an innovator in blood testing for molecular residual disease (MRD) monitoring and early cancer detection through a proprietary genome-wide methylome enrichment technology, reported initial results demonstrating the ability of its MRD test to predict recurrence in early-stage non-small cell lung cancer, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting from April 25-30, 2025 (Press release, Adela, APR 28, 2025, View Source [SID1234652264]).

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Adela’s MRD test is a blood-only, tissue-free approach for detecting recurrence prior to clinical exam and imaging, eliminating the need for tumor tissue samples and enabling broader access to MRD testing. A blood-only approach is especially important in lung cancer, where nearly 40% of patients do not have sufficient tumor tissue for tissue-informed MRD tests.1

The ability of Adela’s test to quantify cfDNA cancer signal and predict recurrence was evaluated in 136 samples from 24 patients diagnosed with stage I-II non-small cell lung cancer treated at New York University Langone Medical Center. Blood draws occurred prior to surgery, after surgery and at intervals before recurrence or last clinical follow-up. Adela’s test demonstrated the ability to identify recurrences up to 35.9 months before standard of care clinical exam and imaging, with a mean lead time of 16.6 months. Significant differences in recurrence-free survival (RFS) were observed when patients were stratified by MRD positivity (hazard ratio of 3.58, P=0.038).

"We are greatly encouraged by these results which highlight the ability of Adela’s tissue-free MRD test to detect recurrence in lung cancer well in advance of standard of care," said Dr. Anne-Renee Hartman, Chief Medical Officer of Adela. "Adela’s MRD test has been clinically validated for head & neck cancer. These results further validate the strong performance of Adela’s genome-wide methylome enrichment platform and demonstrate its applicability across multiple cancer types."

Adela’s MRD test based on its genome-wide methylome enrichment platform is currently available to biopharmaceutical companies and other investigators for Research Use Only (RUO), including for biomarker discovery and drug development. Adela plans to commercialize the test in 2025 for use in patients who have received curative intent treatment for head & neck cancer, regardless of HPV status, to detect recurrence earlier and help guide treatment decision-making.

Presentation Details

Abstract #: 3249: The Development of a Tissue-Agnostic Genome-Wide Methylome Enrichment Assay for Lung Cancer

Harvey I. Pass2

Monday Apr 28, 2025 2:00 PM – 5:00 PM

Poster Section 29, Poster Board Number: 14

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 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.