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OncoHost Study Offers New Insights Into Resistance Mechanisms in Immunotherapy-Treated Lung Cancer Patients

On May 30, 2025 OncoHost, a technology company transforming the approach to precision oncology through proteomics and AI, reported the publication of a new study in the Journal for ImmunoTherapy of Cancer (JITC), titled "Decoding Resistance to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: A Comprehensive Analysis of Plasma Proteomics and Therapeutic Implications (Press release, OncoHost, MAY 30, 2025, View Source [SID1234653532])."

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The study provides a critical leap forward in understanding resistance to immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC)—one of the most pressing challenges in oncology today. Through a comprehensive bioinformatic analysis of pretreatment plasma proteomic profiles from 272 NSCLC patients, researchers identified key biological processes associated with resistance and revealed therapeutic targets that could inform future precision treatment strategies.

"This study marks a pivotal step in our mission to equip oncologists with the tools and insights they need to make truly personalized treatment decisions" said Ofer Sharon, MD, CEO of OncoHost. "By leveraging plasma proteomics and AI to decode the biology of resistance, we’re not just uncovering barriers—we’re transforming them into actionable clinical insights. This is the foundation of why PROphet works: it detects resistance mechanisms and tumor-driven processes that impact treatment response. With PROphet, we’re enabling physicians to navigate complexity with confidence and deliver care that is as individualized as their patients."

The analysis focused on 388 resistance-associated proteins (RAPs) previously identified as part of OncoHost’s proprietary PROphet platform—an AI-powered, plasma proteomic-based decision-support tool. Researchers identified five distinct expression patterns when comparing between patients who benefit from ICI-based treatment, patients who do not, and healthy subjects, uncovering both immunologic and tumor-derived drivers of resistance. Notably, the study revealed that 17.5% of the RAPs identified are known drug targets, thereby reassuring that the RAPs are indeed involved in key resistance mechanisms on the one hand, while providing many novel potential targets for intervention on the other hand.

"We have previously reported the PROphet platform as a novel proteomic predictor for immunotherapy efficacy in NSCLC. In this paper we describe the rationale and cancer-related functions of these resistance associated proteins. The therapeutic implications are substantial and should facilitate personalized medicine approaches for our patients" said Dr. David Gandara, Medical Oncologist & clinical-translational researcher in lung cancer, Co-Director-Center for Experimental Therapeutics, UC Davis Comprehensive Cancer Center and Clinical Advisor at OncoHost.

The RAPs explored in the study offer potential utility beyond prediction—they may help direct future clinical trial designs and treatment selection based on individual patient biology. This could result in more effective use of existing immunotherapies, reduced exposure to ineffective treatments, and new opportunities for combination approaches tailored to resistance mechanisms. By extending the understanding of the underlying RAP biology, this new research strengthens the clinical rationale for incorporating plasma proteomics into routine treatment planning for NSCLC.

Diakonos Oncology Closes $20 Million Financing to Accelerate Phase 2 Glioblastoma Clinical Development Program and Expand Use of Innovative Dendritic Cell Platform for Studies in Other Indications

On May 30, 2025 Diakonos Oncology Corp., a clinical-stage biotechnology company developing a new generation of immunotherapies to treat challenging and aggressive cancers, reported the closing of a $20 million private placement of Simple Agreements for Future Equity (SAFE) to accelerate the company’s Phase 2 glioblastoma trial for dubodencel, also known as DOC1021, and support the expansion of its clinical portfolio to other indications, including refractory melanoma (Press release, Diakonos Oncology, MAY 30, 2025, View Source [SID1234653531]). The financing includes backing by new investors Baylor College of Medicine (BCM), the Brain Tumor Investment Fund (BTIF), and the Buttonwood Titan QC Fund, with additional participation from existing shareholders including CEO Mike Wicks, MS. BCM is also contributing in-kind services toward the company’s pre-clinical and clinical development programs. This $20 million financing follows Diakonos’ oversubscribed $11.4 million seed financing that closed last year and serves as a bridge to a Series A financing that the company plans to launch in the second half of this year.

"With our Phase 2 glioblastoma trial underway at leading treatment centers across the U.S., the financing comes at a critical inflection point as we begin defining the path toward commercialization," said Jay Hartenbach, President and Chief Operating Officer of Diakonos Oncology. "Early clinical results in both glioblastoma and pancreatic cancer continue to exceed expectations, and when viewed alongside our data from a range of preclinical models, we are increasingly optimistic that this patient-derived immunotherapy holds potential for additional indications with high unmet need."

John Higgins, Managing Director at the Brain Tumor Investment Fund, added, "The promising Phase 1 data for dubodencel in glioblastoma were a strong motivator for us to help fund the Phase 2 trial, and we are pleased that our investment will serve as a catalyst for additional fundraising as the company advances the glioblastoma program and expands its clinical pipeline."

Joseph Petrosino, Ph.D., Chief Scientific Innovation Officer of Baylor College of Medicine, said, "At BCM, we are eager to propel our latest discoveries to the bedside, particularly for new therapies targeting glioblastoma and pancreatic cancer, where patients are in desperate need for better options. We are proud to work with Diakonos to accelerate these exciting early clinical results, and we are eager to support Diakonos as it builds on encouraging pre-clinical data suggesting dubodencel may be more broadly successful for the treatment of other difficult cancers and diseases."

Joseph Gunnar & Co. LLC served as placement agent for Diakonos in the SAFE offering. A SAFE is a non-debt instrument where an investor provides funding and receives the right to convert the investment into equity shares at a later date upon the occurrence of specified events, typically when a company raises a qualified equity financing round or experiences a liquidity event.

About Dubodencel

Dubodencel, also known as DOC1021, is a first-in-class, double-loaded autologous dendritic cell therapy that uniquely combines tumor lysate and amplified tumor-derived mRNA. The immunotherapy is made with a patient’s dendritic cells combined with mRNA and proteins prepared from freshly obtained patient tumor specimens.

The unique double loading approach, which mimics a viral infection, unlocks a synergistic and exponentially more powerful tumor killing TH1 response driven by dual protein and RNA antigen sourcing, and it allows targeting of the complete cancer antigen pool. Moreover, the approach does not require any molecular modification of the patient’s immune cells for manufacturing, and it does not require preconditioning of bone marrow or high dose IL-2 for administration. Dubodencel allows for a simple administration in the outpatient setting and broad reach via community cancer centers.

In addition to the recently opened Phase 2 glioblastoma study, a clinical trial of Diakonos’ dubodencel is ongoing for the treatment of pancreatic cancer. Diakonos received Fast Track designations from the FDA for both the glioblastoma and pancreatic cancer programs in October 2023 and May 2024, respectively. The company received Orphan Drug Designation for the glioblastoma program in January 2024.

ImmunoGenesis to present IMGS-001 Phase 1a/1b Clinical Study Updates at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting

On May 30, 2025 ImmunoGenesis, a clinical-stage biotech company developing innovative, science-driven immunotherapies, reported that a Trial in Progress poster for its first-in-human, Phase 1a/1b clinical trial of IMGS-001 will be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, Illinois from May 30 to June 3, 2025 (Press release, ImmunoGenesis, MAY 30, 2025, View Source [SID1234653530]).

This Phase 1a/1b first-in-human, open-label, multicenter study (NCT06014502) includes a dose escalation and an expansion portion to evaluate the safety, pharmacokinetics, and preliminary anti-tumor activity of IMGS-001 in adult patients with locally advanced or metastatic solid tumors refractory to standard-of-care treatment. The study will enroll approximately 25 patients in Phase 1a and up to 250 in Phase 1b. The first three of five planned dose cohorts have completed without any dose limiting toxicities (DLTs), with cohort 4 (10 mg/kg) now enrolling.

"This clinical trial is an important first step to understand how IMGS-001 may potentially remove immunosuppressive cells while improving PD-1 pathway blockade to treat otherwise immunoresistant tumors that represent a significant unmet medical need," stated Charles Schweizer, PhD, Senior Vice President of Clinical Development at ImmunoGenesis. "We are pleased to discuss the study plan and progress at this important conference as we look ahead to sharing results."

"We are encouraged by the early performance of IMGS-001 as we proceed with Phase 1 dose escalation in patients with a variety of advanced solid tumors," said James Barlow, President and CEO of ImmunoGenesis. "Initial low doses administered to date have been well-tolerated with no dose-limiting toxicities, and we are seeing promising early signs of anti-tumor activity in patients who have failed prior treatments. IMGS-001 has the potential to be a foundational therapy for immune-excluded tumors, addressing a major unmet need."

ASCO Poster Presentation

Title: A Phase 1a/1b study to evaluate the safety, tolerability, Pharmakokinetics, and anti-tumor activity of IMGS-001 in Patients with relapsed or refractory advanced solid tumors.
Abstract: TS2686 | Poster Bd #: 324a
Track: Developmental Therapeutics—Immunotherapy
Location: Hall A -Posters and Exhibits | On Demand
Time: June 2, 2025, 1:30 PM – 4:30 PM CDT

Adela to Present Data Highlighting Ability of its Tissue-Agnostic Test for MRD Detection and Response Monitoring to Predict Progression and Identify Non-Responders to Immunotherapy in Solid Tumors at the 2025 ASCO Annual Meeting

On May 30 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 results of two studies demonstrating the ability of its MRD test to predict progression and identify non-responders to immunotherapy at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from May 30 – June 3, 2025 (Press release, Adela, MAY 30, 2025, View Source [SID1234653529]).

"In patients with advanced cancer receiving immunotherapy, it can be challenging to differentiate true progression from pseudoprogression during early treatment cycles based on imaging," said Lillian Siu, MD, FRCPC, Medical Oncologist and Senior Scientist, Princess Margaret Cancer Centre, University Health Network. "To better identify non-responders and guide timely treatment adjustments, more reliable response assessment tools are needed. Methylation-based circulating tumor DNA (ctDNA) technology shows promise in these regards."

The ability of Adela’s test to identify progression in patients treated with immunotherapy was demonstrated in two studies. The first study included banked samples from 64 patients with advanced head & neck, breast, ovarian, melanoma, or other solid tumors who received pembrolizumab. Blood samples were collected pre-treatment and prior to initiation of cycle 3 of treatment. A decrease in ctDNA from the pre-treatment blood draw to the pre-cycle 3 blood draw was associated with a significantly better PFS [hazard ratio (HR) of 0.28 (0.15, 0.49); p<0.0001] and OS [HR 0.42 (0.24, 0.76); p=0.003].

"These results show promise in assessing response to immunotherapy early in a patient’s course of treatment," said Enrique Sanz-Garcia, MD, Medical Oncologist and Clinician-Investigator at Princess Margaret Cancer Centre, University Health Network. "Identifying non-response earlier can support timely treatment decisions and help avoid unnecessary toxicity."

The second study included banked samples from 63 patients with stage III/IV non-small cell lung cancer treated with definitive chemoradiation followed by consolidative durvalumab (stage III) or with PD-1 inhibitors +/- chemotherapy (stage IV). Blood samples were collected pre-treatment, 2-4 weeks after treatment initiation and approximately 6-8 weeks thereafter until progression. Patients with a positive MRD test showed significantly worse PFS than those who tested negative (HR 4.8; 95% CI, 2.1-10.8; P < 0.0001).

"Together, these two studies demonstrate the potential of Adela’s tissue-agnostic test to predict outcomes and support clinical decision-making for patients receiving immunotherapy across a range of cancer types," said Dr. Anne-Renee Hartman, Chief Medical Officer at Adela. "Because tumor tissue is often unavailable in patients with advanced cancer, Adela’s blood-only, tissue-free approach offers a universally accessible solution for this population."

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 #8550: Identification of immunotherapy early treatment failure in non-small cell lung cancer (NSCLC) using a novel cell-free DNA (cfDNA) tissue-agnostic genome-wide methylome enrichment assay

Dr. Tuan Hoang1

Hall A, Poster Board: 30

Saturday May 31, 2025 1:30 PM-4:30 PM CDT

Abstract # 2545: Validation of an optimized tissue-agnostic genome-wide methylome enrichment assay to predict clinical outcomes in patients treated with pembrolizumab

DR. Enrique Sanz-Garcia1

Hall A, Poster Board: 192

Monday June 2, 2025 1:30 PM-4:30 PM CDT

Myeloid Therapeutics Unveils First-in-Human In Vivo mRNA CAR Data, Marking a Breakthrough in RNA-Based Immuno-Oncology at the 2025 ASCO Annual Meeting

On May 30, 2025 Myeloid Therapeutics, Inc. ("Myeloid"), a clinical-stage immunology company advancing RNA therapeutics to conquer cancer, reported it will present two posters at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago taking place from May 30 – June 3, 2025 (Press release, Myeloid Therapeutics, MAY 30, 2025, View Source [SID1234653528]). The presentations will highlight the clinical trial design for MT-303 and preliminary translational findings for MT-302 – the company’s lead in vivo mRNA CAR therapies, which together signify a key milestone in the field of RNA-based immuno-oncology.

"Our presentations at ASCO (Free ASCO Whitepaper) demonstrate the clinical translation of our proprietary mRNA-LNP platform for in vivo immune cell engineering," said Daniel Getts, PhD, CEO and Co-founder of Myeloid Therapeutics. "With MT-302 and MT-303, we are pushing beyond the limits of traditional CAR therapies—removing the need for often complicated ex vivo manipulation while delivering potent, tumor-specific immune activation in patients with advanced solid tumors."

"These data show that we can deliver repeated doses of LNP-mRNA in patients demonstrating that CAR-programmed myeloid cells can penetrate solid tumors and alter the tumor microenvironment (TME), which opens up multiple avenues for potential clinical benefit moving forward," said Matt Maurer, MD, Chief Medical Officer of Myeloid Therapeutics. "The results offer early validation of Myeloid’s platform technologies, and could ultimately change how solid tumors are treated, offering patients a more accessible, potentially more tolerable, and highly targeted therapy option in the future without the burdens associated with traditional cell therapies."

MT-302: TROP2-Targeted mRNA CAR Therapy in Advanced Epithelial Tumors

MT-302 is the first intravenously delivered mRNA-based CAR therapy to enter clinical trials. It uses synthetic mRNA encapsulated in lipid nanoparticles (LNPs) to reprogram circulating immune cells in vivo to express a TROP2-targeted CAR.

Poster Board: 238
Title: First-in-human mRNA CAR Therapy: Correlative Biomarker analysis from the MT-302 Phase 1 Study Targeting TROP2 in Patients with Advanced Epithelial Tumors
Lead Author: Dr. Charlotte Lemach, MBBS
Session Date & Time: June 2, 2025 | 1:30 PM–4:30 PM CDT
Location: Hall A, McCormick Place, Chicago
Key MT-302 Findings Include:

Immune Activation: Single-cell RNA sequencing demonstrated selective CAR expression in myeloid cells and increased pro-inflammatory gene signatures across tumor types.
Target Engagement: Pharmacodynamic markers confirmed successful delivery and CAR expression following systemic administration.
Continued dose escalation: Dose escalation continues with an optimized liner mRNA based on preclinical demonstration of expression beyond 12 days.
MT-303: GPC3-Targeted mRNA CAR Therapy in Hepatocellular Carcinoma

MT-303 is an innovative in vivo CAR therapy specifically designed to reprogram Fc receptor gamma chain-expressing myeloid cells to recognize and destroy GPC3+ tumor cells following intravenous mRNA-LNP administration.

Poster Board: 499b
Title: A First-in-Human Study of MT-303, an Innovative In Vivo mRNA CAR Therapy Targeting GPC3 in Adults with Hepatocellular Carcinoma
Lead Author: Dr. Timothy Humphries, Linear Clinical Research
Session Date & Time: May 31, 2025 | 9:00 AM-12:00 PM CDT
Location: Hall A, McCormick Place, Chicago
MT-303 Clinical Trial Highlights:

Design: Ongoing multicenter, open-label Phase 1 trial in advanced solid tumors expressing GPC3 (including HCC) employing a Bayesian Optimal Interval (BOIN) dose escalation.
Mechanism: mRNA encodes a GPC3-targeted CAR construct driven by CD89, restricting expression to myeloid cells.
Myeloid expects to share additional clinical translational data at an upcoming medical meeting upon completion of the Phase 1 studies of MT-302 and MT-303.

About MT-302

MT-302 is a first-in-class, TROP2-FcA-LNP targeting TROP2, which is overexpressed in many epithelial tumors and corresponds with low expression in healthy tissues. MT-302 has demonstrated promising preclinical results to date, including robust expression in myeloid cells and a favorable safety profile in rodents and non-human primates. Unlike other therapies, MT-302 brings the potential advantages of eliciting a full immune response by also presenting tumor neoantigen to stimulate T cells. MT-302 is Myeloid’s first in vivo CAR clinical program that further builds on the company’s innovative approach to cancer treatment through immune cell programming.

About MT-303

MT-303 is a first-in-class, GPC3-FcA-LNP targeting glypican-3 (GPC3), which is overexpressed in most human hepatocellular carcinomas (HCCs) and exhibits limited expression in healthy tissues. MT-303 has demonstrated promising preclinical results to date, including robust expression in myeloid cells and a favorable safety profile in rodents and non-human primates. Unlike other therapies, MT-303 brings the potential advantages of eliciting a full immune response by also presenting tumor neoantigen to stimulate T cells. MT-303 is Myeloid’s second in vivo CAR clinical program that further builds on the company’s innovative approach to cancer treatment through immune cell programming.