On September 8, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported that it has enrolled the first two subjects, and treated one, in the European Union (EU) in its pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML) (Press release, Moleculin, SEP 8, 2025, View Source [SID1234655831]). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, the EU, and other parts of Europe.

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"We now have active sites recruiting in the US, Spain, Ukraine, Georgia, and Romania with more sites expected to come online by the end of September. For our first site in Spain to have opened up with two subjects enrolled, we believe, indicates the unmet need in treating second line R/R AML," said Walter Klemp, Chairman and CEO of Moleculin. "All of this, importantly, supports our goal to recruit the first 45 subjects for Part A before the end of 2025 for which efficacy and safety will be unblinded."

The MIRACLE study is a Phase 2B/3 clinical trial whereby data from the 2B portion will be combined with the Phase 3 portion for purposes of measuring its primary efficacy endpoint. MIRACLE is subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The protocol for the MIRACLE trial allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). The first early unblinding is expected to yield 30 subjects treated with Annamycin (190mg/m2 and 230 mg/m2) in combination with HiDAC and 15 subjects treated with just HiDAC plus placebo. The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due in part to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

As previously announced with regard to the EU, the clinical trial approval with EMA was granted under the condition that the Company present results of appropriate nonclinical GLP studies before initiating the Phase 3 portion (Part B) of the study. Results will be submitted as a substantial modification to the existing approved CTA.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

Patient dosing has commenced, and the initial data readout is on track for the second half of 2025. For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00.

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA.

On September 8, 2025 Cellworks Group Inc., a leader in Personalized Therapy Decision Support and Best-in-Class PTRS, reported results from a new study showing that the combination of tumor microenvironment (TME) composition and tertiary lymphoid structure (TLS) dynamics is a key predictor of how individual patients with non-small cell lung cancer (NSCLC) respond to immunotherapy (Press release, Cellworks, SEP 8, 2025, View Source [SID1234655846]). The study introduces a novel prediction model that integrates TME cell composition with a 34-gene TLS score. Together, these measures enabled the Cellworks Platform to accurately predict patient-level survival outcomes and reveal meaningful differences among NSCLC patients treated with checkpoint inhibitors.

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Results from the study were showcased in a poster presentation titled, "Cellular Heterogeneity and Tertiary Lymphoid Structure Dynamics Predict Overall Survival in Immune Checkpoint Therapy-Treated NSCLC Patients," as part of the IASLC 2025 World Conference on Lung Cancer (#WCLC25) hosted by the International Association for the Study of Lung Cancer held from September 6-9, 2025 in Barcelona, Spain.

"Despite the promise of immune checkpoint inhibitors (ICIs), only a subset of NSCLC patients benefit from these therapies," said Charu Aggarwal, MD, MPH, FASCO, Leslye M. Heisler Professor of Lung Cancer Excellence in the Perelman School of Medicine at the University of Pennsylvania, and co-author on the study. "This study provides new insights into how the structural organization of tertiary lymphoid structures and the immune cell composition of the tumor microenvironment jointly determine immunotherapy response. By moving beyond single biomarkers, this approach holds promise as a more comprehensive way to guide personalized treatment decisions in NSCLC."

"Our findings highlight that both cellular heterogeneity and TLS dynamics play critical roles in determining whether patients respond to checkpoint inhibitor therapy," said James Wingrove, PhD, Chief Development Officer at Cellworks and presenting author of the study. "By integrating these factors, we created a personalized model that can offer oncologists new insight into which patients are most likely to benefit from checkpoint inhibitors. This study underscores how computational modeling of the tumor microenvironment can advance personalized decision support in NSCLC."

"What makes this work exciting is the ability to connect molecular signals within the tumor microenvironment to real patient outcomes," said Michael Castro, MD, Chief Medical Officer at Cellworks. "By biosimulating how both cellular heterogeneity and TLS dynamics shape immunotherapy response, we move closer to a future where treatment selection is not just based on broad population markers, but on each patient’s unique tumor biology. This level of personalization has the potential to identify which patients benefit from combination chemotherapy and immunotherapy while also sparing other patients from receiving chemotherapy when it is unlikely to benefit."

Key Findings

Strong Predictive Value – The integrated TLS + TME model demonstrated high predictive significance for overall survival in both the training (HR=0.36, C-Index=0.768) and validation cohorts (HR=0.66, C-Index=0.628).
Clear Survival Differences – Patients predicted to have a high benefit from immune checkpoint inhibition showed a significant increase in overall survival, living a median of 30.8 months versus 12 months for patients predicted to have low benefit.
Immune Balance Matters – Survival benefit was tied to immune balance: pro-inflammatory environments enhanced TLS benefit, while suppressive immune cells (like neutrophils and M2-like macrophages) reduced or reversed it.
New Insights for Personalization – The integration of TLS dynamics with TME immune and stromal cell composition provided independent yet complementary insights, showing how structural organization and cellular balance cooperatively determine immunotherapy efficacy and can guide personalized treatment decisions.
Study Design

Cellworks developed and cross-validated an algorithm that deconvolutes bulk transcriptomic data to estimate cell proportions and cell-type–specific gene expression within the TME. This approach was enhanced with a TLS Score based on 34 genes representing cellular interplay and maturity, derived from bulk RNA-sequencing data of tumor samples. By integrating TLS dynamics with immune and stromal cell populations, the model captured complementary and independent contributions, providing collective insight into how tumor structure and cellular composition determine ICI efficacy. A Cox proportional hazards model was trained on advanced NSCLC patients treated with ICIs (n=63, SU2C-MARK cohort) and validated in an independent cohort of 66 patients from the same study. The locked model confirmed predictive performance at the individual patient level, underscoring its potential clinical utility.

The Cellworks Platform

The Cellworks Platform performs computational biosimulation of protein-protein interactions, enabling in silico modeling of tumor behavior using genomic data derived from next-generation sequencing (NGS). This allows for the evaluation of how personalized treatment strategies interact with the patient’s unique tumor network. Multi-omic data from an individual patient or cohort is used as input to the in silico Cellworks Computational Biology Model (CBM) to generate a personalized or cohort-specific disease model.

The CBM is a highly curated mechanistic network of 6,000+ human genes, 30,000+ molecular species and over 600,000 molecular interactions. This model along with associated drug models are used to biosimulate the impact of specific compounds or combinations of drugs on the patient or cohort and produce therapy response predictions, which are statistically modeled to produce a qualitative therapy response score for a specific therapy. The Cellworks CBM has been tested and applied against various clinical datasets with results provided in more than 125 presentations and publications with global collaborators.

On September 8, 2025 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a late-stage immunotherapy company targeting cancer and autoimmune diseases, reported an abstract for the EFTISARC-NEO Phase II investigator-initiated trial has been accepted for oral presentation at the Connective Tissue Oncology Society (CTOS) 2025 Annual Meeting taking place 12-15 November 2025, in Boca Raton, Florida (Press release, Immutep, SEP 8, 2025, View Source [SID1234655800]).

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EFTISARC-NEO is the first study to evaluate eftilagimod alpha (efti) in a neoadjuvant setting (prior to surgery) administered in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS).

Presentation Details
Title: Primary endpoint and translational correlates from EFTISARC-NEO: phase II trial of neoadjuvant eftilagimod alpha (efti), pembrolizumab, and radiotherapy in patients with resectable soft tissue sarcoma
Session: Immunotherapy & Cell Therapy in Sarcoma: Emerging Frontiers
Presenter: Pawel Sobczuk, M.D., Ph.D., Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology
Date: Thursday, 13 November 2025, 1:30 PM – 3:00 PM ET
Format: Oral Presentation
STS is an orphan disease with high unmet medical need and a poor prognosis for patients. The incidence of STS varies in different regions globally. In the United States, the number of new STS cases in 2025 is estimated to be ~13,520 with ~5,420 deaths, according to the American Cancer Society.1

EFTISARC-NEO is is being conducted by the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland. The study is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. For more information on the trial visit clinicaltrials.gov (NCT06128863).

The presentation slides will be available on the Posters & Publications section of Immutep’s website after the presentation at CTOS 2025.

On September 8, 2025 Oncolytics Biotech Inc. (Nasdaq: ONCY) ("Oncolytics" or the "Company"), a clinical-stage immunotherapy company developing pelareorep, reported clinical and translational data from three metastatic colorectal cancer ("mCRC") studies demonstrating consistent efficacy signals, immune activation, and survival outcomes that exceed historical benchmarks in multiple mCRC treatment settings (Press release, Oncolytics Biotech, SEP 8, 2025, View Source [SID1234655832]).

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In the REO 022 trial, pelareorep in combination with FOLFIRI and bevacizumab achieved the following results in platinum refractory 2L mCRC KRAS mutant patients:
•Median progression-free survival ("PFS"): 16.6 months vs. 5.7 months with standard 2L regimen1
•Median overall survival ("OS"): 27.0 months vs. 11.2 months with standard 2L regimen1

In the GOBLET study’s 3L mCRC Cohort 3, pelareorep combined with atezolizumab and TAS-102 met its predefined efficacy endpoint. The regimen achieved durable disease control and survival rates greater than historical benchmarks for 3L mCRC treated with TAS-102.

In the REO 022 trial and the REO 013 translational study, viral replication and immune activation were demonstrated in tumors from mCRC patients, including dendritic cell maturation and CD8+ T cell activation. These findings confirm pelareorep’s mechanism of action, including its ability to modify mCRC tumors to be immune responsive and amenable to checkpoint inhibition.

"These studies validate pelareorep’s mechanism of action and present a clear opportunity to accelerate the pursuit of a registration-enabled study in the underserved KRAS mutant subset of mCRC patients," said Jared Kelly, CEO of Oncolytics. "Given pelareorep’s activity in this difficult-to-treat cancer and other RAS-mutated gastrointestinal ("GI") tumors, including metastatic pancreatic and anal cancers, we believe pelareorep is positioned to become the premier platform immunotherapy in the GI space."

"The efficacy data for pelareorep in the hard-to-treat KRAS mutant population of mCRC are very encouraging," said Dr. Sanjay Goel, professor and attending physician at Rutgers University. "We plan to initiate an investigator-sponsored trial to further explore pelareorep’s promising potential in KRAS mutant mCRC, building on the robust immune activation demonstrated in REO 013 and the survival benefit seen in REO 022."

In addition to establishing an executable investigator-sponsored trial, the company plans to work with leading investigators and engage with regulators to define a clear path to registration in mCRC, including the design of a confirmatory study, leveraging the data in the KRAS mutant patient setting.

On September 8, 2025 NiKang Therapeutics Inc. ("NiKang"), a clinical stage biotech company focused on developing innovative small molecule oncology medicines to bring transformative therapies to patients in need, reported the successful completion of dosing in the first cohort of its phase 1 dose-escalation study evaluating NKT5097 as a single agent (Press release, NiKang Therapeutics, SEP 8, 2025, View Source [SID1234655847]). NKT5097 is a first-in-class, orally bioavailable small molecule designed to selectively degrade CDK2 and CDK4 simultaneously, offering potential therapeutic benefits for patients with HR+ breast cancer and cancers with aberrant CDK2/cyclin E pathway activation.

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The Phase 1, open-label, dose escalation study (NCT07029399) is designed to assess the safety, tolerability, PK, PD and preliminary anti-tumor activity of NKT5097 in patients with advanced or metastatic solid tumors, with a focus on breast cancer and tumors with CCNE1 amplification. The study aims to determine the recommended dose(s) for future expansion cohorts.

"We are pleased to achieve this significant milestone expeditiously after IND clearance," said Zhenhai Gao, Ph.D., co-founder, president, and CEO of NiKang. "Initial PK data from the first cohort indicated favorable oral exposure consistent with human PK projections. In addition, initial PD data from the first cohort showed deep reduction of TKa level in HR+HER2- breast cancer patients previously treated with CDK4/6 inhibitors. NKT5097 has been well-tolerated to date. Due to its superior selectivity against CDK1 and CDK6, NKT5097 has the potential to mitigate neutropenia and/or diarrhea associated with existing CDK2 or CDK4/(6) inhibitors. These early findings underscore the potential of our dual degrader approach targeting both CDK2 and CDK4 – two key regulators of the cell cycle frequently dysregulated in various cancers including breast cancer. Our innovative, first-in-class CDK2/4 dual degrader holds the promise to replace currently approved CDK4/6 inhibitors as the new leader in treating HR+ breast cancer."

About NKT5097

NKT5097 is a first-in-class, highly potent and selective, orally bioavailable CDK2/4 dual degrader, designed to achieve simultaneous inhibition of the CDK2 and CDK4 pathway. By maximizing selective suppression of these pathways, NKT5097 has the potential to exploit the full therapeutic benefits of CDK2 and CDK4 inhibition. NKT5097 is currently under evaluation in a Phase 1 clinical study in advanced or metastatic solid tumors as a single agent (NCT07029399).