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 PhotonPharma, a biotechnology company developing next-generation cancer immunotherapies, reported the issuance of U.S. Patent No. 12,280,039 B2 titled "Cancer Vaccine Compositions and Methods of Use Thereof (Press release, PhotonPharma, SEP 8, 2025, View Source [SID1234655845])." The patent, issued by the United States Patent and Trademark Office on April 22, 2025, covers the Company’s proprietary method for producing cancer immunotherapy products using photochemically-inactivated cancer cells that maintain immunogenic properties.

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Novel Approach to Cancer Immunotherapies

The patented technology, Innocell, represents a significant potential advancement in cancer therapies. Riboflavin (vitamin B2) acts as a photosensitizer that when combined with UV light, inactivates cancer cells while preserving critical tumor antigens. This innovative approach addresses a fundamental challenge in cancer immunotherapy: how to effectively present tumor antigens to the immune system to stimulate immune response specific to the patient’s own tumor.

Key advantages of technology include:

Product Profile: Cancer cells are rendered completely incapable of replication while maintaining their antigenic properties. Cancer cells with enhanced antigen presentation are produced and can be used to stimulate a broad immune response to the patient’s tumor.

Preserved Immunogenicity: Critical surface markers and tumor-associated antigens remain intact for immune recognition. Cell metabolism is preserved. These altered cells can stimulate an immune response that has been demonstrated to target tumor cell destruction in pre-clinical studies.

Scalable Manufacturing: The photochemical inactivation process is rapid, reproducible, and suitable for clinical-scale production.

Broad Applicability: The technology can be applied across multiple cancer types and stages.
Compelling Preclinical Data

The patent includes extensive preclinical validation demonstrating the technology’s potential:

Tumor Growth Inhibition: Significant reduction in tumor growth rates in multiple animal models

Enhanced Survival: Extended survival times compared to control groups in efficacy studies

Immune System Activation: Robust T-cell responses and immunological memory formation
"This patent issuance validates our innovative approach to cancer immunotherapy and strengthens our intellectual property portfolio as we advance toward clinical trials," said Alan Rudolph, Ph.D., PhotonPharma Inc. board member. "Our technology has the potential to transform recurrent ovarian cancer treatments, offering patients a safer and more effective option."

According to the National Cancer Institute (View Source), ovarian cancer will impact 20,890 women in the US with 12,730 deaths in 2025 alone. The average five-year relative survival rate is 51.6% (2015-2021).

Strategic Value and Market Opportunity

The global Cancer Immunotherapy Market Size is projected to reach between $231-277 billion (CAGR 13.6% – 11.9%) by 2031 driven by increasing cancer incidence and growing adoption of immunotherapy approaches (Statista 2025, BioSpace 2022). This patent positions PhotonPharma at the forefront of next-generation cancer immunotherapy development.

Development Timeline

PhotonPharma is initiating Phase I trials, targeting recurrent epithelial ovarian cancer patients.

On September 8, 2025 Atossa Therapeutics, Inc. (Nasdaq: ATOS; "Atossa" or the "Company") reported it has requested a Type C meeting with the U.S. Food and Drug Administration (FDA) to discuss a regulatory strategy aimed at accelerating development of low-dose (Z)-endoxifen for breast cancer risk reduction (Press release, Atossa Therapeutics, SEP 8, 2025, View Source [SID1234655844]). Atossa is a clinical-stage biopharmaceutical company developing new approaches in breast cancer treatment and risk-reduction, commonly termed prevention of breast cancer.

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Beginning in June 2025, Atossa engaged an internationally recognized FDA law firm and senior regulatory affairs experts to review the Company’s extensive (Z)-endoxifen data and the considerable published scientific literature on (Z)-endoxifen. They evaluated whether existing evidence could support a faster regulatory path in breast cancer risk-reduction, specifically, in the adjuvant setting, in ductal carcinoma in situ (DCIS), and in high-risk women without cancer.

The experts recommended Atossa rapidly schedule a Type C meeting with the FDA to align on the requirements needed to complete a New Drug Application (NDA). Atossa has now filed this meeting request and expects to update shareholders on the outcome of the meeting before year end 2025, based on standard agency timelines. While there can be no assurance of success, a favorable meeting outcome could shorten approval timelines by years and avoid tens of millions of dollars in clinical trial costs. Atossa had approximately $57.9 million in cash and no debt as of June 30, 2025.

Market opportunity for low-dose (Z)-endoxifen

An estimated 1.6 to 2.1 million tamoxifen prescriptions are filled annually in the United States, including in three breast cancer risk-reduction settings:

Adjuvant therapy (post-surgery recurrence risk-reduction): According to the American Cancer Society, approximately 4.3 million U.S. women are living with a history of breast cancer, as of January 1, 2025. About 79 percent of U.S. breast cancers are hormone-receptor positive. Professional guidelines recommend ≥5 years of adjuvant endocrine therapy, for these patients, with extension to 7–10 years in selected, higher-risk cases. Approximately 1 million women are currently taking adjuvant endocrine therapy in the U.S. based on initiation and real-world persistence data.

Risk reduction following DCIS surgery: It is estimated that a few hundred thousand women are taking SERMs or aromatase inhibitors for breast-cancer risk-reduction, including post-DCIS and other high-risk settings in the U.S. DCIS alone likely accounts for up to 80,000 women on therapy at any given time.

Risk reduction in high-risk women without prior cancer: 2010 NHIS data estimated that roughly 120,000 U.S. women are using preventive SERM therapy for primary risk-reduction.
In addition, approximately 600,000–800,000 women are currently taking an aromatase inhibitor as adjuvant endocrine therapy in the U.S. About one-third to one-half experience musculoskeletal symptoms on AIs (pooled prevalence about 46 percent) and more than 30 percent discontinue treatment early due to those symptoms (e.g., about 32 percent within two years in a large prospective cohort).

(Z)-Endoxifen has demonstrated equivalent anti-estrogen pharmaceutical activity to tamoxifen, but with important differences. It avoids the CYP2D6 metabolism variability of tamoxifen, in which up to 20 percent of women do not achieve a therapeutic level of (Z)-endoxifen following tamoxifen administration. This exposure variability is well-documented and contributes to inconsistent endoxifen levels on tamoxifen; recurrence rates of 30 percent despite adjuvant therapy highlight the residual unmet need.

In Atossa clinical trials, direct oral (Z)-endoxifen achieved high systemic (Z)-endoxifen concentrations independent of CYP2D6 metabolism, whereas during tamoxifen therapy (Z)-endoxifen constitutes approximately six percent of the total tamoxifen-related metabolites at steady state.

In addition, tamoxifen takes four weeks to reach plasma steady state and its primary intermediate (N-desmethyl-tamoxifen) takes eight weeks. Direct (Z)-endoxifen can achieve target endoxifen concentrations within hours and typically reaches steady state within about one week in clinical studies.

Complementary Role of Project Optimus

Atossa continues to advance its FDA-aligned Phase 2 Project Optimus trial to identify the optimal (Z)-endoxifen dose in metastatic breast cancer. We believe this program not only supports the development of endoxifen in the metastatic setting but also strengthens the scientific and regulatory bridge for development in the low dose risk-reduction setting.

Dr. Steven Quay, Chairman and CEO of Atossa, commented, "This new regulatory strategy could dramatically accelerate the timeline for the development and potential approval of low-dose (Z)-endoxifen in the reduction of the incidence of breast cancer. We see a potential multi-billion-dollar market opportunity given the number of women currently on tamoxifen in the risk-reduction settings, and of women on aromatase inhibitors, half of whom experience painful arthritic symptoms. Importantly, this strategy could bring (Z)-endoxifen to patients, years sooner, at lower cost, and with a more predictable and faster-acting therapy than tamoxifen."

About (Z)-Endoxifen

(Z)-endoxifen is a highly potent Selective Estrogen Receptor Modulator/Degrader (SERM/D) with demonstrated ability to inhibit and degrade estrogen receptors. It has shown activity even in tumors that have developed resistance to other endocrine therapies. Beyond its anti-estrogenic properties, (Z)-endoxifen also targets the oncogenic signaling pathway, protein kinase C beta 1 (PKCβ1), at clinically achievable blood and tumor levels. (Z)-Endoxifen also seems to deliver comparable or superior bone-protective effects relative to tamoxifen.

Atossa is developing a proprietary enteric oral formulation of (Z)-endoxifen that bypasses stomach acid, which would otherwise partially convert the active (Z)-isomer to its inactive (E)-form. We believe this innovation allows for optimal bioavailability and therapeutic integrity. Clinical studies have shown Atossa’s (Z)-endoxifen to be well tolerated in both healthy women and those with breast cancer. In over 700 subjects (healthy volunteers and breast cancer patients) receiving doses up to 360 mg/day, no maximum tolerated dose (MTD) has been identified, supporting continued dose-range exploration.

Atossa is prioritizing development in metastatic breast cancer. In parallel, (Z)-endoxifen is being evaluated in three Phase 2 studies, one in DCIS and two in ER+/HER2- breast cancer. Monotherapy in DCIS and low risk cancer, and combination therapy in high-risk cancer, with Lilly’s CDK4/6 inhibitor, Verzenio (abemaciclib), are being investigated. Atossa’s (Z)-endoxifen program is supported by a growing global intellectual property portfolio, including three recently issued U.S. patents and numerous pending applications worldwide.

On September 8, 2025 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a leading precision medicine oncology company, reported it will present positive interim data at their 10-Year Anniversary R&D Day from their ongoing Phase 2 OptimUM-09 trial of darovasertib in the neoadjuvant setting for primary uveal melanoma (UM) (Press release, Ideaya Biosciences, SEP 8, 2025, View Source [SID1234655843]). The data provide clinical evidence of ocular tumor shrinkage, reduction in radiation doses administered to critical eye structures and, in turn, improved vision with a reduced risk of developing longer-term blindness post-plaque brachytherapy. Today, surgical removal of the eye (enucleation) and invasive radiation treatment applied to the eye (plaque brachytherapy) are the standard(s) of care in the neoadjuvant setting of primary UM and there are no approved systemic therapies. Darovasertib is a potent and selective protein kinase C (PKC) inhibitor being developed to broadly address primary UM and metastatic uveal melanoma (mUM).

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"The data presented in this study represents a potential breakthrough advance for subjects with primary uveal melanoma where there currently is no neoadjuvant therapy available that can shrink tumors in this setting," said Dr. Arun D. Singh, Director of the Department of Ophthalmic Oncology at the Cole Eye Institute, Cleveland Clinic. "We are delighted to see the progress we are making with darovasertib as a single agent in subjects with mid-sized tumors requiring plaque brachytherapy," said Dr. Darrin Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences. "Darovasertib is generally well-tolerated and showing initial evidence of shrinking tumors effectively, and the results imply that the associated radiation reduction observed will likely lead to improvements in vision not only during therapy but post-plaque brachytherapy."

All the data presented are preliminary, and from patients in the plaque brachytherapy cohort of the ongoing Phase 2 OptimUM-09 trial as of a cut-off date of May 23, 2025. A total of 39 patients enrolled were evaluated for safety, including 21 patients who were evaluated for efficacy as of the cut-off date. All efficacy-evaluable patients had received three or more cycles of darovasertib and had baseline and on-treatment tumor assessment, paired dosimetry and visual acuity score (VAS) data available as of the cut-off date.

Key data from the presentation

76% (16/21) of patients achieved ≥20% ocular tumor shrinkage by product of diameters, the response definition proposed for the Phase 3 registration-enabling OptimUM-10 trial
48% (10/21) of patients achieved ≥20% reduction in simulated radiation dose to at least one key visual structure (optic disc/nerve and/or fovea), with 86% (18/21) achieving any reduction. A 20% reduction in radiation dose has previously been shown to correlate with improved visual outcomes.
65% (13/20) of patients observed any visual improvement during neoadjuvant darovasertib treatment, with a median of 6 letters gained, and 40% (8/20) of patients achieving >5 letters gained at two consecutive visits
A vision prognostication tool used to predict the risk of developing 20/200 vision (defined as legal blindness) at 3 years post-plaque brachytherapy showed 67% (14/21) of patients treated with darovasertib observed "any reduction" in their risk, and 38% (8/21) observed a ≥20% reduction in their risk.
Darovasertib was generally well-tolerated with a manageable safety profile. The majority of treatment-related adverse events (TRAEs) observed were Grade 1 and 2, with approximately 10% (4/39) Grade 3 or higher. The most common TRAEs included diarrhea, nausea, fatigue, maculo-papular rash, hypotension, and vomiting. Four patients discontinued treatment due to TRAEs, including two with hepatic transaminase increase, one with nausea, vomiting, fatigue, and one with hypotension, bradycardia and decreased level of consciousness.
IDEAYA will review this interim data at their 10-Year Anniversary R&D Day on September 8th in New York. A link to the webcast will be available on the Investor Relations page of the IDEAYA corporate website: View Source Additional data from over 90 patients in both the plaque brachytherapy and enucleation cohorts of the OptimUM-09 trial will be presented in a Proffered Paper Oral Presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) meeting, taking place on October 17-21, 2025 in Berlin, Germany.

On September 8, 2025 Compugen Ltd. (Nasdaq: CGEN) (TASE: CGEN) a clinical-stage cancer immunotherapy company and a pioneer in predictive computational target discovery, powered by AI/ML reported it will present research at the Single Cell Genomics 2025 Conference taking place September 15-17, 2025, in Stockholm, Sweden (Press release, Compugen, SEP 8, 2025, View Source [SID1234655842]).

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This research reflects Compugen’s computational capabilities in understanding the spatial context of complex cancer biology that may inform drug discovery efforts and therapeutic strategies to potentially provide benefit to cancer patients.

Poster and short talk details:

Title: Bin2Niche: A spatial transcriptomics framework reveals immune-defined epithelial niches in MSI colorectal cancer
Presenting author: Roy Granit, Ph.D., Senior Director, Head of Computational Discovery, Compugen
Poster ID: P035
Date of presentation: September 15, 2025, at 2:10 PM CET

Poster will be available in the publications section of Compugen’s website, www.cgen.com, following presentation.