On September 8, 2025 A2 Biotherapeutics, Inc. (A2 Bio), a clinical-stage cell therapy company developing first-in-class logic-gated cell therapies for solid tumors, reported the presentation of early efficacy and safety data from the EVEREST-2 study (NCT06051695) during the IASLC 2025 World Conference on Lung Cancer (#WCLC25) hosted by the International Association for the Study of Lung Cancer (IASLC) (Press release, A2 Biotherapeutics, SEP 8, 2025, View Source [SID1234655848]).

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In a poster presentation on September 9, Salman R. Punekar, M.D., assistant professor of medicine, NYU Langone, Perlmutter Cancer Center, will share data from the EVEREST-2 study (poster number P3.18.87) during the Clinical Trials in Progress session from 10:00 to 11:30 CEST. EVEREST-2 is a first-in-human, open-label, phase 1/2 study evaluating the safety and efficacy of A2B694 in adult patients with recurrent or metastatic solid tumor cancers expressing mesothelin (MSLN) and tumor-associated HLA-A*02 loss of heterozygosity (LOH)1.

"Mesothelin is a promising cancer therapy target, but to date, mesothelin-targeted therapies have been limited by unacceptable toxicities and death. We are very encouraged by the findings from the ongoing EVEREST-2 study, which demonstrate that A2B694, a first-in-class logic-gated cell therapy, is well tolerated and holds promise for patients with mesothelin-expressing solid tumors. Further updates will be presented at an upcoming medical congress," Dr. Punekar said.

These early findings from the first two dose levels of EVEREST-2 in patients with advanced solid MSLN-expressing tumors with HLA-A*02 LOH are evidence that A2B694 has manageable safety and tolerability in patients with advanced solid mesothelin-expressing tumors with HLA-A*02 LOH. All patients exhibited CAR T expansion, and the dose escalation phase continues to enroll patients. More information about the EVEREST-2 study is available at View Source

EVEREST-2 Poster Summary

As of March 6, 2025, five patients were enrolled in phase 1: four women and one man, with a median age of 59 years, including four non-Hispanic White and one Hispanic patients. Tumor types included three patients with ovarian cancer; one patient with pancreatic cancer; and one patient with non-small cell lung cancer. A2B694 doses were 0.5×108 (n=1), 1×108 (n=3), and 2×108 (n=1) cells.

Lymphodepletion was well tolerated by all patients, with no clinically significant cytopenias. All patients had at least one adverse event (AE); the most common AEs were decreased appetite (n=3, 1 serious), and fatigue (n=3). There were no dose-limiting toxicities, cytokine release syndrome, or related neurotoxicity, and no new safety signals after 8.9 months of follow-up. A2B694 was detected post-infusion in peripheral blood in all patients and was present in a tumor biopsy in one patient 42 days post-infusion.

"A2 Bio is committed to helping patients with solid tumor cancers by advancing our promising precision cell therapies based on our Tmod technology platform. The encouraging findings from our EVEREST-2 study enable us to better understand the efficacy and safety profile of A2B694 as a potential therapy for patients with recurrent or metastatic mesothelin-expressing tumors. Currently, these patients have few treatment options. All of us at A2 Bio are grateful to the patients, investigators, and clinical care providers whose participation in EVEREST-2 is critical to understanding the emerging A2B694 clinical profile," said John Welch, M.D., Ph.D., interim chief medical officer of A2 Bio.

Enabling Efficient Patient Identification Through Precision Medicine

Precision medicine enables efficient identification of patients in the A2 Bio clinical studies. Patients are enrolled in EVEREST-2 through BASECAMP-1 (NCT04981119), a master prescreening study that identifies patients with HLA LOH at any time in the course of their disease via next-generation sequencing. Upon disease progression, the participant may screen for enrollment in EVEREST-2. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course. BASECAMP-1 utilizes artificial intelligence (AI)-enabled precision diagnostics as a cost-effective, high-yield approach to identify eligible patients for all A2 Bio clinical studies.2, 3

A2 Bio continues to advance its clinical development of A2B694, A2B395, the BASECAMP-1 prescreening study, and other preclinical programs as the company pursues additional pipeline expansion opportunities using its proprietary Tmod technology platform. The Tmod platform comprises a suite of technologies that can be used in isolation or in combination, and in both autologous and allogeneic settings, to create novel therapies for cancers and beyond.

About EVEREST-2

EVEREST-2 (NCT06051695) is a seamless Phase 1/2 study evaluating the safety and efficacy of A2B694, an autologous logic-gated investigational cell therapy developed from the A2 Bio proprietary Tmod platform. The Tmod platform provides selective killing of tumor cells and protection of normal cells via a dual-receptor design consisting of an activator that targets tumor cells and a blocker that protects normal cells. A2B694 consists of an activator that targets mesothelin and a blocker that targets HLA-A*02. HLA-A*02 is lost in tumor cells and present in normal cells in the eligible patient population. The study is recruiting participants with colorectal cancer, pancreatic cancer, non-small cell lung cancer, ovarian cancer, mesothelioma, and other solid tumors that express mesothelin and have lost HLA-A*02 expression.

About the Tmod Platform

A2 Bio has pioneered a precision-targeting cellular system – the Tmod platform – that incorporates two receptors, an activator and a blocker, to aim the powerful armaments of immune cells directly at tumors to unequivocally differentiate tumors from normal tissues. The activator recognizes antigens on tumor cells that trigger their destruction, while the blocker recognizes antigens on normal cells that protect them. This novel blocker technology enables precise, personalized and effective T cell targeting. The blocker component equips Tmod cells with the capacity to identify tumors as distinct from normal cells.

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).

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.