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Alnylam Announces Proposed Offering of $500 Million Convertible Senior Notes

On September 8, 2025 Alnylam Pharmaceuticals, Inc. ("Alnylam") (Nasdaq: ALNY), the leading RNAi therapeutics company, reported that it has commenced a private offering of $500 million aggregate principal amount of convertible senior notes due 2028 (the "notes") to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Alnylam, SEP 8, 2025, View Source [SID1234655917]). In connection with this offering, Alnylam expects to grant the initial purchasers of the notes an option to purchase, for settlement within a 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $75 million aggregate principal amount of the notes. The offering of the notes is subject to market and other conditions and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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The notes will be senior, unsecured obligations of Alnylam, will accrue interest payable semi-annually in arrears and will mature on September 15, 2028, unless earlier converted, redeemed or repurchased. Noteholders will have the right to convert their notes in certain circumstances and during specified periods. Alnylam will settle conversions by paying or delivering, as applicable, cash, shares of its common stock, par value $0.01 per share ("common stock"), or a combination of cash and shares of its common stock, at Alnylam’s election. The notes will be redeemable, in whole or in part (subject to certain limitations), for cash at Alnylam’s option at any time, and from time to time, on or after September 20, 2027 and on or before the 21st scheduled trading day immediately preceding the maturity date, if the last reported sale price per share of Alnylam’s common stock equals or exceeds 130% of the conversion price for a specified period of time. The redemption price will be equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date. The interest rate, initial conversion rate and other terms of the notes will be determined at the pricing of the offering. Alnylam expects that the reference price used to calculate the initial conversion price for the notes will be the U.S. composite volume weighted average price of Alnylam’s common stock from 12:30 p.m. through 4:00 p.m. Eastern Daylight Time on the date of pricing.

In connection with the pricing of the notes, Alnylam expects to enter into privately negotiated capped call transactions with one or more of the initial purchasers or their respective affiliates or other financial institutions (the "option counterparties"). The capped call transactions are expected generally to reduce potential dilution to Alnylam’s common stock upon conversion of any notes and/or offset any potential cash payments Alnylam is required to make in excess of the principal amount of converted notes, as the case may be, with such reduction and/or offset subject to a cap.

Alnylam has been advised that, in connection with establishing their initial hedges of the capped call transactions, the option counterparties or their respective affiliates expect to purchase shares of Alnylam’s common stock and/or enter into various derivative transactions with respect to Alnylam’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock or the notes at that time. In addition, the option counterparties and/or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Alnylam’s common stock and/or purchasing or selling Alnylam’s common stock or other securities of Alnylam in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so during any observation period related to a conversion of notes or following certain repurchases or redemptions of the notes). This activity could cause or avoid an increase or a decrease in the market price of Alnylam’s common stock or the notes, which could affect the ability of holders to convert the notes and, to the extent the activity occurs following conversion or during any observation period related to a conversion of notes, it could affect the amount and value of the consideration that holders will receive upon conversion of such notes.

Alnylam intends to use a portion of the net proceeds from the offering to pay the cost of the capped call transactions. If the initial purchasers exercise their option to purchase additional notes, Alnylam expects to use a portion of the net proceeds from the sale of the additional notes to enter into additional capped call transactions. In addition, Alnylam intends to use all or a portion of the remaining net proceeds from the offering, together with cash on hand, to repurchase a portion of Alnylam’s 1.00% convertible senior notes due 2027 (the "existing notes") through privately negotiated transactions entered into concurrently with the pricing of the notes, and the remainder of the net proceeds, if any, for general corporate purposes.

Alnylam expects to repurchase for cash a portion of the existing notes through privately negotiated transactions (the "note repurchase transactions") entered into concurrently with the pricing of the notes. The terms of each note repurchase transaction will depend on a variety of factors, including the market price of Alnylam’s common stock and the trading price of the existing notes at the time of the note repurchase transactions. No assurance can be given as to how much, if any, of the existing notes will be repurchased or the terms on which they will be repurchased. This press release is not an offer to repurchase the existing notes, and the offering of the notes is not contingent upon the repurchase of the existing notes.

In connection with the note repurchase transactions, Alnylam expects that holders of the existing notes who agree to have their existing notes repurchased and who have hedged their equity price risk with respect to such existing notes (the "hedged holders") will unwind all or part of their hedge positions by buying Alnylam’s common stock and/or entering into or unwinding various derivative transactions with respect to Alnylam’s common stock. The amount of Alnylam’s common stock to be purchased by the hedged holders or the notional number of shares of Alnylam’s common stock underlying such derivative transactions may be substantial in relation to the historic average daily trading volume of Alnylam’s common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of Alnylam’s common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price of the notes. Alnylam cannot predict the magnitude of such market activity or the overall effect it will have on the price of the notes or Alnylam’s common stock and the corresponding effect on the initial conversion price of the notes.

The notes will be offered only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act. The offer and sale of the notes and any shares of common stock issuable upon conversion of the notes have not been, and will not be, registered under the Securities Act or any other securities laws, and the notes and any such shares cannot be offered or sold absent registration or except pursuant to an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any other applicable securities laws.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the notes or any shares of common stock issuable upon conversion of the notes, nor will there be any sale of the notes or any such shares, in any state or other jurisdiction in which such offer, sale or solicitation would be unlawful.

A2 Biotherapeutics Presents Data from Ongoing Phase 1/2 EVEREST-2 Study During the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer

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]).

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.

NiKang Therapeutics® Completes Dosing of the First Cohort in a Phase 1 Study of NKT5097, a First-in-Class, Highly Potent and Selective, Orally Bioavailable CDK2/4 Dual Degrader

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.

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).

Cellworks Study Reveals Tumor Microenvironment and TLS Dynamics Together Predict Patient-Level Immunotherapy Response in NSCLC

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.

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.

PhotonPharma Inc. Receives U.S. Patent for Innovative Cancer Immunotherapy

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.

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.