On September 9, 2025 ArriVent BioPharma, Inc. (Company or ArriVent) (Nasdaq: AVBP), a clinical-stage company dedicated to accelerating the global development of innovative biopharmaceutical therapeutics, reported positive final proof-of-concept data from the randomized global Phase 1b FURTHER trial for first-line firmonertinib monotherapy in patients with non-small cell lung cancer (NSCLC) harboring EGFR PACC mutations at the IASCLC 2025 annual World Conference on Lung Cancer (WCLC), in Barcelona, Spain (Press release, ArriVent Biopharma, SEP 9, 2025, View Source [SID1234655873]).

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"Our 16-month prolonged progression free survival with once daily oral firmonertinib monotherapy has been maintained with 16.5 months of median follow up and we are particularly encouraged by the CNS responses including CNS complete responses" said Bing Yao, Ph.D., Chairman and Chief Executive Officer of ArriVent. "Together this data reinforces the potential of firmonertinib to address key unmet needs in the global EGFR mutant NSCLC treatment landscape. Additionally, the rapid clearance of PACC ctDNA in frontline patients observed across a broad range of PACC mutations, including those with frequent, less frequent and compound PACC mutations, is consistent with the broad activity of firmonertinib in PACC mutant NSCLC. We expect to enroll the first patient in our global registrational ALPACCA Phase 3 trial in frontline PACC patients in the second half of the year."

Key Highlights of Longer-term Final Analysis Data for Firmonertinib Monotherapy:

● Maintained Clinically Meaningful PFS and Durable Responses
o 16.0 months mPFS with firmonertinib once daily 240 mg by BICR, with majority of patients remaining on study
o 14.6 months median duration of response with firmonertinib 240 mg by BICR
o 68.2% and 43.5% confirmed ORR by BICR at 240 mg and 160 mg, respectively
◾ Confirmed responses at first tumor assessment in the majority of patients
◾ Responses across a wide range of EGFR PACC mutations including most frequent (G719X, S768I), less frequent (E709X, V774M) and compound mutations

o 42.9% (6/14) CNS confirmed ORR and 35.7% (5/14) CNS confirmed CRs in CNS evaluable disease front-line patients by BICR

● Safety Profile Continues to be Consistent with No New Safety Signals
o Generally well-tolerated and manageable safety profile maintained over longer treatment duration
o Most frequent treatment-related adverse events include diarrhea, hepatic enzyme elevation, rash, stomatitis, and dry skin
o No new safety findings with further follow up and safety profile remains consistent with EGFR-TKI class

● Rapidly Decreased or Cleared PACC ctDNA in Frontline Patients
o 82% (9/11) and 79% (11/14) ctDNA clearance in frontline PACC patients treated with firmonertinib at 240 mg and 160 mg, respectively, in patients with detectable PACC ctDNA at baseline
o Consistent decreases in ctDNA across different PACC mutations were observed including in patients with frequent, less frequent and compound mutations

On September 8, 2025 OncoC4, Inc., a late-stage biopharmaceutical company developing novel medicines for cancer reported that it will have a poster presentation at the upcoming World Conference on Lung Cancer (WCLC) 2025 hosted by the International Association for the Study of Lung Cancer (IASLC), taking place September 6-9, 2025 in Barcelona, Spain (Press release, OncoC4, SEP 8, 2025, View Source [SID1234655992]). The presentation will feature the pivotal trial Stage II design for PRESERVE-003 (NCT05671510), a two-stage, randomized, open-label, active-controlled Phase 3 Study evaluating gotistobart monotherapy compared to docetaxel in squamous non-small cell lung cancer (sqNSCLC) after progression on a PD-(L)1 inhibitor.

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Squamous NSCLC is among the deadliest cancers with very limited treatment options following traditional chemotherapy and immunotherapy (IO) with immune checkpoint inhibitors1. OncoC4 and its strategic partner BioNTech have embarked on this indication based on encouraging Phase 1/2 results and the match between the vulnerability of the sqNSCLC and the mechanism of action of gotistobart (ONC-392/BNT316). The Stage I of the 2-stage PRESERVE-003 study was designed for dose confirmation based on safety, efficacy and exposure-response analyses. The data supported selecting the high dose for Stage II, which consists of 1:1 randomization between gotistobart and docetaxel in patients with squamous NSCLC. Enrollment of Stage II (potentially registrational) continues to progress well with nearly 160 active sites worldwide.

Gotistobart is a next generation, acid pH-sensitive anti-CTLA-4 monoclonal antibody candidate that avoids antibody-induced lysosomal target degradation for better therapeutic index. Together with modifications in Fc, gotistobart induces more potent and selective depletion of regulatory T cells in the tumor microenvironment.

"The mechanism of action of gotistobart has the potential for clinical development of the drug beyond lung cancers for other indications with unmet medical needs, either as monotherapy or in combination with other therapeutic modalities," said Yang Liu, PhD, Co-Founder, Chief Executive Officer (CEO), and Chief Scientific Officer (CSO) of OncoC4.

WCLC Poster Presentation Details

Title: PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC
After Progression on PD-(L)1 Inhibitors (NCT05671510)

Abstract Number: 1363

Session: P3.18 – Ongoing Clinical Trials

Date: Tuesday, September 9, 2025

Time: 10:00 AM CEST

Presenter: Dr. Tianhong Li, Professor, Department of Internal Medicine, Division of Hematology and Oncology at UC Davis Comprehensive Cancer Center, CA

About PRESERVE-003

PRESERVE-003 is a randomized, open label, active controlled, multi-center Phase 3 trial (ClinicalTrials.gov NCT 05671510) sponsored by OncoC4 and consists of two stages. Stage 1, the dose-confirmation stage, assessed the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W in patients with squamous and non-squamous non-small cell lung cancer (NSCLC). Stage 2 assesses the safety and efficacy of gotistobart at 6 mg/kg Q3W with 2 loading doses of 10 mg/kg versus docetaxel (75 mg/m2 Q3W) on squamous cell NSCLC. The primary endpoint is Overall Survival.

About gotistobart (BNT316/ONC392)

Gotistobart is licensed to BioNTech for commercialization and jointly developed clinically by OncoC4 and BioNTech for oncology indications. There are several ongoing clinical trials in different tumor types, investigating gotistobart either as monotherapy or in combination with other therapeutic agents.

About squamous non-small cell lung cancer (NSCLC)

Squamous cell non-small cell lung cancer makes up 25 – 30% of all lung cancers, and is the most common lung cancer found in smokers2. In the US, first-line treatment for metastatic squamous NSCLC commonly involves a combination of chemotherapy and immunotherapy. However, treatment choices diminish when patients progress on prior IO options.

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.

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).