Circle Pharma Announces Agreement with Lilly to Further Enhance AI/ML Capabilities and Accelerate Development of New Oral Macrocycle Therapies

On September 9, 2025 Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for difficult-to-treat cancers, reported an agreement with Eli Lilly and Company (Lilly) that enables the company to use Lilly TuneLab, a pioneering artificial intelligence and machine learning (AI/ML) platform designed to accelerate the development of new medicines by providing biotech companies access to powerful drug discovery models that have been trained on Lilly’s proprietary research data (Press release, Circle Pharma, SEP 9, 2025, View Source [SID1234655875]).

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Circle Pharma will leverage Lilly TuneLab to further strengthen its AI/ML capabilities and proprietary MXMO platform, which is designed to overcome key challenges in macrocycle drug development to enable the creation of intrinsically cell-permeable and orally bioavailable macrocycle therapies, including for historically undruggable targets. Circle Pharma’s lead program, CID-078, is a first-in-class, orally bioavailable cyclin A/B RxL inhibitor that is being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors.

"We are thrilled to partner with Lilly and gain access to TuneLab," said Constantine Kreatsoulas, Ph.D., senior vice president, head of discovery technology sciences at Circle Pharma. "This collaboration will further enhance our MXMO platform, which enables us to better predict how various types of macrocycles may be able to penetrate cells, show oral bioavailability, exhibit desirable drug-like properties, and be manufactured at scale. This collaboration comes at an important time of growth at Circle Pharma with our lead program, CID-078, now in clinical development and our preclinical pipeline advancing rapidly to address cyclins and other historically undruggable targets in oncology."

This agreement is part of the Lilly Catalyze360 model, a comprehensive approach to empower early-stage biotechs to advance groundbreaking science by providing access to capital, cutting-edge lab space and technology, and drug development talent and resources.

About Circle Pharma’s MXMO platform

Circle Pharma’s proprietary MXMO platform combines computationally driven drug design along with advanced, fully synthetic macrocycle chemistry. Through this platform, Circle Pharma’s scientists screen vast permeability-biased physical and virtual macrocycle libraries to identify early hit compounds. Artificial Intelligence (AI), Machine Learning (ML), and rigorous physics-based simulations are used to assess many designs simultaneously and to rapidly explore structure-activity relationships for hit-to-lead progression. These diverse compounds are then synthesized in the lab, utilizing both natural and unnatural chemical building blocks, many of which are custom and proprietary to Circle Pharma, to evaluate them as lead investigational macrocycles.

Case Study: CyPath® Lung Identifies Lung Cancer in Patient with Difficult-to-Diagnose Ground-Glass Pulmonary Nodules

On September 9, 2025 bioAffinity Technologies, Inc. (Nasdaq: BIAF; BIAFW), a biotechnology company advancing noninvasive diagnostics for lung cancer and other lung diseases, reported another compelling case study in which its flagship product, CyPath Lung, identified cancer in a patient with an incidental finding of ground-glass lung nodules (Press release, BioAffinity Technologies, SEP 9, 2025, View Source [SID1234655874]).

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Ground-glass nodules appear in imaging as hazy gray areas distinct from solid nodules. Clinicians often find them challenging to assess because they can remain stable for many years, often mimic benign lesions caused by inflammation or fibrosis, and typically do not light up on PET scans.

"Society guidelines for ground-glass nodules recommend two to five years of watchful waiting with serial CT scans. Obviously, this can put both patients and their doctors in an uncomfortable position of balancing uncertainty against the risks of delayed diagnosis," said Gordon Downie, MD, PhD, bioAffinity Technologies’ Chief Medical Officer. "Adding CyPath Lung to the traditional standard of care can provide actionable results that move beyond watchful waiting to timely, potentially life-saving treatment."

The patient, a 66-year-old former smoker, underwent a CT scan for abdominal pain, suspecting kidney stones. The scan incidentally captured a ground-glass nodule in her lung, and a subsequent CT scan of the chest found multiple ground-glass nodules, the largest 13 mm in length. Because of her smoking history, she was referred to a lung clinic for evaluation and risk stratification. Her physician ordered the CyPath Lung test, which returned a "likely malignant" result. Based on the positive CyPath Lung test, the care team proceeded with robotic bronchoscopy. Pathology confirmed lung cancer, and the patient was referred for surgical treatment.

"This case provides another real-world example of CyPath Lung’s value in the evaluation of both solid and sub-solid lung nodules by providing actionable information in real time that can help direct next steps in care, reduce uncertainty and improve patient outcomes," bioAffinity Technologies President and CEO Maria Zannes said. "CyPath Lung has the potential to significantly reduce the mystery of sub-solid, or ground-glass, nodules when they show up on imaging, and both patient and physician are reluctant to delay diagnosis."

About CyPath Lung

CyPath Lung uses proprietary advanced flow cytometry and artificial intelligence (AI) to identify cell populations in patient sputum that indicate malignancy. Automated data analysis helps determine if cancer is present or if the patient is cancer-free. CyPath Lung incorporates a fluorescent porphyrin that is preferentially taken up by cancer and cancer-related cells. Clinical study results demonstrated that CyPath Lung had 92% sensitivity, 87% specificity and 88% accuracy in detecting lung cancer in patients at high risk for the disease who had small lung nodules less than 20 millimeters. Diagnosing and treating early-stage lung cancer can improve outcomes and increase patient survival. For more information, visit www.cypathlung.com.

Arrivent Presents the Final Analysis of Firmonertinib Monotherapy Data from Global Phase 1b Study in EGFR PACC Mutant Non-Small Cell Lung Cancer at the 2025 World Conference on Lung Cancer

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

OncoC4 to Present Global Pivotal Phase 3 Trial Design for Next-Generation CTLA-4 Antibody Gotistobart Monotherapy Being Co-Developed with BioNTech in NSCLC at the IASLC 2025 World Conference on Lung Cancer

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.

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.