On September 9, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported updates to its active site status and recruitment for its pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML) (Press release, Moleculin, SEP 9, 2025, View Source [SID1234655877]). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, Europe and the Middle East.

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To advance this trial to recruiting the 45th subject in Q4 2025 for its first unblinding for early data insights into the trial’s efficacy and safety endpoints, the Company has the following expectations for September:

Global Expansion: Expanding recruiting beyond Ukraine to include Spain, Georgia, Poland, Romania, Italy, Lithuania, and the US;
Site Expansion: Adding 8 new active sites by the end of September, increasing the total to 20 sites recruiting;
Recruitment Goals: Treating, enrolling, or screening a total of 20 subjects by the end of September; and
Data Insights: Setting a solid footprint to recruit the 45th subject in Q4 2025, allowing for unblinded preliminary data assessment regarding efficacy and safety upon data lock.
Walter Klemp, Chairman and CEO of Moleculin, commented, "Our team is diligently expanding our active site footprint across the US, EU, and neighboring regions. We are confident in our target to recruit the 45th subject by Q4 2025 and achieve our first data unblinding shortly thereafter, especially since the consistent message we are receiving from investigators is that they are very eager to enroll patients in the MIRACLE trial. Moving from our end of Phase 2 meeting with the FDA to screening 13 subjects in just over a year exemplifies our operational efficiency. Of these 13, 10 have been dosed, further supporting our confidence in the speed of recruitment for MIRACLE."

Mr. Klemp continued, "We expect to increase to over 30 active sites by year-end, as we move toward a second data unblinding for the conclusion of Part A of the trial. That will only require an additional 30 to 45 subjects, so we expect to conclude Part A in the first half of 2026, before commencing Part B of the trial. This level of early visibility is, we believe, exceptionally rare for a Phase 2B/3 trial and highly advantageous for investors."

The MIRACLE study is a Phase 2B/3 clinical trial whereby data from the 2B (Part A) portion will be combined with the Phase 3 (Part B) portion for purposes of measuring its primary efficacy endpoint. MIRACLE is subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The protocol for the MIRACLE trial allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). The first early unblinding will yield 30 subjects treated with Annamycin (190mg/m2 and 230 mg/m2) in combination with HiDAC and 15 subjects treated with just HiDAC plus placebo. The Company expects to reach the recruitment of the first 45 subjects in the second half of 2025 with unblinding shortly thereafter, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due in part to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

As previously announced with regard to the EU, the clinical trial approval with EMA was granted under the condition that the Company present results of appropriate nonclinical GLP studies before initiating the Phase 3 portion (Part B) of the study. Results will be submitted as a substantial modification to the existing approved CTA.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00.

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Annamycin also benefits from composition of matter patent protection through 2040 with the potential to extend that protection as far as 2045. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA.

On September 9, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat cancers and viral infections, reported updates to its active site status and recruitment for its pivotal Phase 2B/3, multi-center, randomized, double-blind, placebo-controlled, adaptive design study of Annamycin in combination with cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") for the treatment of adult patients with acute myeloid leukemia (AML) who are refractory to or relapsed (R/R) after induction therapy (R/R AML) (Press release, Moleculin, SEP 9, 2025, View Source [SID1234655877]). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a global approval trial, including sites in the US, Europe and the Middle East.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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To advance this trial to recruiting the 45th subject in Q4 2025 for its first unblinding for early data insights into the trial’s efficacy and safety endpoints, the Company has the following expectations for September:

Global Expansion: Expanding recruiting beyond Ukraine to include Spain, Georgia, Poland, Romania, Italy, Lithuania, and the US;
Site Expansion: Adding 8 new active sites by the end of September, increasing the total to 20 sites recruiting;
Recruitment Goals: Treating, enrolling, or screening a total of 20 subjects by the end of September; and
Data Insights: Setting a solid footprint to recruit the 45th subject in Q4 2025, allowing for unblinded preliminary data assessment regarding efficacy and safety upon data lock.
Walter Klemp, Chairman and CEO of Moleculin, commented, "Our team is diligently expanding our active site footprint across the US, EU, and neighboring regions. We are confident in our target to recruit the 45th subject by Q4 2025 and achieve our first data unblinding shortly thereafter, especially since the consistent message we are receiving from investigators is that they are very eager to enroll patients in the MIRACLE trial. Moving from our end of Phase 2 meeting with the FDA to screening 13 subjects in just over a year exemplifies our operational efficiency. Of these 13, 10 have been dosed, further supporting our confidence in the speed of recruitment for MIRACLE."

Mr. Klemp continued, "We expect to increase to over 30 active sites by year-end, as we move toward a second data unblinding for the conclusion of Part A of the trial. That will only require an additional 30 to 45 subjects, so we expect to conclude Part A in the first half of 2026, before commencing Part B of the trial. This level of early visibility is, we believe, exceptionally rare for a Phase 2B/3 trial and highly advantageous for investors."

The MIRACLE study is a Phase 2B/3 clinical trial whereby data from the 2B (Part A) portion will be combined with the Phase 3 (Part B) portion for purposes of measuring its primary efficacy endpoint. MIRACLE is subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting.

The protocol for the MIRACLE trial allows for the unblinding of preliminary primary efficacy data (Complete Remission or CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). The first early unblinding will yield 30 subjects treated with Annamycin (190mg/m2 and 230 mg/m2) in combination with HiDAC and 15 subjects treated with just HiDAC plus placebo. The Company expects to reach the recruitment of the first 45 subjects in the second half of 2025 with unblinding shortly thereafter, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due in part to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

As previously announced with regard to the EU, the clinical trial approval with EMA was granted under the condition that the Company present results of appropriate nonclinical GLP studies before initiating the Phase 3 portion (Part B) of the study. Results will be submitted as a substantial modification to the existing approved CTA.

For Part B of the trial, approximately 220 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative.

For more information about the MIRACLE trial, visit clinicaltrials.gov and reference identifier NCT06788756. Additionally, the clinical trial in the EU is on euclinicaltrials.eu and the reference identifier there is 2024-518359-47-00.

Annamycin, also known by its non-proprietary name of naxtarubicin, currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Annamycin also benefits from composition of matter patent protection through 2040 with the potential to extend that protection as far as 2045. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the EMA.

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.

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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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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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.

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