On December 9, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), reported an update on enrollment from its November report with an increase to 78% of the target number of subjects for the first planned interim unblinding of data having consented to its pivotal Phase 2B/3 "MIRACLE" study of Annamycin in combination with cytarabine 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). This is up from 60% in its report in November. The targeted number for the first unblinding of data is 45 subjects. Additional subjects beyond the 78% mark continue to be identified by site investigators. This update is as of December 3, 2025, as identification and recruitment are ongoing. The Company expects to complete treatment of the first 45 subjects in the first quarter of 2026.

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Walter Klemp, Chairman and CEO of Moleculin, commented, "We continue to see blinded clinical activity tracking within our expected range, based on historical responses of the trial arm equivalents. With this update, we are quickly approaching the 45th subject, which we expect to be in the first quarter of 2026, to be treated and support the first unblinding in Part A of the MIRACLE trial shortly thereafter. This increase in subjects consented in one month is highly encouraging and demonstrates the enthusiasm of investigators around Europe and the US. Although we saw early enrollment at some sites in Europe being impacted by bed shortages, we are now seeing this situation improve in certain EU countries. Moving toward our first unblinding milestone, we are excited about Annamycin’s potential to fill a major gap in AML treatment. We believe we’re well on our way to determining if Annamycin has the potential to offer a much-needed, safer, and more effective option for patients facing this devastating disease."

Mr. Klemp continued, "While the 45 subject data is not designed to hold statistical significance, we expect to see that at least one of the two arms of Annamycin (at two different dosages) plus cytarabine outperforms cytarabine plus placebo, the control arm. That could be a strong indicator that the MIRACLE trial is on track to support approval of Annamycin. We will continue to recruit the remaining 45 subjects for the full 90 subjects of Part A while we are unblinding the first 45 subjects. The second unblinding should provide enough data to decide on which dose of Annamycin to proceed with into Part B of the MIRACLE trial."

MIRACLE Trial Progress and Next Steps

The MIRACLE study (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) is a Phase 2B/3, global multi-center, randomized, double-blind, placebo-controlled, adaptive designed 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. 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 (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. Before each unblinding, trial data will be subject to audit, database lock and review.

The currently consented subjects are from sites across seven countries, providing a diverse base of patient population. Subjects are identified, consented, screened, enrolled, treated and then evaluated in that order with subjects possibly withdrawing from the trial at any point of this process. The Company expects to reach the recruitment and treatment of the first 45 subjects in the first quarter of 2026 and to complete Part A of the MIRACLE trial with up to 90 patients within the first half of 2026.

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.

(Press release, Moleculin, DEC 9, 2025, View Source [SID1234661315])

On December 9, 2025 Akeso, Inc. (9926.HK) ("Akeso" or the "Company") reported that data from the Phase II study (COMPASSION-25) for its first-in-class PD-1/CTLA-4 bispecific antibody, cadonilimab, in combination with SOX regimen (oxaliplatin + tegafur/gimeracil/oteracil) as neoadjuvant therapy for resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, was presented at the 2025 ESMO (Free ESMO Whitepaper) Asia Congress.

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Currently, Akeso is running the pivotal Phase III study (AK104-310/COMPASSION-33) investigating cadonilimab combined with the SOX regimen for perioperative treatment of resectable G/GEJ adenocarcinoma. This regimen is expected to further push the efficacy boundaries beyond existing single-target immunotherapies and establish a new standard for perioperative immunotherapy in gastric cancer.

Promising Pathologic Complete Response (pCR) Rate

Among all evaluable patients, the overall pCR rate was 28.6%. Notably, in patients receiving the cadonilimab Q3W dosing regimen, the pCR rate reached 50.0%. pCR, defined as the absence of viable tumor cells in both the primary tumor site and regional lymph nodes upon surgical resection, is considered the "gold standard" surrogate endpoint for evaluating neoadjuvant treatment efficacy and predicting long-term survival benefits.

High Rate of Major Pathologic Response (MPR)

The overall MPR rate (defined as ≤10% residual viable tumor cells) across all evaluable patients was 71.4%. For the cadonilimab Q3W regimen, the MPR rate was as high as 85.7%. This suggests that the cadonilimab-based regimen induces substantial tumor regression in the majority of patients.

100% R0 Resection Rate

All patients who underwent surgery achieved an R0 resection (microscopically margin-negative resection), providing a solid foundation for curative intent and potentially reducing the risk of recurrence.

Significant Tumor Downstaging

Among all evaluable patients, 85.7% achieved downstaging of the primary tumor (ypT), and 75.0% achieved nodal downstaging (ypN). These results confirm the efficacy of the cadonilimab regimen in reducing tumor burden and lowering the pathological stage, thereby improving the conditions for successful surgical intervention.

Manageable Safety Profile with Good Tolerability

Treatment-related adverse events were consistent with the known safety profiles of the SOX regimen and immune checkpoint inhibitors. No new or unexpected safety signals were observed, indicating an overall manageable and favorable safety profile.

In perioperative treatment of resectable G/GEJ adenocarcinoma, chemotherapy remains the standard therapy for locally advanced gastric cancer. However, chemotherapy has limited efficacy. Cadonilimab, the first PD-1/CTLA-4 bispecific antibody, works by synergistically activating the immune system, achieving a dual blockade of the tumor immune suppressive microenvironment. This mechanism provides a stronger anti-tumor effect compared to PD-1/L1 monotherapies.

Currently, cadonilimab’s clinical value in gastric cancer is scientifically well-established. Beyond its ongoing phase III clinical trial in the perioperative setting, cadonilimab combined with chemotherapy as a first-line treatment for advanced gastric cancer (with survival benefits across the PD-L1 expression levels) has been approved for commercialization in China. Additionally, a pivotal phase III trial exploring cadonilimab in combination with pulocimab (VEGFR-2) for immune therapy-resistant advanced gastric cancer is currently ongoing and is expected to offer a new therapeutic option for later-line gastric cancer. Collectively, these pivotal phase III studies will expand the use of cadonilimab, paving the way for a comprehensive gastric cancer treatment options that spans from advanced, unresectable gastric cancer to early-stage, resectable disease.

(Press release, Akeso Biopharma, DEC 9, 2025, View Source [SID1234661331])

On December 9, 2025 Novartis reported results showing that one in four patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) remained progression-free for four or more years following treatment with Kisqali (ribociclib) plus endocrine therapy (ET)1. Results were from a pooled, post-hoc exploratory analysis of first-line patients in the MONALEESA trials and will be presented at the 2025 San Antonio Breast Cancer Symposium (SABCS) on December 11, 2025.

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Metastatic breast cancer is cancer that has spread beyond the breasts to other parts of the body. Long-term progression-free survival benefit with Kisqali was observed in patients regardless of their menopausal status and was achieved even in a proportion of patients with unfavorable prognostic factors (liver involvement, ≥ 3 metastatic sites)1. Patients had a median progression-free survival of 6.8 years1. The median overall survival was not estimable.

Kisqali has demonstrated statistically significant overall survival (OS) across all three Phase III MONALEESA trials2-12.

"The latest MONALEESA analysis shows that 1 in 4 patients with metastatic disease remained progression-free for four years or more. Our biomarker analyses demonstrate clinical and genomic factors potentially associated with these outstanding responses, highlighting the importance of precision medicine in identifying which patients may derive the greatest benefit from CDK4/6 inhibitors," said Dr. Pedram Razavi, Breast Medical Oncologist and Director of Translational Oncology Partnership Program at Memorial Sloan Kettering Cancer Center, who is the author and presenter of the analysis at SABCS.

"Kisqali continues to deliver on its promise of potentially offering more time for people living with advanced breast cancer," said Mark Rutstein, Global Head of Oncology Development at Novartis. "The results from the long-term analysis provide continued confidence in the clinical benefit of Kisqali for metastatic breast cancer patients."

Patient and Biomarker Characteristics Associated with Long-Term Response
The post-hoc exploratory analysis of the MONALEESA-2, -3 and -7 trials in first-line HR+/HER2- MBC aimed to identify clinical characteristics and biomarkers of patients who experienced long-term response with Kisqali1.

Characteristic Long-term
Responders (LTR)
(n=153) Non-LTR
(n=349) Directional insight
Median age (years) 59.3 58.0 Comparable across groups
Postmenopausal (%) 78 78 Balanced by menopausal status
De novo disease (%) 43 40 Similar baseline disease presentation
≥ 3 metastatic sites (%) 30 43 Fewer high-burden cases among LTRs
Liver involvement (%) 16 26 Less frequent among LTRs
Bone-only disease (%) 24 20 Slightly more common among LTRs
Mean ctDNA fraction 0.05 0.13 Lower circulating tumor DNA in LTRs
CCND1 alteration (%) 2 10 Less frequent among LTRs
TP53 alteration (%) 3 12 Less frequent among LTRs
Luminal A subtype (%) 38 25 Higher prevalence among LTRs

NATALEE 5-year Data Reinforce Sustained Benefit in Reducing Distant Recurrence

Additionally, Novartis is presenting a sub-analysis from the five-year NATALEE trial that showed Kisqali plus a nonsteroidal aromatase inhibitor (NSAI) continues to result in improved distant disease-free survival (DDFS) compared to NSAI alone13. This was consistent across key subgroups with node-positive and node-negative disease, reinforcing Kisqali plus NSAI as a treatment option to help reduce the risk of recurrence for the broadest population of HR+/HER2- early breast cancer (EBC) patients.

(Press release, Novartis, DEC 9, 2025, View Source [SID1234661316])

On December 9, 2025 CREATE Medicines Inc., a clinical-stage biotechnology company pioneering in vivo multi-immune programming, reported that the first patient has been dosed in the frontline cohort of its metastatic hepatocellular carcinoma (HCC) clinical trial evaluating MT-303. The study is assessing MT-303, an investigational in vivo GPC3-targeted CAR therapy delivered by the company’s proprietary mRNA-LNP platform, in combination with atezolizumab and bevacizumab, the current global standard-of-care regimen for frontline HCC.

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This milestone marks the first time MT-303 is being evaluated in systemic treatment-naïve patients, where immune fitness is better preserved and there is greater potential for deep, durable responses to immunotherapy. Clinical correlative data from CREATE’s ongoing monotherapy programs, including MT-302 and MT-303, have demonstrated in vivo CAR expression, immune activation, and tumor infiltration across more than 40 treated patients. These findings provide strong biological rationale for combination therapy and support the potential for additive or synergistic benefit when MT-303 is paired with atezolizumab and bevacizumab in the frontline setting.

In addition, MT-303 has shown a manageable and differentiated safety profile as a monotherapy, reinforcing the suitability of CREATE’s mRNA-LNP in vivo CAR approach for use alongside established immunotherapies. The platform’s flexibility, redosability, and absence of lymphodepletion requirements position MT-303 well for combination regimens in earlier-line settings where coordinated immune activation is essential.

"Advancing MT-303 into a frontline combination study represents an important evolution for the in vivo CAR field," said Matthew Maurer, M.D., Chief Medical Officer of CREATE Medicines. "Our monotherapy experience across MT-302 and MT-303 has generated compelling correlative evidence of immune activation, myeloid engagement, and tumor infiltration. These data, combined with MT-303’s favorable safety and tolerability profile, support our confidence in evaluating the therapy alongside atezolizumab and bevacizumab. We believe MT-303 is well-positioned to drive deeper and more durable responses for patients with HCC."

"New modalities capable of expanding the benefit of the current treatment options for hepatocellular carcinoma are urgently needed," said Vladimir Andelkovic, M.D., FRACP, Principal Investigator, ICON Cancer Centre, Brisbane, Australia. "Adding the immune engagement potential of MT-303 to atezolizumab and bevacizumab in frontline systemic therapy, where immune fitness is more preserved, is both scientifically compelling and potentially clinically meaningful."

About MT-303

MT-303 is an experimental, in vivo GPC3-targeted CAR therapy that selectively programs myeloid cells using CREATE’s redosable mRNA-LNP system. MT-303 is designed to produce:

CAR expression in circulating and tumor-infiltrating myeloid cells
Direct cytotoxicity against GPC3-positive tumor cells
Immune-modulating effects that recruit adaptive immunity
Repeat-dose capability with improved durability, requiring no lymphodepletion or ex vivo manufacturing
GPC3 is highly expressed across a majority of HCC cases and absent in normal adult tissue, making it an ideal target for directed immunotherapy. In the monotherapy dose escalation cohort of the MT-303 Phase 1/2 trial, the therapy demonstrated human proof-of-mechanism for in vivo CAR expression, myeloid-cell activation, tumor infiltration, evidence of clinical activity and the feasibility of repeat-dose regimens. These results provide the foundation for advancing MT-303 into combination and earlier-line settings.

About the Frontline HCC Study Evaluating MT-303

The frontline HCC study evaluating MT-303 (NCT06478693) is a multi-center, open-label, dose-escalation and expansion trial designed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of MT-303 in combination with atezolizumab and bevacizumab. The trial will evaluate MT-303 in adults with unresectable or metastatic HCC who have not received prior systemic therapy.

The study will also characterize markers of immune activation, including CAR expression kinetics, cytokine/chemokine profiles, tumor infiltration by innate and adaptive immune cells, and early signs of antitumor activity. Data generated from this trial will inform recommended Phase 2 dose selection, further combination strategies, and potential expansion into additional earlier-line or biomarker-defined patient populations.

About Hepatocellular Carcinoma

Liver cancer is among the fastest-growing causes of cancer-related mortality globally, with more than 850,000 new cases diagnosed each year. Hepatocellular carcinoma accounts for most liver cancer cases and often arises in the context of chronic liver disease, viral hepatitis, metabolic syndrome, or cirrhosis. Although recent advances in targeted agents and immunotherapies have improved patient outcomes, durable, long-term benefit remains limited for most patients. Once frontline therapies fail, treatment options become scarce, and prognosis worsens sharply. Novel therapeutic approaches capable of generating coordinated and sustained immune responses represent an urgent and unmet need for the global HCC patient community.

(Press release, Create Medicines, DEC 9, 2025, View Source [SID1234661332])

On December 9, 2025 Novastra Therapeutics ("Novastra"), a Boston-founded, clinical-stage biotechnology company developing next-generation immune reprogramming therapies for cancer, reported that its lead program, OAP-1 from its OmniAntigen XIRT platform, has entered a Phase 1b clinical study in patients with advanced solid tumors. First-in-human data show encouraging effects on how the immune system recognizes and attacks cancer in people with very advanced disease whose tumors have continued to grow despite multiple prior treatments, including chemotherapy, immunotherapy and, for some, radiation therapy. These "last-line" patients have very few remaining standard treatment options and are among the hardest cancer cases to treat.

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OAP-1 is a new type of personalized cancer treatment that focuses on "immune reprogramming." Instead of targeting just one or a few markers, OAP-1 uses a patient’s own tumor cells and coats them with a special ultra-thin nano-layer. This layer helps preserve the full "fingerprint" of the cancer while giving the immune system a strong and coordinated push to see the tumor as a threat again. The goal is to safely "retrain" the immune system to fight the patient’s cancer more effectively.

"Many people benefit from today’s cancer immunotherapies, but too often the cancer finds a way to escape and patients run out of options," said Junling Guo, PhD, Founder of Novastra Therapeutics. "Our next-generation OmniAntigen XIRT platform is designed for system-level immune reprogramming. We want to keep the full picture of each patient’s cancer and, at the same time, give the immune system a stronger, more organized second chance to respond."

OAP-1 is made using a same-day process that is designed to be performed near the patient. Tumor samples are collected, processed, and returned as a personalized dose within hours, without the need for gene editing or complex factory-style manufacturing. This approach aims to make personalized immunotherapy more practical and more accessible over time.

The ongoing Phase 1b clinical study is enrolling patients with advanced solid tumors whose cancer has continued to grow after treatment with PD-1/PD-L1 checkpoint inhibitor drugs, a common type of cancer immunotherapy. The main goals of this study are to evaluate safety and feasibility, and to understand how OAP-1 affects the immune system and tumor behavior over time.

So far, in the initial patients treated, OAP-1 has been well tolerated, with no unexpected safety concerns observed. Tests on blood and tissue samples show several highly encouraging cancer-related immune reprogramming effects, including a clear rise in a natural immune signal called interferon-alpha (IFN-α) which helps "wake up" the body’s defenses, followed by a substantial and sustained increase in specific "attacker" signals (interferon-gamma/IFN-γ). This pattern indicates stronger activation of immune cells that can recognize cancer and more T cells that appear to be targeting the patient’s own tumor. In line with these immune changes, early scan results in some patients suggest that their tumor growth has been brought under control, with signs that the tumors have stopped growing and, in some cases, may even be starting to shrink.

"The early clinical data on these immune reprogramming effects are very encouraging, especially in patients whose cancers have already stopped responding to standard immunotherapy," said Yunxiang He, PhD, Co-Founder of Novastra. "We believe that a next-generation, system-level immune reprogramming approach like OAP-1 could eventually serve as a flexible backbone that works together with existing checkpoint inhibitors and other cancer treatments."

About OmniAntigen XIRT

OmniAntigen XIRT (next-generation immune reprogramming therapy) is Novastra’s platform for rapidly turning patient-derived cells into same-day cancer immunotherapies. Each dose is designed to preserve a wide spectrum of tumor antigens – the unique "fingerprint" of a patient’s cancer – while adding a proprietary ultra-thin coating and immune-stimulating components that help "wake up" and reprogram the immune system at multiple levels. The platform is designed for closed-system, near-patient manufacturing in just a few hours, with the goal of making personalized immune reprogramming practical and scalable.

OAP-1, the first clinical candidate from the OmniAntigen XIRT platform, is currently being evaluated in a Phase 1b clinical trial in advanced solid tumors with prior exposure to checkpoint inhibitor therapy.

(Press release, Novastra Therapeutics, DEC 9, 2025, View Source [SID1234673478])