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GT Biopharma Provides Enrollment Update on GTB-3650 Phase 1 Trial in Patients with Relapsed or Refractory (r/r) CD33 Expressing Hematologic Malignancies

On October 8, 2025 GT Biopharma, Inc. (the "Company") (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary TriKE natural killer (NK) cell engager platform, reported that enrollment in the dose escalation cohorts of the Phase 1 trial, evaluating GTB-3650 for the treatment of relapsed or refractory (r/r) CD33 expressing hematologic malignancies, is well on track (Press release, GT Biopharma, OCT 8, 2025, View Source [SID1234656509]).

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Enrollment in Cohorts 1 and 2 were successfully completed; both patients in Cohort 3 have now initiated treatment with no evidence of dose-limiting toxicities or safety concerns to date. The level of immune activation observed from multiple biomarkers in the first patient of Cohort 3 is consistent with the evidence of heightened immune activity in the first four patients from Cohorts 1 and 2. Assuming Cohort 3 is completed with no new safety findings, the trial will continue to dose-escalate into the higher ranges of GTB-3650 anticipated to be necessary to translate heightened immune activation into clinically meaningful evidence of therapeutic activity. Initiation of dosing in Cohort 4 is planned by year-end 2025 and additional data updates are anticipated in Q1 2026.

The Phase 1 protocol allows evaluation of GTB-3650 in up to approximately 14 patients (two patients in each of seven cohorts), with doses ranging from 1.25ug/kg/day in Cohort 1 to 100ug/kg/day in Cohort 7. GTB-3650 will be dosed in two-week blocks, two weeks on and two weeks off (defining a treatment cycle), for up to four months based on clinical benefit. The trial will assess safety, pharmacokinetics, pharmacodynamics, in vivo expansion of endogenous patient NK cells and clinical activity. More details can be found on clinicaltrials.gov with the identifier: NCT06594445.

EORTC shines a light on advancements in radioligand therapy

On October 8, 2025 EORTC reported it is at the forefront of advancing cancer research, and one of the key areas of focus is Radioligand Therapy (RLT) (Press release, EORTC, OCT 8, 2025, View Source [SID1234656508]). On the occasion of the upcoming European Association of Nuclear Medicine (EANM) Congress (4-8 October 2025, Barcelona, Spain), where EORTC co-hosted a symposium, we are excited to highlight the significant strides being made by EORTC in this innovative field.

EANM-EORTC collaboration
The EANM and EORTC collaborate to advance cancer care by integrating nuclear medicine into clinical research. They leverage their combined expertise to design and run large, multidisciplinary clinical trials, especially in areas like radioligand therapy. This partnership is essential for establishing the robust clinical evidence needed to develop new standards of care and improve patient outcomes across Europe.

To further this partnership, EORTC & EANM co-hosted a symposium at the EANM Congress on Monday 6 October entitled "Oncology & Theranostics Committee / EORTC – Oncological Response Criteria for PET: beyond RECIST, EORTC & PERCIST".

Check the programme here.

EORTC’s Radioligand Task Force: driving clinical innovation
A cornerstone of EORTC’s commitment to RLT, this dedicated Task Force, chaired by Matthias Preusser & Christophe Deroose, was established to address the critical need for robust clinical evidence in this rapidly evolving field.

LINK TO VIDEO: View Source

Its primary mission is to design and implement meaningful clinical trials using radioligands as theranostics-based approach, ensuring the generation of high-quality data to advance patient care. The Task Force also plays a crucial role in promoting standardisation and quality assurance within RLT research.

Learn more about the Task Force

Trials in the spotlight
LUMEN-1 trial: improving patient outcomes recurrent meningioma
The RLT Task Force plays a crucial role in designing and implementing studies that aim to improve patient outcomes. A prime example of this dedication is the EORTC-2334-BTG LUMEN-1 clinical trial. This pivotal trial will evaluate the effectiveness of a new treatment strategy for meningioma called [177Lu]Lu-DOTATATE in patients with recurrent meningioma.

This treatment has shown promising results in smaller studies and is now being tested in a larger, randomised phase II trial involving 136 patients across 35 sites in 10 European countries.

You can also learn more by checking the publication of the protocol of LUMEN-1 in the Journal of Nuclear Medicine by Nathalie Albert et al.: View Source

The study is supported by Advanced Accelerator Applications (a Novartis company).

RENALUT: expanding the therapeutic landscape of renal cancer
Emmanuel Seront, study coordinator, introduces the Renalut study: View Source

The EORTC-2361-GUCG RENALUT is a phase II, single-arm, multicentre trial led by EORTC. The objective of the trial is to evaluate the efficacy of [177Lu]Lu-PSMA-617 in second/third line metastatic clear cell renal cell carcinoma (ccRCC). The utilisation of [177Lu]Lu-PSMA-617, which targets PSMA (prostate-specific membrane antigen), has demonstrated both efficacy and safety in the treatment of metastatic prostate cancer. Although PSMA has been observed to be present on prostate tumour cells, the term is considered inappropriate due to its concomitant expression in neo vasculature and in other organs. Hypervascularization represents a significant consequence of the mutation of the Von Hippel-Lindau (VHL) gene, which is prevalent in cases of clear cell renal cell carcinoma (ccRCC). PSMA targeted imaging has been reported to demonstrate a high degree of accuracy in the evaluation of metastatic ccRCC, thus indicating its potential as a target for radioligand therapy.

The current standard of care involves the combination of a vascular endothelial growth factor receptor (VEGFR)-targeting tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor (ICI). After progression on these regimens, the standard approach is sequential VEGFR-TKI therapy. Nevertheless, the efficacy is modest.

This innovative study introduces a novel therapeutic approach for aggressive disease, leveraging promising outcomes observed in prostate cancer and the known PSMA overexpression in ccRCC. RENALUT aims to expand the therapeutic landscape and provide new hope for patients with limited treatment options.

The study is supported by Advanced Accelerator Applications (a Novartis company).

PEACE III: unlocking the potential of therapeutic radionuclides
The EORTC-1333-GUCG PEACE III phase III trial, which presented its late-breaking results at ESMO (Free ESMO Whitepaper) 2024 (European Society for Medical Oncology) on 14 September 2024 during a presidential symposium, is a landmark study demonstrating a significant improvement in patient outcomes for metastatic castration-resistant prostate cancer (mCRPC) patients with bone metastases.

The trial successfully showed that adding six cycles of the alpha-emitting radionuclide radium-223 (223RaCl2) to enzalutamide, an AR pathway inhibitor, increased median progression-free survival from 16 to 19 months, with an interim analysis also suggesting an overall survival advantage.

This groundbreaking study perfectly symbolises our work in nuclear medicine — specifically, using a targeted therapeutic radiopharmaceutical to provide effective, manageable, combination treatment—to meaningfully prolong life and establish a new standard of care in advanced cancer treatment.

The trial was a collaboration between EORTC, CTI CUOG, LACOG, and GETUG/UNICANCER, and also shows the importance of partnerships in clinical trials.

This trial is supported by an investigator driven clinical trial agreement from Bayer HealthCare Pharmaceuticals Inc. and Astellas Pharma Europe.

EORTC’s broader commitment to Radioligand Therapy: a multidisciplinary approach
To conclude, EORTC’s work in radioligand therapy is highly representative of EORTC’s overarching multi-tumour approach to cancer research, leveraging the organisation’s unique multidisciplinary infrastructure. Its work is intrinsically linked to and supported by various EORTC Disease-Oriented Groups (e.g., Brain Tumour Group, Genito-Urinary Cancers Group) and transversal platforms, like the EORTC Imaging Group. This collaborative model ensures that the expertise in imaging and nuclear medicine is central to designing and executing studies across diverse cancer types.

Circio presents comprehensive circVec in vivo data package demonstrating 40-fold improvement over conventional AAV gene delivery at ESGCT 2025

On October 8, 2025 Circio Holding ASA (OSE: CRNA), a biotechnology company developing powerful circular RNA technology for next generation nucleic acid medicine, reported the publication of a comprehensive data package demonstrating AAV-circVec in vivo tissue-specific proof-of-concept (Press release, Circio, OCT 8, 2025, View Source [SID1234656507]). The results are being delivered in a poster presentation at the European Society of Cell and Gene Therapy (ESGCT) annual meeting 2025 in Seville, Spain.

In the ESGCT poster presentation, Circio is presenting new and expanded in vivo results demonstrating the advantage of circVec as a novel expression system to transform AAV gene therapy. In heart tissue, circVec 3.2 shows highly localized activity that outperforms conventional mRNA-based AAV expression by up to 40-fold. These results have been demonstrated and confirmed both by IVIS scanning and post-mortem ex vivo tissue analysis. To validate the technology in a therapeutically relevant setting, Circio has initiated technical development of circVec-AAV gene therapy constructs for Danon disease, a devastating cardiac genetic disease with no therapeutic options available today.

"Circio has worked systematically to optimize the circVec design for AAV gene delivery over the past two years. The latest circVec 3.2 generation incorporates a novel genetic feature that drives up AAV protein expression to levels that substantially exceed conventional mRNA-based AAVs. We are now advancing rapidly to validate these findings in relevant genetic disease models," said Dr. Thomas B. Hansen, CTO of Circio. "Importantly, the strong advantage in the heart is also observed in several other tissues and AAV variants. This consistency supports broad applicability of our circVec platform, thereby opening development and partnering opportunities in multiple therapeutic areas."

The presentation also includes data showing a strong increase in expression levels with the trend for continued signal accumulation following local delivery of previous generation circVec 2.0 AAV vector to the eye. Testing of the latest generation circVec 3.2 in eye and other tissues is currently being initiated, and a novel circVec generation 4.0, which incorporates further genetic enhancer elements, is due to enter initial in vivo screening experiments.

"ESGCT provides an excellent forum to showcase the circVec platform to a wide academic and industry audience as a potential solution to address the key issue preventing broad adoption and success of AAV gene therapy," said Dr. Erik D Wiklund, CEO of Circio. "The AAV field has recently experienced several major setbacks due to severe toxicity issues in ongoing clinical studies. Switching to circVec-based expression can enable substantial dose reduction, which we expect will lead to considerable improvements in safety for patients and lower treatment cost. The circVec platform could thereby completely transform the clinical and commercial viability of AAV therapy as we know it today and establish circVec as a novel gold-standard gene expression system."

Title of presentation and poster:
CircVec: Enhancing gene and cell therapy using circular RNA vector expression technology (poster no. 1041)

Presenter: CTO Dr. Thomas B Hansen & CSO Dr. Victor Levitsky

Lisata Therapeutics and Catalent Announce Global Antibody-Drug Conjugate (ADC) License Agreement

On October 8, 2025 Lisata Therapeutics, Inc. (Nasdaq: LSTA) ("Lisata" or the "Company"), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, and Catalent, Inc. ("Catalent"), a leader in enabling the development and supply of better treatments for patients worldwide, reported a global product license agreement that allows Catalent to incorporate Lisata’s certepetide into antibody-drug conjugates ("ADCs") developed using Catalent’s SMARTag technology platform (Press release, Catalent, OCT 8, 2025, https://www.catalent.com/media-advisories/lisata-therapeutics-and-catalent-announce-global-antibody-drug-conjugate-adc-license-agreement/ [SID1234656506]). Certepetide, a proprietary, internalizing RGD (arginyl-glycyl-aspartic acid) or "iRGD" cyclic peptide, is being tested by Lisata as a cancer therapeutic to be used in combination with other anti-cancer agents to enhance tumor targeting and penetration and improve treatment outcomes.

Under the licensing agreement, Catalent gains worldwide, non-exclusive rights to develop and commercialize bioconjugate products containing certepetide and its analogs, including the ability to partner with third parties. As part of this collaboration, Catalent will have the right to evaluate certepetide and its analogs as SMARTag payloads in clinical studies across multiple ADCs targeting difficult-to-treat diseases, with the goal of creating a new class of targeted bioconjugate therapies. Lisata is eligible to receive over $10 million in tiered study initiation milestone payments plus revenue sharing on future sales and partnerships.

"This collaboration is based on positive preclinical results generated by Catalent’s use of an iRGD peptide as part of its SMARTag ADC platform," stated Kristen K. Buck, M.D., Executive Vice President of Research and Development and Chief Medical Officer of Lisata. "It underscores our mutual belief in certepetide’s broad potential and is another significant step forward in Lisata’s mission to bring transformative therapies to patients. Catalent’s technology and innovative approach are a perfect complement to certepetide’s biology." Preclinical work supporting incorporation of iRGD peptides into the SMARTag ADC platform will be highlighted at this November’s World ADC conference in San Diego.

"We are excited about the opportunity to explore iRGD biology as it relates to ADC delivery to the tumor microenvironment. Early data suggest that incorporating iRGD peptides into ADCs improves efficacy and pharmacokinetics, leading us to be optimistic about the potential of iRGD as a novel payload class," said Penelope Drake, Head of R&D, Bioconjugates at Catalent.

Alligator announces publication of OPTIMIZE-1 biomarker analysis in Cell Reports Medicine supporting mitazalimab and mFOLFIRINOX in metastatic pancreatic cancer

On October 8, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported the publication of a peer-reviewed article in Cell Reports Medicine, a Cell Press journal (Press release, Alligator Bioscience, OCT 8, 2025, View Source [SID1234656505]). The paper presents biomarkers associated with clinical efficacy endpoints from the Phase 1b/2 OPTIMIZE-1 trial evaluating Alligator’s CD40 agonist mitazalimab in combination with mFOLFIRINOX chemotherapy in patients with untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).

The publication, titled "CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: biomarkers associated with outcomes from OPTIMIZE-1", provides mechanistic insights into determinants of clinical response and offers translational support for a planned randomized Phase 3 trial.

Key findings from the publication include:

Clinical efficacy: The OPTIMIZE-1 study met its primary endpoint, with a confirmed objective response rate of 42.1% in the Phase 2 cohort. Median duration of response was 12.6 months, progression-free survival 7.7 months, and overall survival 14.9 months. The survival rate at 24 months was 29.4%, triple that of chemotherapy alone.
Tumor gene signature linked to outcome: Baseline expression of a tumor-intrinsic fibrotic gene signature, directly linked to the mode of action of mitazalimab, was associated with improved overall survival.
Peripheral immune activation: Mitazalimab-induced increases in circulating activated immune cells correlated with better clinical outcomes.
Intratumoral immune activation: Patients with objective clinical responses displayed mitazalimab-induced immune activation supporting mitazalimab’s contribution to clinical outcomes
Translational impact: strongly supports mitazalimabs contribution to the improved clinical outcomes observed in OPTIMIZE-1 and supports future development of predictive biomarkers for mitazalimab.
"These data provide important guidance for understanding which patients may benefit most from mitazalimab-based immunotherapy in pancreatic cancer, and provides further evidence for mitazalimab’s contribution to the sustained clinical benefit observed in the OPTIMIZE-1 trial" said Søren Bregenholt, CEO of Alligator Bioscience. "The integration of biomarker-driven insights into our clinical development strategy strengthens the foundation for the next phase of mitazalimab’s evaluation in this high-need indication."