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FDA Grants Orphan Drug Designation for Tinostamustine in Malignant Glioma

On November 10, 2025 Purdue Pharma L.P. ("Purdue") reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation (ODD) to its pipeline drug tinostamustine for the treatment of malignant gliomas, a broad category of brain and spinal cord cancers that affect both adults and children and includes rapidly growing, invasive tumors like glioblastoma. As many as 22,000 people are diagnosed with malignant gliomas annually in the United States1. FDA grants ODD status to encourage development of promising medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States.

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Purdue is currently investigating tinostamustine in patients with glioblastoma, the most common malignant glioma, that is aggressive, very challenging to treat and for which there is no cure.2 Most patients do not survive more than 15 months with current treatment approaches.3 The ODD request for tinostamustine was supported by robust epidemiologic, clinical and pre-clinical evidence, as well as mechanistic rationale supporting its potential to address a critical unmet medical need for glioblastoma.

"As many as 15,000 people in the U.S. are diagnosed with glioblastoma each year.3 Unfortunately, there is limited survival benefit with existing treatment options," said Julie Ducharme, Vice President and Chief Scientific Officer, Purdue. "This recognition from FDA is an important milestone in our mission of advancing innovative science in areas of serious, unmet medical need. We look forward to further investigating tinostamustine, which has shown promise in early trials."

Orphan drug designation is intended to facilitate drug development for rare diseases and may provide certain incentives to drug developers.4,5 These benefits include tax credits for qualified clinical trials, exemption from user fees including New Drug Application (NDA), and a potential for seven years of market exclusivity following approval.

Tinostamustine is a potential first-in-class, new chemical entity that combines two potentially synergistic mechanisms of action, bifunctional alkylating activity and pan histone deacetylase inhibition (or HDAC inhibition). Tinostamustine has the potential to be a first-line treatment for glioblastoma.

"Behind every designation like this are real people, patients and families, facing the devastating reality of malignant gliomas, especially glioblastoma," said Craig Landau, MD, President and CEO, Purdue Pharma. "We are deeply committed to pursuing this medicine that has the potential to bring hope where few options exist today. Tinostamustine represents a step forward in our efforts to help address the urgent and unmet needs of those affected by these aggressive cancers."

The Company also recently entered into an agreement with the Global Coalition for Adaptive Research (GCAR) to pursue the Phase 2/3 clinical development of tinostamustine in GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment – NCT03970447), a global adaptive platform trial for glioblastoma.

This press release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that tinostamustine will successfully complete development or gain FDA approval.

(Press release, Purdue Pharma, NOV 10, 2025, View Source [SID1234659749])

Ontada Presents Framework for Accelerating Clinical Development with Real-World External Control Arms in Phase 2 Trials at ISPOR

On November 10, 2025 Ontada, a leader in real-world oncology data and insights, reported it will present new research findings in an oral presentation at the ISPOR Europe 2025 conference, being held this week in Glasgow, Scotland. ISPOR is the leading professional society for health economics and outcomes research globally. The study, titled, "A Framework for Accelerating Clinical Development with Real-World External Control Arms (ECA) in Phase 2 Trials," addresses a critical gap in early-stage clinical research by offering a scalable approach to contextualizing single-arm trial data.

This research highlights the potential of ECAs to enhance Phase 2 trials, which often lack traditional control groups and face challenges related to small sample sizes and slow patient accrual, particularly in oncology and rare diseases.

Key Data Findings

Real-world data (RWD) curation: The framework outlines a systematic approach to identifying and curating structured and unstructured RWD sources to build robust ECAs.
Trial emulation: It applies rigorous eligibility criteria from the trial to real-world cohorts, ensuring comparability.
Adaptive matching strategies: To address limited trial sample sizes, the framework uses simulation techniques to create synthetic datasets that support more robust patient matching.
Pilot application: The framework was successfully applied to a Phase 2 single arm trial of Tucatinib and Doxil in HER2+ metastatic breast cancer, demonstrating feasibility and value.
"Phase 2 trials are essential for identifying promising therapies, but their inherent design poses challenges to achieving rapid and robust inferences," said Jessica K. Paulus, ScD, vice president, Real World Research, Ontada. "This framework leverages high-quality real-world data and extends state-of-the-science methods in ECA development to overcome barriers in Phase 2 trial conduct, offering a practical path to accelerate development while maintaining scientific rigor. It’s a meaningful step toward more efficient clinical research."

Study Methodology

The framework was developed through a literature review of best practices in Phase 3 ECA design and adapted for Phase 2 single-arm trials. It incorporates simulation-based matching to address the challenge of limited trial patient data and was piloted using real-world data for a newly launched Phase 2 trial in HER2+ metastatic breast cancer.

Research at ISPOR Europe 2025

Ontada is showcasing its research capabilities at ISPOR with five accepted abstracts on topics such as evolving trends in patient demographics and diagnosis in gastric cancer, improving data quality in oncology electronic health record-derived databases, assessing secular trends in ovarian cancer diagnoses, and real-world associations between smoking status and genetic driver mutations in metastatic lung cancer. For a complete list of Ontada presentations, visit Ontada’s ISPOR Europe 2025 site. Additionally, visit Ontada at booth #616 at the Scottish Event Campus in Glasgow, November 10–12, to explore our latest research and real-world oncology solutions.

"At Ontada, we are committed to advancing oncology research through innovative applications of real-world data," said Christine Davis, president, Ontada. "Our presence at ISPOR Europe reflects the depth and diversity of our real-world research capabilities. From advancing trial design with external control arms to uncovering trends in cancer diagnosis and treatment, our work is helping shape the future of oncology through data-driven insights."

Ontada is a part of McKesson, which has an unmatched portfolio of oncology and multispecialty solutions and partners that provide research, insights, technologies and services that help to address barriers and improve cancer and multispecialty care.

(Press release, Ontada, NOV 10, 2025, View Source [SID1234659748])

Leucid Bio Provides Update on Phase I/IIa AERIAL Trial Evaluating Lateral CAR-T LEU011 for the Treatment of Solid Tumours

On November 10, 2025 Leucid Bio ("Leucid" or the "Company"), a privately-held biotechnology company developing innovative Chimeric Antigen Receptor T-cell (CAR-T) therapies using its proprietary lateral CAR platform, reported an update on the Phase I/IIa AERIAL trial evaluating the safety and clinical activity of LEU011 in patients with relapsed/refractory solid tumours.

Preliminary data from the ongoing AERIAL trial have established proof-of-concept for LEU011 by demonstrating key biological activity through evidence of encouraging pharmacokinetic (PK) and pharmacodynamic (PD) profiles. In particular, analysis of post-treatment biopsies (as evaluated by ddPCR and RNAScope) has shown tumour infiltration by LEU011 cells.

To date, treatment with LEU011 has been generally well tolerated. In addition, disease control (based on RECIST criteria) has been observed in multiple patients treated with the lowest dose of LEU011. Dose-escalation in the AERIAL trial continues as planned, with additional data from the trial anticipated during the first half of 2026.

Filippo Petti, Chief Executive Officer, Leucid Bio , said: "Although preliminary, we are highly encouraged by these initial data from the AERIAL trial which establish proof-of-concept for LEU011 in the treatment of solid tumours. Furthermore, they highlight LEU011’s dual mechanism of action targeting NKG2D stress ligands for tumour recognition and using CXCR2 signalling to enhance T-cell infiltration into the tumour microenvironment."

Dr. John Maher, Chief Scientific Officer, Leucid Bio, added: "Traditionally, CAR-Ts have struggled to deliver robust clinical responses in the treatment of solid tumours. We believe these preliminary data highlight the functional activity of LEU011 in the treatment of solid tumours given its unique mechanism of action. We anticipate that the early signals observed to date for LEU011 will continue to improve as we advance through the dose-escalation segment of the AERIAL trial."

AERIAL is a multi-centre, dose-escalation trial designed to evaluate the safety and clinical activity of LEU011 in patients with relapsed/refractory solid tumours, following a single intravenous dose of LEU011 after preconditioning chemotherapy. Additional information on the AERIAL trial can be found on ClinicalTrials.gov under the identifier NCT06193902.

Details of the ongoing AERIAL trial were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2025.

Poster Title: A First-in-human Phase I/IIa dose escalation trial evaluating the safety and preliminary efficacy of LEU011, a novel CAR-T, in subjects with relapsed/refractory solid tumors (AERIAL)
Author / Presenter: R. Kristeleit
Session: Clinical Trials In Progress
Date: Saturday, November 8, 2025
Abstract Number: 578

About LEU011
LEU011 is a lateral CAR-T cell therapy targeting NKG2D stress ligands, which are overexpressed on more than 80% of human tumour cells and the cells within the surrounding tumour microenvironment. In addition to its novel architecture, LEU011 also co-expresses the chemokine receptor CXCR2 which is engineered to enhance cell trafficking and tumour infiltration, providing an extra mechanism to overcome significant limitations of CAR-T therapies currently in development for the treatment of relapsed/refractory solid tumours.

(Press release, Leucid Bio, NOV 10, 2025, View Source [SID1234659747])

Akeso Announces First Patient Dosed in Phase I Trial of Personalized mRNA Vaccine AK154 as Monotherapy or in Combination with Cadonilimab or Ivonescimab for Adjuvant Treatment of Pancreatic Cancer

On November 10, 2025 Akeso, Inc. (HKEX: 9926. HK) reported that the first patient has been dosed in a Phase I clinical trial evaluating the personalized mRNA vaccine AK154. This trial is investigating AK154 both as a monotherapy and as a combination with the company’s first-in-class bispecific antibodies, cadonilimab (PD-1/CTLA-4) and ivonescimab (PD-1/VEGF), for the adjuvant treatment of pancreatic cancer following surgical resection.

AK154 is Akeso’s first mRNA-based therapeutic candidate to enter clinical development. This achievement marks a significant breakthrough for the company in the field of mRNA technology, following its established leadership in multi-specific antibodies, and entry into the clinic for its antibody-drug conjugates (ADCs).

AK154 is a personalized neoantigen vaccine developed by Akeso using its mRNA platform. It designs sequence-specific mRNA vaccines by sequencing tumor tissue and identifying immunogenic mutations with high affinity. This approach aims to overcome the "cold tumor" phenotype seen in pancreatic cancer.

AK154 shows a synergistic therapeutic effect with Akeso’s bispecific antibodies in enhancing anti-tumor immunity. Preclinical data demonstrated strong immunogenicity, potent anti-tumor activity, and a favorable safety profile. The combination of AK154 with cadonilimab or ivonescimab offers potentially promising new therapeutic options for pancreatic cancer patients.

(Press release, Akeso Biopharma, NOV 10, 2025, View Source [SID1234659746])

Vascarta and CUNY Report Preclinical Breakthrough in Glioblastoma Treatment

On November 10, 2025 Vascarta Inc., a healthspan focused, clinical stage biopharmaceutical company advancing safe, patient friendly therapies for pain, inflammation, and, in collaboration with the City University of New York (CUNY), reported the publication of a preclinical study demonstrating that STO-1, a first-in-class drug candidate, can selectively eliminate glioblastoma (GBM) cells in mice while avoiding harmful autoimmune reactions.

STO-1 is a proprietary hybrid molecule in which curcumin is linked to paclitaxel with a linker that gets broken when STO-1 enters a cell. In the study, mice treated with STO-1 experienced a 67% long-term survival rate, with several animals achieving complete tumor clearance. The therapy works in part by reprogramming deactivated tumor-associated immune cells to attack the tumor, while leaving healthy immune function intact. This minimizes the prospect of undesirable side effects often seen with immunotherapies.

Dr. Probal Banerjee, the senior author and Professor, Biochemistry, Biology, Neuroscience, Chemistry at the College of Staten Island, CUNY, said:
"Unlike other immune therapies, which can trigger dangerous autoimmune reactions, STO-1 targets only the tumor-associated cells. This study demonstrates a promising new approach to treating glioblastoma safely."

Dr. Richard Prince, Chairman, Chief Executive and President, Vascarta, stated:
"These results highlight the potential of STO-1 to offer a safe and effective option for patients with glioblastoma without the side effects."

(Press release, City University of New York, NOV 10, 2025, View Source [SID1234659745])