AB-1005 / Bayer - LARVOL DELTA

AskBio’s AB-1005 and AB-1002 Receive Pioneering Regenerative Medical Product Designation in Japan (The Manila Times)

Japanese regulatory • Congestive Heart Failure • Parkinson's Disease

A Study of AAV2-GDNF in Adults With Moderate Parkinson's Disease (REGENERATE-PD) (clinicaltrials.gov) - P2 | N=127 | Recruiting | Sponsor: AskBio Inc | N=87 ➔ 127 | Trial completion date: Nov 2027 ➔ Aug 2028 | Trial primary completion date: Nov 2027 ➔ Aug 2028

Enrollment change • Trial completion date • Trial primary completion date • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

Clinical Progress and Plans for Aav2GDNF Gene Therapy for Parkinson's Disease (ESGCT 2024) - No abstract available

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

AskBio Inc…announced that the first European participants have been randomized in REGENERATE-PD, a Phase 2 clinical trial in participants with moderate-stage Parkinson’s disease (PD). (GlobeNewswire) - "REGENERATE-PD is estimated to enroll approximately 87 participants across clinical centers in Germany, Poland, the United Kingdom, and the United States."

Trial status • Parkinson's Disease

Phase II gene therapy trial REGENERATE-PD with AB-1005 initiated randomizing participants in United Kingdom and Poland, with Germany following shortly and ongoing in the USA (Bayer Press Release)

Trial status • Parkinson's Disease

AskBio Announces Completion of Enrollment in Phase 1 Clinical Trial of AB-1005 Gene Therapy for Multiple System Atrophy-Parkinsonian Type (MSA-P) (GlobeNewswire)

Enrollment closed • Multiple System Atrophy

Bilateral Putaminal Convection of Adeno-Associated Virus Vector Serotype 2 Glial Cell Line-Derived Neurotrophic Factor Gene Therapy in Parkinson's Disease May Provide Glial Cell Line-Derived Neurotrophic Factor Transgene Expression to Caudate Nucleus: Potential Role of Perivascular and Other Low Resistance Leakage Pathways. (PubMed, Neurosurgery) - "These findings highlight anatomical and perivascular interconnections as potential contributors to off-target dispersion. Although no clinical benefit was observed, this study underscores the potential for targeted caudate transduction with optimized infusion strategies. The results emphasize the need for further exploration of perivascular dynamics and volumetric coverage in future gene therapy trials for Parkinson disease and other central nervous system disorders."

Journal • Preclinical • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

GDNF Gene Therapy for Multiple System Atrophy (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Brain Neurotherapy Bio, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2028 ➔ Aug 2028 | Trial primary completion date: Dec 2025 ➔ Aug 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Gene Therapies • Movement Disorders • Multiple System Atrophy

AskBio Announces Publication of Complete Results of Phase 1b Trial of AB-1005 Gene Therapy in Participants with Parkinson’s Disease in Movement Disorders (GlobeNewswire) - P1b | N=11 | NCT04167540 | Sponsor: Brain Neurotherapy Bio, Inc. | "AskBio Inc...announced today the recent publication of the complete results of its Phase 1b trial of AB-1005, a glial cell line-derived neurotrophic factor (GDNF) investigational gene therapy for the treatment of Parkinson’s disease (PD), in Movement Disorders, an official peer-reviewed journal of the International Parkinson and Movement Disorder Society....The publication, which is available online, states that treatment with AB-1005 was well tolerated with no serious adverse events related to GDNF gene therapy in all 11 participants and is associated with numerical stability in clinical assessment readouts (mild cohort) and improvement (moderate cohort) in clinical assessments of motor function at 18 months post-gene transfer."

P1 data • Movement Disorders • Parkinson's Disease

Intraputaminal Delivery of Adeno-Associated Virus Serotype 2-Glial Cell Line-Derived Neurotrophic Factor in Mild or Moderate Parkinson's Disease. (PubMed, Mov Disord) - "Bilateral intraputaminal AAV2-GDNF gene therapy was well tolerated and associated with numerical stability (mild cohort) and improvement (moderate cohort) in clinical assessments at 18 months posttreatment."

Journal • Preclinical • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

AskBio Receives FDA Regenerative Medicine Advanced Therapy designation for Parkinson’s disease investigational gene therapy (Bayer Press Release) - "AskBio...announced that investigational gene therapy AB-1005 for the treatment of Parkinson’s disease (PD) has been granted Regenerative Medicine Advanced Therapy (RMAT) designation from the United States Food and Drug Administration (FDA)....The FDA determined that AB-1005, an investigational gene therapy intended to slow disease progression and improve motor outcomes in patients with PD, met the criteria for RMAT designation. This decision follows a review of information and data provided by AskBio, including clinical evidence from the open label, uncontrolled study Phase Ib trial of AB-1005. AskBio’s 36-month Phase Ib data showed that the administration of AB-1005 was well tolerated with no product-related serious adverse events."

FDA event • Gene Therapies • Parkinson's Disease

First participants randomized in AskBio Phase II gene therapy trial for Parkinson’s disease (Bayer Press Release) - "AskBio...announced that the first participants have been randomized in its Phase II clinical trial in patients with Parkinson’s disease (PD)....The objective of this randomized, double-blind, Phase II clinical trial is to evaluate the safety and efficacy of AB-1005 delivered to the putamen in adult participants aged 45–75 years with moderate-stage PD. REGENERATE-PD is estimated to enroll approximately 87 participants across clinical centers that are being opened in the United States, Germany, Poland, and the United Kingdom."

Trial status • Parkinson's Disease

AskBio…presented 36-month Phase Ib data at the International Congress of Parkinson’s Disease and Movement Disorders (Bayer Press Release) - P1b | N=11 | NCT04167540 | Sponsor: Brain Neurotherapy Bio, Inc. | "The data demonstrated that administration of AB-1005 was well tolerated with no attributed serious adverse events. The Moderate PD cohort showed trends for improvement or stability on several motor scales at 36 months, including Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and motor diaries, and trends in reductions in Parkinson’s medications (levodopa-equivalent daily dose [LEDD]). Most participants in the Mild PD cohort showed an overall stable clinical status with little change in MDS-UPDRS, the self-reported PD motor diary, or LEDD."

P1 data • Parkinson's Disease

Preliminary Efficacy of Bilateral Intraputaminal Delivery of GDNF Gene Therapy (AAV2-GDNF; AB-1005) in Parkinson’s Disease: 18-Month Follow-Up From a Phase 1b Study (MDS Congress 2024) - "Patients with mild or moderate PD continued to show stability and/or improvement in PD-specific clinical rating scales at 18 months after AAV2-GDNF (AB-1005) delivery. Data from longer-term follow-up will be available and presented Table."

Clinical • Gene therapy • P1 data • CNS Disorders • Parkinson's Disease

REGENERATE-PD: A Phase 2, Randomized, Double-Blind, Surgery-Controlled Study of GDNF Gene Therapy (AAV2-GDNF; AB-1005) for Moderate Stage Parkinson's Disease (MDS Congress 2024) - P2 | "The trial is expected to begin enrollment by mid-2024 (NCT06285643). Study schema"

Clinical • Gene therapy • P2 data • Surgery • CNS Disorders • Parkinson's Disease

AskBio receives FDA Fast Track and MHRA Innovation Passport designations for AB-1005 investigational GDNF gene therapy for Parkinson’s disease (Bayer Press Release) - "Bayer AG and Asklepios BioPharmaceutical, Inc...announced that the United States (U.S.) Food and Drug Administration (FDA) has granted Fast Track Designation for AB-1005, which is being developed for moderate Parkinson’s disease. AB-1005 has also been awarded the Innovation Passport, the United Kingdom Medicines and Healthcare products Regulatory Agency (UK MHRA) innovative medicine designation, for the treatment of Parkinson’s disease."

European regulatory • Fast track • CNS Disorders • Parkinson's Disease

AskBio Initiates Recruitment to its Phase 2 Parkinson’s Disease Trial (Bayer Press Release) - "Asklepios BioPharmaceutical...announced initiation of recruitment to REGENERATE-PD, a Phase 2 clinical study assessing efficacy and safety of AB-1005, an investigational adeno-associated virus 2 (AAV2) glial cell line-derived neurotrophic factor (GDNF) gene therapy for the treatment of moderate-stage Parkinson’s disease....REGENERATE-PD is a Phase 2, randomized, double-blind, surgery-controlled study of the efficacy and safety of intraputaminal AAV2-GDNF in the treatment of adults (45-75 years) with moderate stage Parkinson's disease."

Trial status • Parkinson's Disease

A Study of AAV2-GDNF in Adults With Moderate Parkinson's Disease (REGENERATE-PD) (clinicaltrials.gov) - P2 | N=87 | Recruiting | Sponsor: Asklepios Biopharmaceutical, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Surgery • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease. (PubMed, Mov Disord) - "After AAV2-GDNF infusion, infused putaminal regions showed increased GDNF gene expression, tyrosine hydroxylase immunoreactive sprouting, catechol levels, and 18F-FDOPA-PET signal, suggesting the regenerative potential of AAV2-GDNF in PD."

Journal • CNS Disorders • Gene Therapies • Infectious Disease • Movement Disorders • Parkinson's Disease • Pneumonia • Respiratory Diseases

Transcriptomic Analysis of GDNF Treatment in MPTP Rhesus Monkeys (ASGCT 2024) - "Group 1 received a striatal Convection Enhanced Delivery (CED) of either AAV2-GDNF (n=2) or PBS (n=1) and was followed for one month...Bioinformatics analysis using Ingenuity Pathway Analysis demonstrated several significant pathways among the common shared upregulated differentially expressed genes based on MPTP doses and the different observational time points. In summary, this study provides clearer insight into the biological mechanisms behind GDNF's therapeutic effects in an MPTP-based PD animal model and highlights further areas of research."

Omic analysis • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

AskBio presents 18-month Phase Ib trial results of AB-1005 gene therapy for patients with Parkinson’s disease (Bayer Press Release) - P1b | N=11 | NCT04167540 | Sponsor: Brain Neurotherapy Bio, Inc. | "Bayer AG and Asklepios BioPharmaceutical...presented results from the 18-month Phase Ib clinical trial for AB-1005, an investigational gene therapy for treating patients with Parkinson’s disease (PD). The data were presented at the American Academy of Neurology 2024 Annual Meeting....The study met its primary objective, which was to evaluate the safety of a one-time bilateral delivery of AB-1005 directly to the putamen. Eleven patients were enrolled into two cohorts, Mild stage PD (6 patients) and Moderate stage PD (5 patients)....As of November 3, 2023, 57 nonserious adverse events (AEs) and 6 serious adverse events (SAEs) were reported. Most AEs were transient and were expected perioperative events (<1 month from treatment)....Based on the...results presented, a Phase II trial (REGENERATE PD) has been developed and is expected to begin enrolling in the U.S., EU, and UK later this year."

P1 data • Trial status • Parkinson's Disease

Phase 1b Safety and Preliminary Efficacy of Bilateral Intraputaminal Delivery of AAV2 GDNF (AB-1005) in Participants With Mild or Moderate Parkinson's Disease (AAN 2024) - P1 | "Analysis of this phase 1b trial is ongoing; topline 18-month data will be presented. These preliminary findings suggest AAV2-GDNF is well tolerated in participants with PD, demonstrating general stability of the Mild Cohort and possible clinical benefit in the Moderate Cohort. A phase 2 randomized controlled study is planned to confirm these findings."

Clinical • P1 data • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

A Study of AAV2-GDNF in Adults With Moderate Parkinson's Disease (REGENERATE-PD) (clinicaltrials.gov) - P2 | N=87 | Not yet recruiting | Sponsor: Asklepios Biopharmaceutical, Inc.

New P2 trial • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

AskBio Phase Ib trial of AB-1005 gene therapy in patients with Parkinson’s disease meets primary endpoint (Bayer Press Release) - P1b | N=11 | NCT04167540 | Sponsor: Brain Neurotherapy Bio, Inc. | "Bayer AG and Asklepios BioPharmaceutical, Inc...announced today the completion of the 18-month data collection in the Phase Ib clinical trial for AB-1005 (AAV2-GDNF), an investigational gene therapy for treating patients with Parkinson’s disease (PD)....The study met its primary objective, which was to evaluate the safety of a one-time bilateral delivery of AB-1005 directly to the putamen. Eleven patients were enrolled into two cohorts, Mild stage PD (6 patients) and Moderate stage PD (5 patients), based upon the timing from a PD diagnosis and the severity of their PD symptoms at screening....Planning is underway for a Phase II trial that is expected to begin screening patients in the first half of 2024. The trial design has been harmonized with feedback from U.S. and European health authorities."

New P2 trial • P1 data • CNS Disorders • Parkinson's Disease

AskBio Announces First Patient Randomized in Phase 1 Trial of AB-1005 (AAV2-GDNF) Gene Therapy for Multiple System Atrophy-Parkinsonian Type (MSA-P) (PRNewswire) - "Asklepios BioPharmaceutical, Inc...wholly owned and independently operated as a subsidiary of Bayer AG, today announced that the first patient has been randomized at the Ohio State University Wexner Medical Center in the Phase 1 REGENERATE MSA-101 clinical trial of AB-1005, a gene therapy being developed as a treatment for multiple system atrophy-parkinsonian type (MSA-P)....AB-1005 is also currently being investigated for the treatment of mild to moderate Parkinson's disease with the enrollment of the Phase 1b study having now been completed."

Enrollment closed • Trial status • CNS Disorders • Multiple System Atrophy • Parkinson's Disease