AAV-GAD gene therapy / MeiraGTx - LARVOL DELTA

AAV-GAD for the Treatment of Parkinson’s Disease (GlobeNewswire) - "The Company plans to initiate a Phase 3 study of AAV-GAD in the second half of 2025 and will continue to work with the FDA to expedite the development of the program supported by MeiraGTx’s end-to-end in-house manufacturing capabilities."

New P3 trial • Parkinson's Disease

MeiraGTx Granted FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for AAV-GAD for the Treatment of Parkinson’s Disease (GlobeNewswire) - "MeiraGTx Holdings plc...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to AAV-GAD for the treatment of Parkinson’s disease not adequately controlled with anti-Parkinsonian medications....This RMAT was awarded following the presentation to the FDA of positive data from 3 clinical studies demonstrating the benefit of AAV-GAD when administered in a one-time stereotactic infusion to the subthalamic nucleus in the brain. A Phase 1 dose escalating clinical study (n=12) was conducted, followed by a double-blind, sham-controlled Phase 2 study (n=45) and a second randomized, double-blind, sham-controlled dose ranging clinical bridging study (n=14)."

FDA event • Parkinson's Disease

MeiraGTx shares jump on $200M deal with Hologen AI for Parkinson's therapy (Firstwordpharma Press Release) - "...on Thursday following an announcement that the company will partner with Hologen AI to leverage its multimodal generative AI (genAI) models to accelerate Phase III development of the biotech's AAV-GAD gene therapy for Parkinson’s disease...MeiraGTx will receive an upfront cash payment of $200 million from Hologen, and together, the partners will launch a joint venture called Hologen Neuro AI. The genAI firm will also contribute $230 million in funding for the JV, which will shepherd AAV-GAD through development to commercialisation. The capital will help support other early-stage clinical programmes targeting the central nervous system (CNS), such as AAV-BDNF for genetic obesity...MeiraGTx will retain 30% ownership in Hologen Neuro AI and take the lead on all clinical development and manufacturing. It will form exclusive clinical and commercial manufacturing supply agreements with the JV."

Licensing / partnership • Obesity • Parkinson's Disease

MeiraGTx Announces Positive Data from Randomized, Sham-controlled Clinical Bridging Study of AAV-GAD for the Treatment of Parkinson’s Disease (GlobeNewswire) - P1/2 | N=14 | NCT05603312 | Sponsor: MeiraGTx, LLC | "AAV-GAD was safe and well tolerated, with no serious adverse events (SAEs) related to AAV-GAD treatment. At Week 26, a statistically significant 18-point average improvement from baseline in UPDRS Part 3 'off' medication score was demonstrated in the high dose group (p=0.03), with no significant change in the sham or low dose groups...In the high dose AAV-GAD group, the PDQ-39 score improved by 8 points from baseline (p=0.02), the low dose group improved by 6 points from baseline (p=0.04), while the 0.2 point worsening in the sham surgery group was not statistically significant."

P1/2 data • CNS Disorders • Parkinson's Disease

A Double-blind Study to Evaluate the Safety of Glutamic Acid Decarboxylase Gene Transfer in Parkinson's Participants (clinicaltrials.gov) - P1/2 | N=14 | Completed | Sponsor: MeiraGTx, LLC | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

Long-term Follow-up of Glutamic Acid Decarboxylase (GAD) Gene Transfer in Parkinson's Disease (clinicaltrials.gov) - P1/2 | N=14 | Enrolling by invitation | Sponsor: MeiraGTx, LLC | Trial completion date: May 2028 ➔ Oct 2029 | Trial primary completion date: May 2028 ➔ Oct 2029

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

A Double-blind Study to Evaluate the Safety of Glutamic Acid Decarboxylase Gene Transfer in Parkinson's Participants (clinicaltrials.gov) - P1/2 | N=14 | Active, not recruiting | Sponsor: MeiraGTx, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2024 ➔ Aug 2024

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

MeiraGTx Announces Third Quarter 2023 Financial and Operational Results (Yahoo Finance) - "The objective of the AAV-GAD trial (NCT05603312) is to evaluate the safety and tolerability of AAV-GAD when delivered to the subthalamic nucleus (STN) of patients with Parkinson's disease. Completion of enrollment is anticipated in the fourth quarter of 2023."

Enrollment status • CNS Disorders • Parkinson's Disease

Chemogenetic Manipulation of Dopaminergic Activity in Subthalamic Nucleus Compares Favorably to AAV-GAD in Animal Model of Parkinsons Disease (CNS Mission 2023) - No abstract available

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Long-term Follow-up of Glutamic Acid Decarboxylase (GAD) Gene Transfer in Parkinson's Disease (clinicaltrials.gov) - P1/2 | N=14 | Enrolling by invitation | Sponsor: MeiraGTx, LLC

New P1/2 trial • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

MeiraGTx Reports Fourth Quarter and Full Year 2022 Financial and Operational Results (GlobeNewswire) - “AAV-GAD for the Treatment of Parkinson’s Disease: The Company is now dosing patients in the AAV-GAD clinical trial under a new IND using material manufactured in its cGMP facility in London, United Kingdom using MeiraGTx’s proprietary production process….The objective of the AAV-GAD trial (NCT05603312) is to evaluate the safety and tolerability of AAV-mediated delivery of glutamic acid decarboxylase (GAD) gene transfer into the subthalamic nuclei (STN) of participants with Parkinson's disease. Completion of enrollment is anticipated by the third quarter of 2023.”

Enrollment status • CNS Disorders • Parkinson's Disease

A Double-blind Study to Evaluate the Safety of Glutamic Acid Decarboxylase Gene Transfer in Parkinson's Participants (clinicaltrials.gov) - P1/2 | N=14 | Recruiting | Sponsor: MeiraGTx, LLC | Trial completion date: Sep 2023 ➔ Mar 2024 | Trial primary completion date: Sep 2023 ➔ Mar 2024

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

MeiraGTx Reports Third Quarter 2022 Financial and Operational Results and Receives $25 Million Investment from Johnson & Johnson Innovation - JJDC, Inc. (Yahoo News) - "The Company is now dosing patients in the AAV-GAD Phase 1 study under a new IND using material manufactured in its cGMP facility in London, United Kingdom. The objective of the AAV-GAD trial...is to evaluate the safety and tolerability of AAV-mediated delivery of glutamic acid decarboxylase (GAD) gene transfer into the subthalamic nuclei (STN) of participants with Parkinson's disease."

Trial status • CNS Disorders • Parkinson's Disease

A Double-blind Study to Evaluate the Safety of Glutamic Acid Decarboxylase Gene Transfer in Parkinson's Participants (clinicaltrials.gov) - P1/2 | N=12 | Recruiting | Sponsor: MeiraGTx, LLC

New P1/2 trial • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

MeiraGTx Reports Second Quarter 2022 Financial and Operational Results (GlobeNewswire) - "MeiraGTx Holdings plc...announced financial results for the second quarter ended June 30, 2022, and provided an update on recent progress....The Company expects to initiate enrollment in its study of AAV-GAD during the second half of 2022 with material manufactured in its cGMP facility in London, United Kingdom."

Commercial • Trial initiation date • CNS Disorders • Parkinson's Disease

MeiraGTx Reports First Quarter 2022 Financial and Operational Results (GlobeNewswire) - "MeiraGTx Holdings plc...today announced financial results for the first quarter ended March 31, 2022 and provided an update on recent progress....The Company is filing an Investigational New Drug (IND) application in May 2022 with material manufactured in its cGMP facility in London, United Kingdom."

IND • CNS Disorders • Parkinson's Disease

MeiraGTx Reports Fourth Quarter and Full Year 2021 Financial and Operational Results (GlobeNewswire) - "MeiraGTx Holdings plc...today announced financial and operational results for the fourth quarter and full-year ended December 31, 2021, and provided a corporate update....AAV-GAD for the Treatment of Parkinson’s Disease...MeiraGTx anticipates filing an Investigational New Drug application (IND) in the coming weeks, with material that has been manufactured with our proprietary manufacturing process at the MeiraGTx cGMP manufacturing facility in London."

IND • CNS Disorders • Parkinson's Disease

MeiraGTx Reports Third Quarter 2021 Financial and Operational Results (GlobeNewswire) - “Anticipated Upcoming Milestones and Corporate Activities: File an Investigational New Drug (IND) application for AAV-GAD for the treatment of Parkinson’s Disease during the fourth quarter of 2021.”

IND • CNS Disorders • Parkinson's Disease

MeiraGTx Reports First Quarter 2021 Financial and Operational Results (GlobeNewswire) - "AAV-GAD for the Treatment of Parkinson’s Disease: The Company expects to file an Investigational New Drug (IND) application in the third quarter of 2021 with material manufactured from its cGMP facility in London."

IND • CNS Disorders • Parkinson's Disease

MeiraGTx announces acquisition of Vector Neurosciences, gains phase 2 gene therapy program for Parkinson’s disease (GlobeNewswire) - "MeiraGTx Holdings...announced that it has acquired Vector Neurosciences...in an all-stock transaction. As a result of the acquisition, which was signed and closed October 5, 2018, MeiraGTx has expanded its portfolio of clinical stage product candidates to include adeno-associated virus encoding glutamic acid decarboxylase (AAV-GAD), a gene therapy product candidate ready for continued Phase 2 clinical development for Parkinson’s disease."

M&A • Parkinson's Disease

MeiraGTx Reports First Quarter 2020 Financial Results (GlobeNewswire, MeiraGTx) - "During the first quarter of 2020, MeiraGTx remained focused on achieving its most important priorities for patients, including...preparing for the next clinical trial of AAV-GAD for Parkinson’s disease....In response to the COVID-19 pandemic, the Company is working closely with its development partners and clinical sites to implement solutions enabling continuity of study conduct while protecting the health and safety of employees, patients and healthcare providers....MeiraGTx has initiated the process for cGMP-grade AAV-GAD material and expects to file an Investigational New Drug (IND) application in late 2020 or early 2021."

IND • New trial • CNS Disorders • Infectious Disease • Inherited Retinal Dystrophy • Parkinson's Disease

MeiraGTx Reports Full Year 2019 Financial Results (GlobeNewswire, MeiraGTx) - "AAV-GAD for the treatment of Parkinson’s Disease: MeiraGTx anticipates that the Company will file an Investigational New Drug application (IND) in the second half of 2020."

IND

MeiraGTx to Host Parkinson’s Disease R&D Day in New York (GlobeNewswire, MeiraGTx) - "The program will focus on MeiraGTx’s investigational gene therapy candidate AAV-GAD in development for the treatment of Parkinson’s disease. MeiraGTx’s president and CEO, Alexandria Forbes, Ph.D., will be joined by additional members of the senior leadership team, in addition to leading clinicians and researchers, to discuss the current Parkinson’s disease treatment landscape and results from Phase 1 and Phase 2 clinical trials of AAV-GAD."

Clinical data

Knockdown of GADD34 ameliorates ALS in mutant SOD1 mice (Neuroscience 2019) - "...Additional experiments involved intravenous injections of neonatal C57BL/6J mice with AAV:control-shRNA or AAV:GADD34-shRNA followed 81 days later with tunicamycin intracerebroventricular injection to induce ER stress...The results show that GADD34 shRNA is effective in ameliorating disease in mtSOD1 mice, and the feasibility of targeting the UPR/ISR as a therapy in mtSOD1-induced FALS. The results also suggest that the UPR/ISR can be targeted in ALS in general and other neurodegenerative diseases in which misfolded proteins and ER stress have been implicated."

Preclinical

Cellular, Molecular and Non-Pharmacological Therapeutic Advances for the Treatment of Parkinson's Disease: Separating Hope from Hype. (PubMed, Curr Gene Ther) - "...The review covered various gene therapy strategies including Adeno-Associated Virus-Glutamic Acid Decarboxylase (AAV-GAD), AAV-Aromatic L-Amino Acid Decarboxylase (AAV-AADC), Lenti-AADC/Tyrosine Hydroxylase/Guanosine Triphosphate- Cyclohydrolase I (Lenti-AADC/TH/GTP-CH1), AAV-Neurturin (AAV-NRTN), α-Synuclein silencing, and PRKN gene delivery. Also, the advantages, disadvantages, and the results of trials of these methods were discussed. Finally, reasons for the failure of PD treatment were described, with the hopes separated from hypes."

Journal