LY3884963 / Eli Lilly - LARVOL DELTA

Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Prevail Therapeutics | Trial completion date: Aug 2029 ➔ Apr 2030 | Trial primary completion date: Aug 2029 ➔ Apr 2030

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN

Bridging HEK293-Produced and Sf9-Baculovirus-Produced AAV Gene Therapy in the Clinic – Evaluation of PR006 (LY3884963), an Investigational AAV9-GRN Gene Therapy for Frontotemporal Dementia Patients with GRN Mutations (ESGCT 2024) - No abstract available

Clinical • Gene therapy • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • GRN

Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2 | N=30 | Recruiting | Sponsor: Prevail Therapeutics | N=23 ➔ 30

Enrollment change • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN

Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results. (PubMed, Nat Med) - P1/2 | "Longer follow-up and additional studies are needed to confirm the safety and potential efficacy of PR006. ClinicalTrials.gov identifier: NCT04408625 ."

Gene therapy • Journal • P1/2 data • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Hematological Disorders • Inflammation • Thrombosis • Venous Thromboembolism • GRN • NEFL

PR006A GENE THERAPY INCREASES PROGRANULIN LEVELS AND IMPROVES FTD-GRN RELATED PHENOTYPES IN AN IN VITRO AND AN IN VIVO MODEL (ADPD 2024) - "PR006A treatment was well tolerated and without adverse findings in mouse and non-human primate studies and demonstrated efficacy in human in vitro and mouse in vivo models of FTD-GRN. PR006A is currently being studied in the Phase 1/2 PROCLAIM clinical trial."

Gene therapy • Preclinical • Gene Therapies • Inflammation • Targeted Protein Degradation • CTSD • GRN • TARDBP

Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Prevail Therapeutics | Trial completion date: Sep 2027 ➔ Dec 2027 | Trial primary completion date: Sep 2027 ➔ Dec 2027

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • NEFL

Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2; N=15; Recruiting; Sponsor: Prevail Therapeutics; Trial completion date: Dec 2027 ➔ Sep 2027; Initiation date: Jul 2020 ➔ Nov 2020; Trial primary completion date: Dec 2027 ➔ Sep 2027

Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • MRI

Eli Lilly Snaps Up Gene Therapy Company Prevail Therapeutics in $1.04 Billion Deal (BioSpace) - "Shares of Prevail Therapeutics have skyrocketed more than 84% in premarket trading after Eli Lilly announced it was acquiring the gene therapy company in a deal valued at approximately $1.04 billion. Since the deal was announced, Prevail’s stock has nearly doubled to $23 per share, higher than the tender offer of $22.50."

M&A • Stock price • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease • Tauopathies And Synucleinopathies

Lilly Announces Agreement to Acquire Prevail Therapeutics (Prevail Therapeutics Press Release) - "Eli Lilly and Company (NYSE: LLY) and Prevail Therapeutics Inc. (NASDAQ: PRVL) today announced a definitive agreement for Lilly to acquire Prevail...The CVR is payable (subject to certain terms and conditions) upon the first regulatory approval of a product from Prevail's pipeline....Prevail's lead gene therapies in clinical development are PR001 for patients with Parkinson's disease with GBA1 mutations (PD-GBA) and neuronopathic Gaucher disease (nGD) and PR006 for patients with frontotemporal dementia with GRN mutations (FTD-GRN). Prevail's preclinical pipeline includes PR004 for patients with specific synucleinopathies, as well as potential gene therapies for Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders."

M&A • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease • Tauopathies And Synucleinopathies

Lilly (LLY) to Acquire Prevail Therapeutics (PRVL) for $22.50 Per Share Plus $4 Per Share CVR (Streetinsider.com) - "Eli Lilly and Company (NYSE: LLY) and Prevail Therapeutics Inc. (NASDAQ: PRVL) today announced a definitive agreement for Lilly to acquire Prevail for $22.50 per share in cash...The CVR is payable (subject to certain terms and conditions) upon the first regulatory approval of a product from Prevail's pipeline as set forth in more detail below."

M&A • CNS Disorders • Frontotemporal Lobar Degeneration

".@LillyPad firmly steps into #GeneTherapy vs #neurodegenerative diseases, acquiring @PrevailTx for $1B Leads incl PR001 vs #GBA1-mutant #Parkinson’s & neuronopathic #Gaucher; PR006 vs #GRN-mutant #frontotemporal #dementia https://t.co/YiEJVqjf9J #neuroscience #FTD @TenBridge" (@DDNewsOnline)

Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Movement Disorders • Parkinson's Disease

Prevail Therapeutics Announces First Patient Dosed in Phase 1/2 PROCLAIM Clinical Trial Evaluating PR006 for the Treatment of Frontotemporal Dementia Patients with GRN Mutations (GlobeNewswire) - "Prevail Therapeutics...today announced that the first patient has been dosed in the Phase 1/2 PROCLAIM clinical trial evaluating PR006, an investigational AAV9 gene therapy delivering the GRN gene, for the treatment of frontotemporal dementia patients with GRN mutations (FTD-GRN)….The Company expects to enroll up to 15 patients, and it currently anticipates it will provide a biomarker and safety analysis on a subset of patients enrolled in the PROCLAIM trial in 2021."

Enrollment status • P1/2 data • Trial status • CNS Disorders • Frontotemporal Lobar Degeneration

Prevail Therapeutics Receives European Commission Orphan Designation for PR006 for the Treatment of Frontotemporal Dementia (GlobeNewswire) - "Prevail Therapeutics...today announced that the European Commission has granted orphan designation for PR006 for the treatment of frontotemporal dementia (FTD)….The U.S. Food and Drug Administration has also granted Orphan Drug designation for PR006 for the treatment of FTD and Fast Track designation for FTD-GRN."

Orphan drug • CNS Disorders • Frontotemporal Lobar Degeneration

Prevail Therapeutics Reports Third Quarter 2020 Financial Results and Business Highlights (GlobeNewswire) - "Patient Dosing Continues in the Phase 1/2 PROPEL Trial of PR001 for Parkinson’s Disease with GBA1 Mutations...The Company expects to provide the next biomarker and safety analysis on a subset of patients in the PROPEL trial by mid-2021....Phase 1/2 PROCLAIM Trial Expected to Initiate Enrollment in Fourth Quarter of 2020: Initiation of patient enrollment remains on track for the fourth quarter of 2020 for the Phase 1/2 PROCLAIM clinical trial of PR006 for frontotemporal dementia with GRN mutations (FTD-GRN)....The Company currently anticipates it will provide a biomarker and safety analysis on a subset of patients in the PROCLAIM trial in 2021."

Biomarker • Enrollment status • P1/2 data • Trial status • CNS Disorders • Frontotemporal Lobar Degeneration • Parkinson's Disease

Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2; N=15; Recruiting; Sponsor: Prevail Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Prevail Therapeutics Reports Second Quarter 2020 Financial Results and Business Highlights (GlobeNewswire) - "PROCLAIM Trial of PR006 for FTD-GRN Scheduled to Initiate Enrollment in Second Half of 2020: Study startup activities are also continuing for the PROCLAIM Phase 1/2 clinical trial of PR006 for FTD-GRN patients....R&D expenses were $12.9 million for the second quarter of 2020, compared to $12.0 million for the second quarter of 2019. The increase was primarily due to an increase of $2.6 million in direct clinical trial costs related to the PROPEL, PROVIDE, and PROCLAIM clinical trials and other trial startup costs and a $1.8 million increase in employee-related costs."

Commercial • Trial initiation date • CNS Disorders • Frontotemporal Lobar Degeneration

Prevail Therapeutics Granted Composition of Matter Patent for Experimental Gene Therapy Program PR006 (Streetinsider.com) - "Prevail Therapeutics...today announced that the United States Patent and Trademark Office (USPTO) on June 23, 2020 issued a composition of matter patent, U.S. Patent No. 10,689,625, with claims directed to the AAV vector used in PR006...for the treatment of frontotemporal dementia patients with GRN mutations (FTD-GRN). The base patent term extends until October 2038, excluding patent term extensions or coverage in additional related patent filings."

Patent • CNS Disorders • Frontotemporal Lobar Degeneration

[VIRTUAL] Design of a Phase 1/2 Study of an AAV9-Based Gene Therapy for Fronto-Temporal Dementia Patients with Pathogenic GRN Mutations (PROCLAIM Trial) (AAIC 2020) - "PROCLAIM will assess dose, safety, tolerability, biomarker and efficacy effects of PR006 and inform its further clinical development."

Clinical • P1/2 data • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • MRI

[VIRTUAL] Preclinical development of PR006, a gene therapy for the treatment of frontotemporal dementia with progranulin mutations (AAIC 2020) - "These in vitro and in vivo preclinical studies demonstrated that PR006 effectively increased expression of progranulin and reduced pathological features of FTD-GRN, supporting clinical development of PR006 for patients with this disease."

Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Immunology • Targeted Protein Degradation • CTSD

Prevail Therapeutics to Highlight Multiple Gene Therapy Programs for Neurodegenerative Diseases at the Virtual 2020 Alzheimer’s Association International Conference (GlobeNewswire) - "Prevail Therapeutics...announced three upcoming poster presentations at the Alzheimer’s Association International Conference (AAIC) 2020. These data underscore the robust preclinical evidence in support of Prevail’s AAV-based gene therapy approach, and highlight the Company’s strategy to validate these data in the planned PROCLAIM clinical trial evaluating PR006 for the treatment of frontotemporal dementia patients with GRN mutations (FTD-GRN). The conference will be held virtually July 27-31, 2020....PR001: These data provide the basis for the Company’s clinical trials for Type 2 neuronopathic Gaucher disease (nGD) patients and Parkinson’s disease with GBA1 mutations (PD-GBA) patients."

Clinical protocol • Preclinical • CNS Disorders • Frontotemporal Lobar Degeneration • Gaucher Disease • Genetic Disorders • Parkinson's Disease

Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2; N=15; Not yet recruiting; Sponsor: Prevail Therapeutics

Clinical • New P1/2 trial • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Prevail Therapeutics Reports First Quarter 2020 Financial Results and Business Highlights (GlobeNewswire, Prevail Therapeutics) - "Clinical Development of PR001: Prevail now expects patient screening to resume by the end of the second quarter of 2020 at certain clinical sites. The Company remains on track to report interim data on a subset of patients in the second half of 2020....In addition, study startup activities are continuing for the PROVIDE Phase 1/2 clinical trial of PR001 for Type 2 nGD....Clinical Development of PR006: Study startup activities are also underway for the PROCLAIM Phase 1/2 clinical trial of PR006 for FTD-GRN patients, which is planned to initiate in mid-2020, subject to any delays related to the COVID-19 pandemic."

P1/2 data • Trial status • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Parkinson's Disease • Tauopathies And Synucleinopathies

Prevail Therapeutics to Highlight Multiple CNS-Focused Gene Therapy Programs at 2020 American Society of Gene & Cell Therapy Annual Meeting (GlobeNewswire, Prevail Therapeutics) - "Prevail Therapeutics Inc....today announced two upcoming oral presentations and two poster presentations at the virtual 2020 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting....Prevail will highlight the design of the planned PROVIDE Phase 1/2 trial for the treatment of Type 2 neuronopathic Gaucher disease (nGD) patients and preclinical data demonstrating the impact of PR001 treatment on key disease biomarkers and functional parameters. These data provide the basis for the company’s clinical programs in nGD and Parkinson’s disease with GBA1 mutations (PD-GBA).....Prevail will present the design of the PROCLAIM Phase 1/2 clinical trial for the treatment of frontotemporal dementia patients with GRN mutations (FTD-GRN) and preclinical data..."

Clinical • Clinical protocol • Preclinical • CNS Disorders • Dementia • Parkinson's Disease • Tauopathies And Synucleinopathies • Type 1 Gaucher Disease

[VIRTUAL] PR006 GENE THERAPY IMPROVES FTD-GRN PHENOTYPES IN MODEL SYSTEMS BY INCREASING PROGRANULIN LEVELS (AAT-ADPD 2020) - "In addition, PR006 effectively reduced lipofuscin accumulation throughout the brain, as well as the expression of both proinflammatory cytokines and immune cell activation markers in the cerebral cortex. Conclusions PR006 administration resulted in expression of progranulin that ameliorated FTD‑GRN‑related phenotypes in vitro and in vivo, supporting further development of PR006 for patients with FTD‑GRN."

CTSD

Prevail Therapeutics to present at AAT-AD/PD Focus Meeting 2020: Advances in Alzheimer’s and Parkinson’s therapies (GlobeNewswire) - "Prevail Therapeutics Inc....today announced three upcoming presentations at the AAT-AD/PD Focus Meeting 2020: Advances in Alzheimer’s and Parkinson’s Therapies, taking place virtually April 2-5, 2020....The presentations include information about Prevail’s PR001 program for Parkinson’s disease patients with GBA1 mutations (PD-GBA), and Prevail’s PR006 program for frontotemporal dementia patients with GRN mutations (FTD-GRN); Design of PROPEL Phase 1/2 Clinical Trial for Parkinson’s Disease Patients with GBA1 Mutations to Be Presented."

Clinical protocol • Preclinical