Picture

Define the Injection Parameters

Commence 14 month long sequential study in three primates starting November. The milestone here is to define the injection parameters (concentration and volume of vector and number spacing of injections across the cortex) needed to delete PTEN in an area 1CM by 1CM. A no-go decision would come if injections of the vector into non-human primates led to tumors, seizures, paralysis, motor symptoms such as tremor or ataxia, neurodegeneration or neuropathology in the cortex. Note that this is “proof of biological action”, not an efficacy study.

November 2017
Picture

Lease incubator space

Lease incubator space near UC Irvine to develop the actual therapeutic candidate (an AAV vector with neurotropism for cortical motoneurons that lacks the fluorescent reporter present in the vectors used in experimental animals). The specific properties of the vector would be defined in the first pre-pre IND (investigational new drug) meeting with the FDA. A no-go decision would come if the discussion with the FDA indicated the need for safety testing in primates beyond a 2 year survival. In this case, the no-go decision is based on a financially unacceptable timeline for product development.

2017
Picture

Process Primate Study Tissue

Process tissue from primate study in Dr. Steward’s laboratory (6-9 months depending on whether additional processing is required if pathology is detected or suspected).

2018
Picture

Pre-Pre IND with the FDA

Hold pre-pre IND meeting with the FDA to begin to define the type of efficacy and safety data that would be required for the pre-IND meeting. An important question here is whether efficacy studies in primates will be required.  A requirement for efficacy studies in primates will extend the development period for at least 2 years.  Note also that the initial round of funding ($1.5million) is not sufficient to carry out efficacy studies in primates.  An additional $2-$3million would be required depending on the survival interval that the FDA would demand.

2018
Picture

Safety and Efficacy Consultants

Contract with regulatory consultants to define what would be needed in terms of safety and efficacy data for a pre-pre-IND meeting with the FDA.

2018
Picture

Present Safety and Efficacy Data to FDA pre-IND

Providing that efficacy studies in primates are NOT required, present safety and efficacy data to the Food and Drug Administration in pre-IND (investigational new drug) meeting

2019
Picture

FDA Recommendations

Incorporate FDA recommendations and conduct further experiments as necessary

2019
Picture

Contract Research Organization

Engage contract research organization (CRO) to carry out required studies identified in the pre-IND meeting (likely to include tox screening, bio-distribution tumorogenicity and long-term safety studies).

2019
Picture

FDA Investigational New Drug Application

File IND (Investigational New Drug) application with the FDA

2020
Picture

Early Stage Clinical Trial Approval

Receive FDA approval for early stage clinical trial (type of trial, inclusion/exclusion criteria number of subjects, test sites, etc. to be defined in the Pre-IND discussions with the FDA).

2020
Picture

Treatment Sites and Budget

Identify eligible sites for treatment and develop budget for the initial clinical trial.

2020
Picture

Fund Clinical Trial

Raise funds for the clinical trial (approximately $20-25 million for a phase I trial).

2020
Picture

Clinical Trial Enrollment Begins

Begin subject enrollment.

2020