Meet The Investigator

Posted on at October 5, 2017
7951 1,885

NAME: Steven Hersch

CURRENT POSITION: Professor of Neurology, Harvard Medical School, Boston, MA, USA; Senior Director for Clinical Development, Voyager Therapeutics, Cambridge, MA, USA

EDUCATION: PhD, Boston University, Boston, MA, USA; MD, Boston University School of Medicine, Boston, MA, USA; Residency, Emory University Hospital, Atlanta, GA, USA; Fellowship, Emory University Hospital and Wesley Woods Geriatric Hospital, Atlanta, GA, USA

Dr. Steven Hersch, professor of neurology at Harvard Medical School and senior director for clinical development at Voyager Therapeutics, speaks with HD Insights about the HD therapies he is pursuing through his work with Voyager Therapeutics.


HD INSIGHTS: Today, we have the pleasure to speak to Dr. Steven Hersch, who is the senior director for clinical development at Voyager Therapeutics, as well as a professor of neurology at the Harvard Medical School. Dr. Hersch, thanks very much for joining us.

HERSCH: Thanks.

HD INSIGHTS: Can you tell us about Voyager Therapeutics?

HERSCH: Voyager was started about three years ago, and it brought together some real all-stars and intellectual property related to vector engineering and neuroscience, as well as experience in delivery, particularly to the central nervous system. The goal of the company was to leverage all that expertise to work in neuroscience, with neurodegenerative diseases being of special interest. The company started with a PD program that has been moving forward very well. That is a program that uses AAV as a gene therapy to provide AAVC to the striatum in patients with advanced PD.

HD INSIGHTS: Can you tell us about Voyager’s therapeutic approach to HD?

HERSCH: HD was one of the preclinical programs that the company decided to invest in, and I started consulting for them a couple of years ago and worked with them on preclinical aspects of the program, as well as on developing a clinical approach and strategy.

The work has gone very well in terms of developing the approaches to delivery and to selecting a candidate microRNA, which is the actual compound that is intended to reduce the expression of the huntingtin protein in the brain.

HD INSIGHTS: Voyager recently announced that it had selected its lead candidate for RNA silencing for HD. Can you tell us about that compound?

HERSCH: I would just say that it is a non-alio selective microRNA that potently knocks down huntingtin expression. It is currently being looked at preclinically to establish its safety profile, and to work on aspects of its delivery.

HD INSIGHTS: As I understand it, the therapeutic approach would involve a one-time surgical injection of the therapy into the brain of HD patients. Can you tell us about that approach, its benefits and limitations?

HERSCH: As you know, gene therapy is constituted as a one-time treatment that is applied to the brain. One of the major challenges of gene therapy is to obtain sufficient distribution to have clinical benefit.

HD is a systems neurodegeneration, and there is not any part of the HD brain that the therapy would not be good to treat. So, the question is, how much of the brain can be reached with a vector that is delivered by intraparenchymal infusion?

HD INSIGHTS: Other companies seem to be taking similar approaches to gene-silencing treatments, including Wave, Sparks Therapeutics, and Ionis. Can you briefly compare or contrast your approach to others?

HERSCH: Ionis and Wave are using antisense oligonucleotides, which are introduced intrathecally to the CSF. Because of that delivery technique, the antisense oligonucleotides are best able to reach the surface of the brain, particularly the cortex, but they have more difficulty reaching deeper structures of the brain, such as the basal ganglia. They also must be applied repeatedly, although hopefully not too frequently.

The gene therapies that are under development by UniCure and Spark, as well as Voyager, are one-time treatments that need not be repeated, but they are most likely to require intraparenchymal infusion, initially at least. The difficulty is getting sufficient distribution to the brain to produce a clinical benefit. One of the ways to improve that distribution is to use capsids that can be more widely distributed in the brain than the immediate location where the infusion is made.

HD INSIGHTS: Can you tell us about your timeline, such as when you expect to see your therapy for HD entering clinical trials?

HERSCH: Voyager is currently working on optimizing certain aspects of delivery, and we anticipate continuing through this year, and being able to move that work into preclinical toxicology studies in 2018.

HD INSIGHTS: Voyager has recently announced collaborations with Sanofi Genzyme and CHDI Foundation to help develop your therapies for HD. Can you tell us about those partnerships?

HERSCH: Voyager has a broad collaboration with Sanofi Genzyme on multiple programs. In fact, the HD program originated at Sanofi Genzyme with some of the science there, and so we have a very active collaboration with scientists at Sanofi on the program, particularly on preclinical studies and animal models. Sanofi has the option to continue to partner with Voyager, depending on the program reaching certain milestones.

HD INSIGHTS: And your partnership with CHDI?

HERSCH: The CHDI partnership on this project began with Sanofi Genzyme and, as Voyager took the lead on the program, that collaboration essentially transferred to Voyager, and we have been working very closely on many aspects of the program.

HD INSIGHTS: You have been a leader in HD research for at least the last 20 years. You have an active lab at Harvard Medical School. You were the co-chair of the Huntington Study Group, and you recently accepted a full-time position at Voyager. Can you tell us what attracted you to join Voyager?

HERSCH: As I said, I started consulting for Voyager on a limited time basis, and the more work that I did with Voyager, the more excited I became at the prospects of both gene therapy itself as a treatment option, as well as the program that was developed that I could see developing there. So, I was very excited to join full-time so that I could play a more decisive role in the project.

HD INSIGHTS: When you are not working at Voyager and still working as an academic, how do you like to spend your time?

HERSCH: Going to Martha’s Vineyard with my family or otherwise spending time with my family.

HD INSIGHTS: Steve, many thanks for all your efforts, and for taking time to talk to us about the promising therapies for HD.

HERSCH: Thank you.


About Voyager

Voyager Therapeutics develops gene therapies, from their discovery, to their clinical development, to their commercialization, for people with neurological diseases such as PD and HD.

Voyager is particularly focused on engineering, optimizing, and manufacturing novel adeno-associated virus (AAV) vectors and dosing, including intraparenchymal, intrathecal, and intravenous delivery techniques.

For example, in a June 2017 press release, the company announced the selection of VY-HTT01 as a clinical candidate for the treatment of HD. VYHTT01 comprises an AAV capsid and a proprietary transgene that makes use of the RNA interference pathway to selectively knock down the production of HTT messenger RNA.

“Direct delivery of VY-HTT01 to the brain with a one-time administration could potentially slow or halt the progression of this uniformly fatal disease,” the company states. Preclinical studies of the pharmacology and toxicology of VY-HTT01 are underway with a goal of filing an investigational new drug (IND) application in 2018.

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