KLARA CZOBOR: Can you please provide us with a brief background about yourself and how you came to be the CEO of ContraVir Pharmaceuticals?
JAMES SAPIRSTEIN: Okay. I’m a pharmacist with an MBA, and for my first 17 years in the industry, I worked in large pharmaceutical companies including Eli Lilly, Hoffmann-LaRoche, and Bristol-Myers Squibb, in a variety of positions exclusively on the commercial side. I then decided to go to a smaller pharmaceutical company and moved to Gilead where I was in the Global Marketing Group. We launched their flagship product, Viread, for HIV infection.
I was then recruited to EMD Serono as a General Manager, Executive Vice President, running the U.S. metabolic and endocrinology group. I then decided to “branch out on my own” and went into the Venture Capital world where I founded a company called Tobira Therapeutics. I was the CEO there for close to five years. It’s since been sold to Allergan.
And then, I was with another small company called Alliqua BioMedical, which I brought up to NASDAQ. We turned Alliqua into a wound care company, and at that point, I decided to leave and join ContraVir Pharmaceuticals. ContraVir is now also on NASDAQ. We’re a virology company. We have a product to treat post-herpetic neuralgia (shingles-related pain), and that’s in Phase 3. We also have two other compounds to treat hepatitis B, one is TXL, which was originally known as CMX-157, which I licensed from Chimerix. The other compound is called CRV-431, which is a cyclophilin antagonist that I licensed from a Canadian company called Ciclofillin.
KLARA CZOBOR: Great, wow, that’s quite impressive. And currently, who would you say are the key members of ContraVir? How big is the company and who do you work with on a daily basis?
JAMES SAPIRSTEIN: We have about 21 full-time employees right now, and we’ve probably got another 6 or 7 consultants that we basically work with on a full-time basis. We have two laboratories or spaces. One is in Edmonton, Canada, and one is in Doylestown, Pennsylvania, the home of the Hepatitis B Foundation.
My key people are my Chief Medical Officer, John Sullivan-Bolyai, MD, MPH, our Chief Scientific Officer, Robert Foster, PharmD, PhD, John Cavan, our CFO, and Terry Matkovits, PhD who is our Executive Vice President in charge of product development; Clinical Operations and Regulatory report to her.
KLARA CZOBOR: Sure, great. And can you please outline the business goals for ContraVir?
JAMES SAPIRSTEIN: Well, our goals are to quickly develop all our compounds. So, for valnivudine, which is our shingles product, we’re looking for a partner for that compound. We’re in Phase 3. The FDA has been great to work with in the development of this compound. We think there’s a market but we’re looking for a partner, a global partner to form a commercial force to launch.
TXL and CRV-431 are two products of what we hope will form the basis of a functional cure for hepatitis B. We believe that multiple products will have to be used to cure hepatitis B, and we certainly have two of them at this point. We believe TXL will be used as backbone therapy for all hepatitis B cure opportunities.
KLARA CZOBOR: Sure. And so, regarding valnivudine, you mentioned that you’re looking for a partner. Are you currently in talks with anyone?
JAMES SAPIRSTEIN: Yes, we are in discussions with several parties. We hope that we can get a deal done before the year is out.
KLARA CZOBOR: Sure. And just for clarification, are the Phase 3 trials already underway?
JAMES SAPIRSTEIN: Yes, we’re in the middle of the Phase 3 trials. In fact, the FDA may accept the results of one trial for approval; we’ll see. It really depends on the results of that trial. But it’s a large trial; it’s 825 patients. Patients are followed for 120 days. So, it’s a fairly intensive trial, and we’re hoping that it’s going to generate the data needed for approval.
KLARA CZOBOR: Sure, great. And just a little bit more about valnivudine, how does it address the unmet need in the treatment of shingles?
JAMES SAPIRSTEIN: Well, valnivudine competes directly with the market leader, which is Valtrex (valacyclovir). Valtrex is a pan-herpetic, meaning it resolves herpes simplex-1 and herpes simplex-2, and it’s not specific for herpes zoster.
Valnivudine is very specific for herpes zoster, and its onset of action is faster than Valtrex, which is why we believe valnivudine reduced the post-herpetic neuralgia pain. Valnivudine works at the site of infection where the virus lives, which is in the spine near the nerve endings. The onset of action is faster and we need less drug to effectively get a result.
We are currently working with both the virology division and the pain division of the FDA and hope to become the first antiviral ever to be approved for post-herpetic neuralgia pain.
KLARA CZOBOR: Sure. Could you please outline the Phase 2 clinical study in post-herpetic neuralgia and its status?
JAMES SAPIRSTEIN: So, in our Phase 2 study of 350 patients, we studied 400 mg once a day (QD) and 200 mg twice a day (BID) of valnivudine versus valacyclovir 1 g three times a day (TID). The patients received one week of therapy, and they were followed for 90 days.
We showed that the valnivudine 400 mg QD arm had a 39% reduction in post-herpetic neuralgia pain. Both valnivudine arms combined, the 200 mg BID and the 400 mg QD, showed an 8-10% reduction in narcotic use as well.
For the Phase 3 trial of 825 patients, we doubled the dose of valnivudine. We went from 200 mg BID to 400 mg BID versus 400 mg QD, versus valacyclovir 1 g TID. The reason for the change in valnivudine dose is that we realized in Phase 2 that we had linear pharmacokinetics, and we thought we might be able to achieve a greater than 50% result in post-herpetic neuralgia relief, and so that’s the way we’ve designed the Phase 3 trial.
So, the primary endpoint is the percentage of patients with post-herpetic neuralgia pain, and the secondary endpoint is an onset of action comparatively.
KLARA CZOBOR: Sure, great. And what is the anticipated timeline for the market introduction of valnivudine? And what will be the possible market competitors to this product?
JAMES SAPIRSTEIN: Well, we’re hoping to get valnivudine into the market by the end of 2020 or early 2021, as long as things go as planned. And the competitor will continue to be Valtrex because right now, when a patient gets shingles or is diagnosed with shingles, they’re put on Valtrex with Tylenol or Advil or sometimes a narcotic.
So, once valnivudine is approved, we’re hoping that physicians will prescribe it with much less pain relief additives, which will help reduce the overall cost for the patient, and also reduce the amount of medication they have to take, including possibly addictive drugs.
KLARA CZOBOR: Sure. And are you anticipating any clinician and payer challenges when bringing valnivudine to market? And how will you be addressing those challenges?
JAMES SAPIRSTEIN: Well, we did some payer research, and we do know that for tier one, if you’re priced below $800, and as long as you can substitute your drug out for another drug, there’s really not a lot of pushback for the payers. Our drug is not going to be expensive. We’re hoping to bring it into a price point between $400-475 for a prescription, and that would substitute for two drugs.
Right now, the people who suffer from severe forms of post-herpetic neuralgia pain, they’ll take, besides narcotics, some Lyrica, and some other drugs. It costs about $2,000 a month. Now, some of these patients suffer for three months, and some can suffer for as long as two years.
If we can cut down on the use of additional drugs then that would be a cost savings for managed care. And certainly, if we can just improve the quality of life at a price point of less than $800, then that’s something of value for the managed care groups.
KLARA CZOBOR: Sure. When do you anticipate getting the next round of exciting data for valnivudine, and which medical conferences will you be presenting at this Fall?
JAMES SAPIRSTEIN: Well, with valnivudine, the big data endpoint is going to be is our Phase 3 data. And until we know when we’re finishing the study, we haven’t selected a conference. Once we know the timing of when the study will be completed, we’ll present at one of the larger conferences such as the Infectious Diseases Society of America (IDSA) meeting.
KLARA CZOBOR: Right. And regarding manufacturing, are you considering or are you developing a manufacturing facility to enable the production of clinical batches of valnivudine?
JAMES SAPIRSTEIN: No. We will outsource that. We’re not going to develop manufacturing capabilities. It’s too expensive. We’re a micro-cap company that must raise funds, and 90% or more of those funds go into clinical research.
KLARA CZOBOR: Right. Absolutely. And do you think that the manufacturing will take place in the U.S. or ex-U.S.? Is that something you know already?
JAMES SAPIRSTEIN: Yes, the manufacturer is actually ex-U.S.
Part 2 of this interview will be made available this time next week, where we will talk with James Sapirstein about the company’s portfolio of novel compounds against hepatitis B, including TXL™, a highly potent prodrug of the antiviral tenofovir (active component of both Vemlidy® and Viread®), now in Phase 2 trials, and CRV431, a next generation cyclophilin inhibitor advancing into clinical development. Stay tuned!