Part 2
Interview with James Sapirstein, CEO at Contravir, on novel compounds against hepatitis B: TXL and CRV431
September 5, 2017 By Klara Czobor 0
KLARA CZOBOR: Can you talk about what TXL is and how it addresses the unmet need in the treatment of hepatitis B?
JAMES SAPIRSTEIN: Well, TXL is a lipid conjugate of a drug that’s already available, a lipid conjugate of tenofovir. And basically, right now, it’s very early stage for hepatitis B. We know that tenofovir, which is Gilead’s drug, effectively treats hepatitis B. Tenofovir is the backbone of hepatitis B treatment. Gilead actually has two tenofovirs, Viread and Vemlidy.
We are conducting another study right now to improve the formulation of TXL, and then hopefully our new formulation will have improved blood levels versus Gilead’s two drugs, and we’ll be able to use a lower dosage. That’s where we’re hoping to get to.
TXL also stays in the liver longer than Gilead’s two drugs, and we’re trying to figure out exactly what that means. Can we effectively eradicate more ccDNA? Can we eradicate more RNA viral replication by staying in the liver a little longer? These are the questions we are asking. From a lipid conjugate perspective, we do know that TXL is a little bit longer-acting than the Gilead drugs.
We also provide an alternative partnership opportunity to Gilead for other pharmaceutical companies.
KLARA CZOBOR: Okay. Thank you for clarifying that. Can you just outline any ongoing clinical trials for TXL and their status, and when you’re anticipating seeing any data?
JAMES SAPIRSTEIN: Sure. So, we just concluded our Phase 2 trial, which was a proof of concept trial. We will be presenting some more data at AASLD in Washington, D.C. this October. We also have an ongoing “new formulation” trial in healthy volunteers. We hope to see data from this trial by November, and then, we’ll go right into the Phase 2 bridging study and we hope to see data in the first quarter of 2018.
KLARA CZOBOR: Sure. So, I guess your next big data presentation will be at this year’s AASLD?
JAMES SAPIRSTEIN: Yes.
KLARA CZOBOR: Okay, great. I also know that ContraVir are developing CRV-431 for the treatment of hepatitis B. Can you talk a little bit about how this drug candidate differs from TXL?
JAMES SAPIRSTEIN: Sure. It’s actually very different from TXL. CRV-431 attacks the hepatitis B replication cycle while TXL only prevents RNA replication. CRV-431 attacks hepatitis B at a variety of different areas in the cell cycle. It blocks HBx, which is a facilitator that is needed to replicate. It also blocks HBx antigen. We just published that data and it will be talked about further at AASLD.
So really what everyone is looking to see is what happens with HBx, and if we actually are able to prove our hypothesis preclinically and then prove it in the clinic, [/]that might be the “Holy Grail”.[/]
KLARA CZOBOR: Oh, wow, interesting. And can you also talk a little bit about more about the ongoing clinical trial for CRV-431, its status, and when you’re planning on presenting data for this drug?
JAMES SAPIRSTEIN: Yes, so for CRV-431 we’re currently conducting IND-enabling trials. It’s all preclinical. We hope to file the IND by the first quarter of 2018. We have two posters that have been accepted to AASLD. There is another smaller conference coming up in December called HEP DART, where we will also present data.
KLARA CZOBOR: Okay, great. And so, what is the timeline for the clinical development and market introduction of TXL and CRV-431?
JAMES SAPIRSTEIN: Okay, so we currently have this new formulation of TXL, and I don’t know if we’re ever going to go into Phase 3, that’s something that we’re discussing because the key to hepatitis B will be combination therapy. What our plan is in 2018 and 2019 is to conduct a variety of Phase 2 programs including CRV-431 with different drug partners and different compounds that are available.
So, in terms of a timeline, we’re examining all sorts of different options with TXL. There might be an opportunity to do a 505(b)(2). We’re in discussions with the FDA with that as well, so that would shorten our timeline. I’m a bit reluctant to say when we think we’re going to do something with TXL because it’s all very much in flux at this point.
And then, with CRV-431, once we finish the IND, we hope to get into the clinic third quarter of next year. So, we’ve got to do some single-dose studies or multi-dose studies in healthy volunteers, and we hope that by 2019 we will conduct combination studies with TXL and CRV-431.
KLARA CZOBOR: Sure. So, regarding pharmaceutical company partners for both these drugs, are you currently partnered? Or are you looking for a partner? Have you had any discussions with any potential pharmaceutical company that you might partner with?
JAMES SAPIRSTEIN: Well, we’re not currently partnered but we have been in a lot of discussions with a lot of different pharmaceutical companies. What I tell people is, “it’s more than one and less than six”, so there are plenty of companies that we’ve spoken to; there is certainly a lot of interest. Some of them have an interest in CRV-431, some of them have an interest in TXL, some of them have an interest in a combination of both.
KLARA CZOBOR: Sure. And is there a timeframe within which you’d really like see a partnership take place? Or is it more of just an ongoing process?
JAMES SAPIRSTEIN: I think it’s an ongoing process. We found a couple of opportunities for new partnerships already and we’ve turned them down because it didn’t make any sense for us at that point in time. I think it’s a process, meaning it must make sense for what we want to do. It has to make sense for our shareholders, and it has to make sense for our compounds.
KLARA CZOBOR: Sure, absolutely. And could you please discuss the possible market competitors to both TXL and CRV-431?
JAMES SAPIRSTEIN: Well, with TXL, the Gilead product, Vemlidy is the main competitor, and you have entecavir, which is Bristol-Myers Squibb’s product. With CRV-431, we’re far more advanced than any of the other cyclophilins. There are several companies now that are looking at developing cyclophilins.
But it’s tough to say what the true competitor is going to be because you also have RNAIs out there, you have CAPS inhibitors, and all sorts of different drugs in different categories, and we’re all trying to figure out how they will all work well together. So, I’m not sure that we would call each other competitors as much as we would call each other “clinical partners.”
KLARA CZOBOR: Okay. Do you anticipate any challenges regarding market uptake for TXL and CRV-431? What type of physician-clinician education gaps will there be regarding these treatments?
JAMES SAPIRSTEIN: Well, let’s compare hepatitis B to the beginning of the HIV epidemic where you literally had a few nucleosides, AZT, DDI, and DZC. None of them could be used together, but what they did is they stopped what was an instant death sentence for people diagnosed with AIDS or HIV. And no one really knew what other medications were out there or what was coming.
It wasn’t until you saw the non-nucleosides and the protease inhibitors that we started using agents that attack the HIV virus in different parts of the cell cycle, and you started seeing some results, and people started living longer.
I think hepatitis B is not quite where HIV was at the beginning of their epidemic, but maybe two or three years into it where there is a very good understanding of what the nucleosides/nucleotides can do, but the other drugs that are the more potent ones, the drugs that attack at different lifecycles of the virus, are in their infancy. A lot of these more potent drugs are preclinical or in Phase 1. There’s only one or two drugs that have made it to Phase 2 so far, and in the middle of Phase 2, and you’re not going to see anything for another 3-4 years.
So, I think from an education perspective, there’s a whole lot that needs to be done, not only in the United States but in Europe, in Asia, because people are being treated with monotherapy and that’s not really working out.
There’s also the hepatitis B vaccine that’s available in this country. Less than 1% of Americans have been vaccinated even though the CDC recommends that every adult at the age of 25 and older should be vaccinated for hepatitis B.
So, in terms of preventing the disease, there’s a whole lot of education that needs to be done. And in terms of treatment, it’s going to be so complicated just like HIV was, that I think you’re going to have to really do some work to educate physicians.
KLARA CZOBOR: Sure. Wow, that is very interesting. And what about payers? What type of payer challenges do you foresee? And how do you guys plan on overcoming the payer challenges if you have identified any?
JAMES SAPIRSTEIN: Well, I think we are just going to see payer challenges. I think that the payers are already gearing up for this. Let’s face it, the new hepatitis C treatment approaches “blew up” the discussion with payers, with Express Scripts, and everybody else. All that anybody could talk about, including congressmen, was the $84,000 price tag of Sovaldi.
So, I think that managed care, the payers, are anticipating very much the same to happen with hepatitis B if you get to a cure. But what I can say without question from a TXL perspective, our price point has already been put together because Vemlidy is out there already, they’ve got a price point of between $16,000-20,000 a year depending on the market. If we’re going to compete with Vemlidy, we’re either going to be the same price or maybe a little bit more expensive if we show superiority. It’s not going to be an $84,000 a year drug…
We’ll see in terms of cyclophilin (CRV-431), it’s also an oral medication. If it makes a big difference clinically and if it gets people closer to a cure, and that’s the panacea, then yes, it’s going to be an expensive drug. It really depends on the data and it’s just too early to tell, but I know managed care has a lot of concerns already in terms of what it’s going to do to the budgets.
KLARA CZOBOR: Sure, okay. So, could you please clarify that TXL and CRV-431 can be used in combination?
JAMES SAPIRSTEIN: Yes, they can. We have data and granted, it’s preclinical data, but we’ve got animal data, we’ve got lab data where we showed very good synergy between the two compounds. We did a lot of that work before I licensed it in. I would not have licensed it in unless I thought they could work together.
KLARA CZOBOR: Okay, great! And regarding further questions about ContraVir, are you looking to broaden your pipeline? So, do you think that you’ll be in-licensing any other agents?
JAMES SAPIRSTEIN: Yes. I think we’re always open to looking at new agents, and I’m actively looking all the time.
KLARA CZOBOR: Sure. And is your main interest the hepatitis B, or do you have any areas that you’re interested in potentially in-licensing in?
JAMES SAPIRSTEIN: Right now, we’re focused on hepatitis B. Again, we’re a micro-cap company. I think if I had a few hundred million dollars, I’d probably be looking at expanding our pipeline to other areas of virology, but we’re currently limited in terms of what we can pay and what we can bring in, so right now it’s hepatitis B.
Part 1 of this interview was made available last week, where we talk with James Sapirstein about the overall business goals of Contravir as well as Valnivudine™, now in Phase 3 trials, for the treatment of herpes zoster and shingles associated pain known as post-herpetic neuralgia.
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