Andy Hsieh: Thanks for taking our questions. I have two. One has to do with DILI. I’m curious, if you can share the approach that you’re taking as a sponsor to derisk this potential regulatory risk? And perhaps in-house emulates kind of the deep investigation that the FDA will likely undertake just to prevent any sort of surprises that we have seen in the field.
Sujal Shah: Happy to answer the question, Andy. Maybe Chuck, if you’d like to give some color here.
Chuck McWherter: Yes. Of course, it’s always important for any drug in development the FDA plays the close scrutiny to the risk for liver toxicity. There’s a tried and true algorithm that’s employed. I believe every sponsor today would be employing that there’s an adjustment to that algorithm that’s implemented in the setting of liver disease. And of course we follow it there’s a published consensus paper and there’s a very specific guidance about how one evaluates the risk for drug-induced severe hepatic toxicity. And we follow that pattern as well. I t I think ink it’s really encouraging for me to say that across our program where we studied 10 milligrams or lower as we’ve reported previously we’ve had a really solid experience.
We feel that in the setting of liver disease that seladelpar really has a really good profile. So there’s not any level of concern that we have at this point. But of course we do use a protocol-specified methodology an accepted way to analyze and report any changes for example in liver enzymes. And that’s all part of the regulatory package that we — that we’re putting together and submitting to FDA as well as other regulators.
Andy Hsieh : Got it. And as you think about commercialization and speaking with some key opinion leaders, there appears to be some stickiness in patients obviously as you kind of think about Wave 1 Wave two in terms of perhaps OCA-treated and discontinued patients being the easiest to penetrate. As you kind of think about expansion into potentially currently on OCA, but having either high frequencies of pruritus what’s the strategy here to overcome that inertia and really communicate with health care providers convincing them that there is a better option out there.
Sujal Shah : Andy, I think it’s a good question first of all. And I’d say in a setting where you only have one approved second-line treatment the concept of stickiness may be very different when you have various alternatives. I think the first most important thing for me to call out as you described is, there are many patients that have been on second line and have already discontinued. In fact, we think that number is greater than even those that have remained on obeticholic acid is the only second line approved here in the U.S. And so I think there’s clearly an opportunity to serve those patients. Overall, there are many more patients that have still not yet been on second-line treatment as well. And so I think the opportunity is very significant before you even contemplate any patients that may switch over from current second-line treatment.
We do expect some of that to occur. Certainly, patients that have ultimately tolerability issues may in fact seek other alternatives. Those that do not and are actually having an adequate response we agree with you. We should remain on the treatment they’re being given. But again, I think, seladelpar really has the opportunity to completely change the treatment paradigm in the setting of PBC. And so ultimately, we’re excited about what we’ve seen with respect to the efficacy profile. Pruritus is something that to-date has always been talked about as a tolerability issue. And for us with seladelpar the effects on pruritus are actually an efficacy parameter the ability to actually reduce pruritus is significant in improving the quality of lives for patients.
We know with existing second-line treatment for example that most patients don’t actually up-titrate from five to 10 milligrams. So, again, I think you’re going to see a very different view and approach to giving patients the most optimal treatment. And so right now our focus is to really get through the regulatory process, because we do believe seladelpar may offer significant advantages to patients if we’re successful.
Andy Hsieh : Great. Thank you very much.
Operator: Our next question comes from Ed Arce with H.C. Wainwright. Please go ahead.
Unidentified Analyst : Hi. Good afternoon everyone. It’s Thomas [ph] yet asking questions for Ed. Really appreciate taking our questions. So just wondering what would be the ballpark figure of incremental U.S. spend in preparation launch in the next 12 months? And then the second question is, I believe, EU launch is on the table as you mentioned. Does that factor in the first half 2020 fixed cash runway and if not what are some major assumptions behind the cash run rate estimate. Thank you so much.
Sujal Shah : Yes. Can you repeat the first question again? I know you asked something related to launch. Were you asking about costs or time line estimates?
Unidentified Analyst : Cost estimate perhaps incremental spend in the next 12 months related to our U.S. launch.
Sujal Shah : Yes. I’ll ask Harish to answer both of the questions related to the balance sheet and costs.
Harish Shantharam : Yes. The way I would answer that question, our cash runway takes into account the investments that were — we’ll see accelerate. Actually now that we’re on the other side of data in all our commercialization efforts actually that Lewis alluded to that we have the medical affairs team on board and we’re actually building on a commercial organization. The sales piece rep probably will come in more closer to the launch time line once we have a sense of what our PDUFA date looks like. So it’s not uncommon probably by one, two months before. So that’s kind of how I would — so that is baked into our assumption in our cash runway. And so you would assume it will build now between now and as we get to commercialization and all the pre-market planning efforts and then you would get — end up having a more of a higher run rate now that we have the post launch when we have the full team on board.
And to your second part of the question, we — our full-scale EU commercialization is not included in our cash runway. We are still — again, we’re making progress with respect to regulatory filings and some early commercial understanding efforts but I wouldn’t say a full base commercialization is not in that estimate.
Unidentified Analyst: Understood. Thank you so much for taking our questions.
Operator: Our next question comes from Mayank Mamtani with B. Riley Securities. Please go ahead.
Unidentified Analyst: Appreciate you taking our questions. This is actually William on for Mayank. So, just a couple of follow-ups here. We were curious if there was any indication that the Ocaliva Article 20 investigation has anything to read into for your review in the EU?
Sujal Shah: No, there’s nothing that we’re aware of frankly. We know little outside of what everyone knows from the public domain with respect to the Article 20 review for Ocaliva. To-date, we don’t believe that this is anything that would affect our discussions and process forward with seladelpar.
