And I suspect that’s what that conversation is going to be about.
Operator: The next question will come from Chris Raymond with Piper Sandler. Please go ahead.
Chris Raymond: Great. Thanks, and congrats from us as well in the data. Just two questions if possible. First, maybe on CASGEVY. We’ve got some physician feedback that — of course, access is a barrier to uptake. But maybe a surprise that we got from some of the questions we’ve asked is the transplant center capacity and prioritization of non-oncology patients is also sort of a consideration. Just curious as you activate these ATCs, maybe talk about transplant capacity, does this factor into the discussions as you’re activating the sites? And then maybe on vanzacaftor, I know you guys have described the royalty differential. I think TRIKAFTA is in the low-double-digits and you’ve described vanzacaftor as down in the single-digits, but are there plans to put some guardrails around this leverage improvement as you get closer to launch of the vanza triple? Thanks.
Reshma Kewalramani: I’m sorry, Chris, I didn’t follow the question on the vanza triple, I got you on CASGEVY, is it about the royalty?
Chris Raymond: Yes, sorry. On vanza — just on the leverage and the royalty differential. I think you guys described the difference, but are there plans to put guardrails around that leverage as people model that?
Reshma Kewalramani: Yes, sure. Let me take CASGEVY quickly, turn it over to Stuart, and then we’ll just do one minute real quick with Charlie and he will tell you about the royalty structure for vanza. Real quickly on CASGEVY, we have not heard of there being a center capacity issue. And honestly, we have not heard about challenges for reimbursement. We’ve actually had very positive reception from payers, but I’ll turn it over to Stuart to make a quick comment on activation and his perspective.
Stuart Arbuckle: Yeah. And — we’re making great progress, Chris, I would say, activating authorized treatment centers just here in the U.S. We’re now up to 12 and I don’t think those centers would be going through the efforts of becoming an activated treatment center if they weren’t fully intending to treat patients with CASGEVY. And then as Reshma said, the reaction we’ve had from payers has been really positive. I think they are incredibly impressed with the clinical data. They are well aware of the unmet need in sickle cell disease and indeed transfusion-dependent thalassemia and the burden that places on patients and indeed the healthcare system. They like the label that we’ve got and they like our value-based pricing. So I’ve been very encouraged by the conversations we’ve been having with payers and I’m fully expecting us to be able to secure great access for sickle cell disease and TDT patients.
Reshma Kewalramani: Charlie, a word on royalties.
Charle Wagner: Yes, just briefly on the royalties. Chris, the blended royalty rate on our current CF portfolio is just under 10% and so high-single-digits call it, and we expect with the vanza triple that that royalty burden will be meaningfully lower in the single-digits. No additional color to add today. And then, of course, if you want to model the impact of that, you have to factor in the rate of switching from TRI and other medicines again. So as we get closer to commercialization we’ll have more to say.
Chris Raymond: Thank you.
Operator: The next question will come from Colin Bristow with UBS. Please go ahead.
Colin Bristow: Hey, good evening, and congrats on all the data. Maybe first on vanza triplet, can you say if there any cases of AST or ALT elevations greater than three or five times the upper limit of normal? And then just secondly, I see that you’ve now three follow-on pain assets in the clinic, 993, 973, and 708, could you just give us more color on how you expect them to be differentiated and just elaborate a bit more on the strategy from here? Thanks.
Reshma Kewalramani: Yes, sure. Colin, quickly on LFT elevations with the vanzacaftor triple as with all of the CFTR modulators, there are some elevations in LFTs. They are approximately the same with the vanzacaftor triple as with TRIKAFTA. On the pain program, Colin, this is exactly what you saw us do in CF, and frankly, what you should expect from us across the portfolio. And that is to say, a portfolio approach to every disease in our sandbox, if there is any way to improve on our assets. We aim to be the ones who do so. So a couple of examples of what we’re doing with 993 for example. 993 is a medicine that may be able to be dosed both oral and IV and we’re pursuing both. We believe that there is a real opportunity here for a patient to come into the hospital and have 993, one of our NaV1.8 inhibitors, be the medicine that they get for pain relief, let’s say, interoperatively and then when they can take by mouth, then they can switch to 548, 993 as an example.
Another example that we’re working on, you know that we also have a pipeline of NaV1.7 inhibitors. Those are still in preclinical development, but they are making good progress. So one of the other elements, we’re working on is formulations in terms of drug-drug interactions and the possibility to combine. So NaV1.7 could be a molecule as a single-agent therapy or it could also be a therapy in combination with NaV1.8 that’s kind of a sense for what we’re doing with our follow-on approach.
Susie Lisa: Chuck, we’ll take one more question, please.
Operator: Yes ma’am. Our last question for the evening will come from Myles Minter with William Blair. Please go-ahead.
Myles Minter: Hi, thanks for sneaking me in. You just mentioned in the first commercial patients on CASGEVY expected to start the journey in the coming weeks. Can you clarify what geographies they are in? And do you have a sense of how many patients you screened out at those ATCs to identify those first patients? Thanks very much.
Reshma Kewalramani: Sure. Hey, Myles, we’re not going to comment in detail on the first patients, but as Stuart said in his prepared remarks, we’re expecting our first patient shortly.
Myles Minter: Thank you.
Operator: This concludes our question-and-answer session as well as our conference call for today. I want to thank everyone for attending today’s presentation. A replay of today’s event will be available shortly after the call concludes by dialing 1-877-344-7529 or 1-412-317-0088, using replay access code 10178829. Thank you and have a great day.
