Jeffrey Dayno: Thanks David for your questions. Kumar you want to address on EPX100 and then I’ll respond to the Europe question?
Kumar Budur: Sure. Thank you, Jeff. Hey, good morning David. Thanks for the question. Regarding [indiscernible] I guess you’re referring to the data from the PACIFIC study right which was recently disclosed. Look it’s a small study 52 patients. The efficacy data looked good. but it’s also short study too and we haven’t seen the long-term safety data yet as we continue to collect. So, I see that as early stage still. And you just need to how it will pan out as it goes to the next of it. And in this particular space David as you know or as we mentioned just now it’s a polypharmacy market a significant unmet need. There is a place for a different mechanism of action to costs even incremental differentiation in efficacy or safety is embed by the providers and the patient alike.
Jeffrey Dayno: And David with regards to your question about TPM1116 and our Orexin-2 agonist while we recognize that it’s an early stage and the other development programs ahead, I think that we’re still learning from. So, I think that we are still learning from those data and those programs and as they are generated. So, with regards to our development plan and approach I think we have optionality. I think that there’ll be optionality based on what we learned from some of these other development orexin development programs ahead. The most logical approach I think as you’re aware going in through NT1 which is the prototypical disorder with orexin deficiency as opposed to NT2 and IH. But we will learn from some of the other programs and have the optionality with regards to what the best cap forward will be as we advance TPM1116 for additional–.
Kumar Budur: Yes. Thank you, Jeff. Yes. Just to add on question regarding is it garden variety NT1, NT2 or something else? David this particular compound, TPM1116, has a real high potency and that actually provides us optionality in terms of looking at other central disorders of hypersomnolence as well. I mean as you know Takeda had to limit the dose to 10-milligram and the study to only pursue NT1 not NT2 or idiopathic hypersomnia this stage. The preclinical profile that we see with the 116 looks pretty good. And based on that we do see optionality here after than the European central deporter of combo.
Jeffrey Dayno: Thanks Kumar.
David Amsellem: All right. Thanks guys.
Jeffrey Dayno: Thanks David.
Operator: We will take our next question from Graig Suvannavejh with Mizuho.
Graig Suvannavejh: Hey thank you. Can you hear me okay?
Jeffrey Dayno: Yes we can Graig. Good morning.
Graig Suvannavejh: Thanks Jeff. Congrats on the great progress that we’re seeing from the company. I’ve actually got a question for Sandip. Sandip just in light of the new BD deals that you’ve done and your plans to potentially continue adding to the pipeline I guess it’s a two-part question. First — or maybe Jeff you can answer this first part of the question. Is the current plan on any next deal that you do the first prioritize on adding in another or a fourth CNS franchise? Or is the current plan or your thoughts currently to build on the existing three seniors franchises you have now? And then the second part of my question maybe this is really more for Sandip as in light of kind of the added pipeline programs which is I think we all think it’s going to positive. Just wondering if you’ve got any initial thoughts on what the P&L might look like for the company both in terms of SG&A and R&D for Harmony over the next one or two three years? Thanks.
Jeffrey Dayno: Sure Graig. Let me address your first question. In terms of the, sort of, the BD growth strategy going forward again I think it’s also optionality again. I’m very pleased with what — how we’ve been able to expand and grow the pipeline diversify our portfolio and these three CNS franchises where we are now each with potential peak sales opportunities of $1 billion to $2 billion. We could either base on we continue to be active in BD and looking at the landscape. So we could go further in either of these franchises with additional assets or if we see another opportunity in another CNS area that we could diversify the pipeline further. We are — that would be another path forward. The other thing I want to comment on and to I think just bring light to this approach also is important that it leverages our internal expertise in the CNS area as well as the commercial model, our internal synergies.
So as we expand and diversify this portfolio in these CNS areas than just the commercial model where we can thoughtfully apply that model to any new indications any new products that would go to market. So I think that’s how we’re seeing the strategy going forward. Pleased with the progress to-date, but we’re not stopping there. Sandip you want to…
Sandip Kapadia: Yes sure. With respect to your question in terms of the financial impact overall. As you talk about these deals, but we continue to be very disciplined in capital deployment. We structured down with low upfront relative to the age of the assets with more success-driven milestones. These are all fairly late-stage programs in terms of actual capital resources or really for the next couple of years maybe just think about it. And also we’ve got growing revenues. We’ve got internal synergies overall that we can also bring and growing profitability that gets the capacity to continue to do additional business development opportunities while still maintaining our relatively profitable in our business that’s self-sustaining and can continue to grow.
So I think I feel good about what we’ve been able to acquire. These are again very late-stage assets, like I mentioned for this year it’s about $35 million more in terms of incremental cost and probably still early to go into next year and we’ll get close to top line. So really a good smart investments upfront to hopefully unlock incremental value.
Luis Sanay: Operator, next question.
Operator: We’ll take our next question from Corinne Jenkins with Goldman Sachs. Please go ahead. Your line is open, Corinne Jenkins.
Corinne Jenkins: Sorry, I was on mute. Good morning, guys. Can you just help us understand how you thought about the market opportunity and potential value for these assets EPX100 and 200? And in particular how do you think about the path to differentiation there? And with that differentiation what kind of the peak sales opportunity could be for such an asset?
Jeffrey Dayno: Good morning, Corinne. So in terms of the market opportunity referring to epigenic and the rare epilepsy franchise. So I think obviously the epilepsy space is significant market opportunity beginning in this area of orphan rare and the developmental epileptic encephalopathies. We are in a registrational trial for Dravet’s kind of a smaller patient population, but planning to initiate a Phase 3 study in Lennox-Gastaut syndrome second half of this year, a larger market opportunity. But we also see this acquisition as sort of the foundation of a broader epilepsy franchise. So with regards to current market opportunity — with regards to what’s currently available. I think as Kumar has been alluding to we see the potential product profile of EPX-100 in terms of overall benefit risk compared to the current treatment options as a significant product offering in terms of therapeutic option in the near-term.
And then we look to draw on our internal sort of expertise in this area look for potentially additional assets to build out a broader epilepsy franchise. And I think that’s the current view on where we are on there. Kumar any other thoughts?
Kumar Budur: I mean as I mentioned earlier based on what we have seen, we believe that it will offer a compelling value proposition with a unique benefited profile for patients especially from a safety profile given some of the significant limitations, we see with some of the drugs that are currently approved in this space.
Corinne Jenkins: Okay.
Operator: We’ll take our next question from Jason Gerberry with Bank of America.
Jason Gerberry: Hey, good morning. Thanks for taking my question. I guess, one question on EPX100. Is the base case here that you have the same class safety labeling around CV talks as FINTEPLA. I’m seeing in the preclinical there’s some affinity for 5-HT2B. So just wondering that coupled with its only a 100-patient pivotal study. If you can — or think you may be able to decouple that safety issue from a safety labeling perspective. And then from a development perspective are you planning to run a second pivotal trial? Would that be done in parallel once you get the asset in-house? Or would that be after you get data in 2026? Just wondering the time line to market for EPX100? Thanks.
Jeffrey Dayno: Good morning, Jason, yes. Thank you for your question. Yeah, I think Kumar can unpack that with regards to the opportunity that we’re seeing near-term with regards to Dravet’s, and then in terms of differentiated from a safety perspective with regard to FINTEPLA.
Kumar Budur: Yeah. Jason, good morning and thanks for the question. I mean, the answer to your first question is, no. We do not anticipate any cardiovascular liability with clemizole hydrochloride that is based on the large body of data from the first generation antihistamine. And then all the preclinical data that we have generated for this particular compound, including [indiscernible] studies in the preclinical space. And also looking at the data, the FDA did not ask us to echocardiogram or monitor for pulmonary arterial hypertension or cardiovascular abnormalities. So we do not believe that this will have any of the safety issues that we do see with FINTEPLA, which has a black box warning and that is subjected to REMS program.
And also based on the long-term extension study, open label types that we have seen so far, we are actually very pleased with the safety profile both in terms of lack of any lab abnormalities and also from the cardiovascular safety perspective, and just safety and tolerability in general. And to your second question about the second study, the current study, and I know that on clinicaltrials.gov which still says it a Phase 2 study but it’s actually a registrational Phase 3 study. It started out as a Phase 2 study. And then the sample size was increased to 100 subsets, equally randomized 1:1 between clemizole and placebo. And now this is a pivotal registration study, and the top line data will be available in 2026. And typically just as you know in rare disorders one adequate and well-controlled study is generally accepted as substantial evidence for effectiveness by the regulatory agencies.
So we do plan to file based off of this study should the data look good.
Jason Gerberry: Got it. Okay. Thank you.
Kumar Budur: Thanks, Jason.
Jeffrey Dayno: Thank you.
Operator: And we will take our last question from Danielle Brill with Raymond James.
Danielle Brill: Hi. Good morning. Thanks for the question. I’m curious how you’re gauging TPM-1116 profile versus Oral Orexin-2 Receptor Agonist? And what type of data should we expect to be presented at the upcoming scientific meeting and which conference are you targeting? Thank you.
Jeffrey Dayno: Thanks, Danielle for your question. Kumar?
Kumar Budur: Sure. Hey. Good morning, Danielle. Thanks for the question. Yeah, just some background information Danielle on TPM-1116. This originated out of TEIJIN PHARMA. This is a conglomerate with deep expertise the drug discovery. They actually worked very closely with — of the study [indiscernible] who many of you know, is the one who actually discovered [indiscernible] and their impact on Sleep/Wake. They have been working on this series of compounds for a while, and the advanced TPM-1116, because that was the best in the series that they filed. TPM-1116 has a very Novel Chemical Scaffolds compared to the Oral Orexin-2 Receptor Agonist, that are out there. And we believe this Novel Chemical Scaffold offers certain unique features that we have seen in our preclinical studies.
First and foremost, high potency, good selectivity, potential for once-a-day dosing and good preclinical safety data, we are completing the rest of the IND-enabling experiments and we plan to submit IND in mid-2025. And start first in human study, in the second half of 2025.
Operator: Thank you. I am showing no further questions. I would now like to turn the call back for any closing remarks.
Jeffrey Dayno: Thank you Madison, and thanks everyone for joining our call today and for your interest in Harmony. As you heard from us this morning, the future is bright at Harmony, based on the strength of our commercial business of WAKIX in Narcolepsy, and the value of our expanding pipeline, which will serve as the foundation for durable revenue generation out beyond 2040. We look forward to providing updates, as we continue to accelerate our strategy for long-term growth. Thank you. And have a great day.
Operator: This does conclude today’s Harmony Biosciences First Quarter 2024 Financial Results Conference Call. You may now disconnect your line. And have a wonderful day.
