FDA Announcement

Jun 18, 2021

Press Release

Good day and thank you for standing by. Welcome to the regulatory updates from the FDA Conference Call. At this time, all participants are in a listen only mode. After the speakers' presentation, there will be a question and answer Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Molly Porch, Head of Global Communications for Orthozyme. Please go ahead. Thank you, Bernard. Good morning, everyone, and thank you for joining us today. On the call with me from Orphazyme are Christophe Gordon, Chief Executive Officer and Anders Baschel, Chief Financial Officer. Before we begin, I would like to remind you that this call will contain forward looking statements concerning Orphan's future expectations, Plans, prospects, corporate strategy and performance, which constitute forward looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in our filings with the SEC. In addition, Any forward looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements. Now I'll turn the call over to Christophe. Christophe? Thank you, Molly, and thanks for joining us on the call today. As you have seen from our press release, we received yesterday night A complete response letter from the U. S. FDA for investigational product, arimoclonal, for NIMAN PIQ Disease Type C or NPC. Obviously, we are very disappointed by this outcome given the urgent need for new therapeutic And we had hoped to deliver better news to this patient community who has been eagerly awaiting for PDUFA date. And while we are not able to share any details outside of what it is in the press release, We felt it was important to hold this call today to communicate our resiliency and dedication to NPC patients and our key stakeholders. We do remain committed to working with the regulators with the goal of delivering arimoclonal to families managing this challenging disease. The CRL stated that the FDA is unable to approve the NDA in its present form Based on needing additional qualitative and quantitative evidence to further substantiate The validity and interpretation of the 5 domain NPC clinical severity scale, NPC CSS and in particular the swallow domain. A primary endpoint of the Phase twothree clinical trial was progression in disease severity as measured by the 5 domain NPC CSS. This is a disease specific measure of disease progression consisting of the 5 clinically most relevant domains to patients with NPC caregivers and physicians. Further, the FDA noted in the CRL that additional data are needed to bolster confirmatory evidence Beyond the single Phase twothree clinical trial to support the benefit risk assessment of the FDA of the NDA. Right now, We plan to focus our efforts on pursuing the European regulatory approval with CHMP Opinion expected in Q4 of 2021 and potential marketing authorization in Q1 of 2022. We will assess a potential path forward in the U. S. In partnership with the FDA. Now in the near term, we will need and we will reduce our costs substantially and freeze all companies' activities Not related to clinical and regulatory activities to support approval for NPC. We have updated our financial outlook for the year. I'll turn it over to Anders to comment on this further. Anders? Thank you, Christophe. Today is a very difficult day for the MPC community and oversight. The FDA has significant influence on our business and the outlook for the full year of 2021. We now expect operating expenses In the range of DKK 700,000,000 to DKK 720,000,000 compared to previously expected DKK 800,000,000 to DKK 850,000,000 Resulting in the expected operating loss of DKK670,000,000 to DKK 700,000,000, previously DKK 100,000,000 to DKK 150,000,000. Our cash position at year end 2021 is expected to be around DKK 50,000,000, previously DKK 350,000,000 in excess of, We've removed our previous stated revenue guidance for IMbocmal in the U. S. As well as the monetization of the priority review We expect to provide further updates in the coming weeks. With that, I'll turn over the call to Molly to begin Q and A. Molly? Thank you, Anders. Operator, we're now ready to take questions. Thank you. Your first question comes from the line of Thomas Powers from Danske Bank. Please ask your question. Yes. Thank you very much and very sorry. I'm surprised about the FDA decision here. So you had a very close dialogue with the FDA when designing the trial and also the endpoints. And then you would say maybe even it was the last couple of years had in the pre and post filing process and Communication. So just help me understand what exactly difference from the communication now regarding the 5 domain scale? And just secondly on this on the swallow domain, what difference did you see compared to placebo in this part? Because I As I remember, it was primarily on the cognitive domain that you only saw maybe at best in numerical difference compared to placebo. So where are you exactly on this swallow domain? And why is the agency Well, potentially even higher highly focused on this specific domain. And then just on the additional data, I know you Can't say much most likely, but do I have any feeling on whether the FDA actually thinks that they need A new confirmatory clinical trial or is there some sort of way to look at maybe existing data or Or confirmatory preclinical work or any additional biopsy work or something like that, that could Be supportive for resuppression. And then just lastly on the safety profile, is there anything also I know you submitted for example the QCC To see data in December. So anything here that may have tilted the risk the benefit risk assessment from the FDA? Thank you. Thanks so much. Christophe here. Thanks for your questions. So I mean Clearly, I'm going to really focus on what's on the press release. At this stage, I won't be able to really disclose much more details. I think the FDA, they clearly stated that their CRL is really based at the moment on needing additional qualitative and quantitative evidence. We will really assess in the coming days how to further what's the path forward with the FDA. That's what the team will be focusing on. On the again, on the additional evidence Beyond clinical, there could be some kind of also like for example pharmacodynamic data. But at this stage, it's very important for us to Ensure that we find the most constructive path forward with the FDA. And as soon as we have no information here, we're going to come back and revert and update you. Okay. But can you just remind me on the domain or the swallow domain, where how did your data look For that domain alone? Maybe I will pass over to, yes, Thomas Bledler, Chief Medical Officer. Yes. Thank you for the question, Thomas. So we had good effect on the swallow domain. It was one of 3 domains that mostly carried the effect. Okay. So that should be supportive for your case if they focus more highly on the swallow domain basically. So meaning that you have a P value of less than EUR5,000,000,000,000, I guess? I think what is still important to emphasize here, it is a Composite outcome measure, where all five domain should be considered In totality, but certainly the swallow domain is one of the strong domains for arimocamol And it's associated with survival. Okay, perfect. And then just maybe I did also A little bit premature, but and you also state that you give some more details on the financials. But just to understand the commercial approach here, so And related to your updated guidance. So does this include preparation ahead for a commercial launch in Europe? And also, I remember, well, you have the whole team in place in the U. S, of course, for the U. S. Launch. And then You would sort of take a little different approach in Europe. So is this still the case? Or are you going To maybe be well, have make some more preparation for Europe in order to actually have A launch with salespeople in the field. Is that how I should see it? So Thomas, as indicated by Anders, I think our key priority is to ensure that we will close the year around SEK 50,000,000 in cash. And we will really ensure a prioritization of all the key activities that are critical to ensure ongoing dialogue with the EMEA [SPEAKER JOSE RAFAEL FERNANDEZ:] And find a path forward with the FDA. And then we're going to reassess As time goes by, but that's really the focus of the core activities and this edge in the coming months. Okay, got it. Okay, great. Thank you very much. Thank you, Thomas. Your next question is from the line of Jamie Janney from Taco Bell. Please ask your question. Sorry, you couldn't hear the question. We just lost Jamie on the line. We have next question from the line of Samir Devani from Rx Securities. Please ask your question. Yes. Hi. Thanks for taking my question. I'm just Quite interesting, I'm trying to understand how a drug with breakthrough designation, where you're supposed to obviously have intensive FDA interactions. How do you get to this point where the FDA is questioning the validity of the endpoint? Surely, this must have been part of The dialogue ahead of filings, perhaps you can just explain how you got to this point? Thanks very much. So Christophe here. So we're going to reassess clearly the detail Of the CRL and look what's the path forward here. I think at this stage, as Thomas was saying, I think the decision of the FDA Based on totality of evidence. And we're going to revert back as soon as we know more and then address your specific issue here. But I'm not going to comment on how the FDA came to its conclusion. And I guess then just as a follow-up. In terms of Europe and regulatory interaction there, can you just comment on any interactions regarding this endpoint with them? Thanks very much. So this is Thomas Fettler. We are in review with EMA and conversations and dialogue is ongoing with EMA. Okay. Thanks very much. There are no further questions at this time. Please continue. All right. So thanks everyone for joining us today. I think While we delivered disappointing news today, what I just wanted to assure you that we are focused on partnering with the FDA to evaluate the path forward, Well, also we continue pursuing registration in Europe. So we look forward to keeping you informed in our progress. And operator, now we can now ready to close the call. Thank you. That does conclude our call for today. Thank you for participating. You may all disconnect.