Lumos Pharma, Inc. (LUMO) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to Lumos Pharma's Clinical Update Conference Call. [Operator Instructions] As a reminder, this conference call is being recorded. I will now turn the call over to Lisa Miller, Senior Director of Investor Relations.

Thank you. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with the SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements. Information presented on this call is contained in the press release we issued yesterday afternoon and in our Form 8-K, which may be accessed from the Investors page of the company's website. Joining me on today's call are Rick Hawkins, CEO, President and Chairman; John McKew, Chief Operating Officer and Chief Scientific Officer; Lori Lawley, Chief Financial Officer and Corporate Controller. Rick Hawkins will provide a brief update on our clinical programs. And following his prepared remarks, we will open the call to questions. I will now turn the call over to Rick.

Thank you, Lisa, and good morning, everyone, and thank you for joining us on today's call. After the market closed yesterday, we issued a press release detailing new guidance for our OraGrowtH210 Phase II and our OraGrowtH212 PK/PD clinical trials. On today's call, I'll briefly summarize the reasons behind the new guidance before we open the call for questions. Yesterday, we issued new guidance for the 6-month primary outcome data readout for OraGrowtH210 trial. The pace of site initiation and enrollment of this trial has been slower than anticipated due primarily to ongoing COVID-19 restrictions. This impact has been particularly pronounced at international sites where faster patient enrollment was anticipated. Given the slower enrollment, the 6-month primary outcome data for OraGrowtH210 is now anticipated in the second half of 2023. As we continue to open clinical sites for this trial, we believe we will continue to see the pace of enrollment increase. Considering that there are signs that COVID might remain a persistent problem, particularly internationally, we thought it was prudent to extend our guidance for data readout. We also announced yesterday the planned 6-month extension of the protocol for this trial. Given the lack of long-term LUM-201 efficacy data among PGHD patients, the FDA has requested 12 months of efficacy data prior to permitting the initiation of our OraGrowtH211 long-term extension trial. And as a reminder, LUM-201 has a novel mechanism of action compared to other growth hormone therapies, and the agency would like us to expand the treatment period before starting the long-term extension study. Therefore, the agency has placed the OraGrowtH211 long-term extension trial on partial clinical hold until additional efficacy data from OraGrowtH210 trial are available for review. The planned protocol extension for the second 6 months of the OraGrowtH210 trial mirrors the previous plan for the first 6 months of the OraGrowtH211 trial long-term extension study and will, therefore, enable us to provide a more robust data package from the Phase II OraGrowtH210 trial as we advance this program. And we are currently reviewing the timing of initiation of a long-term extension study in context of this new extension of the OraGrowtH210. Now the OraGrowtH210's trial's primary outcome continues to be the preliminary validation of our Predictive Enrichment Marker or PEM strategy in selecting LUM-201 responders and to determine the optimal dose for a Phase III registrational trial. Annualized height velocity remains a key clinical outcome measure. We do not anticipate the announced protocol changes on a stand-alone basis to extend the time to the initiation of our Phase III clinical trial. And as a reminder, OraGrowtH210 is a global, multisite trial involving approximately 80 PGHD patients randomized into 1 of 3 dose levels of LUM-201 or a comparer arm of standard of care injectable growth hormone therapy. The 3 doses of LUM-201 being evaluated are 0.8 mg per kg, the highest dose Merck evaluated in children and 1.6 and 3.2 mg per kg. These doses cover the range of pharmacodynamic effect seen with LUM-201 in normal healthy adults with the dose of 0.8 mg per kg produced growth hormone levels only 1/3 up the PD dose response curve. Only those PGHD patients determined to be PEM positive as evaluated by the predictive enrichment markers will be randomized in the treatment portion of the study. Returning now to the OraGrowtH212 trial. We initiated this trial in June and are currently enrolling patients. OraGrowtH212 is a small single-site trial to illustrate the PK/PD effects of LUM-201 in PGHD and replicate the pulsatility data that currently exists for LUM-201 in adults and a small subset of children with PGHD. The study is evaluating the PK/PD effects of LUM-201 in PGHD patients at 2 different dose levels, that is 1.6 and 3.2 mg per kg and up to 24 children to confirm prior clinical data, illustrating the increased pulsatile release of endogenous growth hormone unique to LUM-201 and its potential for efficacy in a sizable PGHD patient population identified by PEMs. This is an open-label trial. And as announced yesterday, we decided to extend the treatment period from 6 months to 12 months to capture additional PK/PD and longer-duration height velocity data. The PD pulsatility assessment will continue to be at 6 months on therapy. Finally, as we noted in our release yesterday, our cash position on an unaudited basis is $107.7 million as of June 30, 2021. We will provide the financial results for the second quarter in the next few weeks. We believe our current cash to be sufficient to support operations through primary data readouts from both the OraGrowtH210 and the OraGrowtH212 trials. Though the FDA's request for a 6-month extension of the treatment period for our OraGrowtH210 trial was unexpected, we are confident that our trial protocol changes will both add impactful data and meet the FDA's request to open the long-term extension trial. We also remain confident that our OraGrowtH210 and OraGrowtH212 trials will confirm the LUM-201 efficacy seen in published analysis of clinical data from prior studies when our Predictive Enrichment Markers will apply. We have a solid financial foundation in place, and we remain confident in the potential of our oral therapeutic candidate, LUM-201, to disrupt the PGHD therapeutic industry for standard of care consisting of daily injections of growth hormone or weekly injections expected to be approved. Operator, we're now ready to take questions.

[Operator Instructions] Our first question comes from Charles Duncan with Cantor Fitzgerald.

I had a couple of questions about the agency action here. That said, I guess I'm wondering if this could be a positive. I'm wondering, first of all, if you could give us an update on the current enrollment and the relative breakdown between U.S. and international patients?

Charles, we haven't given any guidance yet in terms of enrollment. I think that in the coming months, we will. But obviously, part of the reason for this call is to say that we're not enrolling as rapidly as we'd hoped to. And there's -- I think that's kind of predictive of what's going on industry-wide and a number of other trials that have been delayed because of COVID conditions.

But you are enrolling some patients despite the summer months and despite the challenges of COVID at this point?

Yes, we are. And I'm actually encouraged by the recent screens and uptick in activity. But as we noted, I think all of us are suffering in the industry from the effects of the COVID situation.

Okay. And then moving on to this study and implications for the development program. It just -- help me understand, is this now -- is 210 now a 12-month study with a 6-month interim? And then if reading all positive, could you see this being 1 of 2 possible studies that may form the basis of a pivotal program?

John, why don't you go ahead with that question?

So the primary outcome of this study will still be the validation of our Predictive Enrichment Marker strategy at 6 months. The extension that comes after 6 months is just to generate additional growth data, exactly the same growth data that we had planned to collect in our long-term extension study. We're just now doing it within the 210 study, within our Phase II study. Yes, the other way to look at this is that we have a study that's powered to show the enrichment effect, right? We have a comparator from the Merck 020 trial, so we do believe it is an adequate and well-controlled trial.

Okay. And then final question then I'll -- go ahead, John. Were you finished?

I was -- the only other thing I was going to say is that we also think having 12-month data is important, right? We think it's going to help us with variability, assessment as we have discussions with the FDA about noninferiority in our Phase III study. And I think it's going to be a solid -- more solid data package, right? It's the same package we had planned to have either way, but it's just -- it's nice that it's within all-in-one study.

Okay. That makes sense to me. And then final question is with regard to the clinical hold and extension study, long-term extension study. I guess I'm trying to work out in my mind how that would work if patients -- if you can't continue to dose patients, how would they be in an extension study? Or would there be an interruption of dosing? Or would you now plan to do an extension study on the back of another study going forward?

John, go ahead.

Yes. So I think we have a couple of options as we go forward. Our goal is to keep as many patients on therapy that are responding, right? As long as they're responding, we'd love to keep them on therapy and continue to monitor them. The FDA has asked for data longer than 6 months to look at before we open that study. And obviously, our enrollment is quite -- it's spread out, right? We're extending our enrollment period. So we'll have patients at various stages of treatment between 0 and 12 months or between 6 and 12 months as we move forward. So there will be the opportunity to talk to the FDA with a dataset that includes perhaps quite a lot of 6-month data, a decent amount of 9-month data and some 12-month data. And it's -- well, when we see a dataset that looks pretty compelling, I think we'll be able to go back to the FDA and think about opening that extension study. The other option, as you said, is to continue to extend the 210s, right? So we're going to explore both of those options. The extension study may be obsolete if we end up just extending the 210 study by another 6 months.

Our next question comes from Yasmeen Rahimi with Piper Sandler.

This is Felicia on for Yasmeen Rahimi. So we were just hoping to get a little bit more detail surrounding the partial clinical hold and really why the FDA requested it. And we are also wondering, do you guys think that you will be able to use any of the 6-month data from 212 to support lifting the hold on the extension study? And then one last one, I'm just going to slip in. And what can you learn from 212 that will help derisk 210?

John, do you want to start with the answer there?

So I can remember the last 2 questions. You might have to re-ask the first one. But for the last 2 questions, so we're actually very -- the reason that we're extending the 212 study also to a 12-month study is simply to make sure we can quickly generate 9- and 12-month data on a large patient pool. And I think it'll be very helpful for us to use that data as we think about starting the extension study.

And yes, your first part...

You will have to remind me the other 2?

Yes. I think that the agency looked at our compound is not obviously a drug in the current class. And we're a new chemical entity where our mechanism of action is obviously very different. And they wanted more experience in that 210 trial before we go on to a longer-term extension.

So I think what I would add to that is Merck has explored this molecule in 1,200 adults and children, right? There's a very extensive clinical efficacy and safety database. There isn't a lot of data in the 200 kids who were with PGHD, who are treated with LUM-201 for longer than 6 months, right? And so that's really their concern. They would like to see some longer-term data than what Merck generated before opening up the window.

Got it. And yes, remember, the agency gave us a Study May Proceed letter not just at the dose that Merck used at 0.8, but we -- they allowed us to double it and actually quadruple the dose in this study due to the profile of the drug.

Our next question comes from Ed White with H.C. Wainwright.

I just want to circle back to an earlier question. So the 211 trial is a long-term extension study just to review the long-term safety in PK and PD markers and growth outcomes. And that was expected to have -- to enroll the eligible patients who completed 210 and 212. And so now that you're already extending 210 and 212, I'm just wondering why you would run 211 instead of moving right to your first Phase III trial?

It's a good question. And to us, we complied with the FDA in terms of the way they want to do it. And -- but I think the outcome is going to be the same. Traditionally, in this class, in this division, you -- somewhere along the way, you do long-term extensions. The timing of that may change as a result of their recent request of extending, for example, the treatment period in the 210 trial. John, do you have anything to add there?

Yes. So Ed, what I would add is what we'd like to do is keep these patients on LUM-201 as long as we can, right? So we envision this long-term extension study continuing, right? And even having an opportunity at some point for the Phase III folks to roll into it. We want to capture as larger body of extended dosing data as we can. It will help with our safety and long-term efficacy as we go towards a filing. So there is still a role to play for the extension study. Even if we just extend these Phase II studies, right, there will be a role to capture some of the patients that come off of a Phase III study or anything we do after the Phase II.

Okay. And then another question. I know you're not giving enough on enrollment as per the first set of questions that were asked. I was wondering if you could comment on sites. And how many sites are open now in the U.S. and outside the U.S.? And perhaps more importantly, since the enrollment is going slower than expected, are you thinking of opening up even more sites than initially planned?

Ed, we may open up more sites, but we have more than 50% of the sites that have been projected that would open initially, and that is we've told them we're going to open about 50 sites around the world. We have enrollment in U.S. and ex U.S. sites. And as you're probably aware, I mean, there are traditional high enrollment sites in Central Europe and in Australia, as an example. Australia is -- due to recent uptick of the COVID variant, there have been -- they are somewhat in a lockdown. And we certainly expected a high enrollment rate in Australia and other areas where they experienced some -- these additional problems.

So if I may add, Ed, clinicaltrials.gov obviously lists all of our sites. We have 34 sites listed there. You will see sites in Poland, Australia and New Zealand. The ex U.S. site is listed. We had mentioned several months ago that we were expanding our list of ex U.S. sites, right? So we had talked about moving into Ukraine, Russia and Israel. And so those -- that process is still in progress. Those sites haven't opened up yet. We're in the process of moving forward with them, but we do have a number of ex U.S. sites that are up and rolling.

Okay. And my last question is, earlier on the call, you mentioned that the -- you don't anticipate any extension and a time to initiation of the Phase III clinical trial. How should we be thinking about the timing of that Phase III trial? And also, I guess, you don't need any data from 211 to start that trial? Is that correct?

Go ahead, John.

So I think the key point to remember is the change to the 210 trial doesn't change what the primary data readout is, right? It's still going to be that 6 months of treatment, the PEM enrichment validity. And that's going to serve us -- that dataset is going to serve as the basis for our discussions with the FDA about our Phase III trial and the noninferiority ranges and all the other pieces we'll have to negotiate with them. So really, we're just trying to make sure that people understand that, that same dataset is going to trigger our end of Phase II meeting with the FDA. We'll have extra data in that. We'll have additional data in that same clinical trial that we would previously have had in our extension study when we talk to the FDA. So we'll have a very nice data package when we sit and do that planning with the negotiating with the FDA about our pivotal study. So that statement was really just to make sure that people understand. The changes to the protocol don't change when the readout is and they don't change the trigger for when we have our end of Phase II meeting.

Our next question comes from Elemer Piros with ROTH Capital.

So I was just wondering how did this conversation evolve. Did the FDA wake up 1 day and said -- contacted you that, "Oh, let's extend it to 12 months." if you could give us some background on that one, please?

Elemer, thanks for your question. And yes, it was somewhat unexpected. I believe that there are some additional members of the -- of their team that showed up that never -- were not on calls -- prior calls, so that may have been initiated by a new group within the current group that reviewed everything for us. John, do you have any additional color?

Yes. I mean I think the key issue is, we had submitted our extension study protocol for a review and had submitted it several months ago, and we're asking for their feedback before we started that study. And I think that caused them to reassess what they wanted as a starting point for kids to enter into that trial. And so that was really the impetus. It's not anything that was happening with the 210 trial. It was the 211 protocol that went in for review.