Good afternoon and welcome to Lumos Pharma’s 2023 Fourth Quarter and Year End Conference Call. Currently all participants are on a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded.

I will now turn the call over to Lisa Miller, Vice President of Investor Relations. Please go ahead..

Thank you, operator. Before we proceed with this call, I'd 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 this afternoon and in our forum 10-K which may be accessed from the investors page of the company's website. Speaking on today's call will be Rick Hawkins, CEO and Chairman; John McKew, our President and Chief Scientific Officer; Dr.

Duke Pitukcheewanont, Chief Medical Officer; and Lori Lawley, our Chief Financial Officer. Following our prepared remarks, the management team will be available for a question-and-answer session. I will now turn the call over to Rick..

Thank you, Lisa, and good afternoon, everyone. After the market closed today, we issued a press release announcing our results for 2023. I'm pleased to report that 2023 was a successful year for Lumos, led by our announcement of positive top-line results from our OraGrowtH210 and OraGrowtH212 trials of LUM-201 in pediatric growth hormone deficiency.

On today's call, we'll briefly summarize our trial results and other progress made in 2023, recap highlights for recent weeks and layout plans for 2024. Then we'll be happy to answer your questions. Before I begin, I'd like to take a moment to congratulate Dr. Duke Pitukcheewanont on his recent promotion to the role of Chief Medical Officer for Lumos.

Dr. Duke's exceptional credentials are widely acknowledged, given his renowned expertise in growth [hormone] (ph) disorders and his current leadership at the Human Growth Foundation among various other distinguished roles in his esteemed career. Since joining us in 2022, Dr.

Duke has played a pivotal role in steering our oil OraGrowtH trials to fruition, providing invaluable guidance, leveraging his influential network for enrollment, and significantly contributing to analysis of trial data. As our new CMO, Dr.

Duke will continue to advocate for exploration of LUM-201 within the PGHD clinical community, a mission that has already garnered remarkable interest from pediatric endocrinologists globally. Thanks to this advocacy efforts. Furthermore, Dr.

Duke will be an integral part of shaping the trial design for a pivotal LUM-201 trial in PGHD, details of which we're going to delve into later during this call. Dr. Duke will be joining the call today for our Q&A session. So please join me in congratulating him on his well-deserved promotion.

Let's now revisit the key highlights of the results we disclosed last November. As many of you are aware, LUM-201 has successfully met all primary and secondary endpoints in both OraGrowtH trials, demonstrating clear proof-of-concept for its efficacy as an oral alternative to daily and weekly injectables for patients with PGHD.

Results from OraGrowtH210 demonstrated that the 1.6 mg/kg dose of LUM-201 achieved annualized height velocities or AHVs of 8.2 cm a year at six months and 8 centimeters a year at 12 months, aligning consistently with historical growth rates for the moderate PGHD population.

The difference in AHV at six and 12 months between the optimal 1.6 mg/kg LUM-201 dose and the recombinant growth hormone comparator arm fell within the non-inferiority margin of less than 2 centimeters a year. And that's a criterion recently used for FDA approvals.

Although OraGrowtH210 was not specifically designed to establish non-inferiority, we're pleased to note that the growth outcomes observed in this study are in line with the non-inferiority thresholds seen in recent successful FDA applications.

These findings enable us to design a successful Phase III trial to show non-inferiority against the daily injectable growth hormone comparator arm.

Now, the preliminary 24-month LUM-201 data we presented in November were gathered from a subset of the OraGrowtH210 patient or participants who met the protocol requirements for an extension beyond 12 months combined with OraGrowtH212 subjects.

These data revealed a sustained effect showing a minimal decrease of approximately 6% in annualized height velocity from year one to year two, as opposed to the significant decline of approximately 20% reported for daily recombinant growth hormone in moderate PGHD patients.

Now, OraGrowtH210 successfully achieved its pre-specified primary endpoint, validating our Predictive Enrichment Marker or PEM test, while also meeting the secondary endpoint by demonstrating 100% reproducibility of PEM-positive classification.

Additional data from the OraGrowtH212 trial demonstrated that only 20% growth hormone concentration was needed to achieve comparable annualized height velocity. That suggests that LUM-201 is more efficient than exogenous growth hormone to promote growth.

These data confirm the importance of LUM-2O1's unique mechanism of action to restore the natural physiology of [indiscernible] growth hormone secretion. Our data from both trials provided a clear safety profile for investigational LUM-201. Now, following the release of top-line results in November, ongoing data collection and analysis have continued.

We anticipate presenting comprehensive 12-month annualized high velocity data from the OraGrowtH210 trial in the second quarter of this year, most likely at a major medical conference. This data set will include 12-month AHV data on all enrolled patients from the OraGrowtH210 trial.

Additional 24-month data beyond the data set we announced in November will also be available. We expect to present these data in additional analysis at several meetings throughout 2024 to capitalize on the growing interest and excitement in the pediatric endocrine community about LUM-201 as potentially the first oral therapeutic in this population.

And following the announcement of our top-line results, we've been diligently conducting additional analyses in preparation for end-of-Phase II meeting with the FDA and that's scheduled for the second quarter.

Our data package for this meeting is comprehensive, featuring a larger data set compared to other growth hormone counterparts at this developmental stage. These data show LUM-201 induces annualized high velocities consistent with historical levels for moderate PGHD on recombinant growth hormone.

That also demonstrates that oral LUM-201 produces a robust and enduring response at the 1.6 mgs mg/kg dose, making use of our Predictive Enrichment Marker or PEM strategy for selecting suitable moderate PGHD patients, thereby further de-risking our Phase III program.

As a result, we approached this end-of-Phase II meeting with a high level of confidence. Now, long before we announced top-line results from our OraGrowtH trials, we've been actively involved in advanced planning for a pivotal Phase III trial.

Following our Phase II meeting with the FDA, we will finalize the ultimate design of the trial, which we anticipate initiating in the fourth quarter of 2024. We believe that this trial's results will support a new drug application for LUM-201 and the PGHD indication.

With that, I'm going to turn it over to Lori Lawley, our CFO, for a brief overview of our financial results..

Thanks, Rick. Lumos Pharma ended the year at December 31, 2023 with cash, cash equivalents, and short-term investments totaling $36.1 million compared to $67.4 million on December 31, 2022.

Cash on hand as of December 31, 2023, is expected to support operations through the third quarter of 2024, inclusive of our Phase III preparations and other operational activities. Initiation of our Phase III clinical trial by end of 2024 is subject to securing financing in the near term.

Research and development expenses were $22.1 million, an increase of $4.2 million for the year ended December 31, 2023, compared to the same period in 2022, primarily due to increases of $3.3 million in clinical trial expenses, $0.9 million in contract manufacturing expenses, $0.2 million in consulting expenses, and $0.2 million in other expenses, partially offset by a $0.4 million decrease in personnel-related expenses.

General and administrative expenses were $16.6 million, an increase of $0.9 million for the year ended December 31, 2023, compared to the same period in 2022, primarily due to increases of $0.5 million in personnel related expenses, $0.4 million in royalty expenses paid to the Public Health Agency of Canada, and $0.1 million in travel expenses, partially offset by a $0.1 million decrease in other expenses.

The net loss for the year ended December 31, 2023, was $34 million, compared to a net loss of $31.1 million for the same period in 2022. We ended Q4, 2023 with 8,102,555 shares outstanding. And with that, I will turn it back to Rick for his closing remarks..

Thanks, Lori. And to conclude, we're absolutely thrilled by the progress of our program to date and by the excitement among the endocrine community regarding the potential for the first oral therapy for PGHD.

We've been on a podium presenting data on numerous endocrine conferences over the past two years and have seen the overwhelming acceptance of and the excitement for oral LUM-201.

We're confident in the distinct advantages offered by LUM-201 for patients with moderate PGHD and I’m enthusiastic about advancing to the next developmental stage for this asset.

We firmly believe that the data set we are submitting to the FDA for upcoming end-of-Phase II meeting provides ample support for a pivotal trial of LUM-201 at the 1.6 mg/kg dose, affirming its potential as a viable alternative to injectable products for appropriately selected moderate PGHD patients.

And we eagerly anticipate sharing further insights from our OraGrowtH trials throughout this year and keeping you abreast of our progress. So thank you for your attention everyone. And operator, we can now open this up for questions..

Thank you. [Operator Instructions] And our first question coming from the line of Charles Duncan with Cantor. Your line is open..

Hey, good afternoon, Rick and team. Congrats on the progress last year. Looking forward to hearing more updates here in the near term. Thanks for taking our question. I had a question about the end-of-Phase II meeting with agency. Is that actually scheduled? And can you provide us some insight on what the key question is.

Is it really something that needs to be answered, or do you feel like this is more a point of execution in terms of going forward? And then when would you anticipate being able to share the outcome? Would it be post the meeting minutes, or do you think it'll be pretty straightforward and you'll share it shortly after the meeting?.

I'm going to ask a -- good question, Charles, and thank you for it. I'm going to turn that question over to John McKew..

Yes, thanks Charles. I appreciate the question. So before we start our Phase III study, we really would like to use this end-of-Phase II meeting to take everything we've learned from Phase II data that we've read out. We put that into our Phase III protocol and we want to walk away from that meeting with agreement on all the specifics of that protocol.

So I think it's a very important time for us to talk through any questions the agency has on the data, as well as come to agreement on the path to move forward. So, it will be a very -- it will be a good step forward for us when we get through that and we have agreement on the Phase III protocol.

So we expect to communicate that information -- the outcomes of that when we hear back from the FDA probably in the meeting minutes, right? So we've said that that timeframe is in Q2 of this year..

Charles, I might add is that, there are a lot of historical precedents here, where we feel confident about this meeting in really an outstanding briefing book. I think that historically these studies have been 12-month non-inferiority trials against an active comparator.

The non-inferiority margin historically has been 1.8 centimeters to 2 centimeters. And we also expect to have a randomization to the 1.6 mg/kg a day, a 2 to 1 randomization to growth hormone. I think most of these studies have been about 200 subjects. We expect a similar design. And also, of course, we validated our PEM strategy.

I think we de-risk our program pretty considerably, given the fact that we can select patients we believe will be -- our drug will be effective in, and that is a moderate growth hormone deficient patient. So we're pretty confident about our meeting with the FDA..

That's helpful. If I could just ask a follow-on question to that, those two observations.

Rick, would you anticipate the PEM strategy to help you design and conduct a smaller sample size or conduct one about that size with perhaps greater confidence in the signal to noise?.

John, you want to go there?.

Yes. So I think the -- how we view the PEM tests is, it's going to kind of raise our efficiency, right? We're going to be able to bring in subjects that are likely responders to our molecules. So I don't think it's going to reduce that size. It'll make it a more efficient trial..

Okay. Last question in terms of business development activity. At one time you talked about possibly ex-US partnering. I guess I'm wondering if you have any further thoughts on that and then I'll hop back in the queue. Thanks..

Yes, thanks for that question, Charles. And sure, I think that you can imagine as the first oral product in this very large global market, there are certain ex-US regional markets and companies that have completed an outreach to us or vice versa. And we continue with those discussions.

And at the appropriate time, I think that we will partner with anyone who's going to -- we believe is going to be a good partner in those markets. Obviously, this will allow us to bring in some non-dilutive money. And I think that's one of the goals that we would have for ourselves..

Okay. Thanks for taking the questions, Rick..

Thank you. And our next question coming from the line of Leland Gershell with Oppenheimer. Your line is open..

Thank you, Rick and team for the update. Just a question from me with respect to additional indication potential for 201, as we think about use of growth hormone products today and indications such as turners and other such disorders.

Just wondering if you could comment on any plans down the road to explore 201's potential to be approved for those additional label indications. Thank you..

And John, I'm going to let you start with that as an answer. And thank you for the question, Leland..

So we've spent a lot of time, Leland, thinking through the best opportunities to advance LUM-201 and past PGHD. PGHD is a great opportunity, I think, for us to show the effect of the molecule on restoring natural pulsatility.

And we can take that same mechanism and philosophy and apply it to many of the other 11 indications that are approved for injectable growth hormone.

So I think we're getting to the point where we have the data set, where we can start to think about how to move forward, but we have not yet made any decisions on the exact next step that we're going to take. But we have, I think, the data and have done the background research on each one of those indications to make some good decisions shortly..

And Leland also recalled, we've got a pilot program underway in a broader cardiometabolic opportunity of non-alcoholic fatty liver disease at MGH.

Now that's an investigator initiated trial, but this investigator did demonstrate with a -- in a recombinant growth hormone trial in this indication some pretty significant reductions in liver fat in this population. So we're pretty excited to work with this investigator.

I think it's a little premature right now to talk about anything beyond that, but we're always looking for ways to increase shareholder value with additional indications..

Got it.

Rick, so at this point we don't have to view on when she may have data on her study of 201, correct?.

No. She doesn't have the trial fully enrolled yet, and it's a six-month trial. So we haven't really talked about that yet in the marketplace..

Okay. We'll stay tuned, and look forward to hearing updates following your FDA meeting. Thank you..

Thank you. And our next question coming from the line of Ed White with H.C. Wainwright. Your line is open..

Hi. Thanks for taking my questions.

So, how should we be thinking about the Phase III start in the fourth quarter? Is that just when you'll be in opening sites or do you intend or do you think that you can actually treat patients during the fourth quarter?.

Okay. Thank you for that question, Ed. And Duke, will you answer that for us? I think you're on mute..

Thank you. Yes, sorry about that. Thank you, that was a very good question, right? As of now, we due diligent, like -- as John mentioned, right? We already have a plan for the Phase III plan. We get ready to really discuss with FDA what we have planned.

In the meantime, we do a prep work, what we need to get done in regards to have a timeline that will be proposed, right? So we think that by the end of this year, we'll be able to screen the subject and get the timeline enrolled like what we proposed in the past.

And I feel very optimistic because, as Rick mentioned earlier, that we have overwhelming requests from the KOL around the world, because they learn about other Phase II results and they do believe that this can be a great potentially the new drug therapy for their patient, the first oral therapy.

So we do believe that a lot of investigators, actually some of those participate in our Phase III trial and some news to LUM-201.

However, with the request of participation, we do believe the timeline one, we get these survey up and running and we have a final site identified, I think that the rolling is going to go very quickly and as we proposed in the plan in the past..

And, Ed, obviously we have to finalize the Phase III protocol. We're obviously working with our vendor partners very actively. It's good we've been active on the podium at all these endocrine meetings around the world. And we've contacted and direct contact with really experienced investigators as a result.

There's a lot more work that has to be done in terms of qualifying and activating the sites. And of course, we have our Phase III drug product manufactured and ready to go. So we will have it ready to go. And so, all the preparation that needs to be done, we're doing right now.

And we hope to have plenty of patients screened in the study for the end of the year..

Okay. Thanks, Rick, for taking my question..

Thank you. And our next question coming from the line of Catherine Novack with Jones Research. Your line is open..

Oh, hi. Good afternoon, guys. Just one question.

Can you remind us of what percent of the OraGrowtH patients enrolled were boys versus girls? And there is difference between how these two populations might be managed by pediatric endocrinologists, a sense that there could potentially encourage patients who might not choose to have a daily injection, try an OraGrowtH hormone therapy instead..

Duke, why don't you answer that question? Thanks. Appreciate the question, Catherine..

Yes, thank you, Catherine. That's a very good question.

Our trial is very, kind of unique, right? As you know, when you look at most of Phase III trials, especially long-acting [indiscernible] or Pfizer, majority of those subject that enrolled in a trial have male predominance, right? In our study, it's pretty much that, male a little bit more than female, but it's not that huge difference, which is very, very interesting.

I think when we go back to the first global Phase III trial, you can see that the number of countries going to increase, the number of sites going to increase because the timeline we want to enroll, we have a goal that we want to complete enrollment within 15 months to 18 months, which is, again, this goal is actually a little bit better than the goal that those previous Phase III trials have been running.

Part of it is that, that's dealing COVID and now we don't have COVID and not to mention that we do not expect a lot of competitor to run the Phase III trial, right? And in regards to the oral, I think that to enroll these subjects, I heard loud and clear when they start the Phase II trial to increase enrollment and autonomy manner, we realized that a lot of subjects really interested to participate in these oral LUM-201 trials.

Again, I don't think that we expect any issue to get the patient enrolled, especially most of them would like to be able -- to be on this drug and especially during the clinical trial, because it would take years for us to really get the drug approved. I hope that answers all the questions you have..

Yes, that's very helpful. And actually just one more on the end-of-Phase II meeting. We've heard over and over from KOLs that growth beyond 12 months is really the most important aspect to them.

Are these data going to be a part of your discussion with FDA? And how important is that to the Phase II trial design?.

Boy, that is a very good question, Catherine, and I'm going to ask John to answer it..

Yes. Thank you, Catherine. So I think the data that we've shown about the small subset of kids that we have at 24 months on growth has been very telling.

The restoration of normal growth, normal pulsatility, normal IGF-1 levels, and then more natural growth that results from that has led to very consistent and durable growth comparing year two to year one, right? We lose only a small, tiny bit, 6% of our AHV compared to a much larger drop off that you see with daily injectable growth hormone.

So that is a really important piece of data that we certainly will chat with the FDA about.

We do anticipate much, as Rick said earlier, a standard Phase III trial design of 12 months, but because we have a number of subjects already that have gone past that 12-month time frame, we're moving subjects from our 24-month long OraGrowtH210 study into a long-term safety extension.

We will have quite a lot of longer-term data by the time we get to Phase III and get to an NDA. So I think that data will be very helpful in addition to what we see in the Phase III 12-month study that Rick described. So it is very important and it will be a very nice package of durable data that we can bring..

Great, that's very helpful. Thanks a lot, guys..

Thank you. And I'm showing no further questions in queue at this time. And ladies and gentlemen, this concludes the Lumos Pharma Fourth Quarter 2023 Earnings Call. Thank you and have a good day..