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spk35: Good afternoon and welcome to Lumos Pharma's Q2 2023 Financial Results Conference Call. Currently, all participants are in 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, Senior Director of Investor Relations.
spk30: Thank you, Operator. 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 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 Form 10-Q, 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, and Lori Lawley, our CFO. John McHugh, our President and Chief Scientific Officer, as well as Dr. Patuk Chawanna, our Senior Vice President of Global Clinical Development and Medical Affairs, will join for the question and answer section. I will now turn the call over to Rick.
spk11: Thank you, Lisa, and good afternoon, everyone. After the market closed today, we issued a press release announcing our second quarter 2023 financial results and providing an update on our clinical programs. As is our practice, We'll keep our prepared remarks on today's call brief so we can maximize the time available for Q&A. I'll touch on the highlights from the quarter in recent weeks before turning it over to Lori for review of our financial results. Then John McHugh and Dr. Patek Tawana, or Dr. Duke as we call him, will join us to answer your questions. Dr. Duke joined us about a year and a half ago from Ascendus, where he worked on their long-acting injectable growth hormone therapy or therapeutic through approval. He is also president of the Human Growth Foundation, and with his contacts and understanding of the potential of an oral therapeutic in this space, Duke has been instrumental in advancing the enrollment in our Oral Growth 210 trial and in the preparation for our Phase III trial in Pediatric Growth Hormone Deficiency, or PGHD. So let's begin. As reported this afternoon, during our second quarter of 2023, we made continued progress in advancing our oral therapeutic candidate, LUM201, in moderate idiopathic PGHD. We can confirm our expectation to report primary outcome data on up to 82 subjects in the dose range finding oral growth 210 trial, and up to 22 subjects in a mechanistic PK-PD oral growth 212 trial in the fourth quarter of 2023. And at this point, I'd like to remind everyone about our expectations for the primary readout. The primary endpoint for these trials is annualized height, velocity, or AHV at six months on treatment. And based on historical data, the predicted growth rate for LUM201 is between 8.3 centimeters in 8.6 centimeters per year for this moderate idiopathic PGSD population, according to observed growth in several large historical databases. The other objectives of the ERGRO 210 trial are to confirm the utility of the predictive enrichment marker, or PEM strategy, and to determine the optimal dose for a Phase III trial. We also expect our primary outcome readout to include AHP data at 12 months on treatment for up to 12 subjects per oral growth 210 cohort and up to seven subjects for oral growth 212 cohort for a total of up to 62 subjects from both trials. Additional AHP data at 18 and 24 months on treatment are also expected for a small number of subjects. In addition, The Phase II trial should demonstrate a safety profile comparable to the daily growth hormone control arm. And also, as is the case for all Phase II trials, the oral growth 210 trial is not powered to show non-inferiority of annualized high velocity between LUM201 and the control arm, but should inform the design of and dose selection for a successful registration Phase III trial. And as a reminder, the non-inferiority margin between the treatment arm and the controlled growth hormone arm for a pivotal phase 3 trial in this indication has historically been from 1.8 to 2 centimeters a year at 12 months on treatment. This has held true for recent approvals of long-acting growth hormone products as well. For the next steps in the program, we're obviously engaging in meticulous planning for a phase 3 trial. And after a thorough review of the data package, the first step will be to request an end of phase two meeting with the FDA to review the phase two results and agree upon the ultimate design of the phase three trial. And based on regulatory precedence, we expect that this registrational trial will include approximately 180 to 200 PEM positive subjects, randomized two to one versus growth hormone with a likely dose of 1.6 mg per kg of LUM201 to daily growth hormone, stratified by age and other factors to ensure balanced cohorts. Our proposed primary endpoint will be AHP at 12 months on therapy, and the trial will utilize the new LUM201 formulation for which we filed a novel formulation patent application last November enabled by unique properties of our compound, which could extend our IP protection to 2042. This formulation of LUM201 consists of many tablets in capsules, which we believe will provide an easier oral dosage form for the wide age range of our target population. We expect to hear from the US Patent Office later this year. Currently, Loom 201 has patent protection through 2036, plus applicable extensions for the detection and treatment of growth hormone deficiency, as well as orphan drug designation, which offers extended protection for up to 7 1⁄2 and 12 years from the date of drug approval in the U.S. and Europe, respectively. During the quarter, we were pleased to see further data and analysis from these two trials presented at the 2023 ENDO meeting. Data from these two abstracts were presented, including new data from the ORBO 212 trial that showed an increase in ITF1 levels on LUM201 at six months that remained within normal range. an increase in IGF-1 SDS greater than zero, and a durable growth response up to 12 months of LUM201 administration. There's clear evidence of potential drug effect for LUM201. It was also observed in consistent improvement in AHV over baseline. Also, new analysis of combined ORAGRO-210 and ORAGRO-212 trial data at the 1.6 and the 3.2 mixed per day dose levels in 15 subjects from the Orgo 212, 20 subjects from the Orgo 210. These combined results continue to demonstrate that there's a durable response to LUM201 from 6 to 12 months, and that the 1.6 and 3.2 mgs per gigaday doses are comparable in the growth each stimulated. And as many of you know, these data were highlighted in a key opinion leader webinar we hosted on June the 21st, where doctors Fernando Casorla and Michael Tansey shared their insights on the data and their continued convictions in the potential of LUM201 to become the first oral therapeutic to address this patient population treated solely by injectable therapies for the last four years. If you've not seen the webinar, we encourage you to review the replay, which is still available on our website. Additional analysis of data from the Orgo 212 trial was accepted as a late-breaking abstract for oral presentation at the upcoming annual meeting of the European Society of Pediatric Endocrinology, or ESPI, which was held in The Hague in the Netherlands, September 21 to 23. This abstract by Fernando Casorla will include a deconvolution analysis of growth hormone secretion with LUM201 administration in the moderate PGHD population. And turning to other developments, we continue to support our clinical collaboration with Dr. Laura Dichtel in Massachusetts General Hospital to explore the potential of orally administered LUM201 in non-alcoholic fatty liver disease, or NAFLD. Positive results from this investigator's prior trial evaluating injectable growth hormone in NAFLD were recently published in the Journal of Clinical Endocrinology and Metabolism. It was these compelling data that encouraged Dr. Dickel and Mass General to initiate the collaboration with Lumos Pharma to assess oral LUM201 in the same indications. In the prior study, investigators hypothesized that growth hormone might reduce hepatic steatosis or fat buildup in the liver in obese patients with NAFLD. Subjects were randomly assigned to a treatment group, 27 growth hormone and 26 of placebo group with 41 completers overall, 20 on growth hormone, 21 on placebo at six months. Reduction in absolute percent of enterohepatic lipid content by proton magnetic resonance spectroscopy was significantly greater in the growth hormone versus the placebo cohorts. Investigators concluded that growth hormone reduces liver fat without commensurate weight loss. These data are supportive of evaluation of oral LUM201 in the NAPLD indication. LUM201 pilot trial in NAPLD continues to enroll. As a reminder, the company's primary near-term focus remains on advancing LUM201 in PGHD. Now, as previously mentioned, we believe that LUM201 has the potential to address about 10 other indications currently treated by injectable growth hormone. We've done a lot of work internally to assess the potential of LUM201 and other indications in different geographic regions worldwide. And as we've said before, we narrowed our focus to idiopathic short stature, or ISS, and Prader-Willi syndrome, where we see a sizable opportunity both in the U.S. and internationally. And while we assess these opportunities, we remain committed to the prudent use of our cash and ensuring our capital allocation is focused on advancing our core program. So with that, I'm going to turn it over to Lori for a review of our financial results. Lori?
spk25: Thank you, Rick. Lumos Pharma ended the quarter on June 30, 2023 with cash, cash equivalents, and short-term investments totaling $50.9 million compared to $67.4 million on December 31, 2022. We reiterate our expectation for average cash use of approximately $9.5 to $10.5 million per quarter through 2023. Cash, cash equivalents, and short-term investments as of June 30, 2023 are expected to support operations through at least the next 12 months from the date of the filing of our second quarter 2023 financial statement, which is well beyond our announcement of top-line Phase 2 trial results in the fourth quarter of 2023. This guidance is inclusive of estimated costs to be incurred in preparation for a Phase 3 trial, including estimated costs for clinical trial site initiation, contract manufacturing expenses, and regulatory expenses. These costs may change depending on the primary data from the Oregon 210 trial and subsequent feedback from regulatory agencies. Research and development expenses increased by $1.4 million for the three months ended June 30th, 2023 compared to the same period in 2022. Primarily dues increases of $1.1 million in contract manufacturing expenses, $0.4 million in clinical trial expenses, and $0.1 million in personnel related expenses offset by a $2 million increase in consulting expenses. General and administrative expenses increased by $0.5 million for the three months ended June 30, 2023, compared to the same period in 2022, primarily due to increases of $0.2 million in personnel-related expenses, $0.1 million in stock compensation expenses, $0.1 million in travel expenses, and $0.1 million in royalty expenses. The net loss for the quarter ended June 30th, 2023 with $8.9 million compared to a net loss of $7.8 million for the same period in 2022.
spk22: We ended June 30th, 2023 with 8,941,345 shares. With that, I will turn the call back to Rick to conclude for us.
spk11: Thank you, Lori. So, to recap, we can confirm our plan to report top-line data from both Orgo 210 and Orgo 212 trials in the fourth quarter of 2023. New interim data analysis presented at INDO and other medical meetings this year further reinforce our confidence that primary outcome data from these two oral growth trials should achieve the predicted annualized high velocity at six months on treatment in line with historical averages of 8.3 to 8.6 centimeters a year for this moderate idiopathic PGSD population. Though our Phase II trials are not powered to show non-inferiority, primary outcome data from these trials should support selection of the LUM201 dose for a registrational Phase III trial with non-inferiority to growth hormone of approximately 1.8 to 2 centimeters should determine success based on historical approvals. Our novel formulation of Oral Growth 201 should also facilitate adherence to treatment protocols in both this pivotal trial and in the commercial setting. And if a new patent is granted, it would extend IP protection beyond our current 2036 expiration date. We believe Oral Loom 201 represents a platform therapeutic with the potential not only to disrupt the current worldwide $3.5 billion growth hormone market treated by injectable growth hormone products, Now, that excludes China, which is also another $1 billion, but also to expand the market by increasing the historically low compliance and treatment rates due to the high burden of current injectable therapies. Additionally, we'll continue to explore utility in broader indications, such as NAFLD, where initial clinical studies have shown growth hormone treatment to be beneficial. And in the near term, we're focused on advancing our clinical programs in PGHD, and we have the capital to support that effort well beyond our primary outcome readout later this year. And finally, in September, we plan to host both a KOL panel webinar and a KOL dinner where noted pediatric endocrinologists will discuss their experience with PGHD patients, the therapeutic landscape, and the potential for an early administered therapeutic to address other indications currently treated by injectable growth hormone. We're excited to continue to advance our clinical programs and look forward to disclosing top line data in the fourth quarter of 2023. So thank you very much for your time today. And operator, we're ready to take questions.
spk35: Thank you. The lines are now open for questions. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.
spk01: Our first question is from Yasmin Rahimi of Piper Sandler.
spk35: Your line is now live.
spk18: Good afternoon, team. Thank you so much for all the updates. I guess, could you maybe comment on how soon post the aura growth readout you could be in a position to kick off the phase three studies? Maybe also some color on if you've started warehousing patients for the phase three and help us around enrollment timelines. And then third, when do you hope to get color in regards to the patents that are filed with the new formulation? I appreciate color on those topics. Thank you again.
spk11: John, I'm going to let you answer the first question that Yaz asked.
spk17: So, Yaz, right now we're focused on thinking through all the steps to get you know, the data readout in the fall all the way out to the, you know, the end of phase two meeting, an agreement with the FDA on our phase three protocol, right? So there's, you know, there's a lot of work involved there in integrating the data from these two studies, you know, making any necessary adjustments to our phase three clinical plans, putting together that briefing book, you know, waiting those 60 days to get the meeting and then, you know, hopefully quickly coming to agreement with FDA on, you know, what that phase three protocol is going to look like. And really from then is when we'll start to kick off really the extent of our focus on bringing trial sites up and getting ready to go. We've done a lot of the phase three prep work as much as we can. We're working on that right now. But we really need to get that final agreement on the protocol really to start kicking things off. you know, getting sites to be thinking about patients. Remember, the patients that we need are naive to treatment, and so, you know, it's a little bit early right now to, you know, you can be watching patients, but I think going any further than that, we'd want to hold off on. In terms of the patent, so we filed this patent in November of last year, right? So, you know, a 12-month decision time is not... It's kind of an expected timeline for when we might hear back on that guidance.
spk11: And, yes, let me just add, you know, we have an obviously really experienced clinical development team. We've really performed well in the 210 and 212 trials and the extensions of those trials. in terms of time to enrollment. And I think that is due to two things. Number one, you know, highly experienced, motivated staff has really managed these trials quite well. And the second thing is that, you know, there is a lot of interest. Most of these experienced investigators have been working their entire careers with injectable products. This is the first time that an oral product for PGSD has shown up. So they're pretty excited to work with us. And so we get a lot of attention. I might add one other point, and that is, you know, you think about the typical time it takes to enroll a full, you know, 180, 200 patients. And historically, you look at the companies who have done that in the long acting space. And, you know, they were all enrolling in a phase three in competition with each other. They're finished with those studies. Obviously, those products are approved. While we certainly expect there's going to be some competition for these patients, we believe there's going to be a lot less than there was before. And therefore, we think enrollment is going to go well. But I maybe just ask Duke to comment here because, you know, he's really been instrumental in his connection with all these highly experienced sites.
spk02: Thank you, Rick. So let me touch base with the timeline and enrollment, which is, again, most of the phase three trial, that's one of the big hurdles that most companies have experienced, right? With my connection with the KOL around the world, with experience I have done in the past, we hope that if we actually have well-prepared site initiation and potentially could start up site enrollment across the world as pretty much as the same timeline. We'd be able to cut down the number of recruitment and timeline or complete enrollment. But again, a lot of factor involved, but we would do our best based on strategy planning, as John had mentioned.
spk18: Got it. Thank you. Yes, did that answer your question? Yeah, that was very helpful. Thank you, team.
spk15: Thank you, Yaz.
spk35: Thank you. One moment, please, for the next question.
spk01: Our next question is from Leland Gershel of Oppenheimer.
spk35: Your line is now live.
spk13: Hey, guys. Thanks for taking my question and for the comprehensive framing of how to think about things as we head into the readout later this year. A couple questions from me. First, with respect to, obviously, you know, as we look forward to the data from ORA Growth 210 next quarter, wondering if you'd be able to share the PEM screening results or give any color to whether that's the rates of success you've been seeing with the PEM screening have aligned with your expectations. And then number two, As we look forward to the SB conference, you mentioned there'd be some additional analyses of the prior study. Just wondering if you could share what the nature of those additional analyses might be. Thank you.
spk11: All right. John, do you want to start with the PEM and the SB analysis?
spk17: Sure. Thanks for the question, Leland. So, you know, the PEM test has been very effective as an inclusion criteria in the 210 study. We spent a lot of time educating the clinicians in that study as to which subjects to screen, to bring into the trial, and our success rate at inclusion is actually quite high. We had originally said in the entire population about two-thirds of the kids would be PEM positive. We're actually seeing a much higher number of tests returning a positive value simply because of how the clinicians are focusing their efforts and looking for patients, right? Looking towards the more moderate end of the spectrum and kids who kind of fit the criteria of that slice of the patient population. So we're getting, you know, a very high number of kids who are PEM positive versus what you would expect from just looking at the epidemiology data of that, you know, the whole spread of birth limit deficiencies. The second question about the endo, or I'm sorry, the SB meaning. So we've, you know, we've given out the title about the deconvolution analysis of the 212 study. So essentially it's focused on the 212 study and, you know, deconvolution of the PD data that is there. Those abstracts haven't been published yet, but the, you know, the program has been announced. So I think we'll have to wait until they publish the abstract to get a little bit more information about what's going to be released there. But from the title, that should give you a good sense of what's in there.
spk13: Great. Thanks so much for taking the questions, and I look forward to the updates.
spk06: Thanks for the question, Leland.
spk35: Thank you. One moment, please, for the next question. Our next question is from Ed White of HC Wainwright. Your line is now live.
spk14: Hi. Thanks for taking my questions. Just going back to the Phase III study, and this might be difficult to answer, but how are you thinking about the number of sites that you're going to need for the Phase III to enroll that 180 to 200 patients? How is the split going to go between U.S. sites and ex-U.S. sites? And also, how are you thinking about the patient population? Same question, U.S. versus outside the U.S.
spk09: John, you want to start?
spk17: So we haven't released the total number of sites. We're kind of deep in discussions with CROs and trying to get their input on what they've seen in the past. Obviously, we're reviewing what some of the folks in these successful long-acting programs have done. So we haven't really decided on a firm decision on the number of sites. Obviously, we are going to do a global trial, as we've talked about. I think it's important. You know, we do expect to get different recruitment rates in different regions, you know, depending on access to growth hormone. And so I think we have to put all those together. In terms of what the FDA wants, obviously, I think we can certainly use, you know, almost all the U.S. and European sites are quite acceptable. And I think, you know, some of the Asian countries have, you know, requirements. which patients have to be have to be or what number of patients have to be enrolled so i think we're working through all those those thoughts right now uh we don't have a final plan yet but they are all things that we're thinking through yeah uh let me just continue with that uh and you know the benefit of being on the podium at all of these intricate meetings uh around the world
spk11: is that all these experienced investigators have really attended those meetings with a great deal of interest because of us being a first oral. The result is that I think more and more people are becoming real believers in what we're doing. And they've been reaching out to us and offering to be, you know, clinical sites. I don't think there's going to be, you know, a problem in choosing the sites. In fact, we have the benefit of more recent historical entry rates from recently just completed trials, you know, by site. And Duke, of course, has a great deal of experience in that. So I think that's going to be much to our benefit.
spk14: Thanks, Rick. And perhaps a question on, you know, what's next for the company? You had mentioned the next indications are ISS and PWS. How should we be thinking about that? Are you prepared to run, you know, perhaps a phase one study concurrently with a phase three study that we've just been discussing, or will this be something that you're thinking about post-phase three data?
spk11: You know, Ed, I think the answer to that question is, you know, if we were a large company, we'd probably have a different plan. Capital markets are what they are. You know, as we go out and do a all the advanced planning for our phase three, that's where we're going to be focused. If the capital markets are going to permit us to raise the appropriate amount of money over time, then we're going to start programs, other programs perhaps sooner than we normally would plan them. In addition to that, typically what happens when companies in their development plans get to the stage at the end of phase two, end of phase three, you know, regional partners show up, or at least that's what we're partners of all times. And as, you know, I think our head of business development is a pretty busy guy at this stage, and we're going to, I think, have some choices here to look at some partners who could help us advance the program. And that could be in other indications, too, although we certainly haven't had those discussions with anyone yet.
spk14: Great, thanks, Rick. And perhaps a question for Lori, just when thinking about R&D moving into the back half of the year, you mentioned that $1.1 million in commercial contracting expenses hitting in the quarter. I take it a one-time event, and we should be thinking about the run rate more like the first quarter?
spk21: I think our research and development experience
spk25: expenses for Q2 are pretty, you know, pretty on par with what we should expect, Leland, going forward, not just in contract manufacturing expenses, but also in clinical. And recall that we are comparing this to 2022, and a lot of the efforts in 2023, you know, are going towards working to prepare for a Phase III clinical trial. So, R&D, we expect overall R&D and G&A operating expenses to be between
spk14: Okay. Thanks, Lori. Thank you, everyone, for taking my questions.
spk05: Thank you, Ed.
spk35: One moment, please, for our next question. Our next question is from Catherine Novak of Jones Trading. Your line is now live.
spk26: Hi. Good afternoon, everyone. Just a question on some KOL issues, you know, what we've heard time and again is that their real focus in PGHD is, you know, 12, 24 months and beyond. And here we tend to see injectable growth hormone attenuate after about the first year. So given the mechanism of action, is it safe to say you wouldn't expect this to be so dramatic with LUM201? And then, you know, how should this change our expectations for what we should see in the data in phase two and phase three?
spk11: Well, thanks for that excellent question, Catherine. John, will you answer that?
spk17: Sure. So, two things to keep in mind. The Phase III study will be a 12-month study, and so kind of the key decision point for that Phase III will be non-inferiority at 12 months. Obviously, we have several ongoing trials now that are longer than 12 months, right? And we'll, you know, hopefully keep as many kids as we can in that trial and transition kids from the phase three into an extension trial as well. So we will have a body of data on treatment past 12 months, but it won't be as comprehensive as the data we have at six and 12 months. And that's the same data package that all the long actings have brought in. You know, that said, you can look at the difference in growth or look at the difference in annualized site velocity for individual patients between, you know, at six months, at 12 months, at 18 months, and look at the slope of that decline. And as you said, it's well documented, you know, that growth hormone has its kind of biggest peak in the three to six month range. And then, you know, every year after that, you get a decline. You don't get the same growth every year, right? You get a decline in returns. You know, LUM 201 has been shown in adults. It's been published in adults that you can elevate IGF-1 and growth hormone levels out to 24 months, right? So in adults that change body composition, we get that same level of continued elevation. In kids, we would expect to see a continued growth. And I think some of the early data that we're going to reveal at the end of this year on the handful of kids past 12 months will really start to help put those pieces together for us. But there are certainly scenarios where you could expect that we're going to modulate kids to a more natural growth pattern that could be a much flatter growth slope than what you might see with kind of the pharmacological or supraphysiological levels of injectable growth hormone. Thank you for that question.
spk26: Yeah, of course. And then just one more, you know, now that we've got a couple weekly injectables in the market for TGHC, you know, what kind of feedback are you getting from KOLs or what are you hearing? How excited are they to use them? And does this factor into your Loom 201 market expectations at all?
spk11: You know, Catherine, look, there's no question that this could be a highly competitive space. And you look at the price on a monthly basis between the three growth hormones, long-acting growth hormones, there's something like $7,000, $8,000, and $9,000 per month, you know, all that, you know, to yearly cost of over $100,000 for a 35-kilo kid. That's expensive treatment. I think there are, you know, there are certain parts of the world where the standard of care is going to continue to be that daily because of restriction in price or longer time to approvals in different markets around the world. We believe, I mean, we've done our market research. We've asked the question both to pedendos and to parents if you had a choice between a weekly injection or a daily oral. They overwhelmingly say they would choose a daily oral. And on top of that, I'm going to remind you, we're a small molecule. Our cost of goods and our flexibility in pricing and margins is, it looks very favorable to us long-term in this market.
spk02: Well, Kathleen may add with the feedback from the KOL industry card. Rick mentioned about the pricing. That's a very important, right? It's more expensive than daily. The other issue that the KRL has some skeptical is the safety data profile. As you know, that in order to get approved FDA, you only have 12-month safety data. However, long-term safety, especially long-acting, not only look at efficacy itself, the long-term side effect, which is, again, you know, it's very unclear at the short-term, right? When you look at, you know, profile, the growth hormone exposure for weekly growth hormone, it's much higher than daily growth hormone and also higher IGF-1. With that said, you know, long-term, post-faithful study or post-marketing study need to continue in order to show off the safety profile in the long-term fashion. So that's something that some KALs feel quite skeptical to really put all subjects in weekly Goldman therapy in regards to efficacy itself, right? So not to mention it's very expensive.
spk11: Yeah, and Catherine, recall, you know, our mechanism of action is very different from growth hormone. You know, we stay within the natural endocrine feedback loop, and those excursions you get with higher levels of growth hormone with especially the long-acting is not possible with our drug. Once again, that feedback loop stays within the natural physiology.
spk26: Great. Okay. That's answered my question. Thanks very much.
spk35: One moment, please, for our next question. Our next question is from Pete Stavropoulos of Cantor Fitzgerald. Your line is now live.
spk39: Hi, Rick and team. Nice to see all the progress made this quarter and movement towards data readout by year end. First question is when you look at the data that you've generated to date using the PEM, the Predictive Enrichment Marker, and the growth that you've observed in these patients, just curious to know, as you move into a later, larger study, you know, if you expect to keep the cutoffs where they currently are, or do you think, you know, you can increase the probability of success by focusing or enriching patients with a greater response, you know, or is the current algorithm sufficient?
spk11: Pete, thank you for that good question, and John, why don't you start?
spk17: You know, I think, Pete, we're comfortable with the, the enrichment that we're getting from using our pen markers right now, but obviously we, you know, we haven't looked at all the data yet, right? So we need to look at the HV data for the other half of the patients that have come in. But I think we feel pretty confident based on, you know, the analysis that we originally did and as well as how things are rolling out now.
spk39: Okay. And, you know, as you think about a phase three design, you know, I understand that, you know, you need to end the phase two meeting and to come to an agreement, you know, with the agency. However, are there any modifications you might make to enrollment or trial design for a pivotal study based on the accumulating data from 210 and 212?
spk07: John, why don't you start with that question?
spk17: You know, I think the, you know, the phase three, design and basic kind of inclusion characteristics are pretty common across all the three long-acting products that have been successful and, you know, are pretty much how we would go forward. Obviously, our patient population has to be PEM positive. That's a distinction. But other than that, I think, you know, the timeline and the approximate ends, I think, are pretty pretty close to what we would expect after we do the analysis at the end of the study. So we don't see any radical departures from, you know, from those that have gone before us here.
spk39: Okay. And sorry, go ahead. Do you have something to add?
spk04: No, go ahead. Please go ahead.
spk39: And last question, you know, directed towards the Duke, but, you know, Rick, John, more than welcome. You know, so, you know, you've presented, you know, Lumos presented a number of at different endocrinology meetings, you know, most recently at Endo 2023. So just wondering, you know, when you speak to KOLs, you know, some of your former colleagues and even practicing, you know, clinicians about womb 201, it's a mechanism of action and how it may be differentiated from standard of care. You know, just curious to hear, you know, what the reception of this candidate and approach is and the data presented today is.
spk10: Yeah. And so, Duke, why don't you go ahead?
spk02: Yeah. So, actually, it's very, very positive. As you may know, right, this is oral growth hormone secretion have been proposed for the treatment for years, but none of those trials have been, you know, successful. So, here is the LUM201, which is mechanism of action of the drug itself. It's somewhat different shape in itself from the oral growth hormone secreting peptide or secretagogue out there, right? They have long acting, you generate IGF-1 that's sustained. And based on the presentation at PES and at ENDO, one represents only 210 data alone in regards to growth velocity, and it's very clearly shown that compared to historical data, moderate idiopathic population, the growth velocity somewhat match. And we look at the combined data, try to see that, you know, what the response looked like. It seemed like, you know, the dose that had been selected, especially 1.6 and 3.2, it's pretty comparable. And you can see those data in six-month and 12-month, you know, results. But again, it's a very small number. But most of the physicians really feel intrigued about the data. They did not know that this growth hormone, oral secretes, will work as good. And again, because it was failed in the past. Not to mention that if these drugs get approved, will be alternative for their patient, and especially the impact of compliance should be less. And again, we expect that the burden of injection with the majority of those patients suffering from daily or long acting could be somewhat overcome by this new therapy. But again, overall, it's very, very positive. They all just need to looking forward for the top line data and especially the new phase three pivotal trial in the future.
spk17: The only thing I would add to that, Pete, is that, you know, when we do these presentations at INPEI in March and PES and at ENDO, the room's packed, right? And there are lots of good questions, lots of excitement, lots of people, you know, wanting to talk to the presenters about this product. So, you know, One-on-one and then in the lecture halls, we feel a lot of excitement and a lot of interest. Yeah.
spk11: Yeah. And I might add, Pete, that, you know, we always have a booth at each one of these meetings. And right alongside of all the competitors in the growth hormone space. And I am absolutely amazed at the level of interest and the number of really great questions and just overall excitement that everybody feels, oh, the fact that there's a possibility of an oral alternative for their patients. I mean, it's a very important and exciting space to be in right now, just based on the feedback from these clinicians.
spk39: That's great to hear. Thank you for taking our questions and congratulations on the progress.
spk08: All right. Thank you, Pete.
spk35: Thank you. I'm showing no further questions on the line. This concludes the Lumos Pharma second quarter earnings call.
spk01: Thank you and have a great day. Hello. Thank you. Thank you.
spk00: Thank you. you Bye.
spk35: Good afternoon and welcome to Lumos Pharma's Q2 2023 Financial Results Conference Call. Currently, all participants are in 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, Senior Director of Investor Relations.
spk30: Thank you, Operator. 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 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 Form 10-Q, 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, and Lori Lally, our CFO. John McHugh, our President and Chief Scientific Officer, as well as Dr. Patuk Chawanna, our Senior Vice President of Global Clinical Development and Medical Affairs, will join for the question and answer section. I will now turn the call over to Rick.
spk11: Thank you, Lisa, and good afternoon, everyone. After the market closed today, we issued a press release announcing our second quarter 2023 financial results and providing an update on our clinical programs. As is our practice, We'll keep our prepared remarks on today's call brief so we can maximize the time available for Q&A. I'll touch on the highlights from the quarter in recent weeks before turning it over to Lori for review of our financial results. Then John McHugh and Dr. Patuk Tawana, or Dr. Duke as we call him, will join us to answer your questions. Dr. Duke joined us about a year and a half ago from Ascendus, where he worked on their long-acting injectable growth hormone therapy, or therapeutic, through approval. He is also president of the Human Growth Foundation, and with his contacts and understanding of the potential of an oral therapeutic in this space, Duke has been instrumental in advancing the enrollment in our Oral Growth 210 trial and in the preparation for our Phase III trial in Pediatric Growth Hormone Deficiency, or PGHD. So let's begin. As reported this afternoon, during our second quarter of 2023, we made continued progress in advancing our oral therapeutic candidate, LUM201, in moderate idiopathic PGHD. We can confirm our expectation to report primary outcome data on up to 82 subjects in the dose range finding oral growth 210 trial, and up to 22 subjects in a mechanistic PK-PD oral growth 212 trial in the fourth quarter of 2023. And at this point, I'd like to remind everyone about our expectations for the primary readout. The primary endpoint for these trials is annualized height, velocity, or AHV at six months on treatment. And based on historical data, the predicted growth rate for LUM201 is between 8.3 centimeters and 8.6 centimeters per year for this moderate idiopathic PGSD population, according to observed growth in several large historical databases. The other objectives of the ARGO 210 trial are to confirm the utility of the predictive enrichment marker, or PEM strategy, and to determine the optimal dose for a Phase III trial. We also expect our primary outcome readout to include AHP data at 12 months on treatment for up to 12 subjects per oral growth 210 cohort and up to seven subjects for oral growth 212 cohort for a total of up to 62 subjects from both trials. Additional AHP data at 18 and 24 months on treatment are also expected for a small number of subjects. In addition, The Phase II trial should demonstrate a safety profile comparable to the daily growth hormone control arm. And also, as is the case for all Phase II trials, the oral growth 210 trial is not powered to show non-inferiority of annualized high velocity between LUM201 and the control arm, but should inform the design of and dose selection for a successful registration Phase III trial. And as a reminder, the non-inferiority margin between the treatment arm and the controlled growth hormone arm for a pivotal phase 3 trial in this indication has historically been from 1.8 to 2 centimeters a year at 12 months on treatment. This has held true for recent approvals of long-acting growth hormone products as well. For the next steps in the program, we're obviously engaging in meticulous planning for a phase 3 trial. And after a thorough review of the data package, the first step will be to request an end of phase two meeting with the FDA to review the phase two results and agree upon the ultimate design of the phase three trial. And based on regulatory precedence, we expect that this registration trial will include approximately 180 to 200 PEM positive subjects, randomized two to one versus growth hormone with a likely dose of 1.6 mg per kg of LUM201 to daily growth hormone, stratified by age and other factors to ensure balanced cohorts. Our proposed primary endpoint will be AHV at 12 months on therapy, and the trial will utilize the new LUM201 formulation for which we filed a novel formulation patent application last November enabled by unique properties of our compound, which could extend our IP protection to 2042. This formulation of LUM201 consists of many tablets in capsules, which we believe will provide an easier oral dosage form for the wide age range of our target population. We expect to hear from the US Patent Office later this year. Currently, LUM201 has patent protection through 2036, plus applicable extensions for the detection and treatment of growth hormone deficiency, as well as orphan drug designation, which offers extended protection for up to seven and a half and 12 years from the date of drug approval in the U.S. and Europe, respectively. During the quarter, we were pleased to see further data and analysis from these two trials presented at the 2023 ENDO meeting. Data from these two abstracts were presented, including new data from the ORBO 212 trial that showed an increase in IGF-1 levels on LUM201 at six months that remained within normal range. an increase in IGF-1 SDS greater than zero, and a durable growth response up to 12 months of LUM201 administration. There's clear evidence of potential drug effect for LUM201. It was also observed in consistent improvement in AHV over baseline. Also, new analysis of combined ORAGRO-210 and ORAGRO-212 trial data at the 1.6 and the 3.2 mixed per day dose levels in 15 subjects from the Orgo 212, 20 subjects from the Orgo 210. These combined results continue to demonstrate that there's a durable response to LUM201 from 6 to 12 months, and that the 1.6 and 3.2 mgs per gigaday doses are comparable in the growth each stimulated. And as many of you know, these data were highlighted in a key opinion leader webinar we hosted on June the 21st, where Doctors Fernando Casorla and Michael Tansey shared their insights on the data and their continued convictions in the potential of LUM201 to become the first oral therapeutic to address this patient population treated solely by injectable therapies for the last four years. If you've not seen the webinar, we encourage you to review the replay, which is still available on our website. Additional analysis of data from the Orgo 212 trial was accepted as a late-breaking abstract for oral presentation at the upcoming annual meeting of the European Society of Pediatric Endocrinology, or ESPI, which was held in The Hague in the Netherlands, September 21 to 23. This abstract by Fernanda Casorla will include a deconvolution analysis of growth hormone secretion with LUM201 administration in the moderate PGHD population. I turn to other developments. We continue to support our clinical collaboration with Dr. Laura Dictel in Massachusetts General Hospital to explore the potential of orally administered LUM201 in non-alcoholic fatty liver disease, or NAFLD. Positive results from this investigator's prior trial evaluating injectable growth hormone in NAFLD were recently published in the Journal of Clinical Endocrinology and Metabolism. It was these compelling data that encouraged Dr. Dickel and Mass General to initiate the collaboration with Lumos Pharma to assess oral LUM201 in the same indications. In the prior study, investigators hypothesized that growth hormone might reduce hepatic steatosis or fat buildup in the liver in obese patients with NAFLD. Subjects were randomly assigned to a treatment group, 27 growth hormone and 26 of placebo group with 41 completers overall, 20 on growth hormone, 21 on placebo at six months. Reduction in absolute percent of intrahepatic lipid content by proton magnetic resonance spectroscopy was significantly greater in the growth hormone versus the placebo cohorts. Investigators concluded that growth hormone reduces liver fat without commensurate weight loss. These data are supportive of evaluation of oral LUM201 in the NAPLD indication. LUM201 pilot trial in NAPLD continues to enroll. As a reminder, the company's primary near-term focus remains on advancing LUM201 in PGHD. Now, as previously mentioned, we believe that LUM201 has the potential to address about 10 other indications currently treated by injectable growth hormone. We've done a lot of work internally to assess the potential of LUM201 and other indications in different geographic regions worldwide. And as we've said before, we narrowed our focus to idiopathic short stature, or ISS, and Prader-Willi syndrome, where we see a sizable opportunity both in the U.S. and internationally. And while we assess these opportunities, we remain committed to the prudent use of our cash and ensuring our capital allocation is focused on advancing our core program. So with that, I'm going to turn it over to Lori for a review of our financial results. Lori?
spk25: Thank you, Rick. Lumos Pharma ended the quarter on June 30, 2023 with cash, cash equivalents, and short-term investments totaling $50.9 million compared to $67.4 million on December 31, 2022. We reiterate our expectation for average cash use of approximately $9.5 to $10.5 million per quarter through 2023. Cash, cash equivalents, and short-term investments as of June 30, 2023 are expected to support operations through at least the next 12 months from the date of the filing of our second quarter 2023 financial statement, which is well beyond our announcement of top-line Phase 2 trial results in the fourth quarter of 2023. This guidance is inclusive of estimated costs to be incurred in preparation for a Phase 3 trial, including estimated costs for clinical trial site initiation, contract manufacturing expenses, and regulatory expenses. These costs may change depending on the primary data from the ORAGRA 210 trial and subsequent feedback from regulatory agencies. Research and development expenses increased by $1.4 million for the three months ended June 30, 2023 compared to the same period in 2022. Primarily due to increases of $1.1 million in contract manufacturing expenses, $0.4 million in clinical trial expenses, and $0.1 million in personnel related expenses offset by a $0.2 million increase in consulting expenses. General and administrative expenses increased by $0.5 million for the three months ended June 30, 2023, compared to the same period in 2022, primarily due to increases of $0.2 million in personnel-related expenses, $0.1 million in stock compensation expenses, $0.1 million in travel expenses, and $0.1 million in royalty expenses. The net loss for the quarter ended June 30, 2023, with $8.9 million compared to a net loss of $7.8 million for the same period in 2022. We ended June 30, 2023, with $8.9 million and 41,345 shares.
spk22: With that, I will turn the call back to Rick to conclude for us.
spk11: All right. Thank you, Lori. So, to recap, we can confirm our plan to report top-line data from both Orgo 210 and Orgo 212 trials in the fourth quarter of 2023. New interim data analysis presented at INDO and other medical meetings this year further reinforce our confidence that primary outcome data from these two oral growth trials should achieve the predicted annualized high velocity at six months on treatment in line with historical averages of 8.3 to 8.6 centimeters a year for this moderate idiopathic PGSD population. Though our phase two trials are not powered to show non-inferiority, primary outcome data from these trials should support selection of the LUM201 dose for a registrational phase three trial where non-inferiority to growth hormone of approximately 1.8 to 2 centimeters should determine success based on historical approvals. Our novel formulation of Oral Growth 201 should also facilitate adherence to treatment protocols in both this pivotal trial and in the commercial setting. And if a new patent is granted, it would extend IP protection beyond our current 2036 expiration date. We believe Oral Loom 201 represents a platform therapeutic with the potential not only to disrupt the current worldwide $3.5 billion growth hormone market treated by injectable growth hormone products, Now, that excludes China, which is also another $1 billion, but also to expand the market by increasing the historically low compliance and treatment rates due to the high burden of current injectable therapies. Additionally, we'll continue to explore utility in broader indications, such as NAFLD, where initial clinical studies have shown growth hormone treatment to be beneficial. And in the near term, we're focused on advancing our clinical programs in PGHD, and we have the capital to support that effort well beyond our primary outcome readout later this year. And finally, in September, we plan to host both a KOL panel webinar and a KOL dinner where noted pediatric endocrinologists will discuss their experience with PGHD patients, the therapeutic landscape, and the potential for an early administered therapeutic to address other indications currently treated by injectable growth hormone. We're excited to continue to advance our clinical programs and look forward to disclosing top line data in the fourth quarter of 2023. So, thank you very much for your time today. And operator, we're ready to take questions.
spk35: Thank you. The lines are now open for questions. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster.
spk01: Our first question is from Yasmin Rahimi of Piper Sandler.
spk35: Your line is now live.
spk18: Good afternoon, team. Thank you so much for all the updates. I guess, could you maybe comment on how soon post the aura growth readout you could be in a position to kick off the phase three studies? Maybe also some color on if you've started warehousing patients for the phase three and help us around enrollment timelines. And then third, when do you hope to get color in regards to the patents that are filed with the new formulation? Appreciate color on those topics. Thank you again.
spk11: John, I'm going to let you answer the first question that Yaz asked.
spk17: So, Yaz, right now we're focused on thinking through all the steps to get from you. you know, the data readout in the fall all the way out to the, you know, the end of phase two meeting, an agreement with the FDA on our phase three protocol, right? So there's, you know, there's a lot of work involved there in integrating the data from these two studies, you know, making any necessary adjustments to our phase three clinical plans, putting together that briefing book, you know, waiting those 60 days to get the meeting, and then, you know, hopefully quickly coming to agreement with FDA on, you know, what that phase three protocol is going to look like. And really from then is when we'll start to kick off really the extent of our focus on bringing trial sites up and getting ready to go. We've done a lot of the phase three prep work as much as we can. We're working on that right now, but we really need to get that final agreement on the protocol really to start kicking things off and, you know, getting sites to be thinking about patients. Remember, the patients that we need are naive to treatment. And so, you know, it's a little bit early right now to, you know, you can be watching patients. But I think going any further than that, we want to hold off on. In terms of the patent, so we filed this patent in November of last year. So, you know, a 12-month decision time is not – it's kind of an expected timeline for when we might hear back on that patent.
spk11: And, yes, let me just add, you know, we have an obviously really experienced clinical development team. We've really performed well in the 210 and 212 trials and the extensions of those trials. in terms of time to enrollment. And I think that is due to two things. Number one, highly experienced, motivated staff has really managed these trials quite well. And the second thing is that there is a lot of interest. Most of these experienced investigators have been working their entire careers with injectable products. This is the first time that an oral product for PGSD has shown up. So they're pretty excited to work with us. And so we get a lot of attention. I might add one other point, and that is, you know, you think about the typical time it takes to enroll a full, you know, 180, 200 patients. And historically, you look at the companies who have done that in the long acting space. And, you know, they were all enrolling in a phase three in competition with each other. They're finished with those studies. Obviously, those products are approved. While we certainly expect there's going to be some competition for these patients, we believe there's going to be a lot less than there was before. And therefore, we think enrollment is going to go well. But maybe I just ask Duke to comment here because, you know, he's really been instrumental in his connection with all these highly experienced sites.
spk02: Thank you, Rick. So let me touch base with the timeline and enrollment, which is, again, most of the phase three trial, that's one of the big hurdles that most companies have experienced, right? With my connection with the KOL around the world, with experience I have done in the past, we hope that if we actually have well-prepared site initiation and potentially could start up site enrollment across the world as pretty much as the same timeline. We'd be able to cut down the number of recruitment and timeline or complete enrollment. But again, a lot of factor involved, but we would do our best, best on strategy planning, as John had mentioned.
spk18: Got it. Thank you. Yes, did that answer your question? Yeah, that was very helpful. Thank you, team.
spk15: Thank you, Yaz.
spk35: Thank you. One moment, please, for the next question.
spk01: Our next question is from Leland Gershel of Oppenheimer.
spk35: Your line is now live.
spk13: Hey, guys. Thanks for taking my question and for the comprehensive framing of how to think about things as we head into the readout later this year. A couple questions from me. First, with respect to, obviously, as we look forward to the data from order growth 210 next quarter, wondering if you'd be able to share the PEM screening results or give any color to whether that's the rates of success you've been seeing with the PEM screening have aligned with your expectations. And then number two, As we look forward to the SB conference, you mentioned there'd be some additional analyses of the prior study. Just wondering if you could share what the nature of those additional analyses might be. Thank you.
spk11: All right. John, do you want to start with the PEM and the SB analysis?
spk17: Sure. Thanks for the question, Leland. So, you know, the PEM test has been very effective as an inclusion criteria in the 210 study. We spent a lot of time educating the clinicians in that study as to which subjects to screen, to bring into the trial, and our success rate at inclusion is actually quite high. We had originally said in the entire population about two-thirds of the kids would be PEM positive. We're actually seeing a much higher number of test returning a positive value simply because of how the clinicians are focusing their efforts and looking for patients, right? Looking towards the more moderate end of the spectrum and kids who kind of fit the criteria of that slice of the patient population. So we're getting, you know, a very high number of kids who are PEM positive versus what you would expect from just looking at the epidemiology data of that, you know, the whole spread of birth limit deficiency. The second question about the endo, or I'm sorry, the SB meeting. So we've, you know, we've given out the title about the deconvolution analysis of the 212 study. So essentially, it's focused on the 212 study and, you know, deconvolution of the PD data that is there. Those abstracts haven't been published yet, but the, you know, the program has been announced. So I think we'll have to wait until they publish the abstract to get a little bit more information about what's going to be released there. But from the title, that should give you a good sense of what's in there.
spk13: Great. Thanks so much for taking the questions, and I look forward to the updates.
spk06: Thanks for the question, Leland.
spk35: Thank you. One moment, please, for the next question. Our next question is from Ed White of HC Wainwright. Your line is now live.
spk14: Hi. Thanks for taking my questions. Just going back to the Phase III study, and this might be difficult to answer, but how are you thinking about the number of sites that you're going to need for the Phase III to enroll that 180 to 200 patients? How is the split going to go between U.S. sites and ex-U.S. sites? And also, how are you thinking about the patient population? Same question, U.S. versus outside the U.S.
spk09: John, you want to start?
spk17: So, we haven't released the total number of sites. We're kind of deep in discussions with CROs and trying to get their input, you know, on what's they've seen in the past. Obviously, we're reviewing what some of the folks in these successful long-acting programs have done. So we haven't really decided on a firm decision on the number of sites. Obviously, we are going to do a global trial, as we've talked about. I think it's important. We do expect to get different recruitment rates in different regions, depending on access to growth hormone. And so I think we have to put all those together. In terms of what the FDA wants, obviously, I think we can certainly use, you know, almost all the U.S. and European sites are quite acceptable. And I think, you know, some of the Asian countries have, you know, requirements for which patients have to be or what number of patients have to be enrolled. So I think we're working through all those thoughts right now.
spk11: we don't have a final plan yet but they are all things that we're thinking through yeah uh let me just continue with that uh ed you know the benefit of being on the podium at all of these intricate meetings uh around the world uh is that all these experienced investigators have really attended those uh those meetings uh with with a great deal of interest because of us being the first oral The result is that I think more and more people are becoming real believers in what we're doing, and they've been reaching out to us and offering to be clinical sites. I don't think there's going to be a problem in choosing the sites. In fact, we have the benefit of more recent historical entry rates from recently just completed trials. you know, by sight. And Duke, of course, has a great deal of experience in that. So I think that's going to be much to our benefit.
spk14: Thanks, Rick. And perhaps a question on, you know, what's next for the company? You had mentioned the next indications are ISS and PWS. How should we be thinking about that? Are you prepared to run you know, perhaps a phase one study concurrently with a phase three study that we've just been discussing, or will this be something that you're thinking about post phase three data?
spk11: You know, Ed, I think that the answer to that question is, you know, if we were a large company, we'd probably have a different plan. Capital markets are what they are. You know, as we go out and do them, all the advanced planning for our phase three, that's where we're going to be focused. If the capital markets are going to permit us to raise the appropriate amount of money over time, then we're going to start programs, other programs, perhaps sooner than we normally would plan them. In addition to that, typically what happens when companies in their development plans get to this stage, into phase two, into phase three, you know, regional partners show up, or at least that's what we're partners of all times. And as, you know, I think our head of business development is a pretty busy guy at this stage, and we're going to, I think, have some choices here to look at some partners who could help us advance the program. And that could be in other indications too, although we certainly haven't had those discussions with anyone yet.
spk14: Great. Thanks, Rick. And perhaps a question for Lori, just when thinking about R&D moving into the back half of the year, you mentioned that $1.1 million in commercial contracting expenses hitting in the quarter. I take it a one-time event, and we should be thinking about the run rate more like the first quarter?
spk25: I think our research and development experience expenses for Q2 are pretty, you know, pretty on par with what we should expect, Leland, going forward, not just in contract manufacturing expenses, but also in clinical. And recall that we are comparing this to 2022, and a lot of the efforts in 2023, you know, are going towards working to prepare for a Phase III clinical trial. So, R&D, we expect overall R&D and G&A operating expenses to be between $9 million to $10 million.
spk14: Okay. Thanks, Lori. Thank you, everyone, for taking my questions.
spk05: Thank you, Ed.
spk35: One moment, please, for our next question. Our next question is from Catherine Novak of Jones Trading. Your line is now live.
spk26: Hi. Good afternoon, everyone. Just a question on some KOL issues, you know, what we've heard time and again is that their real focus in PGHD is, you know, 12, 24 months and beyond. And here we tend to see injectable growth hormone attenuate after about the first year. So given the mechanism of action, is it safe to say you wouldn't expect this to be so dramatic with LUM201? And then, you know, how should this change our expectations for what we should see in the data in phase two and phase three?
spk11: Well, thanks for that excellent question, Catherine. John, will you answer that?
spk17: Sure. So, two things to keep in mind. The Phase III study will be a 12-month study, and so kind of the key decision point for that Phase III will be non-inferiority at 12 months. Obviously, we have several ongoing trials now that are longer than 12 months right and we'll you know hopefully keep as many kids as we can in that trial and transition kids from the phase three into an extension trial as well so we will have a body of data on treatment past 12 months but it won't be as comprehensive as the data we have at six and 12 months and that's the same data package that all the long actings have brought in you know that said you can look at the difference in growth or look at the difference in annualized site velocity for individual patients between, you know, at six months, at 12 months, at 18 months, and look at the slope of that decline. And as you said, it's well documented, you know, that growth hormone has its kind of biggest peak in the three to six month range. And then, you know, every year after that, you get a decline. You don't get the same growth every year, right? You get a decline in returns. You know, LUM 201 has been shown in adults. It's been published in adults that you can elevate IGF-1 and growth hormone levels out to 24 months, right? So in adults that change body composition, we get that same level of continued elevation. In kids, we would expect to see a continued growth. And I think some of the early data that we're going to reveal at the end of this year on the handful of kids past 12 months will really start to help put those pieces together for us. But there are certainly scenarios where you could expect that we're going to modulate kids to a more natural growth pattern that could be a much flatter growth slope than what you might see with kind of the pharmacological or supraphysiological levels of injectable growth hormone. Thank you for that question.
spk26: Yeah, of course. And then just one more, you know, now that we've got a couple weekly injectables in the market for TGHC, you know, what kind of feedback are you getting from KOLs or what are you hearing? How excited are they to use them? And does this factor into your Loom 201 market expectations at all?
spk11: You know, Catherine, look, there's no question that this could be a highly competitive space. And you look at the price on a monthly basis between the three growth hormones, long-acting growth hormones, there's something like $7,000, $8,000, and $9,000 per month, you know, all that, you know, to yearly cost of over $100,000 for a 35-kilo kid. That's expensive treatment. I think there are, you know, there are certain parts of the world where the standard of care is going to continue to be that daily because of restriction in price or longer time to approvals in different markets around the world. We believe, I mean, we've done our market research. We've asked the question both to pedendos and to parents if you had a choice between a weekly injection or a daily oral. They overwhelmingly say they would choose a daily oral. And on top of that, I'm going to remind you, we're a small molecule. Our cost of goods and our flexibility in pricing and margins looks very favorable to us long-term in this market.
spk02: Well, Kathleen, may I add with the feedback from the KOL industry card? Rick mentioned about the pricing. That's very important, right? It's more expensive than daily products. The other issue that the KRL has some skeptical is the safety data profile. As you know, that in order to get approved FDA, you only have 12-month safety data. However, long-term safety, especially long-acting, not only look at efficacy itself, the long-term side effect, which is, again, you know, it's very unclear at the short term, right? When you look at, you know, profile, the growth hormone exposure for weekly growth hormone, it's much higher than daily growth hormone and also higher IGF-1. With that said, you know, long-term, post-faithful study or post-marking study need to continue in order to show off the safety profile in the long-term fashion. So that's something that some KALs feel quite skeptical to really put all subjects in weekly Goldman therapy in regards to efficacy itself, right? So not to mention it's very expensive.
spk11: Yeah, and Catherine, recall, you know, our mechanism of action is very different from growth hormone. You know, we stay within the natural endocrine feedback loop, and those excursions you get with higher levels of growth hormone with especially the long-acting is not possible with our drug. Once again, that feedback loop stays within the natural physiology.
spk26: Okay. That's answered my question. Thanks very much.
spk35: One moment, please, for our next question. Our next question is from Pete Stavropoulos of Cantor Fitzgerald. Your line is now live.
spk39: Hi, Rick and team. Nice to see all the progress made this quarter and movement towards data readout by year end. First question is, when you look at the data that you've generated to date using the PEM, the Predictive Enrichment Marker, and the growth that you've observed in these patients, just curious to know, as you move into a later, larger study, you know, if you expect to keep the cutoffs where they currently are, or do you think, you know, you can increase the probability of success by focusing or enriching patients with a greater response, you know, or is the current algorithm sufficient?
spk11: Pete, thank you for that good question, and John, why don't you start?
spk17: You know, I think, Pete, we're comfortable with the the enrichment that we're getting from using our pen markers right now, but obviously we, you know, we haven't looked at all the data yet, right? So we need to look at the HV data for the other half of the patients that have come in. But I think we feel pretty confident based on, you know, the analysis that we originally did and as well as how things are rolling out now.
spk39: Okay. And, you know, as you think about a Phase 3 design, you know, I understand that, you know, you need to end the Phase 2 meeting and to come to an agreement, you know, with the agency. However, are there any modifications you might make to enrollment or trial design for a pivotal study based on the accumulating data from 210 and 212?
spk07: John, why don't you start with that question?
spk17: You know, I think the, you know, the Phase 3, design and basic kind of inclusion characteristics are pretty common across all the three long-acting products that have been successful and, you know, are pretty much how we would go forward. Obviously, our patient population has to be PEM positive. That's a distinction. But other than that, I think, you know, the timeline and the approximate ends, I think, are pretty pretty close to what we would expect after we do the analysis at the end of the study. So we don't see any radical departures from, you know, from those that have gone before us here.
spk39: Okay. Sorry, go ahead. Do you have something to add?
spk04: No, go ahead. Please go ahead.
spk39: And last question, you know, directed towards the Duke, but, you know, Rick, John, more than welcome. You know, so, you know, you've presented, you know, Lumos presented a number of of times at different endocrinology meetings, you know, most recently at Endo 2023. So just wondering, you know, when you speak to KOLs, you know, some of your former colleagues and even practicing, you know, clinicians about womb 201, it's a mechanism of action and how it may be differentiated from standard of care. You know, just curious to hear, you know, what the reception of this candidate and approach is and the data presented today is.
spk10: Yeah. And so, Duke, why don't you go ahead?
spk02: Yeah. So, actually, it's very, very positive. As you may know, right, this is oral growth hormone secretion drug have been proposed for the treatment for years, but none of those trials have been, you know, successful. So, here is the LUM201, which is mechanism of action of the drug itself. It's somewhat different shape in itself from the oral growth hormone secreting peptide or secretagogue out there, right? They have long acting, you generate IGF-1, that's sustained. And based on the presentation at PES and at ENDO, one represents only 210 data alone in regards to growth velocity, and it's very clearly shown that compared to historical data, moderate idiopathic population, the growth velocity somewhat match. And we look at the combined data, try to see that, you know, what the response looked like. It seemed like, you know, the dose that had been selected, especially 1.6 and 3.2, it's pretty comparable. And you can see those data in six-month and 12-month, you know, results. But again, it's a very small number, but most of the physicians really feel intrigued about the data. They did not know that this growth hormone, Oral Secretor Glove, would work as good. right and again because it was failed in the past not to mention that if these drug get approved will be alternative for their patient and especially the impact of compliance should be less and again we expect that you know the burden injection with the majority of those patients suffering from daily along acting could be somewhat overcome by this new therapy but again overall I is very, very positive. They all just need to look forward for the top-line data, and especially the new Phase III pivotal trial in the future.
spk17: The only thing I would add to that, Pete, is that when we do these presentations at INPEI in March, at PES, and at ENDO, the room is packed, right? And there are lots of good questions, lots of excitement, lots of people wanting to talk to the the presenters about this product. So, you know, one-on-one and then in the lecture halls, we feel a lot of excitement and a lot of interest. Yeah.
spk11: Yeah. And I might add, Pete, that, you know, we always have a booth at each one of these meetings and right alongside of all the competitors in the growth hormone space. And I am absolutely amazed at the level of interest and the number of really great questions and just overall excitement that everybody feels, oh, the fact that there's a possibility of an oral alternative for their patients. I mean, it's a very important and exciting space to be in right now, just based on the feedback from these clinicians.
spk39: That's great to hear. Thank you for taking our questions and congratulations on the progress.
spk08: All right. Thank you, Pete.
spk35: Thank you. I'm showing no further questions on the line. This concludes the Lumos Pharma second quarter earnings call. Thank you and have a great day.
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