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spk03: Good day and welcome to the GOMED conference call to discuss financial results for the third quarter 2021. Today's conference is being recorded. Before we begin, please note that we will be making 34 statements on today's call, including those regarding financial results, statements and forecasts regarding anticipated timelines and expectations with respect to our regulatory and clinical development programs, as well as other statements that relate to future events. These statements are based on the beliefs and expectations of management as of today, and actual results, trends, timelines, and projections relating to our financial position and projected development programs and pipeline could differ materially. We urge all investors to read carefully the risks and uncertainties disclosed in our filings with the SEC, including without limitation the risk under the heading risk factors described in our annual report on Form 20-F filed with the SEC. and the risks and uncertainties, including in the form 6-3, filed with the SEC earlier today. GOMID assumes no obligation to update any further statement or information, which speak as of their respective dates only. I would now like to turn the call over to Alan Barra, President and Chief Executive Officer.
spk07: Alan, please go ahead. Thank you, Shamali. Good morning, and thank you for joining us on today's conference call. I'm pleased to be here today with our Chief Scientific Officer, Dr. Liat Hayar-Deni, and our Chief Financial Officer, Yochai Stensler. We are also grateful to have with us today our guest KOL, Professor Vlad Ratio, from the Sorbonne University and RMO Study Co-Principal Investigator. Professor Ratio will present the results from the first dataset of the open-label part of our Phase III RMO Study also referred as the ARCON cohort. Professor Rassio will be happy to take questions following his presentation. As the second part of our today's call, we will report to you on our financial results for the third quarter of 2021, and we'll be happy to take questions addressed to management. As you know, early this year, an open-label part was added to the phase three RMO study designed to provide effect size on a higher dose of Aramcol 300 mg BID with 153% elevation in exposure and optimized treatment duration for Aramcol. GALMED also added to the study a rigorous and robust pathology reading process confirmed and designed in consultation with the FDA, including a committee of three independent experienced liver pathologists. Biopsies are read by each pathologist individually, followed by a consensus reading. The data, which will be soon presented by Professor Razzio, is aligned with the hypothesis that higher Aramcol dose results in an improved efficacy profile and that a direct anti-fibrotic effect of Aramcol may occur as early as 24 weeks. This is demonstrated by histology and corroborated by fibrosis biomarkers. Analysis of biomarkers in the larger ARCon cohort support anticipation that further biopsy analysis will continue to show that Aramcol treatment provides a highly meaningful effect on fibrosis. Importantly, Aramcol continues to show excellent safety and tolerability profile. Now let me transfer the call to Professor Razio. Professor Razio, please.
spk04: Thank you, Alan. I'm always honored and very happy when I can get to present positive results. So, thank you for inviting me to do so today. So, hello, everyone. I hope you can see the slides we have prepared for you here. I would like to start by reiterating what Alain Beharoff explained very well, which is that this is an innovative study which was designed within the randomized control trial, the phase three trial of the ARMOR study. And this is an open-label part which tests three different durations of exposure to Armco, as explained, a six-month duration, a 12-month duration, and the 18-month duration in three groups of patients of 50 patients each. It is an open-label study. We know basically the rate of response in terms of fibrosis reduction of the placebo arm from the many studies that have been conducted and reported so far. So the interest of this study is not the comparison with placebo, but rather to understand whether changing the pharmacopresentation of the drug by delivering it twice a day, which increases, as you were told, considerably the exposure in blood, if this results in higher level of histological effect, than what was previously tested and published in the Phase IIb trial. Moreover, this study will try to understand what would be the optimal period of treatment that results in a strong antifibrotic effect, and for that reason, the three lengths of the three durations are being compared simultaneously. Now, the study will continue after the respective 6, 12, or 18 months time where a control liver biopsy has been performed. It will continue in the same open-label fashion, and it is scheduled to end around the same time as the randomized control phase three trial R-more will end. And the only difference here being that only patients who are non-responders will have a third biopsy in order to understand whether prolonged exposure beyond the initial timelines will result in an antifibrotic response, a delayed antifibrotic response in people who are initially non-responders. So this is a very exciting design because it tests several things at the same time, and usually things that are not being tested in traditional phase 2b or phase 312 because, like always, everybody wants to rush to take the shorter route to success. but here it is important to understand very well how to use this drug. Now, another thing that Mr. Baharov explained is that nowadays a single pathologist is no longer sufficient, so therefore it is important to have a very strong histological adjudication process, and in agreement with the FDA, what was decided and what is being implemented for this trial is to have a committee of three pathologists So it's no longer just one deciding whether it works or not, but the three of them need to agree and provide a total consensus on the staging and the grading of the disease. And that is, of course, done blindly, not to the allocation, because this is open label, but to the sequence of the biopsies. So the pathologists do not know whether they're reading the first or the control biopsy. So all this is explained here on the slide. I'm going to move on now to present you the preliminary results on the first patients that have completed their assigned allotted time of exposure. And we're very happy to tell you that the results that will, part of the results that we'll present here have been accepted for presentation as a late breaker at the liver meeting, the American Association Study of the Liver Disease meeting that will be held later this week. So the part that has been submitted and accepted as a late breaker concerns 20 patients and is labeled here late breaker ASLD. But then we'll also present the data available today of the larger cohort of patients that participate in this open label study, which by the way is called ARCOM, ARAM called open label. and this is the ARCon cohort, and this concerns 139 patients. So the 20 patients that are being presented at ASLD are part of this 139. So you can see here on this slide that basically the epidemiology and the demographics are pretty much the same between the first 20 and the subsequent 119. You can see here that females are a majority of the patients. Mean age is around 58 years. BMI is rather high, 32 to 33. And then ethnicity, there's a majority of Caucasians. Most patients have advanced bridging fibrosis with stage three between 57 and 65%. And then there are some patients that are F2 and others that are stage one. So this is as far as the baseline characteristics. And now is the main result. You can see here the proportion of patients that had an improvement by one stage or more after exposure to Aramcol. And apologies. The good news is that actually out of 20 patients that had a control liver biopsy, 12 of them had a fibrosis reduction by one stage or more, and actually seven by one stage and five by two stages. which is a quite remarkable result because that places the level of response in terms of fibrosis improvement at 60%. And of course, this is very impressive compared to the figures that are available in the literature because by all accounts, the placebo rate in the different studies is between 15 or 13, even in the phase three trial, and I would say 30% maximum. So 60% goes way beyond that. Of course, These are preliminary results on a small number of patients, but this high level of fibrosis reduction has not been seen so far in other studies. What is interesting here, you can see on the right part of the diagram how these biopsies are distributed in regards to the length of exposure. So basically half of the patients, at least an equal number, nine of them have been biopsied after one year and other nine of them have been biopsied after six months, and two of them only have been biopsied at week 72. And so you can see that. And for the moment, numbers are too small to see a trend, but it looks like 48 weeks would have the best response rate in terms of fibrosis, with 67% of them, six out of nine, improving fibrosis by one stage or more. But this, of course, needs to be confirmed as the trial continues. So these are the very exciting histological results. A more visual way to see the changes in the liver of patients with IRM call are these pie charts. So on the left side before a baseline, on the right side after treatment. And two things are quite striking here. If you look at the proportion of patients with bridging fibrosis, those in orange, you go from 65%, it shrinks down to 25%. So that's what the numbers indicate, 13 here and five there. Now, conversely, if you look at the number of patients with very early fibrosis stages, so the blue ones, F1s, this goes from, this increases from 15% to 45% when you put together F0 and F1. So clearly there's a shift here in terms of fibrotic severity. that is being induced by exposure to Aramco. Now if we're looking at converging evidence from biomarkers, which is always very important because we would like to see all needles moving in the same direction. Now what you can see on this slide here is the response on aminotransferase levels. So ALT on the left side, AST on the right side, Top graph is from the late breaker cohort, 20 patients. And the bottom part, and this is interesting, is all patients included so far, so which have been now looked at at different lengths of exposure. Not all of them completed the study, but the results are cumulative of the different times of exposure. And the important part here is that both enzymes, both amino transferase go down, as you can see here, clearly, significantly. And this is true whether you're looking at the first 20 patients or at the subsequent 139 patients that were included and analyzed in total so far. So quite robust reduction, which is confirmed beyond the initial 20 patients, which are reported at the liver medium. Now, if we look specifically at some very popular fibrosis markers, let's look at P4. Here again, the results are very encouraging in the sense that they go in the same direction as the results observed by histology. If you look on the left side, you have the ASLD late breaker cohort, the 20 patients a clear drop in PIP4, and this is replicated in the larger cohort of 139 patients. Their behavior is the same. So one can surmise from that that the histological result when this will be available from the entire cohort will be quite similar to the one obtained in the small earlier cohort of 20 patients. Of course, the needs to be seen, but the fact that FIB4 goes down in all the patients, if this is an indicator of fibrosis reduction, the histological results should be the same on the larger number of patients, which is, of course, the final result that we're looking for in this study. Now, looking at another very emergent biomarker of fibrosis, which is PROC3, it is a a marker of not only of established fibrosis, but also of active fibrogenesis, because it is a fragment of procollagen that is being released as collagen is being deposited in the tissue. So ProC3, now every trial measures ProC3, and what is here also reassuring is that in the 20 late breaker cohort, 20 patients where histological regression of fibrosis has been documented by liver biopsy, you can see a strong reduction in ProC3. But that is also replicated as for FIP4 in the larger cohort of 139 patients for which not everyone has a liver biopsy yet. But the fact that this biomarker of fibrogenesis goes down makes us think that the histological trend will be the same in the larger cohort. And whether you look at absolute change or relative change, the results are quite consistent. What is interesting here is that ProC3 was measured by Nordic Bioscience, which is the biotech company that initially invented and created this biomarker. However, they did change the methodology for measuring it, the assay precisely, and that results in a more robust and more reproducible assay according to Nordic Biosciences, and also to a higher baseline level, which is explained here, 48.8 micrograms per liter. Now, if we look at the statistical significance of the results that I've just shown you, whether you're looking at aminotransferases and the two most popular fibrosis markers, you can see that there's a significant drop from baseline, which is shown here on this slide. And this is true at week 24, and it is maintained at week 48, with a high level of significance for all of the biomarkers that are being presented on this slide. So again, aminotransferases, FIB4, and PROC3. And as a reminder, the ASID Lead Breaker cohort, the documented proportion of patients who had a reversal of fibrosis was 60%. So why are these results important? It is because they confirm and actually go beyond what was demonstrated in the Phase IIb trial, which was called the ARES study, and the results of which has been published in extenso in a very prestigious medical journal, which is Nature Medicine, less than one month ago. So the results that we're presenting currently today are sort of reinforcing the optimism in the ability of this molecule to induce histological improvement and, in particular, fibrosis reversal. So that's why it is always good to have the same results coming from a different cohort. So this is why this study is important to conduct. And also, they do support the effect of a higher dose of Aramco. which is the one actually that will be used in the Phase III R-more study. So the practical implication of these results, if they are confirmed on the larger cohort of the open-label trial, is that they will enable us to conduct discussions with the FDA so that the interim analysis of the Phase III trial, which is the analysis that, if positive, allows for conditional marketing authorization. So it allows us to negotiate that this interim analysis is performed on a smaller number of patients and maybe after a shorter period of exposure, say for instance instead of 72, 48 weeks, which will of course be an important thing because that will help bring the drug earlier to the market. So very positive initial results so far from this open label trial. And I'll pass it over to you, Alan, for the question and answer session.
spk06: Thank you, Professor Ratio.
spk07: And we will open the floor now for Q&A for Professor Ratio. And then we will continue with our regular call.
spk03: Thank you. At this time, we will be conducting a question and answer session for Professor Ratio. If you would like to ask a question, please press star 1 on your telephone keypad. The confirmation tone will indicate the line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question that we have is from the line of Steve Seedhouse. Raymond James, please proceed with your question.
spk02: Hi there. This is Ryan Descheron for Steve Seedhouse. Wanted to see if any of the patients in these cohorts are receiving any other therapies like vitamin E, piaclitazone, fibrates, anything like that. And then also, were the patients consulted on lifestyle management, eating well, exercising more, et cetera? Thank you.
spk04: Yeah, thanks. So this is... This is akin to all the other studies that are being conducted in the field. Patients are allowed to be on other medications, particularly the ones you specified, if they have been on that medication for an extended period of time before the initial biopsy was taken, the biopsy that is used for randomization. Because the assumption, like for all the other trials, is that If you have taken vitamin E or purulazone for a number of months or years and then you have a liver biopsy that shows active mesh with fibrosis, that means you're not a responder to that particular medication. If the patient started that medication only a few weeks before the selection visit, then, of course, they were not allowed in the study. So all these patients can be considered as non-responders to pioglitazone or vitamin E. Now, pioglitazone is not even marketed in some European countries, and the use of vitamin E is actually pretty low, including in the United States. I cannot give you the exact numbers of those that are on these medications, but what is important is that they are basically equivalent to non-responders to these drugs. Now, you're also asking about diet and lifestyle measurements. So here again, like all the other trials in NASH, people are given the information. They are educated about what they need to change in their lifestyle and their diet and the exercise they're doing or not doing. And they are constantly being reminded that at each study visit. But there is no systematic ancillary program of implementation of the dietary and lifestyle changes. I'm not aware of any pharmacological trial that does that. So it's active reinforcement, but it's no more than that. Of course, any changes in weight, any changes in alcohol consumption, any changes in the amount of activity are captured at each visit, and this will be one of the confounders that will be taken into consideration when analyzing the final results on the effects on histology.
spk06: Got it. Thank you very much. Our next question comes from the line of Ed Arth with AC Wainwright. Please proceed with your question.
spk08: Hello, everyone. This is Thomas Yip asking a couple questions for Ed. Congratulations on the very exciting open label data so far. I have a couple of questions. First, among the five patients who achieved a two-point reduction in fibrosis, as we've seen in one of the slides, at approximately what time point was that achieved, and when should we expect the next set of biopsy data from the larger Archon cohort?
spk04: So thanks so much. I don't have the exact detail of these five patients. Maybe GallMed has it, whether that was week 24-48. I think it's quite equal in between the groups, but with the small numbers, I'm not sure we can be confident about that. So these results will be given. Now, for the next... So the study is ongoing. So there are each week, there are people who have their second biopsy being taken. So this will continue. We hope that the next time we report findings on this cohort, it will be when the first 50 patients instead of the current 20 will reach the end of treatment biopsy. So then we'll have a picture, a larger picture on the number of patients that is higher than the one presented here, so 50 patients. So I don't know when that exactly will happen, but we hope that this can be available by the time we hold EASL next year. So I hope that we can show you more data at that time.
spk08: Okay, Tata and Melo next year. And I just want to confirm for the biomarker data analysis that was presented today, is the ASLD cohort of 20 patients a part of the overall open-label Archon cohort of 139 patients, or are they separate cohorts?
spk04: The 20 patients are part of the 139 cohort that I presented. They're in there.
spk08: Okay, so the data of approximately 50 patients of the open label overall does contain the ASFP cohort.
spk04: Yes, and it contains additional patients that have been followed for variable periods of time. Some of them only four weeks, other eight weeks, other 12 weeks, but the repeated measurement methodology that has been used takes into account the individual period of exposure for each one of these 139 patients, and the graph was built using these data.
spk08: Right, got it. And then perhaps one last point about the study, about the demographics so far. We see that over 77% of patients enrolled in the open label are female patients. Is this by design, and also do you expect any potential impact?
spk04: No, it's absolutely not by design. It happens to be that way. Actually, if you look at most studies, at least most trials that have been published so far, there is a majority of women. Maybe not 77%. It's more like 60%, 65%. But that is a fact.
spk06: The majority of women is always something that we see in this series. Okay, understood. Thanks. Thank you so much for taking our questions, and we look forward to the next data set. Thank you. Our next question comes from the line of Kristin Kluska with Cantor.
spk03: Please proceed with your question.
spk00: Hello, this is Rick on for Kristin. Could you please discuss how you look at the importance of time to onset in these results, particularly in comparison to other announcements in the NASH space? What importance do you believe the time to onset could ultimately have for physicians and patients?
spk04: Thanks, Rick. So you're saying time to onset, you're meaning the duration of exposure in the trial?
spk06: 24, 48, or 72?
spk04: Yes, that's correct.
spk06: Yes.
spk04: So we're just trying to understand the dynamics of the anti-fibrotic potency of the drug. Because it can well happen, you know, that you have people who are, for one particular drug that responds much earlier than, let's say, no, you can have one particular drug which has a much earlier response and other drugs that you need to use for a longer period of time to obtain the same results. So that's one thing. Let's say some drugs act very fast, others act very slowly. That's one thing. The other thing, and we don't know which one is Aramco because all these studies that have been performed so far for all the drugs, including Aramco, the Phase IIb trial, they only have one period of time. The only trial where we tested two, we did serial biopsies so that to understand the dynamics to understand if there's an early or a late response was the Senequivir trial, where biopsies were performed one year and two years. But in all the other trials, it's just one fixed time period. So you don't know whether you're at the maximum of the effect or if you're at a time point where you're just starting to see the effect. So in order to get a better understanding of how this drug acts on fibrosis and the other aspects of liver injury, it is good to have more than one time point to understand the kinetics of the response. That's one thing. The second thing is that there is individual variability. So there might be early responders and late responders, people who need to be treated for a longer period of time in order to have a response. So that also is the basis for comparing three different time periods, three different lengths of exposure. So that's all. And of course, if the results are clear enough, If we see, for instance, that you already reach the maximum response level, say, at 48 weeks and prolonging by six months, it does not add any more to the response. It doesn't reduce it, so it stays the same, but it does not add to it. Then, of course, that's a very good indication to perform the interim analysis for the phase three trial at an earlier time point rather than to wait without particular reason, six more months, which adds a lot of problems to the trial and cost and you're familiar with that. So that's the third thing that it would be interesting to understand from this design that compares three different time periods of exposure to the drug. That's all there is to it. Now, how this will translate to treating patients in clinical practice once you have a drug available, that's a different story. And it will depend on other considerations, such as the effect on clinical outcomes. Most probably, what everybody says today is that treatment for NASH will have to be for a very long period of time. So it's not something that you will stop once you get a response. But it is important to understand whether that response occurs earlier or later in order to have the patients be compliant and stick with the medication for the appropriate period of time.
spk06: All right. That's helpful. Thank you. Our next question comes from the line of Justin Zelen with BTIG.
spk03: Please proceed with your question.
spk01: Hi. Thanks for taking the question. Just curious if you could help us put into context how you view these results on fibrosis improvement as compared to some of the other data sets available in the field currently.
spk04: So, you know, as an academic, I have to be very careful the way I answer your question because it is very hard to compare studies that are not head-to-head, as you know, and which can differ in terms of duration of treatment in terms of populations and so on and so forth. Nonetheless, for the moment, Practically speaking, there are many studies out there that have shown a clear effect on fibrosis regression. Even drugs such as the GLP-1 receptor agonist, semaglutide, which is very well known, has not shown an intention to treat an effect on fibrosis. Madrigal has not shown yet. I mean, rosmetirum has not shown yet convincingly that effect. We'll see the results of the phase 3 trial. But so... The only exception is actually obetecolic acid over a period of time, an extended period of time of 72 weeks, but in a large Phase III trial. So there aren't many examples out there of drugs that were successful in reducing fibrosis. So in that sense, Adam Cole is positioned, I think, in a particularly good position here with the results that have been presented in the Phase IIb trial and the ones that I show you today. Obviously, this is not sufficient. A phase three trial is necessary to prove beyond doubt that there is an anti-fibrotic effect. And this will be done, hopefully, with everybody's efforts. But for the moment, if you simply consider the level of response in the patients I've shown you today, and if you consider the historical placebo response rate, you can see that the magnitude of effect is higher than what has been shown with OCA. All other things, you know, considered, which are the fact that there is no direct comparison and this is not a placebo-controlled trial. But even if this were a placebo-controlled trial, I don't think that, especially with three pathologists, the level of response of a placebo arm would be as high as 60%. No way that would happen. So... I think there's a clear difference here. There is something quite clear. Very difficult to compare with the other studies. The only other thing you could compare is with OCA because that's the only other positive trial on fibrosis. And that comparison just between us, because you can't say that in a scientific meeting, is in favor of this drug in the sense that the effect size versus placebo appears to be much higher. But that's about as optimistic I can get. given the design of this trial and the one from the Regenerate trial.
spk06: Great. Thanks for taking the question.
spk04: It's very encouraging because we really need drugs that work on fibrosis. And the disappointment lately, based on the results reported so far, is that actually very few drugs have clearly shown anti-fibrotic effects. So it's very good news that we have some strong candidates.
spk06: Absolutely. Thanks again. And our next question is from the line of Steve Seedhouse with Raymond James.
spk03: Please proceed with your question.
spk02: This is Ryan Deschner on again for Steve Seedhouse. I wanted to ask, Can you give us any more detail on NASH resolution or how the individual components, such as ballooning and steatosis, and the N equals 20 cohort compared to a RES, and also what you're seeing in terms of weight loss across these cohorts? Thank you.
spk04: So the other histological effects are being studied underway, and we haven't presented them. We did not stress these results. We did not analyze fully these results for the moment. So we keep that for the next scientific meeting because obviously this is particularly important. So I cannot give you more detail. I gave you everything we had so far. So nothing is hidden here. So you've got all the information that has been rigorously analyzed on a cleaned up database. you've got it all here. So there's nothing else that can be shown so far, but it will come. Stay tuned, and I'm sure that at each one of the two major meetings in the year, you will have additional information, and hopefully when we get to the 50 patients, fully analyze histologically, then we will get also all the other details of the histological impact of the drug.
spk06: But for the moment, that's all we have so far. Thank you. And then in terms of weight loss?
spk04: In terms of weight loss, for the moment, there is no weight loss induced specifically by this drug. So we will see whether with a larger number of patients, there is a change in that. But for the moment, there is no clear effect. It's weight neutral.
spk02: Got it. Thank you. And then maybe one quick question, one last question. The ProC3 data from these cohorts It looks like it's, I mean, definitely wide error bars, but it looks like it's continuing possibly to improve from week 24 to 48, whereas that doesn't appear to be the case for ALC, AST, FIB4, et cetera. How are you taking this into account in terms of how you're looking at this in terms of, you know, will you continue, do you think that you'll continue to see ProC3 improve, and what would the relationship theoretically be to further improvements in fibrosis?
spk04: Yeah, I don't know how much we can over-interpret that. As you say, the confidence intervals are wider than for aminotransferase and so on. It's still a bar marker that we are investigating, all of us. We were learning what it is worth and how it changes in regards to pharmacotherapy or other lifestyle changes. So for the moment, I would not I will not elaborate too much on a continuous reduction. Obviously, it's good it doesn't shoot up after week 24. So it's sort of reassuring. I'm very prudent myself in terms of interpreting the biomarkers of fibrosis. So to me, what will be really important is as a first step to document the histological effect, and then see whether the biomarkers sort of reflect those histological changes or not. And if that is the case, then we will use those biomarkers based on that. I would not today use them primarily as an indication of the antifibrotic effect, but rather as supporting evidence because we simply don't know enough about that. Plus there might be, you know, individual variability in how this particular biomarker response, which can be to some extent uncoupled from the individual variability to fibrose itself. So there are too many unknowns to be extrapolating too much from this continuous reduction in PRO-CT, but obviously it is probably a good sign that it continues to drop. We will see with a larger number of patients if this holds true.
spk06: Got it. Thank you very much.
spk03: And we have reached the end of the first question and answer session. I'll now turn the call back over to Alan Barrow to continue.
spk07: So thank you very much, Professor Ratio. And let me continue now. So obviously things are moving fast at Galmed. Given the excitement and the energy in the company from the data, We view the result we presented today a game changer for both the company and more importantly for the treatment of liver fibrosis. Nonetheless, we hear the skepticism regarding the NASH space over the last years. As a result, the government makes enormous efforts in optimizing its NASH program. We focus on fibrosis improvement, which is the most important endpoint. We increase the magnitude of the effect by over 50% thus far by elevating the dose. We employed a robust pathology reading process of three readers to minimize the primary endpoint discrepancies, and we designed a specific study to address the open question of optimal treatment duration. The data we are presenting today reinforces three main facts. One, downregulation of SCD1 results in significant improvement in liver fibrosis. Aramcol's mechanism of action, directly targeting collagen production and fibrosis, is translated into the results we are seeing today. 60% of patients experience one point or more in fibrosis improvement, with only one patient experience a worsening. Two, the hypothesis that a higher dose results in significant clinical efficacy has been confirmed to date. We have so far doubled Aramcol effect on fibrosis, and may end up with a shorter and smaller conditional approval phase three study. The data we are generating will allow us to have an evidence-based discussion with the FDA on these points. And three, data is corroborated by small and large cohorts. The totality of the data at this point is highly encouraging for the next milestones. With our open dialogue with the FDA, based on our fast track designations, We look forward to continuing our updates as the study proceeds. Now, let me transfer the call to our CFO, Yochai Stentzler. Yochai Stentzler Thank you, Allen.
spk05: This morning, I will be providing you with our financial results for the third quarter ended September 30th, 2021. For more information, please refer to our report on Form 6-K, filed earlier today with the FCC, which among other things provides a summary of such financial results. For the third quarter of 2021, our net loss totaled $7.7 million, or $0.31 per share, compared with our net loss of $6.9 million, or $0.32 per share, for the corresponding quarter in 2020. Research and development expenses totaled $6.5 million for the third quarter of 2021, the same as for the corresponding quarter in 2020. General and administrative expenses for the quarter totaled $1.3 million, compared with $1.1 million for the corresponding period in 2020. Our cash balance as of September 30, 2021, which includes cash, cash equivalents, restricted cash, and marketable securities, totaled $42 million, compared with $51 million on December 31, 2020. With that said, operator, please provide instructions for the second Q&A portion of the call.
spk03: Operator? Again, we will have our second Q&A session. If you'd like to ask a question, you may press star 1 on your telephone keypad. If you would like to remove the question, you may press star 2. Our first question would be from the line of Ed Arts with HC Wainwright. Please proceed with your question.
spk08: Hello again, everyone. This is Thomas Yip asking a couple questions for Ed. First question, can you tell us when we should expect the double-blind portion of AMR to begin enrollment, and can you also discuss preparations for manufacturing of the new Aramco and Maclamin formulation for clinical trial?
spk07: Thank you, Thomas. So, as we've previously announced, we are planning to reinitiate the double-blind part of the study in the second half. of next year of 2022. There is no need in fact to submit new protocols because the existing protocols allow us to shift from the open label part to the double blind part without the need for a protocol update. We will do that when and we'll have sufficient data to discuss with the FDA the new design that we're anticipating, which we believe will be shorter. To remind you, at the moment, the design of the double-blind part is 72 weeks. I can almost certainly tell you that at this stage, we believe this is going to be shorter. We'll discuss with the FDA how short it will be. And same is the effect size. Clearly, the initial design was based on the Phase II study, on the ARREST study. We've doubled the effect on fibrosis, and the effect size has changed, and we need to discuss with the FDA the new number of patients that will be required for significant p-value. We are continuing in full force with the manufacturing of iron-colomeglumine clinical batches. We are preparing for beginning of next year the bioequivalent study It's when ARAM called twice daily, the BID, the current BID, and ARAM called megalamine, regulatory bioequivalent studies. And once these are done and confirmed, we can initiate the double-blind study.
spk08: Okay, got it. Perhaps to follow up on that, when should we see the bioequivalence data? I suppose it's, as you said, ahead of the second half of 2022 when the randomized portion begins.
spk07: So that will be in parallel. I mean, these are the same clinical batches that will be used. We are working with the clinical batches that first, of course, will have to demonstrate the bioequivalence, and then we can move to the double-blind. But we are preparing the manufacturing and packaging, supplying, et cetera, of the drugs for the second part, for the double-blind part.
spk08: Right. Okay, got it. And then, for us, one final question. When should we expect to see the next update for mineral fiber? I know you guys have made a lot of progress for Aramco.
spk07: So, here we are struggling between, you know, two forces. We have the scientific conferences, NASHTAG, HEPDART, EASL. We are presenting. We just presented the the data recently in the fibrosis conference. So we have to juggle between the financial community and the scientific community, and we will do our utmost to satisfy both. So we are restricted with data embargo, of course, by scientific committees that we would like very much to have the data presented there. And at the same time, we try to synchronize that, as we did this time with AASLD. So around EZL, I would expect around EZL, we will release another set of data.
spk08: Okay, understood. Thank you again for taking our questions, and we look forward to a very exciting upcoming 12 months.
spk06: Thank you for joining our call. Our next question comes from the line of Christian Kluska with Cantor.
spk03: Please proceed with your question.
spk00: Hello, this is Rick on again for Kristen. Congrats on the data again, and we like to look at the new GalMed website. One thing in particular you've always emphasized is the greater attention you've taken to individual sites and the number of countries you are enrolling in, even despite looking at the speed of the U.S. trial site enrollments. So we wanted to ask, based off this recent Nature Medicine publication, if you could speak to the diversity of this patient population and any key findings observed there.
spk07: Okay, so we still envisage very much that the population for the double-blind part would be about 50% would come from the U.S., and the rest would come from the rest of the world. And with that said, we have, of course, Europe, and we have Latin America, and we have Korea, and we have China, and we have Australia. So we have not changed the demographics because different countries We're looking at potentially different partnering deals in different geographical areas, and we need to satisfy the number of patients which are needed for approval in every single jurisdiction. So this has not changed. We are working with a selective number of sites in the U.S. We have partnered with a group called OG Health, they are the majority of the US patient comes from og health together of course with the leading universities that usually participate in enough studies same for Europe Europe we have London and France and Germany and Italy and Spain and Belgium etc so all of the leading sites, university sites that you would find in other NAR studies are also participating and will participate in the double-blind part.
spk00: Okay, and maybe just one more quick one. Could you please discuss the Phase 1 data readout for mylo5MR and perhaps how you're thinking about getting steps in initiating a Phase 1B proof-of-concept study?
spk07: So we are in the process of finalizing the data. The in-life has been completed in effect of the three phases. There is one additional phase that we've added. So we are really in the process. This is not a public information yet, so of course we cannot give any data. But we are proceeding, as you've alluded to, quickly embark into a 1B and potentially 2A study early next year.
spk06: Okay, thank you very much. Thank you.
spk03: And our next question comes from the line of Steve Seedhouse at Raymond James. Please proceed with your question.
spk02: Hi, this is Ryan Deschner again on for Steve Seedhouse. In the recent data set, the ALT reduction looks like it could be a little more pronounced in the N equals 20 cohort. Are you seeing a correlation between ALT reduction and baseline ALT or fibrosis stages? And can you tell us what the baseline ALT levels for the N equals 20 and full Archon cohorts were? Thank you.
spk07: So, as Professor Ratiu alluded, we presented all the data that we have. We did not run any correlations or any other analysis apart from the ones that we've provided.
spk06: Okay, got it. Thank you.
spk03: And we have reached the end of the question and answer session. And we will now turn the call back over to Alan Barra for closing remarks.
spk07: So thank you all for joining our conference call today. And thank you again for Professor Ratio for your presentation. um today's presentation will be uploaded on our website under the events and presentation section and you'll have a great opportunity also to view our new website which very soon will include also additional link to the almost study and as always we welcome any question that comes during the quarter you can communicate directly with me or to anyone in the team, and we're very happy to correspond. Thank you very much, and have a nice day.
spk03: This concludes today's conference, and you may disconnect your line at this time.
spk06: Thank you for your participation.
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