Good morning, and welcome to NGM Bio's conference call. At this time all participants are listen only mode following prepare remark there will be a question-and-answer session. As a reminder todays call is being recorded. I would now like to turn the call over to Alex Schwartz, Head of Investor Relations. You may begin. Thank you, Catherine, and good morning, everyone. Thank you for joining us to discuss the top line data from ALPINE 2/3, phase II-B study evaluating treatment of aldafermin in patients with NASH in Stage 2 or 3 liver fibrosis over 24 weeks. During this call, we will refer to our press release issued this morning, as well as accompanying slides, which are available in the investor and media section of our corporate website at ngmbio.com. On the call with me today with prepared remarks are David Woodhouse, Chief Executive Officer, and Hsiao Lieu, Chief Medical Officer, as well as Siobhan Nolan Mangini, Chief Financial Officer, who will join us for the question-and-answer period. We remind you that during this call, we will be making forward-looking statements, including those detailed on slide two and any other statements that relate to future events or our future performance rather than historical fact. These forward-looking statements involve numerous risks and uncertainties that could cause actual events, performance, and results to differ materially from those described. These risks and uncertainties are identified and described on slide two and in today's press release, as well as under the caption Risk Factors in our quarterly report on Form 10-Q for the quarter ended March 31st, 2021, which can be found on our website. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. I will now turn the call over to David Woodhouse, CEO. David? Thanks, Alex. Good morning, everyone. Thank you for joining the call. We've listed here the topics we will be covering today, starting with the first topic. Earlier this morning, we announced topline data from ALPINE 2/3, our 24-week phase II-B study evaluating aldafermin 0.3 mg, 1 mg, and 3 mg doses compared to placebo in patients with NASH with liver fibrosis stages F2 or F3. As disclosed in our press release, the ALPINE 2/3 study did not meet its primary endpoint of fibrosis improvement versus placebo. These results are certainly disappointing, particularly for the many patients with F2, F3 NASH who are in dire need of treatments for this disease. Moreover, the lack of significant fibrosis improvement in ALPINE 2/3 was unexpected given the consistency of fibrosis histology findings previously seen with aldafermin in our adaptive phase II study. As Hsiao will discuss in more detail shortly, consistent with our adaptive phase II study, ALPINE 2/3 achieved statistical significance versus placebo on certain secondary endpoints, including NASH resolution and multiple non-invasive measures. In addition, aldafermin continued to demonstrate a favorable safety and tolerability profile. However, in terms of the primary endpoint, the fibrosis data provide a clear signal that the outcome of ALPINE 2/3 was not successful. Before we discuss the detailed study results, I'd like to just take a moment to review our overarching vision and where NGM is today. Our goal is to build a next generation leading biologics company that leverages emerging human biology to develop transformational life-changing medicines. This has been our objective since day one when our founder and Chief Scientific Officer, Dr. Jin-Long Chen, sketched out the four guiding principles you see on this slide. Since that time, our in-house discovery engine, the heart and soul of our company, has enabled important progress toward that goal. Moving on to our expansive pipeline. It's important to note that NGM is a markedly different company than we were when we initiated ALPINE 2/3 in May of 2019. At that time, we primarily had liver and metabolic programs in the clinic. Today, just two years later, we have established a solid clinical footprint in both ophthalmology and oncology, including four ongoing phase II phase II-B studies. Once Hsiao has walked you through the ALPINE 2/3 results, I'll provide a recap of where we are with our pipeline programs, including next steps for aldafermin, and I'll also review our multiple anticipated upcoming milestones. With that, I'll turn the call over to Hsiao. Thank you, David. By way of a high-level overview, as David mentioned, ALPINE 2/3 did not meet its primary endpoint of fibrosis improvement. The primary endpoint was analyzed using the Multiple Comparison Procedures and Modeling or MCP-Mod approach, which is a statistical approach that aims to test dose response and identify optimal dose effect across a range of doses. Analyzing the primary endpoint with observed values using a pairwise statistical approach, the study also did not meet statistical significance. Consistent with what we have seen our adapted phase II study of aldafermin, ALPINE 2/3 did achieve statistical significance versus placebo on certain secondary endpoints, including NASH resolution and multiple non-invasive measurements such as liver fat content reduction, ALT and AST, which are liver enzyme measurements, and PRO-C3, which is a biomarker of fibrogenesis. Finally, aldafermin was generally well-tolerated with an overall safety and tolerability profile similar to placebo. Let's quickly review the ALPINE 2/3 study design and patient demographics. In this multicenter, double-blind, randomized, phase II-B study, 171 biopsy-confirmed NASH patients with F2 or F3 liver fibrosis were randomized equally across the four arms to receive daily subcutaneous injection of 0.3 mg, 1 mg, and 3 mg of aldafermin versus placebo over 24 weeks. Per protocol, patient liver biopsies were performed at baseline screening and at 24 weeks of treatment. They were read using the NASH CRN criteria by one central independent hepatopathologist who was blinded to patient and treatment assignment. Key inclusion criteria were biopsy-confirmed F2, F3 liver fibrosis by NASH CRN criteria with NASH greater or equal to four points and one point in each component, and absolute liver fat content of greater or equal to 8% as measured by MRI-PDFF. As you can see, patient baseline demographics were well-balanced across the arms and are similar to what we have seen in our prior F2, F3 NASH studies. The primary endpoint for this trial was fibrosis improvement of greater or equal to one stage with no worsening of NASH at week 24. We designed the primary objective of ALPINE 2/3 to show a dose response in fibrosis improvement with no worsening of NASH at 24 weeks across the 3 doses of aldafermin. Secondary endpoints included NASH resolution, composite endpoint of both fibrosis improvement and NASH resolution, liver fat content reduction by MRI-PDFF, ALT, AST, and PRO-C3 at week 24. Moving now to the study results. Here, we're showing the primary endpoint as analyzed using a pairwise statistical approach, which only evaluated patients who completed a biopsy both at baseline and at week 24, or a total of 143 patients. Patients in the 0.3 mg arm, which will be depicted in light green throughout the presentation, had a 31% fibrosis improvement versus 19% in the placebo arm, depicted in gray. Patients in the 1 mg arm, depicted in green, had a 15% fibrosis improvement, and patients in the 3 mg arm, depicted in dark green, had a 30% fibrosis improvement. As I mentioned earlier in my summary slide, the key analysis of the primary endpoint using MCP-Mod, which included the full intent-to-treat population of 171 patients, likewise revealed the study did not meet their primary endpoint with a p-value of 0.55. Obviously, we expected and certainly on behalf of patients, wanted a much different outcome on fibrosis in this study. We plan to conduct further analysis to more fully understand the fibrosis findings. That said, the overall fibrosis outcome and primary endpoint in this trial from both a dose response and overall magnitude were unsuccessful. I turn to secondary endpoints we evaluated in ALPINE 2/3, all pairwise analyses. Looking at NASH resolution and the composite endpoint of NASH resolution and fibrosis improvement, we saw statistically significant NASH resolution, with 22% of patients in the 3 mg arm achieving NASH resolution with no worsening of fibrosis at 24 weeks versus 6% in placebo. The composite endpoint of fibrosis improvement and NASH resolution did not reach statistical significance, which is not surprising given the fibrosis results. This next slide provides a summary of the consistent results aldafermin demonstrated across multiple non-invasive measures, including liver fat reduction, ALT and AST decreases, and PRO-C3 reductions, with statistically significant differences versus baseline in both the 1 mg and 3 mg of aldafermin dose arms compared to placebo. These findings are in line with what we observed in our adaptive 4-cohort phase II study of aldafermin. Consistent with our adaptive phase II study of aldafermin, both adverse events and serious adverse events were similar to placebo, with no serious adverse events deemed related to study medication by trial investigators. In line with our adaptive phase II study, an aldafermin-induced LDL cholesterol elevation was safely and effectively managed with concomitant statin use. There was one fatal adverse event in the aldafermin 1 mg arm, which occurred 30 days after the last confirmed aldafermin dose and was determined unrelated to treatment by site investigators. In the future, we anticipate submitting complete results from the ALPINE 2/3 study for future publications and/or presentation at a scientific congress. Before I turn the call back to David, I just wanted to personally acknowledge and thank our clinical development team here at NGM, as well as all the clinical trial investigators, site staff, and most importantly, the patients who participated in ALPINE 2/3. Clearly, NASH continues to be an area of high unmet need while simultaneously proving to be a difficult area for clinical development. I will now turn the call back to David for concluding remarks. Thank you, Hsiao. What does this all mean for aldafermin going forward? First and foremost, at our core, we are a deeply disciplined, science-driven organization that will always follow and respect where the science leads us. To that end, the fibrosis data we reported today do not support moving forward with the Phase III study of aldafermin in the F2, F3 population. We plan to continue enrollment in our ongoing 48-week ALPINE phase II-B study to understand the profile of aldafermin in patients with F4 NASH with compensated cirrhosis, which represents a particularly acute unmet need given this patient population's advanced disease. Turning to the status of our other product candidates and our multiple potential near-term catalysts. For anti-complement C3 antibody, NGM621, we expect to complete enrollment in our ongoing phase II CATALINA study in patients with geographic atrophy in the middle of this year. We will guide on timing for data once we reach that milestone. In the meantime, we expect Apellis will be reporting out phase III data for its complement C3 inhibitor in geographic atrophy, which we anticipate will be an interesting read-through to our program and its potential for differentiation, including the possibility for every other month dosing with an improved safety profile. Our lead oncology program, NGM120, is currently in a phase II study for metastatic pancreatic cancer and cancer-related cachexia, a severe muscle wasting syndrome. You can expect interim data from the NGM120 phase I-A/I-B dose-finding study that preceded the phase II in the second half of this year. Our second oncology program, NGM707, is an ILT-2/ILT-4 dual inhibitor that we are advancing rapidly toward initiation of the phase I component of a phase I/II study in the near term. This will be a robust trial in which we plan to enroll approximately 180 patients with select solid tumor types. We also anticipate initiating a phase I study of our third oncology program, NGM438, a LAIR-1 antagonistic antibody, by the end of this year. Finally, our partner, Merck, is conducting phase II-B study with MK-3655 in patients with NASH and F2, F3 liver fibrosis. As a reminder, the phase I-B study with this agent that we conducted prior to Merck licensing the program suggests a profile of a potent insulin sensitizer and de-lipidator of the liver, which may provide a potential two-pronged benefit for the approximately 60% of NASH patients who also suffer from Type 2 diabetes. As you can see, we have multiple potential value drivers in the pipeline at NGM. What's not reflected on this slide are multiple undisclosed research and early development programs competing for the next candidate nomination spot. We have a healthy cash position with more than $400 million on the balance sheet as of the end of the first quarter, and a multiyear runway that we expect will support these advancing programs through multiple catalysts. In closing, I think I speak on behalf of our entire team when I say it is a great and humbling privilege to be involved in the business of advancing potential medicines to improve patients' lives. As we were reminded today that drug development is also a complex endeavor that is not without risks and unexpected outcomes along the journey. Nevertheless, we remain as focused as ever on our mission to deliver life-changing medicines for patients with serious unmet needs. Thank you all again for joining today's call and for your support of NGM. We look forward to providing you with further updates in the months to come. I would now like to open the call for questions. Operator? Thank you. To ask question press the star then one on your touchpad telephone to withdraw your question press the pound key. Our first question comes from Steve Seedhouse with Raymond James. Your line is open. Hi. Good morning. Sorry about the outcome, I do commend you on a data-driven and prudent decision, I would say, which others in the field have not made in the past and ultimately paid a price in phase III. I suspect you probably did debate whether or not to just advance to phase III anyway based on these data. I'm curious, for example, why you thought NASH resolution wasn't a path forward as a primary endpoint at phase III, and also wanted to understand just your interpretation of the fibrosis result with respect to how you read biopsies. How were samples scrambled and read? Did you change that process versus Cohort 4? Maybe I'll stop there for now. Sure. Thanks for the question, Steve. I'll address the first one and then Hsiao can cover the conduct of the biopsies. Yeah, as you know, we've held a high bar of efficacy for this program since its inception. It's a once daily subcutaneous injection, and it requires a statin, a concomitant statin. We've really looked for that fibrosis endpoint, which by the way, is the endpoint that's correlated with outcomes in this disease. From a resource allocation point of view within NGM, we have a lot of other programs that have high potential as well. I think perhaps if this was our only asset, we might be really looking sideways at this data and seeing what we can see. From just a prudent resource allocation point of view, it seems like actually a relatively easy decision, not one we were hoping to have to make, but the data is what the data is, and we're going to follow it. Hsiao, do you want to talk about the biopsies? Sure. From the biopsy and also from the slide perspective, the procedure and process were the same in this trial compared to Cohort 4. It is also the same hepatopathologist who read this trial and Cohort 4. She was blinded to the slides, to screening, and to week 24 slides. Okay. Thank you. The other question on just the data that you're presenting, the non-invasive biomarkers look great, obviously, and yet you did not get the fibrosis result you were hoping for. I'm curious if you think that's an indictment on all of these biomarkers or an indictment on the 24-week time point that you used for histology, or maybe neither or both? Would be interested in your conclusions there. Yeah. More great questions, Steve. These are top-line data. I think we're going to be interested to look back at correlations and see where we saw fibrosis improvement versus the non-invasives. I think generally, when you stand back and look at the data, I think this highlights the variability of the biopsy endpoint, and it's really something we hope, particularly by the time we read out ALPINE 4, we've made some progress on, in particular around artificial intelligence assisted reads of these biopsies to try and make those less variable. There are obviously multiple components that go into the variability. I think that's the most telling as you look back at the data. The non-invasives are very consistent when you look not only internally with the dose response, but also when you look at it back at our prior results. Last question from me. Is it safe to assume the efficacy bar for MK-3655 in terms of looking for that fibrosis improvement is the same, or would you and Merck advance this asset to phase III if you had a NASH resolution result like this, just given that the metabolic profile is obviously different for the FGF21 analogs? Yeah. The asset's in Merck's hands. It's in their control. What I would just remind you is the trial is structured a little differently in that it's actually a year treatment period. It does have a different profile on this insulin sensitization and metabolic drivers, so they're using NASH resolution as their primary endpoint. Yet, of course, they'll be measuring fibrosis as well. Just like with ALPINE 4, we hope we can learn something from this and really use a data-driven approach to determine what the right next step is with that program. I think there is opportunity here. This is a severe unmet need, a big population. While we're not making the decision to go forward in phase III, I think this area deserves as much activity as possible to try and converge these measurements with these potential treatments. Thank you, David. Thanks, Steve. Thank you. Our next question comes from Ritu Baral with Cowen. Good morning, guys. I also want to commend you on a very practical decision, and probably a really tough one given slide 11. First question, then I've got a follow-up. Can you talk about the rationale for continuing ALPINE 4 at this point? Is this a decision that's been made, or is this sort of TBD? Well, we're well along in conducting that trial, Ritu Baral. I know you know that this is a distinct patient profile. It's got a different regulatory pathway associated with it. Importantly, we're treating the patients for 48 weeks in that trial. While it's advanced as it is, we think it's important to read that out. We'll assess it. We obviously think we can learn something from these ALPINE 2/3 results that we might be able to apply to that trial. We'll see what we uncover at that point. The drug has proven to be quite reproducibly safe and tolerable. I think that's another important aspect of continuing to run that trial. The plan is to continue to enroll that trial and complete it. Okay. I noticed you had baseline BMIs in the slides. Can you talk to any changes in weight that you saw over the course of this study? Less so from a treatment effect perspective. I'm just wondering, since so much of the trial was conducted during COVID and some of the feedback from our KOLs about what's been happening to patient weight over that period. Yeah. I'll let Hsiao address the BMI question. We certainly did assess whether there was something about conducting this trial during COVID time. We don't see any obvious signals that that may have been an influence here. Hsiao, do you want to cover the BMI? Sure. We looked at all these measurements. We did not see any changes compared to placebo. Got it. Okay. The last question that I have relates again to slide 11 and the PRO-C3 changes, except 26%, which is pretty profound compared to everything else we've seen, yet we have the histopath. One of the other biomarkers you mentioned before is C3M. Wondering if you had a chance to look at sort of a flip side of fibrogenesis and was there any movement in C3M? I'll let Hsiao confirm this, but these are top-line data. I don't think we've gotten to that level of some of these exploratory fibrogenesis markers. Is that correct, Hsiao? That's correct, David. We'll be looking at that later. Got it. Thanks for taking my questions. Thanks, Ritu. Thank you. Our next question comes from Paul Choi with Goldman Sachs. Hi. Good morning, everyone. Sorry about this. A tough break with the data. Just a couple from us, please. With regard to the biomarker data trends, clearly you are seeing a dose response there, but I guess as you look at the results here and just thoughts on the FGF19 mechanism here, any particular gleanings based on these top-line results that you would have on the mechanistic approach with regards to fibrosis? I had a follow-up. Yeah, I just reiterate these are top-line. They're unexpected. We thought we'd see a reproduction of what we'd seen in Cohort 4. We'll certainly be looking into those things, Paul. At a surface, we do continue to see strong C4 suppression, which would suggest the mechanism, particularly the FGFR4 pathway, is strongly inhibited. As I mentioned earlier, I think looking at these correlations of some of these non-invasives with those that we did see liver fibrosis responses will be important. I think what's particularly telling is the lack of dose response on the fibrosis improvement. That's one thing we really want to understand better because it's, as you just pointed out, quite different from a consistent dose-response curve across the other measurements. Okay. Thanks, David. Just maybe some basic blocking and tackling questions with regard to trial execution. I know you mentioned you had 140-ish something patients complete the paired biopsies at the 24-week endpoint. Could you maybe just speak a little bit to drug adherence and consistency of doing the injections? Any issues there that you could highlight? Yeah. We don't see any major conduct issues as we unblinded the data. Hsiao, do you want to expand on that a little? Sure. We did not see any non-compliance in this trial, maybe one or two patients at most. Otherwise, I think this trial was a well-conducted trial, and overall call to the data that we received is fairly high. Okay. Thank you very much. I'll jump back in the queue. Thanks, Paul. Our next question comes from Matthew Luchini with BMO Capital. Your line is open. Hi. Good morning, guys. Thanks for taking the questions and certainly disappointing outcome this morning. First, I guess, as we've been leading up to this day, there's been a lot of discussion about similarities in trial between trial populations during the study and Cohort 4. I'm just curious, as you look at now we have the demographics and actual patients that went through the study, whether it's the proportion of patients that were at F3 or something else. Is there anything here that jumps out as being perhaps meaningfully different from what you were expecting that perhaps could have influenced the result that we saw? As a follow-up to one of the prior questions, it sounds like it certainly wouldn't have affected maybe the outcome. I'm just curious your perspective on the dropout rate if any, as it relates to COVID. I have one more after that, thanks. Yeah. Maybe I'll just address one thing on COVID, and then I'll hand it over to Hsiao about the similarities. As you might imagine, at a high level, we wanted to get as close to patient populations we've seen in Cohort 4 because we felt those were quite impressive results. We intentionally tried to create a similar population. As it relates to COVID, yes, we did see a slightly higher dropout rate. I can tell you our clinical operations team was just working in overdrive during this pandemic time, and so they did a terrific job, I think, even keeping that dropout rate and getting those end-of-treatment biopsies during this time. Unfortunately, the chips didn't fall our way. Sure populations? We compared the demographics in ALPINE 2/3 with our cohort four, and we looked at each one of these parameters very carefully. We did not see any major differences that could explain our trial result. Most of these parameters are the same. Okay. Then, obviously, with the decision not to move the program forward into phase III, we'll be looking at some changes in spending going forward. It looks like we spent $50 million last year on all the programs. I just wondered if you're able to provide any, at least directional color on expense outlook from here. Yeah. Thanks for the question. We do have a lot of other great programs in the pipeline, and so part of this decision, as I mentioned earlier, was governed by the fact that we have a lot of interesting areas to invest. Siobhan, do you want to go through the outlook on the expense line? Sure, I'd be happy to. It's still early, as you said, Matt, when we look at operating expenses looking forward, we actually expect them to be relatively consistent compared to what you saw in 2020 and Q1 2021. What's going to change, as you alluded to, is that we'll see aldafermin expenses trending towards the low end of the range as we're completing enrollment with ALPINE 4 and finishing studies there. What's going to be offset is an increase in our oncology clinical spend as we're seeing multiple programs entering through the clinic this year, as David alluded to earlier. Overall, we expect our cash balance to provide us with a runway over the next few years, given where we landed at the end of Q1. Great. Well, thanks for taking the question. We'll go ahead and get back in the queue. Thanks, Matt. Okay, we have a question from Mayank Mamtani with B. Riley Securities. Your line is open. Good morning, team. Thanks for taking our questions and again, commend you on a science-driven decision here. Three quick questions for me. Just coming back on the theme, what field could learn from these dramatically different results in Cohort 4 versus ALPINE 2/3 on fibrosis? Any comments you have on the placebo response here where clearly on the non-invasives, we are seeing a lower number in line with what we would expect in COVID but the fibrosis improvement endpoint definitely ticked higher? Then also how should we think about that for the ALPINE 4 study, which obviously, is there like a time component to this, where the longer you go, maybe the placebo response normalizes? Thanks for the questions, Mayank. If you recall back in Cohort 4, placebo's response rate was 18%, and so 19% is actually pretty similar. It seems, as you're pointing out, unusually high, given the non-invasives. I think that particularly over a relatively short period of six months, I think that just points to the biopsy variability. I know we and others have been looking at these kind of assist tools that exist from an artificial intelligence point of view. I think that's probably part of the solution here, and Hsiao, I don't know if you want to expand further on that aspect of it. Just in terms of the biopsy reads and how we may be able to bring that placebo rate down a little bit. We are still learning from ALPINE 2/3 result. I think we are looking at our procedures very closely and try to understand that, and also trying to understand the control process of staining for these slides. We are also doing other studies internally to understand the variability of intra and inter-reader variability. We'll hope to learn from all this and try to apply it for ALPINE 4. Okay. Just pivoting to GA for a minute, on the CATALINA study, which seems to be enrolling ahead of plan. David, could you just lay out the expectation for the GA lesion reduction and perhaps the CNV background rate you're expecting there? Mayank, I think we disconnected during your question. Sorry about that. I'd be happy to answer again. No. Okay. Sorry about that. I'm happy to repeat. Just the question was, on the phase II CATALINA study that seems to be enrolling a little ahead of plan. Could you just sort of lay out your expectation for the GA lesion reduction and perhaps the CNV background rate in the study? Yeah. Thanks for the question. I think our enrollment rate in this trial really reflects the unmet need. These patients are really motivated to seek treatment and even in the midst of a pandemic. We started this in July of last year, this enrollment, and we've been really pleased with the rate that the trial has been proceeding with. I can't really comment yet on, as it relates to anything we're seeing in the trial. It's obviously blinded. As I mentioned in my prepared remarks, we do think the Apellis read-through in the third quarter of this year will be an interesting one for our program, given it's the same target. It's a well-controlled phase III trial. Our expectations, and I'm sure theirs is, that we'll repeat the pretty significant reduction in progression of disease they saw when they hit that target. We think we have some important advantages of less frequent dosing with our molecule, with some safety advantages. We're eager as at Merck is as well to get this program moving as quickly as possible. Excellent. My final question quickly on exactly that, on the Merck's interest, the longer term strategic collaboration you have. Is it fair to assume that their interest is going to move like how your pipeline is evolving towards ophthalmology and IO? Is that fair to assume that? Well, we've been operating under this collaboration for six years now, and one of the great things about it is they allow us to proceed many of the different areas that we want to. It's really as we are oriented as a science-driven company, and they expect us to actually kind of pull them into areas they might not normally go into. I would say ophthalmology falls in that category. We obviously overlap a little bit in oncology. Frankly, when they licensed MK-3655, they got pulled into metabolic diseases and NASH. Their objective here is really to gain some access to our deep and expansive pipeline and we continue to work away with that funding as well. We are working closely with them on ophthalmology. They seem to really be interested in NGM621, and yet we don't expect they will take all of our programs. Part of the beauty of this arrangement is we get $75 million a year in funding, and we've been able to produce this expansive pipeline on the back of it. Great. Thanks for taking the questions. Thank you. Our next question comes from Derek Archila with Stifel. Your line is open. Hey, guys. Good morning. Sorry about the outcome here. I think it sounds like the right decision to move on with other programs. That's what I'll ask about. I just want to follow on to Mayank's questions on NGM621. Just want to understand if there's any additional data that you'll present from the phase I-B in the next 12 months or so. Just remind us in terms of the phase II design for CATALINA, how that mirrors the enrollment criteria and design of the Apellis phase III trial. I have one follow-up. Okay. Thanks, Derek. Short answer on the phase I study with NGM621 is we don't expect to release more data from that. We've been at the last few ophthalmology conferences and really have presented all of the data out of that trial. It certainly allowed us to go into CATALINA. We were able to safely administer the highest dose we can intravitreally with the drug. That's what gives us confidence about every other month dosing profile potential. As it relates to the design, it is very similar to Apellis, both in terms of patient population, but with a couple of improvements, we think, around double-masking of the trial, which gives it a rigor that potentially could allow it to be treated as one of the first pivotals, if we hit statistical significance. Got it. I just want to follow up on NGM120. You highlighted the phase I-B dose finding data, especially in the second half of this year. Just wanted to understand if you could shed some light on what we should be expecting in that data set. Thanks. Thanks. NGM120, we're looking at two different signals. One is its effect on cancer directly, and then also through inhibiting a metabolic path that we think could alleviate the cancer cachexia that many of these patients suffer from. The phase I-A/I-B design was looking. The phase I-A was in solid tumors. Phase I-B was in metastatic pancreatic cancer. We'll have some biomarker data to address whether we're seeing the signals we want to see in terms of the translation that we've seen in our preclinical models into those early human studies. We've already progressed into the expansion stage of phase II in metastatic pancreatic cancer, which is a placebo-controlled trial over a background of standard of care chemotherapy. The phase I-A/I-B will be sort of a preview of some of the biomarkers we're looking at. I think it just represents, as you're pointing out, that NGM has a rich set of catalysts coming forward. That will be one of them. It'll be at a medical conference later this year. We hope that that will continue to generate enthusiasm in the community for this particular pathway. Great. Thank you. Thank you. Thank you. We have time for one more question. It comes from Yasmeen Rahimi with Piper Sandler. Your line is open. Hey, team. Thank you for taking my questions, and I'm sorry for the outcome. I have a number of questions. Maybe the first place to start off would be to highlight whether you saw differences in the F3 population. Previously, you have commented on that if you would run a phase III in F2, you would enrich for F3. Did you look at the F3 response in one point improvement of fibrosis and made the decision to pull the plug? The second question that I'm very interested in is to understand what percentage of the patients had to be titrated up, or if had to be titrated up on statins. That would be helpful. Thank you. Okay. Thanks for the question, Yas. Yeah, we looked at the F3 population, and it didn't change our decision in terms of not proceeding. Hsiao, do you want to talk about the statin? Sure. Yeah. What we have showed is the top-line data regarding the statin titration. These are the data we'll be analyzing and hope to get that soon. Thank you. Another question for you is in the past, you have also noted that patients who have a remarkable MRI-PDFF response show a fibrosis benefit. At the highest dose group, you're seeing quite a robust relative change. Did you look into that subgroup? Do we think about MRI-PDFF still as a responder for one point improvement of fibrosis? If you could just comment on that patients who had the greatest fat reduction, if there was histological benefit seen in that subgroup? Yeah. Thanks for the question, Yas. We haven't gotten to that level of detail yet in terms of analyzing the data. As I alluded to earlier, I think as we unpack this data set and look at correlations with different non-invasives, that's something for sure we'll look at. Historically, when we've looked at that, the large liver fat responders tend to be the ones who start with high liver fat content, and you don't necessarily see the correlation. I think the more data we can generate, and as we look across all our different trials, that might be an interesting area to dig into. Thank you. Do you think now with the data that we have you considered to maybe add more patients to the ALPINE 4 study? Do you think that maybe the size of the cohort per arm could have contributed? Given that we know now that there's quite a lot of variability in histology, is there an optionality to enhance the ALPINE 4 data set with more patients? Yeah, it's an interesting question. At this point, we think we've designed these trials in an appropriate way. As I mentioned earlier, we're obviously reacting to this data, thinking about any changes we might make to ALPINE 4. I doubt we'd over enroll it in some way at this point. We might think about maybe overloading some of the higher doses. As a reminder, we've got 0.3 mg, 1 mg and 3 mg doses in there, too. We might bias towards 1 mg and 3 mg in order to improve some of the powering there. Thank you for taking my questions. I'm sorry about this outcome. Well, thank you, Yas. Thank you. There's no other questions in the queue. I'd like to turn the call back to David Woodhouse for closing remarks. Thank you, Catherine. In closing, the ALPINE phase II-B study fibrosis improvement outcome is disappointing, most notably for people living with NASH who remain in dire need for effective therapeutic solutions. We look forward to advancing the rest of our growing pipeline and remain as focused as ever on our mission to deliver life-changing medicines for patients with serious unmet needs. Thank you again for joining us today, and we look forward to seeing many of you in the coming months. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.