Good day, and thank you for standing by. Welcome to the Aligos Therapeutics Top Line Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker, Jordyn Tarazi, Vice President of Investor Relations and Corporate Communications. Please go ahead.
Good morning, and thank you for joining today. With me on today's call is Lawrence Blatt, Chairman, President, and Chief Executive Officer at Aligos, Sushmita Chanda, Chief Development Officer, Lesley Ann Calhoun, Chief Financial Officer, and Stanley Wang, Executive Medical Director. We will begin the call with prepared remarks from Dr. Blatt, followed by a Q&A session. Before we begin, I'd like to remind listeners that this conference call will contain forward-looking statements. All statements other than the statements of historical facts contained in this presentation, including statements regarding our product candidates and business strategy, are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.
These statements involve known and unknown risks and uncertainties and other important factors that may cause our actual results, performance, or achievements to be materially different from any future results. Performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or qualified or are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statement may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements.
For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to our business in general, see our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on August 6th, 2024 , and our future periodic reports. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances, or otherwise. This conference call concerns drugs that are under clinical investigation and that have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to its safety or effectiveness for the purpose for which it is being investigated.
Now, I will turn the call over to our Chairman, CEO, and President, Dr. Lawrence Blatt.
Thanks, Jordyn, and good morning to everyone on the call. Earlier today, we issued a press release announcing the positive top-line results from our phase 2B HERALD study evaluating ALG-055009, our potentially best-in-class thyroid hormone receptor beta agonist, in subjects with metabolic dysfunction-associated steatohepatitis or MASH. We are excited to detail the top-line results after 12 weeks of treatment with ALG-055009, which I will now refer to as ALG-009. Following our prepared remarks, we will open the line for questions. Before we discuss the HERALD data, I would like to take a few moments to introduce Aligos. Aligos was founded in 2018 with a mission to improve patient outcomes by developing best-in-class therapies for the treatment of liver and viral diseases.
Today, we'll be talking about the liver disease, MASH. We are advancing a pipeline of purpose-built small molecule drug candidates, including ALG-009 for MASH, ALG-000184, our potential best-in-class capsid assembly modulator for the treatment of chronic hepatitis B, and I know many of you are aware that ALG-000184 has demonstrated potent antiviral activity after long-term treatment in patients living with HBV. We believe our programs have potential to improve patient outcomes globally. Now, I'll begin to focus on the HERALD top-line readout. Prior to presenting the data, I would like to remind everyone that this data is only recently received. To date, we have evaluated safety and primary efficacy data and a subset of the biomarker data through the treatment period of week 12.
We therefore feel confident in reporting the top-line MRI-PDFF data, certain biomarkers, and the tolerability data today. In the coming weeks, we plan to evaluate additional biomarkers and follow-up safety data. We plan to submit these data for presentation at future scientific meetings, as well as submit our data for publication in a peer-reviewed journal. As a reminder, ALG-009 was discovered in-house by scientists at Aligos. It is a purpose-built molecule with enhanced pharmacokinetic and pharmacodynamic properties, and we've engineered it to be more potent, more beta selective, and have optimized PK compared to other beta thyroid agonists on the market or in development. Following the completion of Phase 1 studies that demonstrate ALG-009 was well-tolerated with dose proportional and low variability PK, as well as expected thermogenic effects, we initiated the Phase 2A HERALD study.
As you can see on the slide, HERALD is designed as a randomized, double-blind, placebo-controlled trial that enrolled 102 subjects with presumed MASH and stages of one to three liver fibrosis, or F1, F2, F3. 32 centers across the United States participated in the study. Subjects were randomized to receive one of four doses, ranging from 0.3 to 0.9 milligrams of ALG-009 or placebo. We had roughly 20 patients per arm. They were given oral once daily dose of our drug, ALG-009, for 12 weeks. Now, it's important to mention that only subjects weighing greater than 85 kilos were enrolled in the 0.9 milligram dose group, and no body weight restrictions were implemented for the other dose cohorts.
This dosing stratification was implemented in order to account for the wide distribution of body weights among MASH patients. Key endpoints assessed were safety, tolerability, PK, and relative change in liver fat, as measured by MRI-PDFF, as well as, other non-invasive biomarker tests, and you'll see some of that today. Dr. Stephen Harrison played a pivotal role in designing the study, aiding in protocol design, site selection, and made huge scientific contributions. We are very grateful for Dr. Harrison's contributions to our study. However, following his unexpected passing, Dr. Rohit Loomba, another, key opinion leader in the field of MASH, graciously stepped in as principal investigator. The HERALD study was enrolled very rapidly over just a six-week period, and we believe this was a testament to the excitement for MASH treatment alternatives from clinicians and patients and was based on the pharmacological improvements we had for ALG-009.
Looking at the baseline demographics with 102 patients enrolled, you can see that the characteristics were generally well-balanced across the five groups and consistent with today's at-risk MASH population. It's important to iterate, reiterate that only subjects weighing greater than 85 kilos were enrolled in the 0.9 dose group, and no body weight restrictions were implemented in other dose groups. Now I'm gonna turn towards the efficacy of our compound. Just waiting for the slide advance. There we go. So I will initially highlight the liver fat changes by MRI-PDFF, and then we'll walk through the biomarker data and safety data.
As you can see from the data presented on this slide, we achieved our primary endpoint, demonstrating statistically significant reductions in liver fat by MRI-PDFF at week 12 in the 0.5, 0.7, and 0.9 dose groups, with a maximum of 46.2% placebo-adjusted median liver fat reduction, and you can see that's in the 0.7 dose group. Additionally, we saw a dose-related reductions in placebo-adjusted median liver fat across 0.3, 0.5, and 0.7 dose groups, which were 19.7%, 24.1%, and 46.2% respectively. I'm sorry. We believe that the body weight reductions at the 0.9 dose group likely led to similar efficacy to 0.7 and 0.9 mg dose groups, which were again 46.2% and 43.5% respectively.
We can move on to the next slide. Now I'd like to discuss comparison of our data to the approved drug, resmetirom, which is also a beta thyroid agonist. Our hypothesis when designing ALG-009 was that the enhanced potency in PK would correlate with improved efficacy and potentially improved tolerability. I think it's clear that we validated our hypothesis today, demonstrating that ALG-009 is differentiated compared to the approved drug. Although the data on the slide are not a head-to-head comparison, the top-line HERALD data demonstrated a higher placebo-adjusted median liver fat reductions at week 12, 46.2% for ALG-009, versus 26% placebo-adjusted median relative fat reductions reported in the published literature pertaining to the MRI-PDFF week 12 data for resmetirom.
These data further strengthen our belief that ALG-009 has the potential to be best in class, and that this positive MRI-PDFF data readout will translate to improved histological outcomes for these patients. On this next slide, we also show the proportion of subjects who had greater than or equal to 30% relative reduction in liver fat, and that was at 70%, with both the 0.7 milligram dose and the 0.9 milligram dose achieving statistical significance. This is important, as the greater than 30% relative reduction in liver fat is shown to correlate with histological improvements in the liver.
Based on the placebo-adjusted median liver fat reductions and the response rates we have observed, we can conclude that ALG-009 is potent, it's a low-dose oral drug, and it has the potential to become an important treatment alternative for patients living with MASH. Now looking at the biomarker data, and again, I want to emphasize or reiterate that not all of our biomarker data is available in this top-line data set. However, here we're showing reductions in LDL-C, lipoprotein (a), and apolipoprotein B. We saw significant reductions across the dose groups for these biomarkers. In particular, we are pleased to see the dose-related reductions in lipoprotein (a) while on treatment with ALG-009. We also observed dose-related increase in sex hormone binding globulin or SHBG. That data is not shown in this deck.
That is also a marker of thyroid beta target engagement in the liver. Now we'll turn to tolerability. We are pleased to report that ALG-009 data demonstrated a favorable tolerability profile with no serious adverse events or clinical evidence of hyper- or hypothyroidism. The majority of treatment emergent adverse events were mild and moderate, with no clinically meaningful findings in laboratory tests, electrocardiograms, vital signs or physical examinations. Importantly, ALG-009 had similar incidence of gastrointestinal-related events compared to placebo across the range of doses studied. In particular, we actually observed a lower incidence of diarrhea, which lacked the dose-response compared to placebo in the ALG-009 treatment groups. The currently approved MASH drug has reported relatively high incidence of diarrhea, so this is an important differentiator as we look to improve patient outcomes.
That's because patients will likely be on this drug and other beta thyroid agonists for prolonged period of time, and we believe that ALG-009's tolerability is an important differentiator that will likely lead to treatment adherence for these patients. Now, in conclusion, we are very pleased to report the positive top line results for the HERALD. With once daily oral dosing ALG-009, we observed robust reductions in liver fat at week 12, significant reductions in atherogenic lipids, dose-dependent increases in SHBG, and the drug was well tolerated with a differentiated safety profile or tolerability profile. Based on these data, we believe that ALG-009 warrants further development into advanced clinical studies. We've been working to complete activities to enable the Phase 2B study, and we estimate that these activities will be completed by mid-2025.
We are collaborating with key opinion leaders, and we're consulting with the FDA to finalize the design of subsequent studies. These activities have already been budgeted, and we continue to believe our cash will provide sufficient funding through the end of 2025. Additionally, we are currently in early discussions with potential partners, and we are evaluating a variety of options to fund continued development of ALG-009. We plan to provide additional updates as they become available, including presentation of these data at an upcoming scientific meeting. After today's positive announcement of ALG-009 for the treatment of MASH, as well as the best in class antiviral activity observed for ALG-000184 for the treatment of chronic hepatitis B, we believe we now have two differentiated drugs with clear paths to regulatory approval.
In closing, I'd like to thank the patients, the investigators, our internal and external teams for their contributions to the discovery of this molecule and to the conduct of this study. Operator, please open the line for questions.
Certainly. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster, and our first question will be coming from Yasmeen Rahimi of Piper Sandler. Yasmeen, your line is open.
Hey, good morning, team. Jung on behalf of Yas. Congrats on the data, and thanks for taking our question. First, could you comment on what the breakdown of the patient population was across F1, F2, and F3 patients? And also, given these data, could you provide additional color on which doses you're considering moving forward into Phase 2B? Thank you.
So the first question, we don't precisely know that because we did not do baseline liver biopsies. We did have FibroScan, and some of the patients had historical biopsies. But given that it wasn't uniformly done, we couldn't characterize these consistently. So we don't know that information. In terms of the doses going forward, one of the most important things we're gonna be doing now with the data set is evaluating the PK/PD relationship. We did have PK on all of these patients, and we'll be making assessments for the doses or dose moving forward, based on those analyses, which we have not done at this point.
Thank you so much.
Our next question will be coming from Michael Yee of Jefferies. Your line is open, Michael.
Hi, good morning. Congrats on your data. We had maybe two questions. On the highest dose of 0.9 , can you just clarify what you were trying to imply regarding the caveats around some of that result, given that there was a minimum weight enrollment into that cohort, and how you think about that impacting the results, and whether-
Yeah, yeah
or not you think that you may have hit a most efficacious dose. So maybe some PK/PD data there would probably help some of that. So clarify what you see in that cohort and the results. And the second question relates to the Phase 2B. Can you maybe just describe some of the scenarios around what that might look like? And would you need a partner to start that study, or would you go ahead? Thank you.
Okay, so the first question involved the dose escalation, and particularly the stratification around the minimum weight of 85 kilos, actually greater than 85 kilos. And basically what we saw in the Phase 1 study was that there was a relationship between the body weight and body surface area of patients and the exposure. And so what we wanted to do was to make sure that on the one hand, the patients that were smaller weren't overexposed. So we didn't want particularly female patients that had a lower weight and lower body surface area to be overexposed to the drug. But on the other hand, we didn't want the patients with a higher weight to be underexposed.
And that's why we stratified the study, allowing only 85 kg greater in the highest dose group. So that's what we're talking about. And we'll be looking at our PK. Again, can't comment yet on that, as that analysis hasn't been completed, to try to understand the dose response relationship, and understand what doses we would go forward. The Phase 2B will likely be a probably two doses, although I can't say for sure. Again, it depends on this MRI-PDFF analysis by PK.
Probably one or two doses will be also blinded and randomized. It will be a longer study, will have paired liver biopsies as well as MRI-PDFFs, as well as the biomarker readouts in a larger set of patients to allow us to make assessments and judgments around what dose to take forward in Phase III. In terms of whether or not we would go forward with that with a partner or not, it kind of really depends on the type of partnership we would get. You know, I always like to say we're not gonna give this drug away. So if the partner is willing to financially reward the company for the value created, then we'll move forward with the partner.
If not, we'll find other means to finance the movement forward of the drug.
Got it. Thank you, guys.
I would now like to turn the conference back to Jordyn Tarazi for closing remarks.
Thank you all for joining this morning. Have a great rest of your day.
This concludes today's conference. Thank you for participating. You may now disconnect.