Good afternoon, and welcome to Fractyl Health's First Quarter Financial Results and Business Updates Call. As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode. There will be a Q&A session following management's prepared remarks. I will now turn the call over to Stephen Jasper. Stephen, you may now begin.

Thank you. This afternoon, we issued a press release that outlines the topics we plan to discuss today. This release is available at www.fractyl.com under the Investors tab. Today on our call, Dr. Harith Rajagopalan, Chief Executive Officer; Lisa Davidson, Chief Financial Officer; Dr. Timothy Kieffer, Chief Scientific Officer and Adrian Kimber, Chief Commercial Officer will review our recent business highlights and first quarter financial results. Before we begin, I would like to remind everyone that statements made during this conference call that do not relate to matters of historical fact, including statements about our objectives and anticipated clinical milestones, preclinical or clinical trial data, the impact of any of our product candidates, the design, initiation, timing and results of clinical enrollment and any clinical trial or readouts, the potential launch or commercialization of any of our product candidates or products and the sufficiency of our cash, cash equivalents and investments to fund our operating activities for any specific period of time should be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are intended to be subject to the Safe Harbor protection provided by the Reform Act. Actual results could differ materially from those indicated by the forward-looking statements due to the impact of risks, uncertainties and other important factors. Participants are directed to the risk factors set forth in Fractyl's quarterly report on Form 10-Q for the period ended March 31, 2024 and the company's other filings with the Securities and Exchange Commission. Any forward-looking statements made today speak only to Fractyl's operations as of today. Fractyl disclaims any duty to provide updates to its forward-looking statements even if subsequent events cause the company's views to change. It is now my pleasure to pass the call over to Harith.

Thank you, Stephen and good afternoon everyone. Thank you for joining us for our first quarterly results call. Over 10 years ago, I co-founded Fractyl with a singular and audacious goal to eradicate metabolic disease. As a physician, I saw firsthand how Type 2 diabetes and obesity and their comorbidities impact patients and their families. I witnessed patients experience complications of disease despite following all of their doctors' advice, spouses becoming caregivers and children losing parents far too young to diseases that should be entirely treatable. I knew that there had to be a better way to address these issues by tackling the diseases at their root cause in the gut and in the pancreas, and thus, Fractyl Health was born. We have always been clear with our vision to develop transformative therapies that can prevent and eliminate metabolic disease. We have never wavered in our focus because we knew that treating the underlying disease is the most patient centered approach to better long-term health. I'm pleased to be here today to present these results because we are so close to achieving the goals we set forth for ourselves a decade ago. 2024 is shaping up to be a pivotal year for Fractyl. We are executing on our strategy, we are clear about the future and we are ready to bring Fractyl to the next level to help even more patients around the world. The treatment landscape for metabolic disease has radically changed over these last several years with the emergence of GLP-1 drugs. These therapies are incredibly effective and exciting developments, but they also have significant limitations. Their need for chronic administration, their high discontinuation rates and the dramatic weight regain and loss of metabolic benefits observed as soon as people stop treatment. To address this unmet need, we…

Thank you, Hari. Prior to joining Fractal Health as CSO, I was a professor in the faculty of medicine at the University British Columbia and CSO at Biocyte. Given my training in gastrointestinal hormones and islet biology, I'm a passionate believer in Fractal's therapeutic approaches targeting the gut and pancreas, the key metabolic organs where dysfunction is a root cause of diabetes and obesity. I'll begin with a review of Revita platform progress and then turn to Rejuva. As previously mentioned, we recently provided an update from our ongoing real world German registry study of Revita in patients with type 2 diabetes after German Diabetes Association Annual Meeting. In 14 participants where we have six months of post Revita follow-up, there was an average body weight loss of 8.1% that was generally sustained through six months thus far and a fall from median baseline blood glucose levels of 153 mg/dL to 116 mg/dL, accompanied by a hemoglobin A1C dropping from 9.2 to 7.6. These are particularly exciting findings given these are patients with advanced Type 2 diabetes who have been unable to control their diabetes through the use of multiple medications or lifestyle changes. We plan to continue enrolling patients in this registry and to provide updates on an ongoing basis. In March, we received IDE approval to initiate Remain-1, a two part parallel cohort study for weight maintenance in patients with obesity who have lost at least 15% total body weight on GLP therapy and wish to discontinue GLP-1 without weight regain. Alongside, we will have our Reveal-1 open label cohort of patients who will be managed in exactly the same way, and we expect to begin providing open label study updates in the second half of the year. With the Remain-1 study, we hope to evaluate how Revita…

Thank you, Tim, and good afternoon everyone. Since joining the Fractyl team a few months ago, I've been consistently impressed by our people, our science and our technology. My short tenure here has only strengthened my initial belief that Revita represents a significant opportunity both clinically and commercially. It's evident that there's a significant issue with weight maintenance within our society. In recent times, GLP-1 therapies have been widely prescribed by physicians and adopted by patients to tackle this very issue. However, despite the widespread good coverage by insurance and the observed benefits of weight loss and glucose reduction, over 50% of patients discontinued GLP-1 therapy within the first year. When examining obesity, it's staggering to note that nearly 100 million individuals in the United States suffer from obesity and prediabetes, while globally this number surpasses 800 million. Now turning to type 2 diabetes, there are over 500 million adults grappling with this condition worldwide. Within the United States alone, 27 million individuals are on medication for type 2 diabetes with over 4 million relying on insulin therapy for advanced Type 2 diabetes. In 2022, approximately $65 billion was allocated to drugs targeting glucose control and weight management. Notably, all of these expenses were tied to medications necessitating chronic administration yet non-effectively address the underlying disease progression. We perceive this as an immense opportunity and firmly believe that Revita holds a distinctive position to capitalize on this by tackling disease progression and prevention. For individuals currently managing type 2 diabetes with medications and insulin, Revita aims to enhance glucose control and halt or slow down the disease's advancement. Moreover, for those with prediabetes and obesity, Revita is engineered to target the metabolic dysfunction at its source, mitigating the risk of individuals progressing to Type 2 diabetes and obesity. Revita is…

Thank you, Adrian. In the first quarter of 2024, revenue was generated from our commercial pilot in Germany, which launched in the first half of 2023. Turning to operating expenses. Research and development expense in the first quarter of 2024 was $14.4 million compared to $9.3 million for the same period in 2023. The increase during the quarter was primarily due to increased investment in the Revitalize-1 clinical study, advancement of the Rejuva program and increased personnel related expenses, including stock-based compensation. Selling, general and administrative expense in the first quarter of 2024 was $7.1 million compared to $2.8 million in the same period in 2023. The increase was primarily due to increased personnel related expenses, including stock-based compensation and professional services expenses and other costs associated with operating as a publicly traded company. For the first quarter of 2024, we reported a net loss of $3.3 million compared to a net loss of $11.9 million for the same period in 2023. The decrease in net loss was primarily related to a $17.1 million non-cash decrease in fair value of the notes payable and warrants on our balance sheet, $0.7 million in increase in interest income earned offset by an increase of the $9.4 million in operating expenses. As of March 31, 2024, we had cash and cash equivalents of $121.4 million. Based on our current development plans, we believe cash and cash equivalents will be sufficient to fund our operations through expected key company milestones through 2025. I will now turn the call back to Harith.

Thank you, Lisa. Fractyl is at a critical point in our growth trajectory. As you heard from Tim, our two platforms, Revita and Rejuva have the potential to help us realize our vision of creating durable disease modifying therapies that target the organ level root causes of obesity and Type 2 diabetes with key catalysts coming in the next several quarters across both of our programs in both disease categories. And as Adrian told you, there is significant unmet need in this market for this type of therapy. Fractyl is a different company with a different approach, which we believe meets the needs that are identified by the obesity and Type 2 diabetes patient communities for better health with less medicine. For the remainder of 2024, we are focused on executing on our clinical studies in Type 2 diabetes and obesity, formulating our commercialization plans to introduce Revita to the U.S. and European markets, advancing RJVA-001 through IND enabling studies and efficiently allocating our capital to ensure that we have the runway that we need to meet all of our objectives. It is an incredibly exciting time at Fractyl, and I would like to take a moment to thank the patients and the physicians who have supported us over the past 10 years. We deeply appreciate your trust in us and in our mission. I would also like to acknowledge the hard work and dedication of my fellow Fractylians. They spend a tremendous amount of time and energy focused on helping us achieve our mission and vision, and we truly appreciate their efforts to build something great together. And finally, I'd like to thank you for your continued interest and your support of Fractyl. We look forward to sharing updates on our progress as we work toward bending the curve of metabolic disease globally. And with that, we will now open the call up to questions. Thank you very much.

Thank you. [Operator Instructions]. Our first question comes from the line of Jason Gerberry of Bank of America.

Hey, this is Chi [ph] on for Jason. Thanks for taking our questions. I have two questions on the Real World Registry study and one on Rejuva. So curious on the Real World Registry study, can you talk about how similar the patient enrolled in the study relative to those enrolled in Revitalize-1? What proportion of the patients were on insulin for the Registry study? Curious if the data from the Real World Registry study can be extrapolated to Revitalize study in some way? Second question on the same study is you provide three month and six month follow-up data from the same study. I'm curious if you can talk about durability of the data with respect to HbA1c reduction as well as weight loss. Are those data in line with your expectation? And do you expect the durability to translate into Revitalize-1 and Reveal-1[ph]/Remain-1 respectively? And my lastly on Rejuva, you talk about you look to nominate your first gene therapy candidate for obesity. I'm curious what attributes are looking for the obesity candidate. How might that be similar or different than RJVA-001 that you have selected for diabetes? Thank you.

Thanks, Chi. I look forward to seeing you later this week at the BAML conference in Vegas. We're heading out tomorrow. I'm not sure if you're there yet.

We are there. Jason is traveling in, but we look forward to hosting you.

Awesome. We're looking forward to that as well. It'll be my first time attending an investor conference in Vegas, but thanks for your questions. So let's talk about the Real World Registry first. I'll tackle them, and then I'll ask Tim if he has anything that he would add. Your first question was whether it's a similar patient population to Revitalize-1. And I'll say that it is a similar patient population, but it's a larger cohort of individuals than that. In Europe, our CE Mark covers patients who are inadequately controlled with Type 2 diabetes, who are failing at least one glucose lowering agent that affords us an opportunity to have an ability to treat people across the spectrum of medical therapies. And there are roughly 20% of patients with Type 2 diabetes who are on insulin. There's a little bit more than that who are on insulin who have entered the Revitalize-1 study. I don't have an exact number for you on how many of them are on insulin. And what is interesting about this is that we thought naturally that people with more advanced disease would be more interested in undergoing Revita. And as it turns out, there is interest that seems to be very broad based. People who are on one or two medicines seem just as interested in Revita as people who are on multiple medicines. And we might be inclined to think that this is like people are driven to choose a procedural therapy when they have exhausted all other medical -- all other medical options, but as it turns out, many people are wanting to try something that addresses a root cause even before progressing to what might be considered advanced therapies that are already in the guidelines. So that is an interesting learning…

Great. Thanks so much.

Thank you. Our next question comes from the line of Mike DiFiore of Evercore.

Hi, guys. This is Mike DiFiore in for Umer. Thanks for taking my question and congrats on all the progress. A few from me, one is on the Remain-1 trial. The question is, how will you ensure compliance post procedure in terms of having patients stick to a uniform reduced calorie diet throughout the entire trial? And how will the stat plan handle dropouts? And I have a follow-up.

Okay, great question. So the Remain-1 trial, just for those people who may not be familiar with it is our pivotal study that just got IDE approval at the beginning of April -- end of March, beginning of April for weight maintenance. The plan will be to take people who are obese, not type 2 diabetic, who are GLP-1 drug naive, initiate tirzepatide therapy, which is the active agent in Zepbound, the obesity drug. And then to up titrate them over a period of several weeks to a maximum tolerated dose and achieving 15% body weight loss. At that time, we're going to discontinue the tirzepatide, and then we are going to randomize them to Revita treatment or a sham, and everyone is going to get through from the initiation of the study all the way through to follow-up, a recommendation for a diet that matches diets that have been used in similar studies of GLP-1 drugs for weight loss. So the idea is to really try to mimic the same kind of nutritional advice that they have gotten from other studies that have been targeting a similar patient population. And we're going to have visibility into their ability to comply with dietary recommendations during that open label run-in phase. And I think that our expectation is that several months of adherence to that during the open-label phase will then translate to adherence during the follow-up. You had a great question about the stat plan on dropout. We do think that if we have a therapy that is really effective as we expect that we will, then people who are in the control arm may be more likely to drop out than the people who are in the treatment arm. And as a result, one -- we have made a decision to seek a primary endpoint at 24-weeks rather than at 48-weeks, and we are considering whether to offer Revita to those patients who did not get the treatment as a crossover in order to help keep them in the study. But I will note that there's a lot of studies of withdrawal that have followed patients now -- from of drug GLP-1 withdrawal that have followed patients for one year and have been able to keep patients in that study for that length of time, and so we're encouraged by that background. You had another question, Mike?

Yes. But before I move on, just to clarify what you said about the Remain study. Will the dropouts be centered altogether or will it be like a lapse observation carried forward type of analysis for the dropout?

Good question. We have not yet -- we have a view on what that should be. We have not yet reviewed that with the FDA, so I think it's premature to answer that. I would say that there is -- last observation carried forward is no longer the preferred statistical technique, and there are imputation techniques that tend to be preferred in this situation, but exactly how to do that will require a dialogue with the FDA that we have not yet ready to chat about.

Got it. And just a simple question on the RJVA-001. Obviously, you switched to the fully humanized GLP-1 promoter versus the last year you had the GLP-1 analog in your prototype. I think in the prototype, the percent beta cell transduction was around 30%. Was curious to see if that -- if the transduction percentage with this humanized GLP-1 promoter, is this in the same ballpark or if it differs in any way?

Great question. The transgene sequence itself might differ, but the AAV9 that delivers it remains the same. And we have seen levels of transduction that are very comparable between the candidate and the surrogates that we used beforehand. And so part of the dose bridging strategy as we get ready for a human will need to be able to demonstrate all of this with the candidate in preclinical models and will -- we get closer, we will walk through those data with you in order to share, how we're thinking about dose bridging when we get to people.

Okay. Very helpful. Thanks so much.

Thanks, Mike. Appreciate it.

Thank you. Our next question comes from the line of Mike Ulz of Morgan Stanley.

Good afternoon. Thanks for taking the question. Maybe just to follow-up on Remain-1 study, looks like you guys are on track to start that fairly soon. Just curious if there's any remaining steps there to getting that study going? And then maybe secondly, you mentioned sort of providing some early looks at that data set as it starts to move forward? Just thoughts on potential timing there and maybe some types of data that might be shared in the sort of interim updates? Thanks.

Yes. Great. Thanks, Mike. Great to hear from you. We are super excited about the Remain-1 study. And now that we have an IDE approval, we've been able to talk to investigators and to sites about it, and we are incredibly encouraged by the feedback that we are getting about this trial and physicians' perception of its attractiveness to patients. So what needs to happen in order to get us service standard stuff, site selection, IRB approval, et cetera, we are able to leverage the fact that we have active clinical trial sites from Revitalize-1, where we have good relationships with physicians and built clinical trial networks that we intend to leverage in order to help us accelerate remain. And so we are enthusiastic about being able to leverage a lot of our existing infrastructure, which we've worked so hard to build. With respect to data updates, as you know, there will be an open-label cohort that we call Reveal-1, and the Reveal-1 cohort patients can be treated in exactly the same way as Remain with one exception. We will allow patients to come into Reveal who have already been on or currently on a GLP-1 drug and wish to discontinue it in order to be able to see if they can maintain weight loss and not have to stay on drug. You may or may not have seen just today some a tracking poll from the Kaiser Family Foundation came out talking about how nearly 50% of the people who are taking GLP-1s are concerned about the costs of ongoing GLP-1 therapy as one reason why people may be looking to stop. Another reason as you know that, I know we think that the FDA is really interested in is patients who achieve weight loss benefit, but are having tolerability issues with GLP-1. And so the Reveal-1 cohort is going to allow us to look at those people and also in drug naive people who will be treated in exactly the same way as in Remain. So our plan is to give you study updates starting in the fourth quarter. We'll get earlier efficacy data in the cohort who are already on a GLP-1 because they won't need to be titrated up on the therapy, and then we'll get -- it'll take us longer to get study efficacy or effectiveness updates in the Reveal-1 cohort. But nonetheless, we think together it's going to paint a picture for us for what we think both the Remain-1 study might look like, but also what are the motivating drivers that patients might have to select Revita for this type of an opportunity and may inform how we would pursue the commercialization. And as the year progresses, we're going to give you ongoing updates on what we're seeing in Reveal and what kind of data you're going to get and when.

Got it. That's helpful. Thank you.

Thank you. I would now like to turn the conference back to Dr. Rajagopalan for closing remarks. Sir?

Thank you very much. I appreciate all of your time, and attention this afternoon. As I hope you can see, we're firing on all cylinders here, working on Revita for both type 2 diabetes and for weight maintenance, Rejuva heading towards the first-in-human. What we are excited about is if you fast forward over the period of say one year from now, what types of conversations might we be having, if we have Revitalize-1 data from our type 2 diabetes program in Revita, and if we have some open-label data on weight maintenance after GLP-1 discontinuation from Reveal and IND enablement heading to a first-in-human for Rejuva, we could be having a conversation that is vastly different than the one we are having now about what the future of type 2 diabetes and obesity might look like with disease modifying options on the horizon. We're excited about what that could mean for patients first and foremost, and we are motivated by the desire to accelerate that path to that future as rapidly as we possibly can. So appreciate everyone's attention today and look forward to following up.

This concludes today's conference call. Thank you for participating. You may now disconnect.