Central Garden & Pet Q2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
August 14, 2024

There are 7 speakers on the call.

Operator

Good afternoon and welcome to Fractal Health's Second Quarter Financial Results and Business Update 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 and A session following management's prepared remarks. I will now turn the call over to Steven Jasper.

Operator

Steven, you may now begin.

Speaker 1

Thank you. This afternoon, we issued a press release that outlines the topics we plan to discuss today. This release is available at www.frackel.com under the Investors tab. Joining us on the call today are Doctor. Harit Rajagopalan, Chief Executive Officer and Lisa Davidson, Chief Financial Officer.

Speaker 1

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 in any clinical trial or readouts, the potential launch or commercialization of any of our product candidates or products, 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 Fractal's quarterly report on Form 10 Q filed with the Securities and Exchange Commission on August 14, 2024 and the company's other filings with the SEC. Any forward looking statements made today speak only to Fractal's operations as of today.

Speaker 1

Fractal 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.

Speaker 2

Thank you, Stephen, and good afternoon, everyone. Thank you for joining us on today's call. I'm proud of the progress we've made in the past quarter at Fractal Health as we continue to deliver on our promise to develop transformative therapies that can prevent and reverse metabolic disease. Several recent achievements underscore the potential of our platform. In the past quarter, we have seen the FDA has awarded Revita a breakthrough device designation for weight maintenance after GLP-one drug discontinuation.

Speaker 2

We've also seen Revita's real world registry in Germany having demonstrated through 1 year of follow-up in an initial cohort substantial and sustained weight loss and blood sugar control in patients living with obesity and type 2 diabetes. We have had a significant expansion of our REVITALIZE 1 pivotal study protocol and potential patient population for Revita for glucose control in type 2 diabetes and an award winning data presentation of our REJUVA gene therapy platform at the American Diabetes Association, which I will discuss later. At the same time, we are disappointed in the disconnect between our substantial progress over the last several quarters and our share price. Considering the challenging financial circumstances in the market, we are committed to managing our business with financial discipline, a heightened sense of urgency and a keen focus on operational execution. We value the support and feedback from our shareholders and would be happy to engage further to discuss our strategy and prospects.

Speaker 2

The management team and I are incredibly optimistic about the near term prospects for the company and based on our track record and significant progress made since going public in February, we are confident in our ability to execute upon major upcoming value drivers over the next few quarters, which I am excited to walk through today on our call. As we advance our 2 platforms, Revita and REJUVA, we see an opportunity to truly bring an end to obesity by developing and delivering disease modifying therapies that offer scalable, sustained solutions to the disease. We are laser focused on achieving key upcoming data milestones across both programs that will de risk our clinical, regulatory and commercial opportunity. Beginning with Revita. Our Revita platform is a proprietary device and delivery system that targets the duodenum to reverse pathology in the duodenum lining that is a root cause of obesity and type 2 diabetes.

Speaker 2

You can think of it as LASIK, but for obesity. Revita is on a path towards pivotal data in 2 very large markets with extraordinary unmet need. The first is weight maintenance after discontinuation of GLP-one based drugs in obesity and the second target market is glucose control for people with type 2 diabetes who do not want to escalate medical therapy. Obesity is the single most significant opportunity in healthcare today. We know GLP-one drugs have been shown in large clinical trials to be very effective in helping patients achieve weight loss and other cardiometabolic benefits.

Speaker 2

However, there is considerable debate about how to quantify the true impact these drugs will have on healthcare outcomes in the real world. Why is that? Higher rates of GLP-one discontinuation have been reported by multiple groups and are now in fact already old news. According to IQVIA data, Wegovy had adherence rates of roughly only 41% over a 12 month period and a recent Blue Cross Blue Shield report suggests that a growing number of patients are not staying on drug past 3 months of initial use. Some have suggested that patients who stop taking one obesity drug will simply switch to another drug for long term maintenance, but more recent data do not support that theory.

Speaker 2

A report from Truveta just last month was the first publication to look at GLP-one reinitiation within 1 year of stopping a prior GLP-one. The group studied nearly 100,000 individuals who initiated a GLP-one drug between 2018 2023 and found that 2 thirds of patients stopped taking their GLP-one for obesity within 1 year consistent with earlier reports. What's new is that they found that only 1 third of those individuals who stopped taking one drug try another drug within 1 year. This implies that there is a very high rate of GLP-one experimentation in the market today, but also that the majority of patients who stop taking the drug do not start another drug within 1 year at least and therefore are not going to benefit from the drugs that are available long enough to see the benefits that the clinical trials are showing. What's more, there are a large number of individuals who have not yet tried the GLP-one drug.

Speaker 2

Broad payer reimbursement has become a key hurdle to unlocking access and it is clear that expanded coverage will depend on real world results to demonstrate durable weight loss maintenance, the kind of results that we believe Ruvita can offer. So it's becoming clear that chronic administration of GLP-1s combined with potential side effects, high costs and distribution issues has resulted in truly abysmal long term adherence. The obesity market is in a situation where having now substantially solved the problem of short term weight loss, the incredible unmet need in obesity has shifted to the problem of durable weight maintenance. What is so differently needed for patients is a reliable and effective off ramp from GLP-one drug therapy. However, innovation in this space by other competitors cannot solve the problem of adherence and is rather therefore focused on a 0 sum game of superiority to existing drugs.

Speaker 2

All these alternatives are competing against each other for only one piece of the puzzle, which comprises the minority of patients who are willing to comply with a lifelong chronic drug regimen. It is clear that major players are beginning to pay very close attention to the issues around weight maintenance and the limitations of the drug product form in the treatment of obesity. We were incredibly proud to share that earlier this month, the FDA recently granted breakthrough device designation for our Rubida system for use in maintaining weight loss after discontinuing GLP-one drugs. Breakthrough device designation allows for acceleration of development, assessment and FDA review for pre market approval. We and our scientific advisors believe that this is a momentous event in the field of obesity management, because to our knowledge, Revita is the 1st and only device developed for obesity to receive breakthrough device designation.

Speaker 2

The FDA has clearly specified that weight maintenance is defined as the achievement and maintenance of clinically meaningful weight loss for 1 year after the discontinuation of therapy. And despite the development of a range of products for obesity ranging from peptides to small molecules to antibodies to even siRNA approaches, we are unaware of any other products in development that can come anywhere close to maintaining metabolic benefits for 1 year after discontinuation. Our confidence in Revita is validated by what we're seeing in our real world registry study in Germany, which continues to show impressive clinical results in the first tranche of patients who have achieved 1 year of follow-up. At baseline, prior to Revita, these 11 patients had a median age of 62 years, median body weight of 111 kilograms and advanced type 2 diabetes with an average of 15 years since diagnosis of diabetes. Despite using up to 3 different glucose lowering medications, patients type 2 diabetes remained uncontrolled prior to intervention with a median baseline HbA1c of 9.6%, which is quite high.

Speaker 2

As in prior studies of Revita, a majority of those who enrolled in the study have been men. These factors advanced age, advanced type 2 diabetes, predominantly male gender have all typically been associated with reduced efficacy of drugs to lower weight and blood sugar. And despite the fact that these individuals represent a hard to treat patient segment, at 12 months post Revita, median weight decreased from 111 kilograms to 97 kilograms, representing nearly 13% total body weight loss and median HbA1c decreased from 9.6% to 7.2%, which is a substantial improvement in blood sugar control in individuals who had truly poorly controlled disease. We will be presenting data in larger numbers of patients at a scientific meeting later this year. So data from this real world registry, while relatively small numbers at 1 year so far, validate the results that we have seen from pooled analyses of over 100 Revita clinical trial patients who had previously been followed for a year or more.

Speaker 2

The data from Germany are a promising indicator therefore for our weight maintenance remain 1 pivotal study as well as our Type 2 diabetes REVITALIZE 1 pivotal study. We believe the German registry experience also provides important read through for the potential on label results Revita may see in other regions, including the United States, if and when approved. What's more, we look ahead to the next several quarters in Germany, where Revita has a CE Mark label to treat inadequately controlled type 2 diabetes despite the use of glucose lowering medications, where we have enthusiastic investigators and patients who are now 1 year post REVIDA leading lives that are generally healthier and less burdened by disease and disease management than before Revita. Given the feedback from physicians and patients within the registry and these remarkable clinical results for patients who would rather live with poorly controlled type 2 diabetes than take another medication and are opting for Revita to improve their glucose control and to lower weight without needing more medicines, we are gratified to have a waiting list of hospitals and physicians throughout Germany who would like to begin offering Revita for their patients. And we anticipate offering Revita at additional centers in Germany over the course of the next several quarters and to turn attention from purely running a registry in the As we've been ramping up our REMAIN-one study for weight maintenance, our focus has been on leveraging centers of excellence with GI endoscopists who are already involved in our revitalized clinical program.

Speaker 2

In particular, we've developed strong relationships with GI endoscopists who have a specific area of interest in bariatric and metabolic endoscopy given the critical role of the gut in controlling obesity and metabolic disease. Something we've been told time and again from doctors is that they have an overwhelming number of patients who are desperate to lose weight and to keep it off and many bariatric and metabolic focused endoscopists who we are recruiting for the clinical trials are already building obesity practices due to high demand for their services. Many of them have a ready pool of patients who are potential RAVITA candidates within their own GI groups and a motivation to build these practices to offer additional therapies for a larger number of patients. These GI doctors also have deep relationships with primary care physicians who already refer patients to them, allowing for a natural referral network for patients to be identified and treated in endoscopy centers. After speaking with these doctors, we are confident that our focus on these highly trained specialists will allow us to build a significant network of physicians who can easily introduce the approximately 40 minute RAVITA procedure seamlessly into their practice.

Speaker 2

Millions of patients with obesity and type 2 diabetes are already seeing gastroenterologists regularly and millions of endoscopies are performed annually for people with obesity and type 2 diabetes. Of the estimated 20,000,000 endoscopies that are performed each year in the United States, roughly 40% of people or 8,000,000 endoscopies are already being performed annually for people with obesity in the U. S. So these patients are already coming to endoscopy, already getting procedures and Revita is purpose built to fit into this high volume, highly scalable workflow. What this allows is a targeted and efficient commercial model that would allow us to focus on bariatric and metabolic endoscopists to help build on their existing practices to offer Revita for potential indications that they cannot currently offer today.

Speaker 2

This is not the same approach as prescribing an oral or injectable agent for weight loss, but we do believe this is a highly attractive therapeutic alternative to the clearly very large segment of patients who are looking for a durable weight loss solution without being on chronic drug therapy. We look forward to speaking more about our targeted and efficient commercial model and the path forward to that in future quarters. Back to RAVITA clinical development. As you'll remember, REMAIN-one is our pivotal study for weight maintenance after GLP-one drug discontinuation in obesity. Having obtained FDA IDE approval for this study at the end of Q1, we are pleased to report that we have now initiated the study and are actively enrolling at several centers in the United States.

Speaker 2

We see incredible enthusiasm from physicians and patients as we begin to ramp up study enrollment and we anticipate reporting a midpoint data analysis in the Q2 of 2025, which will evaluate approximately 45 patients who have been randomized and followed for 12 weeks post treatment with Ruvita or sham. These are patients who were not previously on tirzepatide who will be achieving 15% total body weight loss and then tirzepatide will be discontinued and they will be randomized and then followed for 12 weeks. In parallel, we are beginning to enroll patients in our open label REVEAL 1 cohort for people who are already on a GLP-one drug and looking for an off ramp to keep the weight off after stopping these drugs. We anticipate reporting early data from the REVEAL-one open label cohort in the Q4 of 2024. Both REMAIN-one and REVEAL 1 underscore our important commitment to this area of weight maintenance after GLP-one discontinuation.

Speaker 2

Turning toward Revita for type 2 diabetes. Our goal with Revitalize 1 is to establish Revita as a safe, effective and straightforward treatment alternative to medication escalation for patients with Type 2 diabetes. As we are beginning to see in Germany, we believe patients may choose this as early as second line or as an alternative to initiating injectables or insulin or escalating insulin therapy. The common factor influencing patient behavior is the desire to have better disease control while avoiding medication escalation. In June, we announced our plans to significantly expand our REVITALIZE-one pivotal study of Rubida to include patients with type 2 diabetes who are inadequately controlled on any glucose lowering agent, including GLP-1s and or insulin, thereby expanding our potential U.

Speaker 2

S. Treatment population by about 6 fold. We continue to enroll this study and anticipate reporting top line data in mid-twenty 25. Finally, we wanted to turn to our nutrient responsive GLP-one gene therapy platform, REJUVA. We continue to generate preclinical data that excites the scientific and medical community for the potential game changing nature of this platform.

Speaker 2

We have shared new head to head preclinical data comparing REJUVA to semaglutide, which demonstrated that treatment with REJUVA yielded robust and durable weight loss in mice with diet induced obesity and also enabled sustained weight maintenance following semaglutide withdrawal. Importantly, mice treated with REJUVA demonstrated a greater relative proportion of loss of fat mass to lean mass than those treated with semaglutide and this has been flagged as you know as a significant potential risk with currently approved GLP-one drugs. With these exciting accomplishments, we are now gearing up for a catalyst rich second half of twenty twenty four, including key inflection points across both platforms. In REVEAL 1 open label cohort in weight maintenance by the end of the year, in addition to ongoing updates from our Germany real world registry data impacting Revita's potential in both obesity and in type 2 diabetes. In REJUVA, we anticipate completing IND enabling studies for REJUVA1, our first candidate targeting type 2 diabetes, as well as additional data presentations on the REJUVA GLP-one platform and major scientific congresses in the second half of the year.

Speaker 2

We will also be nominating our 2nd candidate, REJUVA 2 for obesity in the second half of the year. We are very excited with the progress our team has made and the near term data we plan to share across both programs, which we believe will reinforce our leadership position in addressing the massive unmet need in obesity to offer sustained solutions for obesity and metabolic disease. And before I pass the call over to Lisa, I also want to provide another business update. Alan Will, our long time Chair of the Board has decided to step down from our Board after 12 years of distinguished service. We are fortunate to have benefited from Alan's guidance as Chair over these last 12 years.

Speaker 2

His leadership helped us to grow from an early stage research company to a public company with 2 pivotal studies in 2 major disease categories and an exciting gene therapy pipeline. We are grateful for his years of service and we wish him the very best. Alan will serve as an advisor to Ajay Royan, who has been appointed as the new Chair of the Board. I am pleased that Ajay will step in as Chair during this critical inflection point for Fractal. His passion, extensive experience and strategic vision will be invaluable as we accelerate development of our products towards potential regulatory approval and commercialization.

Speaker 2

With that, I will now turn the call to Lisa to provide an update on our Q2 financials. Lisa?

Speaker 3

Thank you, Harith. In the Q2 of 2024, revenue was generated from our commercial pilot in Germany and enabled patients to enroll in the German Railroad Registry Study. Turning to operating expenses. Research and development expense in the Q2 of 2024 were $16,800,000 compared to $9,100,000 for the same period in 2023. The increase during the quarter was primarily due to the initiation of the REMAIN-one study, the progress made in the REVITALIZE-one study and continued development of the REJUVA program as well as increased personnel related expenses, including stock based compensation.

Speaker 3

Selling, general and administrative expense in the Q2 of 2024 was $6,200,000 compared to $2,800,000 in the same period in 2023. The increase was primarily due to professional service expenses and other costs associated with operating as a publicly traded company and increased personnel related expenses, including stock based compensation. For the Q2 of 2024, we reported a net loss of $17,200,000 compared to a net loss of $30,200,000 for the same period in 2023. The decrease in net loss was primarily attributed to the non cash change in fair value of notes payable and warrant liabilities as well as increased interest income offset by the increase in operating expenses. As of June 30, 2024, we had cash and cash equivalents of $102,400,000 Based on our current development plans, we believe cash and cash equivalents will be sufficient to fund our operations through expected key company milestones into Q4 2025.

Speaker 3

I will now turn the call back to Harid.

Speaker 2

Thank you, Lisa. As you can see, we've made significant progress over the last quarter to take advantage of our unique opportunity to become an industry leader in weight maintenance. While there seems to be a new drug targeting obesity every month that promises improved tolerability or a new mechanism, the truth remains that they are all seeking to tackle the obesity epidemic in the same way through chronic administration, which is simply not sustainable for most people. At Fractal, our goal is to provide solutions that free people from the burden of obesity and metabolic disease through sustainable solutions that have lasting benefits and do not depend on long term adherence. As we enter the second half of twenty twenty four, we have several key clinical and preclinical milestones that have the potential to help us realize our vision of delivering durable disease modifying therapies to patients suffering from metabolic disease.

Speaker 2

I would like to take this opportunity to thank the patients and physicians who continue to put their trust in us and our products, the employees at Fractal who are laser focused on delivering life changing therapies and you, our shareholders. We are grateful for your support and more optimistic than ever before about our prospects to deliver on our promises. And with that, we will now open the call up for questions. Thank you very much.

Operator

Our first question comes from the line of Jason Gerberry of BofA.

Speaker 4

Hi. This is Chi on for Jason this afternoon. Thanks for all the update and thanks for taking our questions. We have two questions. Maybe the first one on BRAVITA, given you have some data coming out from the BV1 open label data in Q4.

Speaker 4

I'm hoping that you can maybe provide a little bit more color on your expectation for the open label data in 4Q. How large might the sample size be and would you expect the follow-up to be sufficiently long enough to get an initial read on the efficacy and weight maintenance. And looking more broadly into next year, you will also have some control data from the RE MAIN-one study in Q2 2025. Hoping you can provide some color to discuss how might the initial REVEAL 1 data help inform the REVEAL 1 therapeutic potential ahead of the Baker second quarter 25 update? And then I have a follow-up after this.

Speaker 5

Great. Thank you, Chi.

Speaker 2

Appreciate the question. As everyone knows, we are really excited about the REMAIN pivotal study. It has two arms. One of them is the REVEAL one arm for people who are already on GLP-1s and looking for an off ramp. And that will be an open label study, wherein we will be enrolling subjects who are currently taking either semaglutide or tirzepatide and will be discontinuing the therapy immediately before giving them Revita.

Speaker 2

We anticipate that within 4 to 8 weeks, patients will have an increase in hunger and will have steadily increasing weight regain if they do not benefit from the therapy, because that is what we have seen from studies of cevaglutide withdrawal or tirzepatide withdrawal in the randomized trials that they have presented, but also in routine clinical practice. We're giving patients digital scales that will allow us to get daily readings on what their weights are and we'll be getting them to come into the clinic at week 4 and then again at week 12. And we're going to have data from the first ten patients emerging in the 4th at the end of the year. And we anticipate enrolling a total of 20 patients in this open label study. So we'll have accruing data into Q1 of 2025.

Speaker 2

I do believe that if Revita is helping preserve weight loss in these individuals, you're going to begin to see that very soon after they stop their GLP-one. You're going to see that based on how hungry they feel. You're going to see that based on how their weight trajectories look. And I do believe that that will be predictive as is the German registry data of what we might expect to see in terms of the ability to sustain a lower weight for a prolonged period of time. Now turning to your question about the remain midpoint data analysis, we have heard from players in the space that control data would be valuable in order to be able to derisk the clinical and regulatory opportunity for Revita in weight maintenance.

Speaker 2

And so we have built into the study a plan to do an interim sorry, a midpoint analysis of 45 subjects at 12 weeks of follow-up, wherein there will be a 2:one randomization between Revita and sham. So the basic question is, what does the trajectory of weight regain look like in the Revita arm versus the sham arm over that 12 week period of time? And are we beginning to see that there is a separation between the two groups that would enable us to predict the likelihood of success in achieving our primary endpoint efficacy endpoint at 24 weeks. And that's the data that we will begin to present in Q2. And you can obviously imagine that we'll be continuing to follow those patients and we'll give you data updates into the back half of twenty twenty five as well.

Speaker 4

Got it. Before I move to my second question, I just want to confirm your Q4 data, you said you expect maybe somewhere around 10 patients worth of data. Would they have say, 4 week of follow-up so that you can get an initial week on the efficacy and weight maintenance? Or would that would you expect to follow patients longer, maybe sometime in the 25 before you can get a read of the weight maintenance therapeutic potential?

Speaker 2

I think you're going to start to get a signal with those 10 patients at least at 4 weeks in terms of their clinic visit, but we're also planning to digital scales that will give us a more real time read on how these patients are doing, over the however long they've been followed after the procedure. And the beautiful thing about this is you're just going to see those curves and see how they're beginning to play out over time. We'll have to compare that to what you would expect with tirzepatide withdrawal from the tirzepatide surmount-four study.

Speaker 4

Got it. Thanks. And maybe moving on to my second question on REJUVA, euclid-one gene therapy. I'm curious, can you provide them more color on how close you are to completing the IND enabling work? Do you expect the regulatory hurdle for at least for clinical trial initiation to be pretty straightforward based on conversations you may have already had with the regulator or regulators.

Speaker 4

Given your plan to initiate a 1st in human study first half next year, curious when my investor can expect to see initial human data for the REJUVA program? Thanks so much.

Speaker 2

Yes. Great question, Chi. I think that we have met with regulators in Europe to discuss our REJUVA 1 preclinical development And we have alignment with them on the preclinical animal models to be used, which are the DBDV mice and the Yucatan pig, small animal model for efficacy, large animal model for safety toxicology because it mimics the human route of administration. We already have extensive experience and have already shown data on all of the above with REJUVA 1 candidates and are working our way through the same with our development candidates itself. We do we've also come to an alignment with regulators about the types of biodistribution studies that need to be completed And the patient population being individuals who are inadequately controlled with type 2 diabetes, who are already on a GLP-one drug therapy and are able to benefit from it and tolerate it in order to be able to derisk both the safety and the potential efficacy of the REJUVA 1 candidate in that type 2 diabetes patient population.

Speaker 2

So we have alignment on all of those things. I do think that we have some work to do to finalize the CMC requirements and we will be working to gain greater clarity on that in the second half of twenty twenty four. And that will be the major next step before we feel like we're ready to file for a first in human study.

Speaker 4

Great. So, do you talk about do you have any expectation for any the timing for initial human data? Do you expect maybe some preliminary safety data in second half twenty twenty five or too early to tell at this point?

Speaker 2

We do expect that. I think that you're going to get some the safety that you're going to be looking to pay attention to here is the procedure itself causing any injury and we are feeling confident that it won't based on our expensive experience in preclinical models because of our experts who have been advising us in the development of this technique. Nevertheless, that should be an early signal. And then you're going to be wondering about the safety of the AAV itself. And that's usually a question that emerges over a 4 to 6 weeks period of time immediately after the intervention.

Speaker 2

But the questions around the efficacy and safety of the GLP-one, as you know from other gene therapies, will take weeks to months. And I think that that's going to be a question that we're going to begin to be able to answer in the back half of twenty twenty five.

Speaker 4

Great. Thanks so much for all the color. It looks like a lot of different data updates for various across your pipeline portfolio next 12 months and we look forward to seeing those updates evolved.

Speaker 2

Great. Thank you so much.

Operator

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

Speaker 6

Hey guys, thanks for taking the question. Maybe just to follow-up on some of the earlier questions related to obesity. And not sure how much you can comment here, but just if you could talk about the early rate of enrollment in remain and just maybe how that's tracking versus your expectations? Thanks.

Speaker 2

Hi, Mike. We started enrolling earlier this earlier this month. We just announced it today. What we are seeing is that there's a lot of interest and enthusiasm where there's a bunch of patients who are lining up in the first centers to come in. This is consistent with what other people see in obesity trials, which tend to enroll 5 times as rapidly as some other studies.

Speaker 2

And so we're feeling encouraged, but it's still very early days and we'd be happy to update you later on in the year as it progresses and we have a little few more data points that we can call upon.

Speaker 6

Yes, makes sense. And are you seeing more are you seeing faster enrollment maybe in the REVEAL sort of open label cohort versus remain just because patients will have the sites

Speaker 2

that are sites that are obesity centers, not yet the endoscopy centers. And so we are going to be enrolling the REVEAL portion at hospitals that offer the endoscopy because of for logistical reasons. We anticipate those patients will start coming in later on in the quarter. These first patients who are coming in are the ones that we're starting to put on tirzepatide so that we can see the randomized data because that's a long pull on the tent for us.

Speaker 6

Got it. Makes sense. Thanks.

Speaker 2

Thank you.

Operator

Thank you. Our next question comes from the line of Umer Raffat of Evercore.

Speaker 5

Hi guys. Thanks so much for taking my question and congrats on all the progress this quarter. Just two questions from me. 1, I just want to revisit the open label registry data that you reported recently, I think last week. The weight loss data in this data cut definitely seem to have improved versus the 3 month data cut presented at the DDG meeting in May.

Speaker 5

So I'm curious to see how this new data cut varied among individual patients. Also in the DDG analysis, I think roughly 1 third of the patients were on GLP-1s at baseline. And my question is how far along into their GLP-one therapy were they at baseline? Were they already kind of at steady state or did they just begin? And then I have a follow-up.

Speaker 2

Great question. So if you look back at our pooled analysis from our studies, what you will observe is a trend towards greater weight loss over time over the period of 1 year in about 100 patients who are treated and followed in Revita clinical studies, people with Type 2 diabetes. So that I think is consistent with what we are seeing here in terms of the profile of weight loss over time. And this is a really interesting question. Why is the weight loss increasing?

Speaker 2

You asked about how long people have been on GLP-1s. And of these and I think you've rightly pointed out that of the 14 patients who were at 6 months earlier, 5 of them had been on GLP-1s. Of the 11 patients who are now on GLP-1s sorry, of the 11 patients who are now at 1 year, exactly 4 of them were on GLP-1s, at the time that they enrolled in the study. And we understand from the treating physician that they had been on GLP-1s for some period of time, but we really do not have detailed retrospective EMR data to confirm exactly how long they had been on those drugs. However, a couple of them were on Trulicity.

Speaker 2

And so you could imagine they probably weren't recently put on Trulicity. And so that suggests to me that they've been on the weight loss on their GLP-1s for some length of time. 1 of these patients switched their GLP-1 from one agent to another during the follow-up period, 2 of them stayed on their GLP-1s throughout the follow-up period and the other one stopped their GLP-1 during the follow-up period and then did not resume it through 1 year of follow-up. So there's a lot of in the real world, a lot of medication changes happening for these patients. And as a doctor who took care of these patients and as a son of a person with type 2 diabetes, I can tell you, I'm like super sympathetic to the effort required for chronic medical therapy for people with multiple diseases.

Speaker 2

Lots of different doctors changing medicines all of the time to address symptoms, side effects, formulary changes, drug drug interactions, all of the things in the real world that impact the drug's ability to have an effect or that you don't really see in Phase 3 clinical trials. Despite all of that, what's kind of surprising is that 10 of the 11 patients have these have either reductions or stable medicines over a 1 year period of time and yet are seeing profound improvements in weight and in blood sugar control. That's just as strong, if not stronger at 1 year than it was at 1, 3 6 months. So that's a positive sign for us. But obviously, we'll be continuing to follow more patients and we have a public presentation and more data coming up in the fall where we will we can go through a lot more information, including patient level data at various time points and really give a lot more color on what we're seeing with larger numbers of people, which is going to be important.

Speaker 5

Okay. So that kind of preempted my follow-up question to that. It was that like because I know in the DDG data cut at 3 months there was kind of considerable variability in the weight loss. I was going to ask, whether there were any notable baseline or disease state characteristics or differences in patients who didn't lose that much weight. But if you can't comment now, I'll just wait until later on in the year.

Speaker 2

Yes, I think we'll wait till later on in the year, but I don't think we're seeing anything that's different than what other obesity drugs are showing in terms of a waterfall plot of weight over time, but we will go into that in more detail later in the year. Thank you, Mike.

Speaker 5

Okay. And then my follow-up question is on, it's actually a clarification question on REJUVA regard the seminal obesity data that was presented at ADA in the DIO mice. And my question was the semaglutide dose received in mouse, what was the equivalent human dose of that?

Speaker 2

Well, in order to be consistent to the DBDB data that we had generated earlier, we chose the exactly the same dose per kilogram in the mice that we had used in the earlier DBDB studies, which was the maximum glucose lowering drug concentration seen in semaglutide in those mice. So it would be equivalent to the top dose of what's prescribed for type 2 diabetes in those mice.

Speaker 5

Okay. Excellent. And just I guess one really quick follow-up question. For the REJUVA obesity construct, which is still yet to be nominated. In addition to the human GLP-one promoter that will presumably be included in this construct, Could you speak to any updates as to what you're thinking in terms of additional mechanisms that this construct might include and whether adding those additional mechanisms may kind of offset or mitigate the activity or efficacy of the original GLP-one construct component?

Speaker 2

One of the challenges that we have here is an abundance of riches. Candidly, any all of these metabolic hormones are small peptides. They can put together they can be put together combinatorially or they can be acting independently. For instance, you could imagine a GLP-one alone or you could imagine a GIP GLP-one combination or you could imagine an amylin alone or any combination thereof. So there's a lot of potential variables to work through.

Speaker 2

And so we are liking what we're seeing with GLP-one alone. We're also liking what we're seeing in GIP and GLP-one combinations. And we think that this platform that leverages the human insulin promoter can have a lot of optionality to it. And we're working through some of that. And when we nominate the candidate, we'll explain to you our rationale for why we chose what we chose.

Speaker 2

But just know that we are thinking through all of the possibilities here in order to choose the best path from a clinical regulatory perspective with a principal focus on ensuring that what we're doing is going to be safe for the population that we're treating. And I think that that has to be the first objective for this therapy because the efficacy signal that we're seeing in terms of obesity with GLP-one alone is already very, very meaningful in the preclinical models. So if we're going to add other mechanisms in, we're going to have to be thoughtful about the trade off between what we already know and what we still have to learn. We'll tell you more later this year.

Speaker 5

Excellent. Listen, thanks so much for taking my questions. Again, congrats on the progress.

Speaker 2

Thank you very much. Now, in order to wrap up,

Speaker 4

I

Speaker 2

want to thank everyone for joining us this afternoon. We appreciate your continued interest and your support and we look forward to continuing to share updates on our progress as we seek to change the landscape of obesity and type 2 diabetes. Thank you so much. Talk soon.

Operator

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

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