Q3 2024 Fractyl Health Inc Earnings Call & Business Update
Bye.
Speaker Change: Good afternoon, and welcome to Fractal Health's third quarter financial results and business updates call.
Speaker Change: As a reminder, this conference call is being recorded. At this time, all participants are in a listen-only mode. There will be a question and answer session following management's prepared remarks. I will now turn the call over to Steven Jasper. Steven, you may now begin.
Steven Jasper: Thank you. This afternoon, we issued a press release that outlines the topics we plan to discuss today. The release is available at www.fractal.com under the Investors tab.
Steven Jasper: Joining us on the call today are Dr. Harith Rajagopalan, Chief Executive Officer, and Lisa Davidson, Chief Financial Officer.
Speaker Change: 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.
Speaker Change: The impact of any of our product candidates, the design initiation, timing, and results of clinical enrollment in any clinical trial or readouts.
Speaker Change: The potential launch or commercialization of any of our product candidates or products.
Speaker Change: 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.
Speaker Change: 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 statement due to the impact of risks, uncertainties, and other important factors.
Speaker Change: Participants are directed to the risk factors set forth in Fractal's quarterly report on Form 10-Q, followed with Securities and Exchange Commission on November 12, 2024, and the company's other filings with the SEC.
Speaker Change: Any forward-looking statements made today speak only to Fraco's operations as of today.
Speaker Change: Fractal disclaims any duty to provide updates to its forward-looking statement, even if subsequent events cause the company's views to change.
Speaker Change: It is now my pleasure to pass the call over to Harith.
Harith Rajagopalan: Thank you, Stephen. And good afternoon, everyone. Thank you for joining us on today's call.
Harith Rajagopalan: This is an exciting time for Fractal as we approach multiple critical milestones over the next few quarters. I'm immensely proud of the progress we have made across both of our platforms, Revita and Rejuva, as we develop transformative therapies that can prevent and reverse metabolic disease.
Q3 was another quarter of excellent performance and accomplishment.
A few key highlights.
Harith Rajagopalan: First, we began enrollment in our Remain-1 Pivotal Study for Weight Maintenance after GLP-1 discontinuation, and this study is progressing rapidly.
Harith Rajagopalan: Second, we anticipate reporting data from the REVEAL-1 open-label cohort of this study beginning in Q4 2024.
Harith Rajagopalan: Third, we began enrollment under the expanded protocol for the Revitalize 1 pivotal study for rubida in type 2 diabetes, and we expect to report top-line data in mid-2025.
Harith Rajagopalan: And fourth, we continue to present compelling weight maintenance and blood sugar data from Revita and Rejuva at multiple medical meetings.
Harith Rajagopalan: We are confident in our ability to continue to execute against our upcoming major value drivers, and we continue to be laser focused on demonstrating the potential for our therapies to transform the treatment landscape in obesity and diabetes.
Harith Rajagopalan: To begin, let's talk about the rapidly evolving landscape of obesity and GLP-1 drugs. These drugs have clearly had a positive impact on treatment options for people with obesity and diabetes, but they also carry significant challenges that affect both patients and healthcare systems.
Harith Rajagopalan: There are three main concerns that have emerged in the past year, and they are all intertwined.
Harith Rajagopalan: First, the durability of weight loss effects over time with GLP-1 drugs is beginning to be a major problem, as discontinuation rates and weight rebound are major challenges for the class.
Harith Rajagopalan: Second, there's an obvious and growing gap between the impressive phase three results from these drugs versus their substantially less impressive real-world performance.
Harith Rajagopalan: And third, despite their expense, these drugs are not delivering discernible clinical benefit to payers, leading to fundamental and crucial questions about value.
Harith Rajagopalan: No one doubts the importance of durable, clinically meaningful weight loss, but the question is, why are these drugs not delivering on their promise in the real world, and what will?
Harith Rajagopalan: We've spoken before about poor persistence or durability of therapy from GLP-1 drugs.
Harith Rajagopalan: It's essentially the same issue that has already been seen with other drugs for every other chronic non-acute disease including hypertension, high cholesterol, and diabetes.
Harith Rajagopalan: Investors were assured that in obesity, unlike in other chronic diseases, patients will want to stay on therapy because they can see the benefits. But this is not the case. Discontinuation rates from GLP-1s are high, even when controlling for cost, access, and side effects.
Harith Rajagopalan: In addition, the real-world effectiveness of GLP-1 drugs is not matching data shown in Phase 3 trials.
Harith Rajagopalan: A study from the Cleveland Clinic, published in the JAMA Open Network Journal in September 2024, showed that in nearly 2,000 patients who were prescribed semaglutide in their Ohio and Florida hospital networks,
Harith Rajagopalan: Mean weight loss at one year was only 5.1%, or roughly one-third of the amount of weight loss that was seen from their registrational clinical studies.
Harith Rajagopalan: In addition, a Reuters article from October 24, 2024 highlighted data from Pharmacy Benefits Manager Prime Therapeutics.
Harith Rajagopalan: Key highlights from the analysis, only 1 in 4 patients are still taking their GLP-1 drug at 2 years and drug switching rates are extremely low.
Harith Rajagopalan: Despite the drop-off in utilization, the insurance costs for patients who are using Wigovi rose significantly, leading to a nearly 50% increase in the total cost of care for these individuals.
Harith Rajagopalan: Critically, this analysis found no decrease in obesity-related medical events in the patients who were prescribed GLP-1s, such as heart attacks, strokes, or new diagnoses of type 2 diabetes.
Harith Rajagopalan: So, in summary, what the data are beginning to show are poor durability, higher cost, and absence of real-world clinical benefit.
Harith Rajagopalan: In conversations with key payer stakeholders, a recurring theme has emerged. The primary concern is finding a way to de-prescribe GLP-1s because of the disparity between increased pharmacy costs and lack of consequent medical benefit.
Harith Rajagopalan: There are many drugs in development for obesity today, but if they all lack durability like today's GLP-1s, they will all have the same essential weaknesses as the drugs that already exist.
Harith Rajagopalan: And all of this underscores the biggest unmet need in obesity today, finding a pathway to durable, reliable weight loss maintenance.
Speaker Change: This is precisely what our therapies aim to accomplish, and we do this by offering patients therapies that are designed to provide them a durable metabolic reset.
Speaker Change: Let's move on to discuss our progress across our platforms, starting with Revita, an outpatient endoscopic procedural therapy targeting the duodenum.
Speaker Change: We recently presented compelling weight maintenance data from Revita at two medical meetings, DGVS in Germany and Obesity Week in San Antonio, Texas.
Speaker Change: At DGVS, we presented clinical results from our German real-world registry showing that Revita can deliver sustainable weight loss and metabolic benefits to patients for up to one year post-procedure.
Speaker Change: These results confirm earlier observations from Revita clinical trials of the potential for a one-time Revita treatment to have real-world results that can actually match or exceed clinical trial results.
Speaker Change: In addition, in the presentation, we highlighted some new information on patient-reported outcomes and quality of life, which were remarkably favorable for Revita, even one year post-procedure.
Speaker Change: Last week, at the Obesity Week medical meeting, we presented a new analysis of pool data from five Rovita clinical studies tracking participants for one year after a Rovita procedure.
Speaker Change: These patients, who had poorly controlled type 2 diabetes and advanced age,
typically face significant challenges in losing weight.
Speaker Change: The pooled data post-ruvita showed that 90% of participants lost weight one month after the procedure, with 84% maintaining weight loss for a full year, even in the absence of any prescribed diet or lifestyle changes over the course of the year.
Speaker Change: Compare this to the only 16% of patients who maintained at least 80% of their lost body weight one year after stopping terzepatide in the Surmount 4 study sponsored by Eli Lilly, even when all of the patients were prescribed a diet and lifestyle change.
Thank you.
Speaker Change: The data we presented at Obesity Week, in addition to the data from our German registry, were both presented to the FDA as part of our breakthrough device designation application for Revita, which was granted earlier this year for weight maintenance after the discontinuation of GLP-1-based drugs.
Speaker Change: Ravita is the only device or drug to our knowledge to have obtained breakthrough device designation from the FDA for a broad obesity indication.
Speaker Change: Our pivotal weight maintenance study, Remain-1, is moving rapidly. As a reminder, Remain-1 is our randomized, double-blind, sham-controlled study testing Revita against a sham procedure.
Speaker Change: This is the first pivotal study of an intervention that aims to demonstrate durable weight maintenance after discontinuation of GLP-1-based drugs.
Speaker Change: People with obesity and a BMI between 30 and 45 kilograms per meter squared who have not been on GLP-1 drugs will be started on terzepatide to achieve 15% total body weight loss.
Speaker Change: Once they have achieved that weight loss, they will discontinue terzepatide and be randomized to either Revita or Sham in a two-to-one treatment allocation.
Speaker Change: All patients will be prescribed a diet and lifestyle program. And we believe that if the pivotal study is successful, the data from this study can support a PMA application for approval in the United States.
Speaker Change: We are announcing today that we have already completed enrollment of a sufficient number of patients for the midpoint analysis of the study, and we continue to expect to report this midpoint analysis in Q2 2025.
Speaker Change: We believe this will be a crucial catalyst for the program, marking the first demonstration of randomized data in this patient population.
Speaker Change: In addition, our enrollment rate in REMAIN-1 is on par with those for GLP-1 drug studies in obesity, demonstrating the substantial interest from patients and clinicians in this much-needed weight maintenance therapeutic option.
Speaker Change: In the Remain One study, we are implementing a comprehensive approach to handling the patient experience, providing GLP-1 drug to clinical trial sites, referring patients to Revita Centers of Excellence for the Endoscopic Procedure, and offering a diet and lifestyle counseling program.
Speaker Change: This integrated obesity solution entails the use of one, best-in-class pharmacology, two, a Revita metabolic reset, and three, a diet and lifestyle program on the heels of Revita.
Speaker Change: The combination of these elements for obesity is quite unique, and it positions us as experts in the implementation of an integrated care solution for people with obesity and related diseases.
Speaker Change: It also creates for us an exciting opportunity for a unique and compelling commercial model that can replicate the clinical pathway for Remain 1 in a real-world setting post-approval. More on this potential commercial model later.
Bye.
Speaker Change: Moving to the REVEAL-1 open-label cohort of the REMAIN-1 study. REVEAL-1 is an open-label study that aims to enroll patients who have already lost at least 15% total body weight on GLP-1s, but who need to stop taking these drugs.
Speaker Change: Patients will discontinue their GLP-1 drug, undergo Revita, and subsequently begin a diet and lifestyle program.
The response to this study has exceeded our expectations.
Speaker Change: What we are hearing from clinical trial sites and from obesity KOLs at Obesity Week is that there is a large and growing pool of patients on GLP-1s who are looking for an off-ramp for a variety of reasons, and this is a population that REVEAL-1 aims to target.
Speaker Change: We anticipate that we will begin sharing the first tranche of Reveal One data at year-end. As mentioned above, we believe that one-month data, while early, will be a key leading indicator of longer-term results.
Speaker Change: After this initial tranche of data, we plan to provide incremental updates in this open label cohort as longer-term follow-up accrues over the course of 2025.
Moving from Weight Maintenance to Type 2 Diabetes with Rubida.
Speaker Change: In our Revitalize 1 study for type 2 diabetes, we've expanded our study criteria to include patients who are not yet on insulin.
Speaker Change: There are a large pool of patients who would rather live with poorly controlled type 2 diabetes than start on insulin, and that's who Revita aims to target.
Speaker Change: In fact, patients with type 2 diabetes who are on two or three agents to lower their blood sugar often avoid insulin therapy for an average of five years and have an HbA1c of nearly 9% before initiating insulin.
despite the high risks associated with their condition.
Speaker Change: What this means is that in the type 2 diabetes market, there is a huge prevalence pool of patients who have high blood sugar and are needing alternatives to insulin, alternatives that do not exist today. And we estimate this prevalence pool to be approximately 10 million people in the United States.
Speaker Change: Revitalize I is positioned to address this critical unmet need by offering a viable and compelling treatment alternative to medication escalation and in particular to insulin initiation.
Speaker Change: The choice is simple. One, start insulin, gain weight, constantly manage your diabetes, or two, try Revita and potentially improve your blood sugar, lower your body weight, and prevent the need for insulin.
Speaker Change: We are enrolling under the expanded version of our protocol and expect to report top-line data in mid-2025.
Speaker Change: Moving to our Revita German commercialization plans, the past quarter has been focused on setting ourselves up for controlled expansion in Germany in 2025.
Speaker Change: The first step is to obtain German government reimbursement approval to offer Revita at additional centers around the country.
Speaker Change: We have seen encouraging interest in Revita from numerous hospitals and have worked with GI endoscopy clinical leaders and hospital administrators across Germany over the last several months to submit NUB applications for reimbursement approval.
Speaker Change: We are excited about the positive feedback we've received on the considerable amount of data we have accumulated in our registry and are looking forward to next steps in the German market, and we will provide further updates when we are able.
Speaker Change: Many people ask who would be a candidate for a procedure like Revita.
Speaker Change: You can think of Revita as like LASIK, but for obesity.
Speaker Change: People with poor eyesight can wear glasses or contact lenses, which are easy and necessary for proper vision, and yet nearly a million people a year undergo a one-time procedure that targets a laser to their eye in order to free themselves from the burden of managing their poor eyesight.
Speaker Change: A substantial fraction of the population simply wants freedom from ongoing disease management burden, even if that burden is simply wearing glasses.
Speaker Change: Now think about obesity. There are 10 million people in the United States with obesity who will be on a GLP-1 this year. Roughly 8% of these individuals, or 800,000 people, will also undergo an endoscopy this year for other reasons.
Speaker Change: Before their procedure, an endoscopy nurse will call the patient to help them prepare for their visit, and part of that preparation would be to ask them if they are already on a GLP-1 drug in order to advise them to stop taking that drug at least one week prior to endoscopy.
Speaker Change: What fraction of these 800,000 patients can be converted to Revita to offer them an off-ramp to their GLP-1s as they are being scheduled for their otherwise already planned endoscopy?
Speaker Change: Rovita has purpose-built and developed over the past decade precisely to fit seamlessly into this high-volume, highly scalable GI endoscopy workflow.
Speaker Change: Given that Revita has breakthrough device designation from the FDA, given the desire for patients for persistent and effortless weight loss without drug therapy,
Speaker Change: And given the favorable economic model for GI endoscopy practices to perform Revita, we believe that a substantial fraction of patients and GI physicians would choose Revita.
Speaker Change: Now, let's shift our focus to REJUVA, our innovative pancreatic gene therapy platform.
Speaker Change: As a reminder, REJUVA is enabled by a proprietary endoscopic device that can precisely deliver AAV gene therapy vectors directly to the pancreas and opens the door to gene therapy medicines for the pancreas for the very first time.
Speaker Change: At the beginning of the year, we nominated REJUVA001 for type 2 diabetes, an AAV9 vector containing the human insulin promoter driving a human GLP1 transgene.
Speaker Change: We've presented data over the past several quarters showcasing the drug candidate's innovative SMART GLP-1 mechanism.
Speaker Change: The candidate is designed to auto-regulate GLP-1 levels, amplifying normal GLP-1 signaling rather than mimicking drug action.
Speaker Change: Think of it as you, but better, making enough GLP-1 to be able to survive and thrive in our modern world.
Speaker Change: Our work to support the submission of a clinical trial application, or CTA, for REJUVA-001 is progressing well.
Speaker Change: There are three key in vivo experiments in the pipeline, all of which have been substantially de-risked already. The first study is durability in wild type mice through 12 weeks. The second is dose ranging efficacy in the DBDB mouse model of type 2 diabetes.
And the third is safety and biodistribution in Yucatan pigs.
Speaker Change: During Obesity Week, we presented new REJUVA-001 data on sustained weight maintenance and lowering of blood sugar levels in the diet-induced mouse model.
Speaker Change: The data from Dr. Randy Seeley's lab at the University of Michigan demonstrated significant durability in DIO mice over 13 weeks, marking the longest evidence of durability with REJUVA001 we've recorded in an obesity model to date.
Speaker Change: These data are incredibly exciting because they show how to translate the promise of GLP-1s to the real world.
Speaker Change: This is a one-time therapy that potentially has efficacy that can exceed that of semaglutide and also offer benefits that last long enough to actually see effects on cardiovascular disease, kidney disease, and diabetes prevention in the real world.
Speaker Change: And this is something that we are not seeing with GLP-1 drugs today because of their high rates of discontinuation and lack of durable effect, as we discussed before.
Speaker Change: We plan to communicate more data on the execution of these studies at upcoming scientific meetings, but what we are seeing so far gives us confidence that we are successfully checking off key boxes for our regulatory filing.
Speaker Change: We anticipate completing these key CTA-enabling studies by the end of the year, and if the CTA is approved, we plan to initiate a first in-human study for REJUVA-001 in the first half of 2025.
Speaker Change: Last week at Obesity Week, we also announced the nomination of REJUVA-002 as our first SMART-GIP GLP-1 dual agonist gene therapy lead candidate, designed for the treatment of obesity.
Speaker Change: REJUVA-002 is a locally administered AAV9 viral vector that expresses human GLP-1 and GIP hormones from a human insulin promoter.
Speaker Change: RGVA002 is designed to activate both GIP and GLP-1 receptors, which both play crucial roles in regulating blood sugar and body weight when combined, as we have seen with many of the injectable dual agonists that are in the market or under development.
Speaker Change: The nomination of REJUVA-002 represents a significant milestone in the development of the REJUVA platform as it reflects the ability to combine multiple therapeutic modalities within the same construct.
Speaker Change: And with that, I will now turn the call to Lisa to provide an update on our third quarter financials. Lisa?
Lisa Davidson: Thank you, Harith. In the third quarter of 2024, revenue was generated from our commercial pilot in Germany and enabled patients to enroll in the German Real World Registry Study.
Lisa Davidson: Turning to operating expenses, research and development expense in the third quarter of 2024 was $19 million compared to $9.4 million for the same period in 2023.
Lisa Davidson: The increase during the quarter was primarily due to the progress made in our Remain-1 and Revitalize-1 clinical studies, continued development of the REJUVA program, and increased personnel-related expenses, including stock-based compensation.
Lisa Davidson: Selling general and administrative expenses in the third quarter 2024 was 4.8 million dollars compared to 4.5 million dollars in the same period in 2023.
Lisa Davidson: The increase during the quarter was primarily due to the professional service expenses and other costs associated with operating as a publicly traded company, and increased personnel related expenses, including stock based compensation.
Lisa Davidson: For the third quarter of 2024, we reported a net loss of $23.2 million compared to a net loss of $15.7 million for the same period in 2023.
Lisa Davidson: The increase in net loss was primarily attributed to the increase in operating expenses discussed above and the non-cash loss from changes in fair value of notes payable, offset by a non-cash gain from changes in fair value of warrant liability.
well as an increase in net interest income.
As of September 30th, 2024.
Fractal had approximately $84.7 million in cash and cash equivalents.
Lisa Davidson: Based on our current development plans, we believe that our existing cash and cash equivalents will be sufficient to fund our operations through expected company milestones into the fourth quarter of 2025.
I will now turn the call back to Harit.
Harit: Thank you, Lisa. As the obesity market continues to evolve, we have found that losing weight and maintaining weight loss are two very different problems.
Harit: The market has now largely solved the problem of short-term weight loss, but there remains an incredible need for durable weight maintenance and an off-ramp to GLP-1 drugs.
Harit: Obesity is a chronic disease, but it's only a chronic disease because we do not have therapies today that can truly have durable effect on the condition. And unless we are able to address the root cause, we will never break the pattern of chronic maintenance therapy in obesity.
Harit: While most next-generation GLP-1 therapies face fierce competition to improve on existing drugs,
Speaker Change: Revita and Rejuva stand alone as we pioneer a new weight maintenance category.
Speaker Change: Since Fractal Health began to focus on weight maintenance in the first quarter of this year, there has been a very interesting dynamic with both Revita and Rejuva. The size of the problem that we are addressing is coming into focus.
Speaker Change: And the size of the opportunity is becoming clearer as major players are beginning to see how differentiated the profile of Rovita and Rejuva are. It's been encouraging to see large companies intrigued by the unique value proposition these therapies will represent in the market.
Speaker Change: Fractal is reaching a critical inflection point. Over the next several quarters, we look forward to sharing data from our two pivotal studies of Rovita in weight maintenance and type 2 diabetes, in addition to advancing our REJUVA-001 pancreatic gene therapy candidate into the clinic.
Speaker Change: We are grateful for the continued support of our employees, our physician partners, our patients, and our shareholders as we aim to free people from the relentless pattern of metabolic disease progression.
Speaker Change: And with that, we will now open the call up for questions. Thank you very much.
Speaker Change: As a reminder, to ask a question, you will need to press star 11 on your telephone. To remove yourself from the queue, you may press star 11 again. Please stand by while we compile the Q&A roster.
Thank you.
Our first question.
Speaker Change: It comes from the line of Jason Gerberry of B of A. Your question, please, Jason.
Bye now.
Speaker Change: Hey, hello everyone. This is Chi for Jason. Thanks for taking our questions and congrats on all the progress.
Speaker Change: And I have three if I may. The first question is regarding the main one. You have mentioned the enrollment for the midpoint analysis has been.
Completed.
Speaker Change: Can you remind us the sample size and role and also the duration of follow-up for the midpoint analysis?
Speaker Change: If I recall correctly, correct me if I'm wrong, I think the last time we spoke, we could be looking at around 45 subjects at two-to-one randomization between Rovetia and Sham.
Speaker Change: with a 12-week follow-up. And along the same line, can you also talk about expectation for the midpoint analysis?
Speaker Change: Sure, T. Very good to speak with you. You're correct. The sample size is 45 subjects with a two-to-one treatment allocation of Rovita to Sham.
Speaker Change: and we will follow these patients for 12 weeks after the...
discontinuation of terzapatide and randomization to either Revita or Sham.
We expect that based on prior data from
Speaker Change: surmount four and from step one extension of trazepatide and somatotide respectively, that the
the sham arms should be regaining roughly 3% body weight.
over the course of that 12-week period of time.
And we would expect that Revita would hold.
Wait steady
Speaker Change: over that 12 week period of time and the objective would be to begin to demonstrate a
Speaker Change: treatment difference that is emergent between the two arms that we believe will be predictive of the likelihood of success of the full data set which has a six-month primary end point.
Speaker Change: Got it. It's just a quick follow up on that. You have already complete the enrollment is a 12 week follow up. Should we expect some level update early in the 2nd quarter?
Speaker Change: Well, remember, the way that the study is designed, we're taking people who are de novo, not on terzepatide yet. We are actually starting them on terzepatide ourselves, getting them to 15% total body weight loss, and then we will be randomizing them.
Speaker Change: And so what we are accounting for is that we have to enroll enough patients that we know that we're going to have 45 of them who will have achieved 15% body weight loss by
Speaker Change: by Q1 in order to be able to randomize them and then see the data in Q2. So the weight maintenance trials, because you've got to get the weight loss in the first place, do have that added time at the beginning, which is what explains
Speaker Change: the difference between your understanding of completing of enrollment and when the data will actually be available.
Speaker Change: Got it. Thanks for the clarification. And my second question is on review one. What's the current thinking on the venue for the initial data at year end?
Speaker Change: I'm curious, can you also talk about your latest expectation for the initial review one data? I think in terms of the size and the makeup of the data, I think last time we spoke, you may be, we may be looking at initial data in the range around maybe 10 patients after four to eight weeks of follow up. Can you talk about that? Thanks.
Speaker Change: Yeah, that's right. So we will have initial 10 patients at at least four weeks of follow-up and we're going to be showing you what's happening to their weight. And our aim is to demonstrate that we're able to hold weight steady.
Speaker Change: As you may know from prior studies of Rovita in type 2 diabetes, one-month results are actually pretty predictive of what happens at 3, 6, and 12 months afterwards. And so we feel like the one-month time point can be quite informative for us here as well. And we think that the Reveal 1.0...
Speaker Change: data in general, give an open label view on what the remain randomized data might look like. And so it does help from that perspective as well.
Speaker Change: Got it. And last one from me, just want to quickly touch upon a rejuva.
How did the program...
tracking towards CTA filing by year end.
Speaker Change: Are you close to wrapping up all the in vivo studies needed for the filing?
Speaker Change: And, if we were to assume CTA approval by year end, what's the typical turnaround time for CTA review and approval and setting up clinical trial sites subsequently? Curious, what level of human data can we expect from REJUVA in 2025? Thanks so much.
Speaker Change: Yeah, so the the key point here Chi is the key
Speaker Change: CTA-enabling studies will be completed by year-end, and then we aim to
Speaker Change: filed for that CTA in the first half of 2025, just for a clarification. And what I was, what we shared earlier was that there are three key
CTA enabling studies. One of them is durable demonstration of
Rejuva activity in a wild-type mouse out to 12 weeks
Speaker Change: A second one is dose-dependent efficacy in the DBDB mouse model of type 2 diabetes. And then the third one is safety in biodistribution studies.
Speaker Change: through with our proprietary needle catheter with our route of administration in the Yucatan pigs.
Speaker Change: And what we're seeing, so all of these studies are underway or at various stages of completion, but what we are seeing so far gives us a lot of encouragement that we're heading in the right direction.
Speaker Change: and we feel confident in our ability to complete these three key studies by the end of the year, and we'll be giving further updates as we enter into the first half of 25 on timelines.
Got it. Thanks so much.
Thank you.
Thank you.
Speaker Change: Our next question comes from the line of Mike Oles of Morgan Stanley. Your question, please, Mike.
Mike Oles: Good afternoon. Thanks for taking the question. Maybe just to follow up on the reveal one open label update, you know, expected by the end of the year.
Mike Oles: You mentioned about 10 patients at least four weeks of follow-up. I guess, you know, what are you expecting for the
Bye.
Mike Oles: You know, what you'd expect for sort of the control arm at.
at four weeks.
Speaker Change: would you expect to see any difference at that point or not?
Speaker Change: Yeah, I mean looking at what you know from surmount four and step one extension as I mentioned with terzapatide and semaglutide respectively you'd expect 3% body weight gain by the end of that four-week period of time and so and Importantly you the trajectory of weight will also be important And so what we're hoping to be able to show is that we're holding weight constant You'll be able to see the trajectory of that weight from baseline out to four weeks
Speaker Change: versus what you would expect from a control. And we can walk you through that as the date comes up on what prior studies have shown as a point of comparison. Of course, it's always hard to do.
Speaker Change: cross-trial comparisons, but we've endeavored to do everything we can to mimic what those trials have done for those patients when they stop GLP-1s.
Speaker Change: Yep, makes sense. That's helpful. Thanks. And then maybe just on the controlled expansion in Germany, maybe talk a little bit more about the rationale there. Is it to generate more data or just get more experience at more centers, you know, prior to a potential launch?
Speaker Change: Obviously, you can satisfy both, and we are excited about the opportunity to satisfy both.
Thank you.
Speaker Change: We're going to be, why we say it's controlled is because we're going to be careful about our spend going into 2025. But we have a list of hospitals that are eager to offer Rovita for their patients, some of whom have...
Speaker Change: patients who they would like to be able to offer this for already.
Speaker Change: and we see an opportunity to be able to ensure that
Speaker Change: Then some dates still work for monitoring and as you said in the quarter comeback. Here's looking at seeds that are performing encouraging changes as well as fruits and vegetables and other things that are growing under with the COVID 19 pandemic. Soeed Amani hits for now. You know, a lot of food markers so walnuts. There's a lot of information out there so there's a series of categories, a lot of the corn mud filters and how that's d qualities and a lot of damage damaging and staff or and all of the practices that eluciate only with concerns, even when I do think that it contributes to
Speaker Change: That the stuff that we're seeing in Dusseldorf and our clinical trials, we can expand that commercial model and footprint in order to be able to penetrate the German market.
Speaker Change: And we feel optimistic about our ability to prove out the commercial model of driving patients into Rovita Centers of Excellence in order to be able to give them a treatment alternative to medication escalation and diabetes. And in the process, we're obviously going to be able to generate revenue and additional clinical data.
Thank you.
Thank you.
Got it. Thank you. Thanks.
Thank you.
Speaker Change: Our next question comes from the line of Michael DeFiore of Evercore ISI. Please go ahead, Michael.
Michael DeFiore: Hey guys, thanks so much for taking my question and congrats on all the progress. Three questions for me on REJUVA. The first one is regarding the presentation at obesity week. I noticed that a slightly lower dose was used.
Michael DeFiore: in the 12-week analysis compared to the eight-week analysis. I think in the 12-week analysis, it was...
Michael DeFiore: 7.5 e to the 12th, whereas in the 8-week analysis was 1 times e to the 13th. I was wondering why that was done. And a similar question is that I noticed that the mean body weight reduction is maintained.
Michael DeFiore: but the error bars start to get really wide by 18 weeks. And curious to see if this was due to expiration of the mice over time or weeding of effect. And I have one more follow-up. Thank you.
Thank you.
Speaker Change: Great, so this is a study conducted by Randy Seeley, a collaborator at the University of Michigan.
Speaker Change: And he selected the dose based on what we had seen from.
Speaker Change: from the work that we had done before, which you highlighted, and he's doing a bunch of other mechanistic work that we'll be publishing next. We're looking to present and or publish next year.
Speaker Change: So, it was his selection of dose, but I think it proves the point that we've been making, which is a low dose of virus can deliver a very meaningful clinical effect.
Speaker Change: You're right to point out that the error bars get wide. I was confident that you would ask a question about that, actually. The wild-type DIO mice...
Speaker Change: really begin to have pretty variable weight when they're fed effectively a McDonald's diet for over 90 days.
Speaker Change: And so what you're seeing there is a reflection of just the dispersion that's happening as DIO mice are.
Speaker Change: are seeing that weight gain over time. And what we showed was placebo-adjusted weight. And that's the reason for the error bars there.
Got it.
Speaker Change: Very helpful. And my last question is regarding the Rejuva-002 candidate that you just nominated for obesity. At this point in the game, Harit, are you able to comment on their relative affinities for GLP-1 versus GIP relative to the native ligands, as well as any comments on beta arrest and recruitment?
Speaker Change: At this point in the game, I'm not able to comment on any of that, but of course, we're looking at these things, and we'll be able to share that with you as we get further along in development.
Got it. Thanks.
Thank you so much.
Thank you, Mike.
Speaker Change: Thank you. Our next question comes from the line of William Wood of B Reilly Securities. Your line is open, William.
Bye.
Thanks so much.
Speaker Change: Thank you for your questions and congratulations on a very nice quarter. Just maybe one from us to start, I was just kind of curious in terms of your RGVA 002, in terms of
Speaker Change: How closely mimics in design 001 just in terms of the machinery used, the overall design, essentially the 001 de-risk 002 in terms that it's essentially just a plug and play now with a GIP added in.
Thank you.
Thank you.
Speaker Change: It's the same delivery catheter, it's the same AAV9, and it's the same insulin promoter. So yes, Rejuva-1 does de-risk Rejuva-002.
Speaker Change: And it has the same SMART mechanism, which is to leverage the fact that the insulin promoter allows the proportionate release of the hormones.
Speaker Change: in response to the body's needs, which we think is a clear differentiator for the strategy compared to the drugs that are out there today or the other drugs that are in development.
And I think that
Speaker Change: What you'll see as the data mature and as we reveal them publicly over the course of the next several quarters,
Speaker Change: is that you're able to leverage both the GIP and the GLP-1 mechanism simultaneously with Rejuva-002.
Speaker Change: And we have conviction that based on what you see with terzapatide and with the dual GIP GLP-1 agonists that are in development, that you can achieve superior potency with
Speaker Change: with better tolerability compared to GLP-1 alone at higher doses. And I think that that's a good reason for why we went there with obesity.
Got it. I appreciate that and then one secondary
Speaker Change: You've obviously got your post-market registry ongoing in Germany and maybe I've missed this in the past. Are there any additional plans to try to expand into other EU countries or has there been any interest in doing that or is this sort of a focused target with Germany and then sort of moving back into the States with your ongoing FDA studies?
Speaker Change: Well, we are doing work to be ready to have a global launch at the time that we're ready to launch in the United States. There's this unique opportunity in Germany to be able to.
Speaker Change: generate real-world data earlier in a market that has many similarities to the U.S. market.
Speaker Change: and to do so under a reimbursement schema that the German government has set up called the NUB. But we are actively working to make sure that we're set up to be able to launch in other countries in key geographies as well. But that will be more in line with the U.S. launch.
Speaker Change: Got to make sense. I appreciate you taking our questions and how that can be cute. Thank you. Thank you. Appreciate it.
Speaker Change: Thank you. I would now like to turn the conference back to Dr. Raja Gopalan for closing remarks, sir.
Harith Rajagopalan: Well, thanks everyone for your time. You've been patient with us and very happy to continue to share the progress that we're making every quarter here through our earnings calls and look forward to continuing to show some very exciting results that are going to be coming in the next several months. Look forward to following up with you all then.
Speaker Change: This concludes today's conference call. Thank you for participating. You may now disconnect.
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