Vimeo Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 7, 2023

There are 12 speakers on the call.

Operator

Good morning. I'm Rashmi Nafner, Vice President of Corporate Affairs and Investor Relations at Scholar Rock. Welcome, and thank you for joining us today for our Q3 2023 business update call. This call is audio only. You can access the slides that we'll be referring to on the Events and Presentations section of the Investor Relations page on the Scholar Rock website.

Operator

Moving to Slide 2. Before we begin, I want to note that we'll be making various statements about Scholar Rock's expectations, plans and prospects that constitute forward looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Any forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any future date. Please refer to our SEC filings for the full disclosure of all the risks. Turning to Slide 3, I'd like to introduce the members of the Scholar Rock team who will be presenting during today's call and will be available for questions after the conclusion of the formal remarks.

Operator

I am joined by Jay Backstrom, CEO of Scholar Rock Ted Miles, Chief Operating Officer and Chief Financial Officer and Moe Cutsanani, Head of Research. I will now turn it over to Jay.

Speaker 1

Thank you, Rashmi, and good morning and welcome to our Q3 business update call. We've made excellent progress so far this year and in particular in Q3. I want to start with Scholar Rock's pioneering approach to targeting TGF beta superfamily of growth factors. The picture on the left of the slide depicts the latent complex that contains the inactive growth factor. The scientific insight that led to the understanding of the structure of this latent complex is part of the foundation of our industry leading platform that targets TGF beta superfamily of growth factors by selectively and specifically blocking their activation by locking up The Growth Factor in the Precursor or Latent Form.

Speaker 1

This highly specific approach limits the off target effects that have been observed with less selective approaches that target the active forms of the growth factors or interfere with their receptors such as the activin receptors. Apitikramab, our lead clinical program targeting latent myostatin prevents the formation of the active form of myostatin, A negative regulator of muscle growth and leads to an increase in muscle mass and function in non clinical models and is the first anti myostatin therapy to demonstrate clinical proof of concept. Moving to Slide 5. I was very excited to announce that we are leveraging our R and D platform and deep knowledge of myostatin biology to expand into a new therapeutic area of cardiometabolic disorders with our novel, highly potent and selective anti myostatin antibody SRK-four thirty nine in combination with the GLP-one receptor agonist. Scholar Rock has a long standing interest in targeting myostatin for cardiometabolic disorders, giving the role that muscle plays in glucose metabolism and insulin sensitivity.

Speaker 1

As you'll hear from later in this morning's presentation, our approach to blocking myostatin is ideally suited for use in both SMA and in cardiometabolic disorders since by blocking myostatin and only myostatin, we avoid off target toxicities. Safety is critically important in treating SMA and in weight loss therapy. And we believe our selective approach as we've seen with apitigramab in our SMA program to date should lead to a favorable overall benefit risk profile. Moving to Slide 6. Targeting the TGF beta superfamily has broad therapeutic applications given the central role this family of growth factors plays in wide range of cellular processes, including growth and differentiation.

Speaker 1

Our research teams have produced a robust pipeline of product candidates targeting latent myostatin and latent TGF beta-one. And very pleased with significant progress that we've made on our pipeline since the beginning of the year. Moving to Slide 7. For this morning's call, I will start with an update on our clinical programs, highlighting the status of SRK-1 hundred and eighty one, our selective anti latent TGF beta-one antibody in immuno oncology followed by an update on the progress we've made with our number one priority opidigramab in SMA and then turn to Moe to discuss our entry into cardiometabolic disorders with our novel anti myostatin SRK439. Moving to Slide 8.

Speaker 1

Slide 8 provides an overview of the DRAGEN trial. As a reminder, the main objectives of the DRAGEN study in addition to dose ranging and safety included establishing proof of mechanism and proof of concept that by blocking TGF beta-one, a key driver for resistance to checkpoint inhibitors with SRK-one hundred and eighty one in combination with Pembrolizumab That we could overcome the immune suppressive environment and restore responsiveness to the checkpoint inhibitor. To achieve these objectives, the Part B portion of the study included expansion cohorts in several tumor types and required all patients to have progressed on the most immediate prior anti PD-one or PD L1 treatment. The study is rich in biomarkers, including paired biopsies to assess if SRK-one hundred and eighty one could overcome an immune exclusion phenotype and DRIVE CD8 positive T cells into the tumor as was demonstrated in our non clinical models. The team made excellent progress with the DRAGEN study since start of the year, culminating in 2 poster presentations at the annual meeting of the Society For Immunotherapy of Cancer this past weekend.

Speaker 1

The first poster focused on biomarker data in support of proof of mechanism and the second provided a clinical and biomarker update from the renal cell carcinoma cohort from the Part B expansion, the cohort with the most patient data including follow-up. I will start with a review of the biomarker poster. Moving to Slide 9. This poster focused on biomarker data and support a proof of mechanism and based on paired biopsy data demonstrated that SRK-one hundred and eighty one in combination with an anti PD-one therapy increase the infiltration of CD8 positive T cells across several tumor types including melanoma shown here. This was seen in the compartmental analysis that measures the percentage of CD8 positive cells in the tumor, tumor margin and stroma from 2 melanoma patients.

Speaker 1

As shown on the graphs on the left, there was an increase in CD8 positive T cells observed after treats, overcoming an exclusion or desert phenotype, which was present at baseline. Similarly, as shown in the histopath image on the right, There's an increase in intensity of brown staining representing CD8 positive T cells in the post treatment biopsy, also demonstrating the influx of CD8 positive T cells into the tumor. We were excited to see these data, which essentially reproduced the non clinical findings that formed the scientific rationale for SRK-one hundred and eighty one. Turning to Slide 10. The second poster presented at SITC provided an update on the renal cell carcinoma cohort from Part B.

Speaker 1

Overall, 28 patients were evaluable for response. It's important to note that the patients enrolled represented a heavily pretreated population who received the median of 3 prior lines of treatment, including a checkpoint inhibitor and tyrosine kinase inhibitor. All had disease progression on their prior anti PD-onePD L1 treatment. The slide includes 3 graphical displays from the poster and highlight the treatment duration as shown in the swimmer's plot, anti tumor activity as shown in the waterfall plot and the spider plot that illustrates both duration and tumor response. As can be seen, there is clear evidence of tumor reduction with a 21% overall response rate that is durable beyond 6 months and a disease control rate of 57%.

Speaker 1

The overall response rate is significantly above what we would expect from a checkpoint inhibitor alone in the setting of prior anti PD-onePD L1 progression, which is expected to be less than 5%. With respect to safety, the combination was generally well tolerated with the most common treatment emergent adverse events predominantly skin toxicities of rash and pruritus. Moving to Slide 11. In summary, the DRAGON trial delivered on its objectives of showing proof of mechanism and proof of concept with promising overall response rates and a heavily pretreated relapsed refractory patients with clear cell renal carcinoma all who progressed on prior treatment with a PD-one or PD L1 therapy. Now that Dragon has met its objectives, we plan to enclose enrollment in December, begin closeout activities, while we continue to treat those patients who continue to benefit from therapy and remain on study.

Speaker 1

We also plan to present ongoing data from Dragon at future medical meetings. We would like to take this opportunity to thank the investigators, study staff and in particular the patients and their families who participated in or currently participating in Dragon. Regarding the SRK-one hundred and eighty one program overall, we believe the data from Dragon support advancing the program and we plan to conduct an end of Phase 1 meeting with FDA and the first half of twenty twenty four to determine the next steps. Turning to Slide 12. I'll now focus on our lead clinical program with apitigramab in spinal muscular atrophy or SMA.

Speaker 1

As a reminder, SMA is an inherited neuromuscular disorder caused by a deficiency in a protein, the SMN protein that is essential for the survival of the motor neuron, which in turn is responsible for controlling muscle movement. When the SMN protein is deficient, the motor neuron degenerates resulting in muscle weakness and atrophy leading to significant impairments including the inability to sit, stand and walk depending on the extent of involvement. Currently, there are 3 approved therapies for SMA, all work to increase the amount of SMN protein, But none target the muscle directly. Opidigramab by targeting latent myostatin prevents the formation of the active form of myostatin, A negative regulator of muscle growth and is the 1st anti myostatin to result in improvements in motor function as shown in our Phase 2 proof of concept study, Topaz. Moving to Slide 13.

Speaker 1

As we shared at the QSMA event in June, we were excited to present 36 month data from the pooled non ambulatory patients from TOPAZ, the same patient population included in our Phase 3 registration study Saphyr. As shown there was robust, consistent and sustained improvement in the motor function scales, the extended Hammersmith and revised upper limb module, which are also the primary and secondary endpoints in Saphyr, as well as improvements in the patient reported outcome measures as reflected in an increase in activities of daily living and reduction in fatigue, all measures that are consistent with improvement in muscle strength. Turning to Slide 14. I'm very pleased with the progress we've made this year toward executing on the promise of opidogromab and SMA. We have met or are on track to meet all of the 2023 goals for the program that we outlined at the beginning of the year.

Speaker 1

In addition to reporting the 36 month TOPAZ data in June at Cure SMA, we also opened the On X long term extension study, which will serve as a platform for patients from both TOPAZ and Saphyr to continue to receive opidigramab. Importantly, On X provides an opportunity to further strengthen the body of evidence on long term safety and efficacy. As we announced in September, we completed enrollment of our Phase duration study Saphyr, a major milestone for the study and look forward to reporting our top line results in Q4 2024. Assuming success and regulatory approval, we expect to be a commercial company in 2025. And from a commercial perspective, launch of opidigramab will be leveraged by the established SMA market.

Speaker 1

And finally, our team is in the planning stages for additional follow on SMA studies, including in children under the age of 2 and in ambulatory patients, allowing us to extend the potential benefit of opidigramab to the broadest patient population possible. Now moving to Slide 15, I'd like to turn this portion of the program over to Mo, who will provide an overview of the cardiometabolic program. Mo is the Head of Research and brings a wealth of experience in both neuromuscular and cardiometabolic diseases. As I mentioned in my opening remarks, Moe's team has been working on targeting anti myostatin for cardiometabolic diseases for quite some time and Moe will walk you through this research. Moe?

Speaker 2

Thank you, Jay, and good morning, everyone. Now on Slide 16. Our approach of targeting the pro n laitin forms of MyStat allows us to have exquisite selectivity to inhibit myoscan signaling and nothing else. A non selected approach that targets pathways outside of myoscan or muscle has the potential to have deleterious effects. For example, inhibition of the closely related GDF11 growth factor signaling May have negative impacts on bone.

Speaker 2

An inhibition of Actavance has demonstrated effects on reproductive biology, likely limiting the use of products target this pathway in women of childbearing age. By inhibiting MyStat and only MyStat, our antibodies provide a profile that drives efficacy without the potential liabilities that come with non selective approaches, which is critical, especially in this patient population. We are now on Slide 17. Obesity is recognized as the top global public health challenge with an estimated 1,000,000,000 adults worldwide, including half of the population in the U. S.

Speaker 2

Projected to be obese by 2,030. This is associated with several serious comorbidities Like heart disease and Type 2 diabetes and staggering costs to the healthcare system. Weight loss by any means Lease to loss of not only fat, but also lean mass. And this is evident in the GLP-one receptor agonist mediated weight loss that are experiencing rapid uptake and where lean mass losses may be 25% to 40% of the total body weight loss. Loss of lean mass is a key predictor of adverse outcomes in older patients and maintaining lean mass through exercise during weight loss has demonstrated longer term benefits versus weight loss alone.

Speaker 2

Therefore, it is important that it is possible that maintaining lean mass in the context of weight loss May promote additional fat loss as well as greater long term metabolic benefits. Moving to Slide 18, where we'll be discussing SRK439. SRK439 is a novel preclinical anti mycetinibody that is in development. As mentioned earlier, we leveraged our extensive expertise in MyoTAN structure and biology to develop this molecule to specifically address the patient population with cardiometabolic disorders. ASAK-four thirty nine has attractive properties and potential to address the muscle loss associated with weight loss.

Speaker 2

It has high inbutro affinity for pro and latent mystand to potentially lead to efficacy at lower doses. It maintains mystand specificity with no GDS11 or active NA binding to limit any potential undesirable off target effects, especially in this patient population. It also maintains a good development profile and is amenable to subcutaneous formulation and dosing. Now on Slide 19, where we show our efficacy data with SRK439 in combination with GLP-one receptor in diet induced obesity mouse model, a standard model used in the field. As expected, the decrease in body weight induced by GLP-one receptor agonist, liraglutide in this case, led to a decrease in not only fat mass, but also lean mass as you see with the TAM bar.

Speaker 2

Combining SRK439 with a GLP-one receptor agonist confirmed our therapeutic hypothesis and led to dose dependent reversal of lean mass loss in addition to enhancement of fat mass loss. Now on Slide 20. Slide 20 highlights the efficacy of SRK-four thirty nine in diet induced obesity mouse model in combination with semaglutide, and more effective GLP-one receptor agonist. Semaglutide did lead to significant loss of lean mass in addition to fat mass loss as seen in the TAM bar. However, when combined with SRK439, the loss in lean mass induced by semaglutide alone was dose dependently reversed leading to maintenance of lean mass while enhancing fat mass loss.

Speaker 2

It is worth noting that we see lean mass preservation with doses as low as 0.3 milligram per kilogram of ASRK-four thirty nine, which highlights the favorable profile of SRK-four fifty nine for development in this indication. Turning to Slide 21. To summarize, our approach is exclusively selective in targeting myastatin and myastatin only and avoids potential liabilities of off target inhibition. The selective inhibition of myastin in combination with GLP receptor agonist driven weight loss may lead to healthier, more durable weight management we look forward to testing this in the clinic. Now on Slide 22.

Speaker 2

In summary, our preclinical data supports Advancing SRK439, a novel investigational nystine inhibitor for the treatment of cardiometabolic disorders with an initial focus on obesity. We are moving SRK439 towards IND submission in 2025. To inform the development of SRK-four thirty nine, We plan to initiate a Phase 2 proof of concept trial of apetikumab in combination with GLP-one receptor agonist in obesity in 2024. The data readout of that trial is expected in mid-twenty 25. Now I will turn it over to Ted for a summary.

Speaker 3

Thanks, Moe. Moving to Slide 24. 2023 has been a year of significant execution across our portfolio and we're well positioned going into 2024. We're seeing great productivity coming out of our scientific platform as our unique approach of targeting the latent form of growth factors to achieve exquisite selectivity appears to be proving patient outcomes in SMA and in oncology. We are excited to be applying this selectivity toward cardiometabolic disease areas where we believe safety is so important and our approach is highly differentiated.

Speaker 3

Our upsized public offering that we completed last month puts us in a strong financial position with our cash runway that extends into the second half of twenty twenty five. We're focused on advancing the myostatin programs, SMA and Cardiometabolic. Additionally, we believe we're well positioned to bring in non dilutive funding as we continue to evaluate promising programs by leveraging the infrastructure, capital and expertise of other companies. We ended the 3rd quarter with $219,000,000 of cash and cash equivalents and our October capital raise netted approximately $93,000,000 Our capital allocation strategy includes a substantial reduction in our spend on SRK-1 hundred and eighty one as we complete enrollment of Dragon and continue to support remaining patients on study. Our primary focus as we conclude 2023 and look to 2024 includes investments to advance apitigramab in SMA and our newly announced cardiometabolic program.

Speaker 3

With the capital in hand, promising programs underway strategic imperatives aligned with our core competency, unparalleled selectivity of myostatin inhibition, we are excited about the future and our ability to serve patients with our important novel therapies. This concludes our formal remarks. I'll now turn it over to the operator so we can start the Q and A. Operator?

Speaker 4

Thank you. The floor is now open for your questions. Your first question comes from the line of Michael Yee with Jefferies. Your line is now open.

Speaker 5

Hey guys, thanks for the question and congrats on all the progress. We had two questions, 1 on SMA and 1 on Cardiometabolic. On SMA, in your Phase 3, I believe the primary analysis Based on 2 to 12. And I was wondering if you have any thoughts around the proportion of the study that is probably more 2 to 5 versus say older and whether there is any pre specified analysis that has a analysis to look at the younger patients versus the older patients in that study after observing what happened with DMD gene therapy and how that played out if there's a pre specified analysis for younger patients. And then on cardiometabolic, An interesting hypothetical question, Appreciate that this is an obesity drug that you're trying to develop.

Speaker 5

Do you anticipate that the regulatory path is traditional obesity just weight loss, whether there's an endpoint also that would be accepted by the FDA for muscle gain. And I was wondering how you think about that. Thank you.

Speaker 1

Yes, good. So Michael, thank you. This is Jay. Thanks for the question. Let me start with the SMA.

Speaker 1

So yes, our primary analysis is the 2 to 12. We haven't disclosed the proportion of that group who are between the ages of 25. And at this juncture, our primary analysis certainly include the older cohort, but as you know upon top line data we have the opportunity to look across the age groups. So we will certainly look at that in the top line results. So I think that took care of the question on the SMA patient population.

Speaker 1

With respect to cardiometabolic, yes, very interesting question. I think with respect to the current approval for weight loss, it is the amount of weight loss that occurs that is the primary endpoint. As you know, this is an evolving field and I think recognizing that the need to preserve lean muscle mass is really critical and the efforts now function or patient reported outcomes. So I think that will need to be a standard part. But I think it's a stay tuned as I think as we move forward.

Speaker 1

For our proof of concept study. We're certainly going to be focused on demonstrating that we can preserve and maintain the muscle mass. I think for a proof of concept that's mechanistically sound and that's our approach going forward.

Speaker 5

Thank you, guys.

Speaker 4

Our next question comes from the line of Allison Bradshaw from Piper Sandler. Please go ahead.

Speaker 6

Hi, good morning team. Thanks for the update today and thanks for taking my questions. So first on SRK439, maybe a question for Moe. Could you just provide some more color on the different properties of of 439 compared to opidogromab and just really distill for us why 439 is better suited to go forward in obesity. It seems the subcu format is a major differentiator there.

Speaker 6

Just curious if subcu administration of apetikumab is something you've explored. Any color there would be helpful. And then just on a related note, could you help us understand what is gating to IND filing for apetikumab in obesity? And also same question, what's gating to IND filing for 4/39 and what gives you confidence that IND filing will be ready to go in mid-twenty 25. Thanks.

Speaker 1

Hey, Ali, this is Jay. Maybe I'll take one part of that 3 part question and then I'll And here's the question around the IND, what's required to get the IND filed for apitigramab. Why I'm really delighted that we have the opportunity to proof of concept with apitigramab is because it's already a clinical stage asset. So it's a matter of really putting together the scientific rationale and submit the IND for a new division to agree and we get to cross reference a lot of the existing documents in the current epidermis IND and SMA. So it's really a matter of kind of completing the regulatory dossier to do that and then engage FDA.

Speaker 1

So that work frankly we had started even prior to announcing our going into this area. And then maybe I'll let Moe talk about the IND enabling work that's required for SRK439 and then more details.

Speaker 2

Yes. Thanks, Shay. I mean, I'll start with talking about XRK-four thirty nine. XRK-four thirty nine is a novel molecule that we developed based Our extensive understanding of Myastand and the structure and the epitope space. It is highly selective.

Speaker 2

As we mentioned, it only binds Myastand utilizing our platform. It has attractive property and from the get go we developed it to target this patient population. So it has very high in vitro affinity leading to potentially lower doses when you're looking at efficacy with these and we've seen that in Again, this is to support subcu profile, especially for this patient population. So the overall profile of SRK-forty nine Was designed by design for this patient population to have higher affinity efficacy with lower doses and concentration to enable subcutaneous dosing. From an IND enabling studies, we're going forward with the typical IND enabling studies.

Speaker 2

We're initiating, all of the IND enabling studies, as we move forward into next year, as you see the talks, the PK studies and all of these things as well as cell line developments, etcetera.

Speaker 6

Got it. Thank you.

Speaker 4

Our next question comes from the line of Tess Romero with JPMorgan. Please go ahead.

Speaker 7

Good morning. Thanks for taking our questions. Two questions from us this morning if we could. First one is, how do you disclose the statistical test you are using and what the powering assumptions are for the Saphyr trial around the primary endpoint of the mean Hammersmith change from baseline at 12 months. If not, what can you tell us at this time as to how we should be thinking about this.

Speaker 7

And secondly, a related question, will you consider disclosing the baseline characteristics before the top line results next year. Thanks guys.

Speaker 1

Yes. So this is Jay, I'll take the questions. From the statistical powering assumptions. We've really not fully disclosed it, but just to kind of put color to that for the Hammersmith, we expect to Certainly be able to demonstrate a 3 point change by the way we powered the trial and we have adequate power to demonstrate that. And again, we're doing hierarchical testing on that and then the following secondary endpoints.

Speaker 1

So I think we're well positioned to replicate in Saphyr what we saw in the TOPAZ study. And then with regard to baseline characteristics, Ali, we're looking at that very critically as sort of our publication planning and data disclosure plans. Really, we try to do that time to important conferences as we think in conferences we think about over the year. So more to come as we disclose that, But not likely to occur anytime in the near term given the cadence of the medical conferences.

Speaker 7

Okay, great. Thanks for taking our questions.

Speaker 4

Our next question comes from the line of Srikripa Divarakonda from Tuohy Securities. Your line is now open.

Speaker 8

Hey guys, thank you so much for taking my question. As you develop apitagramab and SRK-four I actually had a couple of maybe basic questions on myostatin in obesity. Some studies have shown that myostatin is do you think that could potentially impact how effective the drug could be in these patients, especially if you consider the background of obesity versus SMA where you've shown activity?

Speaker 6

Thank you.

Speaker 1

Yes. So maybe I'll start just talking about what we would expect to see in clinic with apitigramab and then following with SRK439 in obesity. I think what we can say, which is I think very clear now, and we've shown that I believe in the TOPAZ study is that targeting myostatin does result in preservation, if not increase in lean muscle mass. Think we've shown that functionally in Topaz. I think there's consistent observation across.

Speaker 1

Somaiastan is a very good target. And it certainly should be Able to do that in the setting of obesity where you have normal muscle. So I think that's the case. The fact that There was up their signaling is high in myostatin, I think is interesting, but I do believe that we have an opportunity to demonstrate that in this setting just as we all demonstrated in the SMA setting.

Speaker 8

Great. Thank you.

Speaker 4

Our next question comes from the line of Etzer Dara from BMO Capital Markets. Your line is now open.

Speaker 9

Great. Thanks for taking the questions and Congrats on the progress. How are you thinking about the development of SRK-four thirty nine, I mean, given the size of the obesity indication and I guess is the proof of concept data with apetegumab the catalyst for an update if you will on development plans. And then maybe on SRK-one hundred and eighty one, just maybe next steps for the program, maybe a little bit more color on what you described earlier during opening remarks and maybe the opportunity for future programs to be in sort of an earlier lines of RCC for example. Thank you.

Speaker 1

Yes. So let me start with 439 and proof of concept and sort of overall path forward. Again, I think we're designed we've shown to date at Scholar Rock that we can run randomized Phase III studies, we can run proof of concept trials. And so as I think about the cardiometabolic space, certainly to get vinigramab proof of concept, which will really, in my opinion, validate our approach. And as we report that out, we'll then at the time open up with 439 getting right into clinic really positions us to drive 439 Rapidly forward also to that proof of concept.

Speaker 1

And so that's our near term horizon. Anything beyond that, I think really we're still open for discussions around how we get to bigger, broader trials. But I think for what we can do on our hand, I think we can certainly drive value, if you will, for the company by driving to the clinical data in that proof of concept So that's really our thinking around and what Moe laid out very beautifully about how we're looking at both apetigramab and 439. For 181, the data that I shared in a way I try to put the color on it, This is really a tough group to treat and to see this level of response rate in this heavily pretreated, failed on checkpoint inhibitor, I think really shows that proof of concept, which is why we reached those conclusions. But I think like in any therapy and particularly in immunotherapy, earlier lines of therapy are really the place to Take any such treatment if you really want to have major impact because patients have been so beat up and progressed so much through these therapies that getting earlier makes sense.

Speaker 1

And so frankly that's the whole concept behind that end of Phase 1 meeting is really to engage FDA and review our data and then begin to work with them to kind of lay out what would be the next logical steps in any further development of 181. And as Ted said, right now for us today, Really pleased with the way Dragon performed. I think it's met its objective. It's done its job, if you will. We'll wind that down, reset, take a look at what's happening with the FDA interaction.

Speaker 1

But in the meantime, in 2024, it's really all on our focuses on our anti myostatin programs.

Speaker 9

Great. Thank you.

Speaker 4

Our next question comes from the line of Andres Maldonado with H. C. Wainwright. Your line is now open.

Speaker 10

Hi, thank you for taking my questions. And I'll reiterate Congratulations on all the progress. So one quick question from us on 439. So I guess in the context The goal of next generation obesity programs aims to really hone in and solve The issue of variability of patient response. Could you maybe talk about how much In this variance, you ascribe muscle loss driving that variation in patient response.

Speaker 10

And then follow-up question to that would be, given the safety and tolerability of ipidogromab, which has been positive, Are some of the treatment emergent events more worrisome in the context of the combination? Thank you very much.

Speaker 1

So, okay, maybe we'll do a tag team with Moe. I think, your question is sort of the variability in weight loss that occurs with the current GLP-one receptor agonist. And you see kind of a range across some patients do well, there gets to be a plateau for I think it probably in my as I review the literature and look at the data, some of it may very well be starting points for the patient's ability to get to adequate doses. I think there's a lot of things that affect the overall weight loss. From the muscle mass loss that we've seen, There is a range, but it's a fairly it's between 20% and say 40% that is definitely related to that.

Speaker 1

And so those are kind of related events, But our focus really is on that preservation of lean muscle mass, which we believe we should have a consistent effect across. Hence, we'll look at our proof of concept studies To move forward, but I think that's the thinking there. And again, I think it's really interesting to your point about safety. And we've emphasized this It really matters. It really matters.

Speaker 1

I think about weight loss therapies over time, they've been affected, But they've all been troubled by toxicities and safety issues that have prevented their continued use. I think what we're seeing with the GLP-one receptor agonist is to date and there's been wide patient exposure, we're seeing some effects, but nothing like what we've seen in past that would really warrant stopping these therapies. So that's a good thing. But any additional therapy that comes into this space That's an add on therapy that's used to kind of offset some of the negative effects like loss in the muscle. In my mind really needs to bring no additional risk of toxicities if possible.

Speaker 1

And that is where I believe if you look at all of the conversations going on in other areas, other companies coming into lean muscle mass. I do think our approach by hitting myostatin and only myostatin We'll avoid off target effects. And I think Moe walked through that. If you look at what happens when you hit active in receptors A and B, you start to get into some things You may not want to see, right, that over time could potentially be troublesome. And that's also true with GDF11.

Speaker 1

So I like our approach. It Shouldn't bring any additional risk to that risk benefit profile. We'll obviously see that when we report out our Phase 3 data. But so far and we're seeing that in Topaz. We have patients coming on 4 years with really a very, very clean safety profile.

Speaker 1

I think in the cardiometabolic space, we certainly want to continue with that and I think we're positioned to show that.

Speaker 4

Our next question comes from the line of Ernesto Rodriguez Tumor with Cowen. Please go ahead.

Speaker 11

Hi, thank you for taking my questions and congratulations on the progress. Just to follow-up on the obesity program functional endpoints for regulatory purposes. So, other pyromiostin programs that show muscle gains in other settings. Are there any hints of functional changes from those programs that could lead The way to identifying a functional endpoint for the obesity program. And then also do you expect the Therapy to be a chronic therapy in conjunction with the GLP-1s or do you expect that there to be some kind of biomarker and limit to the therapy.

Speaker 11

Thank you.

Speaker 1

Yes. So I think there's a couple of things again back to the regulatory endpoints and we're going to begin the engagement with FDA and other agencies as we advance through IND and get more interaction with our clinical programs. But as an example, the functional measures, well, as you know, we've included functional measures in the SMA program. Those were tailored specifically for the underlying disease. There's other ways to measure the grip strength and certain other measures that we could assess that would show that you're preserving and maintaining motor function.

Speaker 1

So that's something to consider. There's also measures that we can include that would look at quality of life measures. As you know, there are some significant associated GI effects with the current therapies. It's possible for our approach And what Moe showed, which I think is very intriguing is that we do have the potential to have some additive effect on weight loss. And by that activity potentially getting the same effect on weight loss at lower doses.

Speaker 1

So there's really I mean, we've got a lot of ideas around this. We're really at the beginning of this effort, beginning of the effort of kind of mapping out the full clinical program to registration, But not at the beginning efforts of our deep thinking around myostatin and targeting this space, right. So we've got a lot of good ideas, more to come, but I think we can And then in terms of chronic therapy, that's very, very interesting question. As you know, I think there is a challenge with maintaining therapy on the current GLP-one receptor Dragonists. There is the potential for rapid rebound.

Speaker 1

If we take a look at muscle as a metabolic organ, which it is, The chances of restoring and preserving that could have some very interesting effects on maintaining the weight loss even at lower reduced GLP-one therapy. And what we're showing at least from our perspective is that we certainly can give opidigramab chronically. TOPAZ data is really underscoring that. As I mentioned earlier, we have patients on 4 years. So again, some lot of questions to address in the clinical program, which is exciting for me.

Speaker 1

But I'm really excited by the fact that Mo and Mo's team have 439 that they've moved since I joined the company to now talking about moving toward IND, really good progress from our research team.

Speaker 11

Okay. Thank you. Very helpful.

Speaker 4

There are no further questions at this time. Mr. Jay Backstrom, I turn the call back over to you.

Speaker 1

Yes. So listen, thank you. Thank you for your interest. Again, just to reinforce, I'm really delighted with the work our team has done, very pleased with our progress. And I really look forward to kind of driving through the rest of this year and really running into 2020

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Earnings Conference Call
Vimeo Q3 2023
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