Good afternoon, and welcome to the Structure Therapeutics conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your telephone keypad. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to Danielle Keighley, Head of Investor Relations for Structure Therapeutics. Please go ahead.
Thank you, and good afternoon. Earlier today, we issued a press release announcing the selection of Structure Therapeutics' lead oral small molecule amylin receptor agonist, ACCT-2671, for the treatment of obesity. A copy of this release and the presentation to accompany this call are available on the Investor Relations section of our website. Joining me on the call today to present the development candidate selection are Dr. Raymond Stevens, Founder and CEO, and Dr. Fang Zhang, Executive Vice President and Head of Biology. On the call for Q&A is Dr. Xichen Lin, our Chief Scientific Officer, Dr. Blai Coll, our Chief Medical Officer, and Mr. Jun Yoon, our Chief Financial Officer.
Before we get started, please see the slide containing our note on forward-looking statements included in our presentation and the risks and uncertainties which may cause our actual results to differ materially from such forward-looking statements, including risks which are also referenced in our SEC filings that I encourage you to review. I will now turn the call over to Dr. Raymond Stevens, CEO of Structure Therapeutics.
Thank you, Danielle, and thank you to everyone for joining us this afternoon. We are excited to provide details today around the selection of our first oral small molecule amylin receptor agonist, ACCT-2671, that we'll refer to as 2671 throughout the rest of the call. On today's call, I will start with an overview of how our structure-based drug discovery platform has enabled our discovery of small molecule amylin receptor agonist, including 2671, which we believe represents the most advanced oral small molecule amylin drug candidate today. I will then turn the call over to Dr. Fang Zhang, our Executive Vice President of Biology, to discuss the biology of amylin in its role in metabolism and the preclinical data that supports our development candidate nomination today.
We will then discuss our broad metabolic franchise, which is anchored by our oral GLP-1, GSBR-1290, now in phase 2b development in our oral amylin small molecule program, both backbones for combination treatments that have potential to become important treatments for obesity and the growing number of potential indication expansions, before opening the call to Q&A. At Structure Therapeutics, our mission is clear: to make medicines more accessible for all through the development of oral small molecules. We've done this with our lead oral GLP-1 receptor agonist small molecule, GSBR-1290, and we've done it again with the same approach with our first amylin small molecule.
As an oral small molecule, we envision 2671 as a future backbone therapy to improve scalability, combinability, and ultimately expand patient access to amylin-based weight loss medicines, which we believe will be an important next-generation component of the treatment landscape for obesity and related conditions due to their potential for significant weight loss, favorable tolerability profile, and lean muscle mass preservation. 2671 continues to address the inherent limitations of peptide-based drugs. This includes providing more patient options with our oral form, a potential solution for long-term weight loss maintenance, large-scale manufacturing advantages and lower cost of goods, potential fixed-dose combination advantages, and ultimately broader accessibility. Today, the incretin market is dominated by peptides. These foundational medicines have fundamentally changed patient treatment for obesity, addressing a global pandemic, but they come with scalability and accessibility challenges.
Similarly, with amylin, peptides have led the way, and there are now a number of promising amylin peptides in development, but there are no oral small molecule clinical stage development amylin programs to date. Our vision at Structure is to produce best-in-class oral small molecules that will expand patient access, complementing or replacing marketed peptides. Our discovery engine is now producing an entire metabolic oral small molecule franchise and fueling the expansion of our pipeline portfolio. As a platform company, our business model is very straightforward, going after validated targets that are being addressed with biologics, including peptide drugs, and creating novel oral small molecule solutions for better patient options. GSBR-1290 is our most advanced asset currently in phase 2b development, and we're very pleased with the preclinical data that we are sharing today with 2671.
This is now the third time we've done this in the obesity space and the fourth time we've entered the clinic overall with an oral small molecule, advancing our business model of converting biologics to small molecules. The growing opportunities of GLP-1, amylin, GIP, GCG, apelin medicines, to a broad range of additional indications serve as significant tailwinds to the continued build-out of our pipeline. The discovery of all our small molecules, including 2671, is made possible through our structure-based discovery platform and our deep expertise in the field of G-protein coupled receptors, or GPCRs. Our powerful platform combines the latest scientific advancements spanning cryo-electron microscopy to computational data science. We continue to be at the cutting edge of integrating three-dimensional atomic resolution static structures with molecular dynamic data, including the use of machine learning and AI to advance our programs.
Our insights and capabilities enable highly efficient rational drug design directed at validated drug targets and creating novel oral small molecules to make medicines more accessible to all. Turning now to 2671, we designed this molecule as an oral small molecule dual amylin and calcitonin receptor agonist, or DACRA, with key properties to achieve a highly desirable target product profile. These include competitive efficacy. Our benchmark is to show efficacy that's comparable to cagrilinotide, a peptide DACRA currently in late-stage development. As you'll hear from Dr. Zhang in a moment, our preclinical data demonstrates 2671 to have cagrilinotide-like efficacy with an oral small molecule profile. Second, a favorable safety profile to support chronic disease treatment. Third, a PK profile supporting once-daily dosing for convenient administration. Fourth, inherent characteristics of an oral small molecule treatment, including ease of manufacturing and lower cost.
Finally, combinability advantages with small molecule GLP-1 RAs and other incretins and medicines. We're very excited about the preclinical data we have observed thus far and plan to advance 2671 into clinical development by year-end 2025. Again, we believe this to be the most advanced oral small molecule amylin-based therapy in development in an area that's positioned to become a very important component of metabolic and obesity treatment. With that, I will now turn it over to Dr. Fang Zhang to dive deeper into the biology and preclinical data, underscoring why we are so excited about this molecule. Dr. Zhang?
Thank you, Ray. First, I would like to provide a brief introduction on the amylin biology in comparison with GLP-1. Both amylin and GLP-1 are neuroendocrine peptide hormones that have multiple beneficial physiological effects in metabolism. GLP-1 is secreted from L cells in the small intestine, and the GLP-1 receptor is highly expressed in the pancreatic beta cells and in the brain. Amylin, in contrast, is co-secreted with insulin from pancreatic beta cells, and its receptors are mainly expressed in the brain. Amylin and GLP-1 share common physiological effects in the brain, stomach, pancreas, liver, and white adipose tissues. The effects include reducing appetite, increasing satiety, slowing gastric emptying, inhibiting glucagon secretion, improving insulin sensitivity, reducing fat in the liver and adipose tissues, and related inflammation.
In addition to these common effects, amylin has some unique attributes, including increasing leptin sensitivity, increasing energy expenditure, and a more sustainable gastric emptying slowing effect. Amylin also preserves the lean muscle mass, which is important for the weight loss medicine. The amylin pathway provides an attractive mechanism for both a monotherapy and a combination therapy together with incretin. The amylin receptor system is complex. Its complexity is present at various levels. First, and starting from the left, at the receptor level, there are three amylin receptors: amylin one, two, and three receptors. They are heterodimers formed by the calcitonin receptor CTR and the co-receptor RAMP one, two, three. There is an equilibrium between calcitonin receptor and amylin receptors. Second, at the agonist level, there are two types of the agonist: DACRA and SARA.
DACRA stands for dual amylin and calcitonin receptor agonist, binds to both amylin receptor and calcitonin receptor. SARA stands for selective amylin receptor agonist, preferentially binds to the amylin receptor. Third, the different agonists bind to the amylin receptor or calcitonin receptor and form different receptor agonist complex. Those complex could differ in stability, conformation, G protein and beta-arrestin recruitment, and activation status and cAMP signaling. In summary, the amylin receptor system is complex. The amylin receptor pocket is large, easier for peptides, but difficult for small molecule discovery. Those combined make the small molecule amylin agonist discovery very challenging. Despite all those challenges, we are thrilled that we have been able to crack the code and discover what we believe is the first small molecule amylin agonist. As Ray noted earlier, we tackled the challenge of the small molecule amylin discovery by our powerful structure-based drug discovery platform.
We gained insights from the complex structure of small molecule or peptide-bound amylin receptor or calcitonin receptor and built cryo-EM models to discover and design candidate molecules. Leveraged by the collaboration with Schrödinger, we have established predictive free energy perturbation (FEP) and machine learning models, as illustrated in the right-hand side graph. These models can efficiently predict the small molecule's in vitro potency and physicochemical properties and largely increase our compound design efficiency, leading to the discovery of our lead molecule ACCT-2671. We are utilizing the platform to generate multiple waves of small molecule amylin receptor agonists to achieve the optimal therapeutic benefit. Our first wave of the small molecule discovery was focused on the DACRA profile with cagrilinotide as a key comparator. Here, we are excited to share with all of you our first oral small molecule DACRA development candidate, ACCT-2671.
The table highlights the key preclinical data of 2671 to support the candidate selection. In vitro, 2671 showed nanomolar receptor binding affinity to both amylin and calcitonin receptors and subnanomolar receptor activity in cell-based assays. In vivo and diet-induced obesity DIO rat models, 2671 showed weight loss comparable to cagrilinotide with repeated dosing up to 28 days and also showed robust efficacy in combination treatment with semaglutide. Turning to preclinical safety, 2671 demonstrated tolerability up to 300 mg/kg in the dose range binding study in rats, well above the range of anticipated human doses. 2671 was shown to have minimal effect on the hERG channel with more than 100-fold margin, and 2671 was negative on GSH, low on this risk factor for the drug-induced liver toxicity. Lastly, the preclinical PK supports once-daily oral dosing in humans at the predicted dose of 100 milligrams or less per day.
On this slide, we provide more detail on the in vitro receptor binding affinity and activity of 2671. The left panel shows the receptor binding affinity data. 2671 demonstrated high binding affinity to human amylin receptor and calcitonin receptor, less than five nanomolar respectively, comparable to cagrilinotide. The right panel shows cell-based receptor activity data measured by cAMP induction assays. 2671 demonstrated subnanomolar potency on human amylin and calcitonin receptor and a balanced selectivity profile on the two receptors, similar selectivity profile as cagrilinotide. Now, let's discuss the in vivo efficacy data. The left panel showed the acute food intake effect in the diet-induced obesity DIO rat. After single oral administration, 2671 dose-dependently reduced 24-hour food intake with maximum reduction reaching more than 85% reduction, comparable to cagrilinotide. The right panel shows chronic treatment effects on the body weight loss.
After repeated oral daily dosing for 28 days, 2671 treatment demonstrated a dose-dependent body weight reduction. The high-dose group at 50 mpk achieved about 15% body weight loss, comparable to cagrilinotide. Next, I will summarize why amylin is a promising pathway based on the validated biology, and the preclinical results from 2671 give us conviction in bringing this molecule forward as our first disease. Amylin pathway has validated biology. Amylin promotes satiety, slow gastric emptying, and importantly reduces body weight while preserving lean muscle mass. It shows favorable tolerability with amylin compared to GLP-1 monotherapy, supported by clinical and preclinical data. The efficacy has been pharmacologically validated by a number of the peptide-based mono and combination therapies that are currently in the late-stage development.
Our preclinical data demonstrates 2671 has cagrilinotide-like efficacy with the oral small molecule profile, potent at balanced in vitro activity and robust in vivo efficacy as both a monotherapy and a combination treatment. The PK data supports once-daily dosing in clinical trials. We have a high bar for the safety given the chronic treatment, and the preclinical safety profile supports the development candidate selection. Now, we have announced the DC selection of 2671. We have initiated GMP manufacturing to support GLP-tox studies and early clinical development. We expect to begin our phase I SAD and MAD study by the end of 2025, with data by the end of 2026. We are also planning longer-term tox study to enable us to move rapidly into phase II trials, where we plan to study 2671 as both a monotherapy and a combination therapy for the chronic weight management.
Lastly, given our most advanced oral small molecule amylin position, we are continuing to work on candidate discovery, and we expect to declare additional candidates in the future. With that, I will hand over to Ray to discuss our overall oral small molecule portfolio.
Thank you, Dr. Fang. With ACCT-2671 advancing into the clinic next year, we now have two oral small molecule backbone mechanisms for the obesity market and beyond. A potential best-in-class GLP-1 program with GSBR-1290 now in late phase 2b development and reading out by the end of 2025 in the most advanced oral small molecule amylin with ACCT-2671 entering the clinic next year.
We view both of these approaches as important monotherapies for moderate weight loss and maintenance, and we're very excited about potentially combining these two mechanisms with each other or with other oral non-peptides, which may offer the potential for greater body weight loss and enhanced tolerability, as well as broader label expansion into additional clinical indications. We believe this is just the beginning in building our metabolic franchise. We are in a unique position to develop combination therapies with our GLP-1 and amylin therapies as backbones, in combination with other oral incretins and hormones, including our GIP receptor and GCG receptor agonist, as well as our apelin receptor agonist, which has potential for further selective weight loss.
These combinations enable us to potentially address diseases beyond obesity, including type 2 diabetes, heart failure, sleep apnea, chronic kidney disease, MASH, and potentially even addiction and Parkinson's and Alzheimer's, areas we're starting to see encouraging data with GLP-1s. 2024 was a very productive year for Structure Therapeutics, one where we executed well across all fronts. For GSBR-1290, we showed very encouraging phase 2a obesity data in June that provided us with the data to move into later-stage development. After clearing the IND for chronic weight management, we initiated our phase 2b ACCESS study and ACCESS II study to look at even higher doses of GSBR-1290. Today, we declared our first amylin development candidate, ACCT-2671, the most advanced oral small molecule in development in the amylin field.
For our apelin program, we initiated our long-term tox studies to enable phase II development, and we initiated our phase I study with LTSE-2578, our oral LPA1 for idiopathic pulmonary fibrosis. We raised more than $500 million in capital to advance these programs forward, and we've also continued to build our leadership team and expanded key capabilities on the development and regulatory fronts to enable our next stage of company growth. In closing, I believe that 2025 will be the year of oral small molecules with validation from late-stage development programs, including our own GSBR-1290 phase IIB data. We expect to enter the clinic with our first amylin molecule towards the end of 2025, and as we've discussed today, we'll continue to build out our amylin franchise with additional development candidates to further our leadership position in this important field.
Our business model is fueled by our powerful platform, and we're in a solid financial position with $915 million cash and cash equivalents as of the end of Q3 to continue creating novel oral small molecule medicines that are accessible to all. Thank you for listening, and we'd now like to open the call up to Q&A.
We will now begin the question-and-answer session. To ask a question, you may press star, then one on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. Please limit yourselves to one question. If you have additional questions, you may re-enter the queue. At this time, we will pause momentarily to assemble our roster. Our first question is from Evan Sagerman with BMO Capital Markets. Please go ahead. Hi guys.
Thank you so much for taking my question and congrats on the progress. So I see you noted that 2671 is GSH negative in vitro, but given some recent failures of other assets in development in the obesity space, can you walk me through your confidence in this assay that you won't have any downstream liver toxicity? And say liver tox emerged kind of in your GLP studies, how long do you think you would see that, and how could you pivot? Thank you, guys.
Yeah, thank you, Evan, for the question. I'm going to hand this over to Dr. Xichen Lin, our Chief Scientific Officer.
Thank you, Evan, for the question. This is a great question. So as we keep mentioning, the chronic weight management, longer treatment would take the liver tox and any tox very seriously.
So the two key factors we're looking at is we design the molecule to be very potent and PK profile is fit for a longer treatment. So that allows us to have a dose as low as less than 100 nanograms. Another factor is we're looking at all the in vitro and in vivo tox signaling, including highlighting the GSH negative. So that gives us the confidence the molecule is safe and suitable for chronic treatment. Obviously, we're doing the longer-term GLP tox to further evaluate the molecules.
The next question is from Terrence Flynn with Morgan Stanley. Please go ahead.
Hi, thanks for taking the question. Two-part for me. Just wondering, based on the structure of the molecule, if you foresee any potential DDI issues at this point, not just with oral GLP-1s, but any other classes of drugs that patients might get in this setting.
And then the second part of the question is, when we ultimately get full data for Novo's CagriSema, just curious what you'll be most interested to see there aside from the efficacy and safety data. Thank you.
Thank you, Terrence. I'm going to let Xichen take the first part of the question, and then I'll ask Blai to take the second part of the question referring to CagriSema. Xichen?
Yep, thank you. This is a great question, again. So we're actually looking for the DDI issues very seriously also. We are looking at both CYP3A4, for example, induction and inhibition, and all the transporters. So far, based on preclinical data we have so far, we don't believe there's a significant DDI issues for our molecule.
Blai?
Terrence, this is Blai. Thanks for the question. Of course, a lot of excitement about the CagriSema data coming up anytime soon, hopefully.
You nailed it in the two aspects. I think we're all looking into the degree of efficacy that we can see with CagriSema. Most importantly, the combination of how much of the tolerability can be impacted by adding the amylin receptor agonist to that semaglutide. I think tolerability will be a key cornerstone of that data readout in combination with the degree of efficacy. Very excited about this advancement in the field.
The next question is from Seamus Fernandez with Guggenheim. Please go ahead.
Thanks for the question. Just a couple in terms of the actual profile of the molecule as it relates to half-life and what you see as the kind of ideal amylin agonist relative to GLP-1s. We've talked about CMAX.
With GLP-1s, what do we know about sort of approaching the amylin receptor in terms of the sort of ideal CMAX versus kind of saturating the receptor? Maybe you can just kind of help us understand what your expected ideal half-life would be for this compound and given what we know of the amylin receptor and how it operates, how tolerability and efficacy may trade off with the profile of a small molecule? Thanks.
Yep, thank you, Seamus. So I'll take this question. Given the highly competitive nature of the field, we're not disclosing right now any of the PK parameters for our amylin development candidate. But the same principles apply. We continue to believe that CMAX and AUC really drive efficacy.
As we design this drug in order to be a once-daily dosing C-trough, exposure at 24 hours are our important parameters to continue to sort of watch very carefully after. Half-life I view as an average parameter. It combines a number of different features together. But we'll be updating more on this in 2025.
Great, thank you.
The next question is from Yasmeen Rahimi with Piper Sandler. Please go ahead.
Yes, good afternoon, team. Thank you so much for the great updates and congrats on this great development. I guess the first question is, how should we be thinking about sort of your strategy in being in the clinic? Could you be able to, is your thought to get the IND cleared and start these studies in the US? Is the thought to potentially maybe start the studies outside of the US while you're filing the IND?
Could we be contemplating sort of like if we have first-in-human start, where would you be in tox fast forward next December by now? I feel like I've definitely used up more than one question, so I will jump back in the queue without pissing off my former colleagues. Yeah.
Yeah, Yasmeen, you're asking a really good question, and we've learned a lot from GSBR-1290 in terms of clinical strategy. We're looking to do this as fast as possible. Let me turn this over to Blai to specifically answer your questions or question.
Yeah, thanks, Ray. Thanks, Yasmeen, for the question. A lot to uncover there. Essentially, we'll apply as much efficiency as possible. Of course, we'll need to go through the single ascending dose and the multiple ascending dose that will follow. We're on track, as you've heard from Ray and Dr.
Fang, on starting those studies towards the end of 2025. Whether we'll do this in the US, outside the US, IND, no IND, rest assured we'll find the way to put as much efficiency as possible into the programs, preserving the quality of the execution and making sure that we can advance the program to the next stage as soon as possible.
Okay, thank you.
The next question is from Roger Song with Jefferies. Please go ahead.
Great. And my congratulations to the amylin program selection DC. So I have a question related to the efficacy understanding you shared with us, the weight loss at day 23. Just curious about the weight loss trajectory. Do you see onset versus the maximum weight loss, and then how we think about the maintenance of the weight loss after 28 days dosing?
Just curious about the trajectory if you can share with us a little bit more. Thank you.
Yeah, Fang, you want to take that question?
Sure. For cagrilinotide, in the DIOs, usually it plateaus after 21 days. That's why we stopped the study at 23 days because it's already reached the plateau. Generally, for this class, usually for the chronic study, we do the study for 28 days. Usually, it will reach to the plateau for the amylin class.
The next question is from Chris Shibutani with Goldman Sachs. Please go ahead.
Hi, this is Kevin Otten for Chris, and just wanted to add my congratulations as well. I just had a question on the prioritization of the development of DACRA asset versus a selective amylin receptor agonist. I know you mentioned cagrilinotide, obviously, as a comp there, but anything else that you could say on that?
And then in terms of moving forward and bringing forward more assets, how do you prioritize that over the next couple of years given potential to bring forward another amylin asset or GIPR, etc.? Thanks.
Yeah, Kevin, I'll take this question. So first, I think both DACRAs and SERAs are important molecules to be pursuing. The most data that's out there is really Cagrilinotide. And so we chose that as sort of the benchmark when we started the program, again, just because of the wealth of data that was available and using that as kind of the current standard. But we'll be pursuing both DACRAs and SERAs in parallel in the future.
Got it. Thank you.
The next question is from Hardik Parikh with JP Morgan. Please go ahead.
Hi, this is Hardik. Thank you for taking my question.
Just a couple on. I saw that you're expecting data on this program by year-end 2026. And I'm just wondering, in the meantime, in the next couple of years, what kind of data or updates can we expect from this program from you guys before the end of the trial? And then you mentioned that in phase two, you'll explore as both monotherapy and combo with GLP-1s. Any thoughts on testing with any other incretins? And is there a possibility you could test in combo in phase one as well? Thank you.
Yeah, I'll take the first part of the question here, and then I'll turn it over to Blai for the second part of the question. So the first part of the question, what updates do we expect over the next 12 to 24 months?
First, we do expect we want to make it very clear that this is a relatively new frontier amylin. We're the first to put a molecule into the clinic in this area. As such, we think those likely to be multiple DCs that we're excited to push forward based on the previous call, previous question, both DACRAs and SERAs as good examples of continued development in this space. We think that in 2025, we'll have additional updates with additional DCs. You're correct, we'll be going into the clinic at the end of 2025 and expect to read out that data in 2026. Blai, do you want to take the second part?
Yes, thanks for the question. Of course, it's an important consideration on how we're looking into the future of the program.
Here, as I said before, we'll need to go through the single ascending dose and multiple ascending doses to establish that dose range initially and then plan for the phase two. Of course, there are ways to strategically plan for those, whether it's in monotherapy or in combination. One of the advantages that we have at Structure is that we have multiple assets, and we can do those combinations, whether it's with the GLP-1 or other incretins that, as you've said in the slide, are in the pipeline. So we have the possibility to establish those combinations. Again, I just want to reiterate that it's important to go step by step, and we'll do the single ascending dose and multiple ascending dose for the 2671.
Just to add on to what Blai said, I think the fixed dose combination is a real exciting area.
With oral small molecules, we have a lot of flexibility looking at whether it's the different molecules that we're combining or different ratio of molecules to really optimize for both tolerability and efficacy as well. So a lot of exciting opportunities that we'll be reporting out in the next 12 to 24 months.
The next question is from Jonathan Wolleben with JMP Securities. Please go ahead.
Hey, thanks for taking the question. Ray, just piggybacking off that last comment, what do we know about amylin's ability to preserve lean mass when it combines with a GLP? And it sounds like 2671 and 1290 could play well together. Is your expectation that this could be formulated into a single pill eventually?
Yeah, so on the first part, so I'll take the first part.
Co-formulation is one of the things we've always had in mind, particularly with a GLP-1 and amylin. As mentioned on the call, we think either of these are very good for monotherapy or maintenance. If you want more significant weight loss, then combining them, there's a lot of opportunity there as well. In regards to amylin and selective weight loss, I'll turn it over to Fang, who knows the information about selective weight loss and amylin.
Yeah, amylin can preserve the lean muscle mass. That's a very exciting observation from the preclinical studies. The detailed mechanism of the muscle preservation is not clear yet. People are actively studying on it.
Regarding the combination of amylin together with the GLP-1, whether they can preserve the muscle mass in that context, we haven't seen the published data on that yet, but it's definitely an interesting area, and we are also investigating in that.
The next question is from Miriam Belgiddi with LifeSci Capital. Please go ahead.
Hey, this is Dennis Otten for Miriam. Thanks so much for taking our question and congrats on the candidate nomination. We hear that amylin agonism is maybe more tolerable because it induces satiety, which is maybe slightly different from the way that GLP-1s prevent hunger. Just curious if you had any thoughts on the satiety induced with amylin and if this is what's really making the difference in tolerability. Is there any good way to kind of measure satiety in a clinical trial? And is that something you'll be looking at? Thanks.
I'll let Fang or Blai take that question. Fang, you want to go first?
I can comment on the preclinical part, and Blai probably can comment on the clinical part, so satiety is actually one of the very attractive parts of the amylin mechanism. If it increases satiety, and actually, it's better than the reduced appetite and also reduced hunger and fulfilled needs and happiness, so this is part of the attractiveness of the mechanism, but regarding for the clinical measurements of satiety, I will pass to my colleague Blai to answer.
Yeah, thanks, Fang, and thanks, Dennis, for the question. As you know, and we have a lot of experience right now with measuring those parameters through 1290. Of course, there's no validated score. There's no validated tool, but hopefully, in the future, we will also contribute to that validation process, but we're learning a lot from the 1290.
As we've communicated, we're asking those questions to the participants in our clinical programs. And whether it's with direct questions or visual analog scales, there may be ways to assess that aspect, and we're planning to do that for the amylin as well.
Great. Thank you.
The next question is from Prakhar Agrawal with Cantor. Please go ahead.
Hi, thank you so much for taking my questions. Maybe a couple of preclinical. What's the selectivity of this candidate 2671 for the dimer? Specifically, which dimer does it bind to amongst RAMP1, 2, 3, plus calcitonin, as well as your confidence on avoiding binding to other GPCR complexes? And I think in the preclinical slides, it's mentioned tolerability up to 300 mg/kg in rat. Did you see any additional tox in larger animals, such as dog? And on the clinical side, you've talked about taking multiple amylin candidates into the clinic.
Could the phase 1 trial that will be initiated have the option to include multiple amylin candidates? I'm just trying to understand what's the optimized path to find the right candidate. Thank you.
Yeah, how about Fang? Why don't you start with that question, and then Xichen, if you want to add anything onto it afterwards?
I will comment for the first couple of questions on the receptor binding and also the other GPCR receptor selectivity question. So our current molecule, 2671, has affinity binding, as shown in today's data, with the amylin-3 receptor and the calcitonin receptor because it's a DACRA. It's expected to bind both. Regarding the other GPCRs, we have counter-screened with the CGRP receptor and also a list of the other 50-panel off-targets. So far, it's pretty selective and no activity on the CGRP receptor or other GPCRs.
Yeah, regarding the tox evaluation, as we mentioned, we complete the rat DRF to see if the drug's relatively quite safe. And we currently scale up the molecule for the large animal species, including dog, for the tox evaluation. And we're going to start the GLP tox next year, early next year, to support the phase one trials. Regarding other molecules, obviously, as Blai mentioned, we need to complete the GLP tox and take the first molecule, ACCT-2671, first, and have the following molecules, next wave molecules, get to the queues.
And Prakhar, this is one of the reasons why we're in a very fortunate position to have multiple different scaffolds and molecules. And so we'll continue progressing them because we know in drug discovery, it's important to parallel process these candidates to increase the probability of success.
And so we'll continue on that path, both in novel discovery as well as additional molecules.
Thank you.
This concludes our question-and-answer session. I would like to turn the conference back over to Dr. Raymond Stevens for any closing remarks.
Thank you all for listening to this call. And on behalf of all of us at Structure Therapeutics, we wish you and your families a very happy holiday season.
The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.