I know.All right, guys.Welcome everyone.Thank you for joining us for the Sagimet Fireside Chat here at the TD Cowen Healthcare Conference.I am covering analyst Ritu Baral, and joining us on stage from Sagimet Management is CEO David Happel.Happel.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
I pronounced that wrong.I apologize.
David Happel
President, CEO, and Director, Sagimet Biosciences
David Happel.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Dave Happel.Eduardo Martins, Chief Medical Officer, and Rob D'Urso, SVP of New Products.We also have CFO, Terry Cochet in the front row for anybody who wants to say hello to them.Let's start actually with some recent business development you guys have done around the resmetirom API license.
David Happel
President, CEO, and Director, Sagimet Biosciences
Mm-hmm.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Of course, you have denifanstat, which is really phase III ready for NASH should you have chosen to do monotherapy.
David Happel
President, CEO, and Director, Sagimet Biosciences
Correct.
Ritu Baral
Senior Biotech Analyst, TD Cowen
You have taken a different development strategy for combination going forward into the MASH sector.Is combination really how you're thinking about your future MASH franchise?Are you looking at, you know, have you done your resmetirom API license as a backbone for different combination approaches?Are you looking at Deni as a backbone?Maybe you can talk about that a little bit.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah, no, that's a great question, Ritu.Thank you for inviting us out today.Our approach really is foundational on denifanstat.It's the only FASN inhibitor in the space for the treatment in MASH.The data to date has been clearly differentiating in terms of its antifibrotic effect, anti-inflammatory effect.Really, as you pointed out, we're moving towards combinations.I think one, because we started looking at the combination of our FASN inhibitor in combination with resmetirom that we presented that data.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
About two years ago at EASL.Maybe a bit ahead of the curve in terms of how everybody's looking at the space, but I think we recognized at the time that combination therapies were going to be the standard of care to help patients achieve optimal outcome.That's very clear in the cirrhotic or F4 population.While the FGFs have made some progress, there's still nothing approved.It's an area of significant unmet need at the moment.Our data to date with denifanstat strongly suggests in the F3 population that the drug works exceptionally well.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
as the liver becomes less fatty.As we reported at EASL and AASLD this last year, patients who are digitally diagnosed as having F4 stage disease, 11 of the 13 had a one or two-stage improvement, they moved out of the F4, disease severity into F2, F3, which is really promising.Even on its own, we know the molecule has a strong effect.When we combined it with resmetirom in the preclinical data, in the preclinical model, we showed a nice synergistic effect, a magnified effect in reduction of inflammation and fibrosis.I'm sure we'll talk a little bit why that mechanism is, they work so well-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... together. that's really the crux of it.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.That was actually gonna be the next question.Like, what is it about the mechanisms of the two drugs that are synergistic?
David Happel
President, CEO, and Director, Sagimet Biosciences
Eduardo.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Sure
David Happel
President, CEO, and Director, Sagimet Biosciences
... you could touch on that.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
That's a very important point.Deni is the only molecule that actually impacts the production of fat.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
In inhibiting the de novo lipogenesis cascade.Resmetirom, on the other hand, works on the processing and elimination of the fats or beta oxidation.The two mechanisms are not non-overlapping, but complementary.
Ritu Baral
Senior Biotech Analyst, TD Cowen
One turns off the tap, one opens the sink.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
More or less that.Interestingly, however, is when you give a THR-β to a patient, you up-regulate FASN.It's a counter-regulatory loop.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
You effectively increase fat production, and that's a normal biological response.By inhibiting it with Deni, you are actually increasing the efficacy of Res as well.Deni does most of the work, having something to lead to an even greater drop in fat.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... will be useful since we have, the ability to not only impact the other two cells, directly, inflammation and fibrosis, but also the downstream effects of defatting.Finally, as we know, compensated cirrhotics, they still have fat in their liver.That is, a nice, bump that we get.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it. you're thinking you could see additive efficacy?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
well, let me-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Strictly added, like numerically added efficacy, or could you actually see synergy?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
In animals, we showed synergistic activity.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Of course, we haven't conducted a study.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... in people as of yet, but our data in animals are clear.
Ritu Baral
Senior Biotech Analyst, TD Cowen
How are you looking at the strategic advantages of your, license, the new license, the 20 novel forms of the API for the Rezdiffra...I'm sorry, resmetirom API, from Teva.It was Teva API?
David Happel
President, CEO, and Director, Sagimet Biosciences
Yes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yes.How do you think it differs from the approved form of resmetirom, and could there be any pharmacodynamic differences in the different, in the different backbones?
David Happel
President, CEO, and Director, Sagimet Biosciences
Well, Amelia, I'll answer the second question first, and we don't anticipate any pharmacodynamic differences at all.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
David Happel
President, CEO, and Director, Sagimet Biosciences
I mean, the how the body responds to the medications should be the same.That's really the basis for choosing the specific form of resmetirom that we end up working with.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
David Happel
President, CEO, and Director, Sagimet Biosciences
We're in the process right now of selecting one of those 20 versions.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... those innovative forms of resmetirom and going through assay testing, and once we complete that, then we'll have a better sense.Right now, all of those 20 forms are independent and separate from Resdiffra's IP.T here's not an overlap.Those applications are public, by the way.
Ritu Baral
Senior Biotech Analyst, TD Cowen
That's the polymorph IP.
David Happel
President, CEO, and Director, Sagimet Biosciences
Correct
Ritu Baral
Senior Biotech Analyst, TD Cowen
that they have?
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.What are the factors by which you will select whatever final polymorph?
David Happel
President, CEO, and Director, Sagimet Biosciences
Well, we're gonna look obviously at the PK.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
David Happel
President, CEO, and Director, Sagimet Biosciences
... the PD and the, you know, the.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... solubility of the molecules.It's ...Ultimately, we want to identify the one that most closely resembles, and functions like, resmetirom-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
as it should.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
doesn't interfere or infringe upon their IP.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Is there-
David Happel
President, CEO, and Director, Sagimet Biosciences
... and I see the numerous ones available.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Are there considerations for co-formulation with Deni as far as how you pick which of the 20?
David Happel
President, CEO, and Director, Sagimet Biosciences
Oh, well, sure.We'll certainly test them.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... combination with denifanstat, to ensure that they, you know, that they function as we anticipate.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
David Happel
President, CEO, and Director, Sagimet Biosciences
It's really not that complicated.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Any, any formulation concerns or sort of chemical, sort of ADME concerns around a co-formulation?
David Happel
President, CEO, and Director, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
David Happel
President, CEO, and Director, Sagimet Biosciences
I mean, we've completed the phase I study that we reported out before the end of the holidays last year.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Oh.
David Happel
President, CEO, and Director, Sagimet Biosciences
The combination, there was no safety signal.They were very compatible, extremely well-tolerated and really supported.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... moving forward into phase II, so we don't anticipate any.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.The combo strategy in F4, we, Eduardo touched upon it a little bit.What were the key findings from that phase I, and how do they support further F4 development?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Sure.I Dave already mentioned.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... the key components, safety-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... and that the two are compatible.We'll be submitting the data to...Well, actually, we have submitted the data to EASL.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
If accepted, we'll be presenting, and, we'll then expand, the, details in addition to other experiments-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... that we conducted.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Were you able to pick F4 patients with residual liver fat?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
The main study was in healthy volunteers.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... of course.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We are studying also in patients with compensated cirrhosis.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
The thing is, the phase I studies, they're very short.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We're talking a couple weeks.Participation of a patient is two weeks.It's too soon to be able to say anything about the clinical effect.We're looking at a number of other things, such as gene activation and different omics.
Ritu Baral
Senior Biotech Analyst, TD Cowen
I see.What's the first biomarker that might move?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
It's a good question, actually.
Ritu Baral
Senior Biotech Analyst, TD Cowen
If it's not PDFF, right?I mean, PDFF might move in three days, right?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Probably PDFF would come really early.The others would be, if abnormal-.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
...ALT, AST.
Ritu Baral
Senior Biotech Analyst, TD Cowen
They might move already.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.If they are abnormal in the beginning, and GGT.
David Happel
President, CEO, and Director, Sagimet Biosciences
Lipids.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Lipids.That's a big-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Lipids.Yeah, they respond fast as well.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
I always think about the liver biomarkers.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah.Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
you're absolutely correct.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah.No, lipids will see something.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Plan, design, and timeline for the phase II factorial.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Sure.
Ritu Baral
Senior Biotech Analyst, TD Cowen
I assume it's a factorial.I don't think-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
All of those studies for combinations, they are.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We haven't disclosed the specific details, but, as you know, the regulations require testing against the individual components.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... as well as against placebo.There are probably going to be 2 different arms, with the combination, and, whatever we come out of it in the end goes wise, and, the combination to move forward into a phase III
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... is not gonna be weight dependent.It's not gonna be weight based.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
That's going to be a one.
Ritu Baral
Senior Biotech Analyst, TD Cowen
That would also fall outside of IP.
David Happel
President, CEO, and Director, Sagimet Biosciences
Correct.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
It does.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Competitor IP.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.Got it.That was one of my questions about how you're approaching dose selection.As you think about dose selection, how much could this trial inform your ability to potentially slot in one of the new resmetiroms into this combination, into the next study?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
It will inform everything we need to know-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... to move into, phase III.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
All I'm saying is, of course, dependent upon discussions-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Sure
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... with
Ritu Baral
Senior Biotech Analyst, TD Cowen
With the regulators.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
FDA-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Of course.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
...EMA, and the likes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
The final PK, PD.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
yes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
This study will define, what we're going to...
Ritu Baral
Senior Biotech Analyst, TD Cowen
The proprietary combination.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yep.
Ritu Baral
Senior Biotech Analyst, TD Cowen
The pr-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
For the phase III.
Ritu Baral
Senior Biotech Analyst, TD Cowen
The phase III
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Mm-hmm
Ritu Baral
Senior Biotech Analyst, TD Cowen
proprietary combination-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Correct
Ritu Baral
Senior Biotech Analyst, TD Cowen
... in F4.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The, remember the phase III proprietary formulation will be a single fixed dose.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Tablet.It'll be just one tablet, not two.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
One tablet at a time.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Co-formulated.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Once daily.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah, once daily.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Okay.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Weight-independent.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Right.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Alternate resmetirom.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Uh-huh.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Correct.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Polymorph.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Correct.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.What safety data do you need to generate and when for, either in phase II?Do you need to generate any new safety data with the new polymorph?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
as part of the phase II trial.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Before the phase II?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
No.Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yep.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
It's part of the phase II.
Ritu Baral
Senior Biotech Analyst, TD Cowen
As part of the phase II, what will you need to generate before phase III?I remember distinctly in the first couple generations of MASH drug development, you know, you had the original version of Terns going after combination.You had Intercept pursuing potential combinations very early stage.You know, the feedback there was combination development for chronic disease is more complicated than you would think or two.That comes back to me when I ask the safety.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
I think the issue with Intercept was it was an FXR that had fatalities in PBC patients with cirrhosis.That is probably where the complication is.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
In our case, a THR-β, it's very well characterized.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
denifanstat is very well characterized.I don't anticipate surprises.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
clinical trials are clinical trials.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
I don't anticipate any issues.Like any monotherapy development, the expectation will be to move from there to phase III dependent upon the conversations.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
with the regulators.
Ritu Baral
Senior Biotech Analyst, TD Cowen
There isn't an expectation for some sort of new preclinical talks that might be necessary.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
...for chronic-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We don't anticipate.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
again, any drug study is a study.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Right.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We don't anticipate any issues given, again, the fact that both molecules.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... independently are very, very well tolerated, and they are compatible with each other.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
I don't expect any issues there.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What's gating to phase II start?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
What's gating?
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yep.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We're gonna have an FDA meeting the first half of this year.That is the defining step.It's agreement with the regulators.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Have you submitted like the briefing book and everything for-?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We haven't gone into that level.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... of, detail publicly.
Ritu Baral
Senior Biotech Analyst, TD Cowen
That is essentially the next, the next and only regulatory interaction, of course?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
The with FDA, that is the next one.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
For MASH.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
For MASH, yes.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
You should expect it in the next couple of months.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
After this factorial, do you need to do a phase IIb confirmatory?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
This is the phase II.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
This is it.
Ritu Baral
Senior Biotech Analyst, TD Cowen
like this is.Again.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We don't expect anything else.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... to go into phase III.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Any additional?
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
You don't need a confirmatory.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
No.
Ritu Baral
Senior Biotech Analyst, TD Cowen
You're gonna do phase III.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
From this to phase III.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
You will have your dose.Okay.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.Those are my MASH questions.Now we're ready to move on to acne.Let's talk about that.We haven't spent that much time talking about it.What differentiates FAS inhibitors, either deni or 3567, in terms of safety and efficacy in moderate to severe acne compared to current standard of care?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
First off, acne talk.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Just taking a step back, in the U.S., there's about 50 million Americans that have acne.About 20% of them have moderate to severe. 10 million Americans have moderate to severe acne. 50% currently seeking...In terms of 5 million moderate to severe patient therapy.Why that is the standard of care that you're asking about is largely governed by a mix of generic and branded generic topical and oral products.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... that have been reformulated over the last 40 years.
Ritu Baral
Senior Biotech Analyst, TD Cowen
The retinoids, right?Like-
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The retinoids.
Ritu Baral
Senior Biotech Analyst, TD Cowen
A-
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Side colon antibiotics.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Products are occasionally-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Those are the three mechanisms.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
More or less.Then on the side, and you have isotretinoin.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Tretinoin kind of, option is that it's the gold standard, very good efficacy, the challenges with the safety.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Within that severe acne patient, there's a lot of room for improved and enhancements in the safety also.Antibiotics have challenges with GI effects, with sensitization, and also the people for resistance.
Ritu Baral
Senior Biotech Analyst, TD Cowen
It's mostly doxycycline, right?Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Doxy, Mino, and there's been a recent product, Sarecycline, that's been approved...
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... that again, improves that.It doesn't kinda make that next step.It's not an innovative mechanism.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Oral first real improvement in acne in over 40 years.How works is that if it's the genesis, which is the thing drive or the mechanism drive C is the oil food that the bacteria eat on.You know, benefit here is that we're a mono of action that I know we've already demonstrated with our partners' data.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... that the product is efficacious in moderate to severe and is a very well-rated safety.
Ritu Baral
Senior Biotech Analyst, TD Cowen
... status and expected timing from your phase I, II, V, VI, VII study.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The study kicked off in June, of last year.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We're expecting the readout sometime this year in preparation for us to start our phase II program.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... by the end of this year.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What's gonna be included with the data release?These are healthy volunteers.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
For the phase I program?
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The phase I, it'll have your standard SAD, MAD cohorts.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The unique thing here is that patients with moderate specific-.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Right.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Um, and-
Ritu Baral
Senior Biotech Analyst, TD Cowen
In a MAD cohort.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
In a MAD cohort.I think what's really interesting there is that we'll be able to look.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
and how we impact that, and also the makeup of sebum in that...
Ritu Baral
Senior Biotech Analyst, TD Cowen
What are you for in the makeup?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The makeup. acne patients have a completely different mech- of their sebum.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
If we can try and regulate that a little bit.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... it'll give us a very good insight.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Like the different types of fatty acid chains that are-.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Exactly, yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
... that make it up.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Specific Sapienic acid.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
You have a direct on that.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yep.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
our phase I programs in ecology-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... metabolic patients-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
we saw that impact.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We're hoping to see that again.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Sapienic acid, does it make the sebum, like, more fluid, or does it make it less digestible to bacteria?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It's just one of the components of sebum.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
One of the main components of the sebum.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What I'm wondering is, Does the main impact come from reduction of production, like reduced production, or is it, differential makeup of the sebum, which we were just talking about?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
You know.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Both?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We actually don't know.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
not us.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
...Sagimet, as us, as in the royal we in dermatology.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We know that there's a difference.We don't know why the increased level of Sapienic acid of sebum.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yep
Rob D'Urso
SVP of New Products, Sagimet Biosciences
in acne patients has a direct, it.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Benefit
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Is it better for?
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... the P. acnes to eat?We just don't know yet.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It hasn't been understood.
Ritu Baral
Senior Biotech Analyst, TD Cowen
It tends to reflect positively on the clinical endpoints of acne.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Exactly.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay, that's what you're going for.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
I think you mean decrease.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Do you mean decrease or increase?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah, we wanna
Ritu Baral
Senior Biotech Analyst, TD Cowen
You wanna reduce the Sapienic acid.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Reduce, yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The raw percentage.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.In 28 days, do you, can you have an impact on, like, lesion count in those 20-something patients?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
This is a safety study.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... where we wanna find the therapeutic doses that we're gonna take into a phase II.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
efficacy study.We will look at some before and after pictures and some lesion counts.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We're not expecting any statistical significance or any efficacy markers.We're really using this acne cohort as better understanding of the mechanism or better impact, and we'll look to see if we can see some lesion reduction.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It would be a nice to have.It's not a need to have.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah, if I may add.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
It's an opportunistic, cohort.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Most people with acne are entirely healthy.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Teenagers actually.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... mostly, isn't it?Since they are healthy, they fit a phase I healthy volunteer trial.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We discussed internally and was the why not?
Ritu Baral
Senior Biotech Analyst, TD Cowen
These aren't, like, technically pediatric patients, right?They're 16.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
They're not.No
Ritu Baral
Senior Biotech Analyst, TD Cowen
... like 16, but they're of sort of
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Oh yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.You mentioned the phase II trial will be longer.What is the sort of design of that?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Uh, so-
Ritu Baral
Senior Biotech Analyst, TD Cowen
... and endpoints?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
If you look at our partner's.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
phase II program in China, it'll mirror roughly the same size.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yep.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Four arms.Twelve-week study, moderate severe acne patients, very, very much aligned.The nice thing about acne in the U.S. is it's a very clear development pathway, and the clinical studies are well established.Acne programs have not really evolved over the last 12, 15 years.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We have a very clear pathway that way.
Ritu Baral
Senior Biotech Analyst, TD Cowen
When do you expect this trial to start? you know, from enrollment time to proof of concept data, what's the rough timeframe?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yep.The expectation is that we'll start the study this year, because it's 12-week and it's, you know.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... they enroll relatively quickly.We'll expect to have top line data sometime the second half of next year.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What were the key learnings from your Asian partners' clinical development that you now take into which you have taken into the phase I, but will likely take into the phase II for?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah, so-.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
I think we're in a really unique position.Our partner has completed successfully a phase II dose ranging-.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... where they studied 25, 50, 75 milligrams in a 12-week moderate severe acne study.They successfully completed a phase III study as well with moderate
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
In with 50 milligrams.I think what we learned from that is that, first off, the design, right, the actual clinical design, and also the mechanism proved out clinical practice.
Ritu Baral
Senior Biotech Analyst, TD Cowen
In the trial.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Trial.
Ritu Baral
Senior Biotech Analyst, TD Cowen
In their phase III study, yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
The mechanism is gender driven.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Those clinical data points are very relevant U.S. population.
Ritu Baral
Senior Biotech Analyst, TD Cowen
There's no hypothesis for any potential genetic component of the population to translate into efficacy-
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Exactly
Ritu Baral
Senior Biotech Analyst, TD Cowen
against acne.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah.There's no genetic differences, and we see that translating into clinical practice as well.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Acne is treated similarly around the entire world.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
As long as the same product.Everybody treats sebum, wants to reduce P. acnes, and everybody wants to get skin turn normalized.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Is quantity, like, bacterial load on the skin a relevant endpoint for the development path?Like, can you swab and see, like, colonies or something like that?Or...
Rob D'Urso
SVP of New Products, Sagimet Biosciences
We have an in on the sebum, the sebum food.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
There are other products that are available.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... benzoyl peroxide.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
That directly target the bacteria.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
I think that endpoint might be more relevant.
Ritu Baral
Senior Biotech Analyst, TD Cowen
It's not on target for you guys.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
someone like that.Yeah.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It's a step down.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... our mechanism.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
I think for us, measuring the quantity and makeup of the sebum is a more relevant-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Is more direct.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
yeah, biomarker versus the bacterial load.
David Happel
President, CEO, and Director, Sagimet Biosciences
We're clearly reducing the amount.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
David Happel
President, CEO, and Director, Sagimet Biosciences
... of sebum.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Just downstream.
David Happel
President, CEO, and Director, Sagimet Biosciences
... that the bacteria
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah
David Happel
President, CEO, and Director, Sagimet Biosciences
... an opportunity to eat and then-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Right
David Happel
President, CEO, and Director, Sagimet Biosciences
... translate into inflammation.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Right.
David Happel
President, CEO, and Director, Sagimet Biosciences
It is sort of the first step in terms of reducing acne overall.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah, the important thing, of course, it's an efficacy trial.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
We're gonna be looking really at the face and upper trunk.Do they look cleaner?
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
The ultra simplifying.
Ritu Baral
Senior Biotech Analyst, TD Cowen
phase III or the phase III final endpoint, the registrational endpoint will be lesion count, correct?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Yeah.It'll be.In acne, we use IGA.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It's a zero-four scale of acne severity.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It kind of gives a general scoring of the acne.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Investigator read.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Investigator global assessment.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
There's total lesions, inflammatory lesions, and non-inflammatory lesions.The primary endpoint.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What's a non-
Rob D'Urso
SVP of New Products, Sagimet Biosciences
...IGA reduction.
Ritu Baral
Senior Biotech Analyst, TD Cowen
What's a non-inflammatory lesion?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It's a more mild lesion.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
In layman's term, mild lesion, non-inflammatory, as they progress, they become inflammatory.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Inflammatory, okay.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Then they become cystic.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Okay.Got it.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
It's kind of a spectrum of lesions.The primary endpoint will be IGA reduction.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... going to 0 to 1-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... which is clear or almost clear, and the patients have to have a minimum of a two-point improvement.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Got it.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Our patients will start with a score of 4 or 3, and they'll have to get to 0 or 1 as a primary endpoint.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Is there any requirement for movement on a PRO, a patient-reported outcome for this?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
Not as a primary endpoint.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
A lot of dermatology companies have moved to patient outcomes.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
In phase IV programs or secondary endpoints.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Rob D'Urso
SVP of New Products, Sagimet Biosciences
In their phase IIIs.It's not a goal.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Is that more relevant from, like, a commercial standpoint?
Rob D'Urso
SVP of New Products, Sagimet Biosciences
I think.
Ritu Baral
Senior Biotech Analyst, TD Cowen
To promote
Rob D'Urso
SVP of New Products, Sagimet Biosciences
the IGA score is still the most relevant.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
You know, I think what we find with dermatologists is once you get a product approved in a disease state, they use that art versus science-
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yes
Rob D'Urso
SVP of New Products, Sagimet Biosciences
... argument very much, and they mix and match and use, you know, co-therapies a lot.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
Rob D'Urso
SVP of New Products, Sagimet Biosciences
As long as the product gets to market and they have a clear understanding of how it... what its role in the treatment approach is, and in this case, it's a very clear role.This is the only product that's oral that'll be reducing sebum and giving them a novel mechanism of action.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Yeah.Ritu, just to complement what Rob said, of course, PROs are very important nowadays, from an agency perspective.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah.That's what I was asking.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... across
Ritu Baral
Senior Biotech Analyst, TD Cowen
They all-
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Exactly.
Ritu Baral
Senior Biotech Analyst, TD Cowen
They all seem to want a PRO.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
Across the spectrum of diseases, any clinical development, not the primary endpoint, but nevertheless, will be collected.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... because the agency most likely, although we have not had discussions to that point.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... most likely they will ask for that.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Will want something.
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
You have well-established tools.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
Eduardo Martins
Chief Medical Officer, Sagimet Biosciences
... questionnaires and validated questionnaires.
Ritu Baral
Senior Biotech Analyst, TD Cowen
As we look at the balance sheet, Well, first of all, when are you guys estimating, your Asian partner to have approval, and what sort of cash flows could that result as part of the deal?
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah.I think once the NMPA accepted the.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
which is really their signal.There is no PDUFA.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Oh.
David Happel
President, CEO, and Director, Sagimet Biosciences
that really.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Right
David Happel
President, CEO, and Director, Sagimet Biosciences
... signals their PDUFA.It's about a 10-16 month window.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... to approval from that point.They had their NDA accepted in December of last year.I believe Ascletis would suggest that they're looking for an approval sometime late this year.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
... is the goal.Sometime late this year, early next year.Yes, that does trigger milestones for us.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
David Happel
President, CEO, and Director, Sagimet Biosciences
Upwards of $122 million.Most of those milestones, that cash is related to commercial performance.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm.
David Happel
President, CEO, and Director, Sagimet Biosciences
There's a royalty of upper single digits to mid-teens.
Ritu Baral
Senior Biotech Analyst, TD Cowen
How would you anticipate the resulting cash flow to
David Happel
President, CEO, and Director, Sagimet Biosciences
Ascletis?
Ritu Baral
Senior Biotech Analyst, TD Cowen
Commercial
David Happel
President, CEO, and Director, Sagimet Biosciences
Well, initially there's.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Yeah
David Happel
President, CEO, and Director, Sagimet Biosciences
... milestone upon approval, then it's really based on commercial thresholds you see pretty typically in the industry.The timing of those will be dependent upon the timing of them reaching the specific revenue thresholds.
Ritu Baral
Senior Biotech Analyst, TD Cowen
A final strategy question.Just how are you prioritizing internal resources and management focus between MASH and the acne-.
David Happel
President, CEO, and Director, Sagimet Biosciences
Yeah
Ritu Baral
Senior Biotech Analyst, TD Cowen
... portfolio?
David Happel
President, CEO, and Director, Sagimet Biosciences
It's a great dilemma to have, right?A molecule and a mechanism that works equally well in the liver and the skin, and it's really important for us to carry both of these programs forward.We have the cash to do so at the moment.We reported out from the end of Q3, $125 million.That's about two years of runway, and that would allow us to complete the phase II acne proof of concept with the next-gen molecule.With MASH, we can get through, practically through enrollment, if not all the way through enrollment for the phase II MASH.You know, we have to figure out how to solve for the remaining.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Mm-hmm
David Happel
President, CEO, and Director, Sagimet Biosciences
financial needs, financing needs, but both programs certainly merit continued development.
Ritu Baral
Senior Biotech Analyst, TD Cowen
Great.With that, we are out of time.Thank you.Thank you, gentlemen-
