The Piper Sandler 35th Annual Healthcare Conference
Nov 29, 2023
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Good morning, everyone.Thank you for joining our second day of our Piper Sandler Healthcare Conference.Very excited to be hosting the team from Edgewise Therapeutics here with us this morning.We have 25 minutes and quite a bit to cover.I would like this fireside chat to really be focused on one of your assets that you're developing in HCM.I think a lot of our clients know we follow the HCM space really closely, and I would love to just dig deep onto the program.
Kevin Koch
President and CEO, Edgewise Therapeutics
Sure.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
First, and then get into the pipeline later.
Kevin Koch
President and CEO, Edgewise Therapeutics
Sure.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Team, I think the first place to start for individuals who are new to Edgewise is maybe talk about your lead asset, 7500, that you're developing for HCM.What is the mechanism, or what is the mechanistic advantage for the treatment of HCM?
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah, great.So we, we're a muscle platform company, so all of our targets are novel targets, targeting muscle.We developed this particular asset, actually, as a counter screen for our skeletal muscle program, and we had a choice.We could create a best-in-class, myosin modulator for cardiovascular treatment.But we also, out of this high-throughput screen, identified a novel mechanism that initially we looked at data, and there was a greater therapeutic index-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
-relative to the CMIs.And so we continued to follow up on that particular mechanism, and we're really pleased to see that, this molecule is not a myosin inhibitor, but does regulate the ability, of the sarcomere, to contract-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in a way that has a much wider range of relationship between the concentration of the drug and the change in ejection fraction.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We knew this very, very early, even one of our first studies with our first-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
in vivo molecule.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Could you help put into context, like, I think a lot of investors know how the myosin inhibitors work.Obviously, we have a first generation that's approved, a second generation, mavacamten, that's currently in Phase III.So how does the mechanism differ in the myosin inhibition, and what is the advantage by targeting this, the sarcomere?
Kevin Koch
President and CEO, Edgewise Therapeutics
So you can think about the physics and the physiology of the sarcomere complex.So the cardiac myosin inhibitors interact directly with the ATPase.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Think of them as a kind of an on/off switch.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
You're either binding or you're not binding.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We bind in an alternative space in the sarcomere-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... which is distal from the ATPase.So what we're doing is changing the rate-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in which the contraction occurs-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and in which, if you think about it physically, it's the crawling event-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... the arm and crawling along the actin filament.We change the rate in which that occurs-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... both on the contraction side-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and the diastolic side-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and the relaxation side.So in both cases, we have a slower contraction-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... which increases the range of the relationship-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... between concentration and ejection fraction-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and we speed the relaxation-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... so the head coming off of the actin filament-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... which leads to greater levels of relaxation.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
That's a very unique mechanism.We can see this in the echo studies-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... both in normal, preclinical species-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and also in the disease models.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Given this differentiation, could you maybe then kind of tell us how does that change the product profile, right?So with this mechanism, what do you hope to show different than the myosin inhibitors that are approved in the development?
Kevin Koch
President and CEO, Edgewise Therapeutics
So what we've shown so far is...And of course, you know that there's the REMS and the black box-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... with the cardiac myosin inhibitors because of the narrow therapeutic index-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and the requirement to titrate to get to exactly the right exposure-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... for each individual.So what we've shown is that we have a much wider range.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Therapeutic index is wider, which would ultimately lead to our ability to have a fixed dose-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... which is a typical dosing strategy for any patient, perhaps based on weight-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... but without a titration.And it would provide a much broader safety window and would, then, the physicians would be much more-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... inclined to provide that drug-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... given the efficacy all being the same.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Now, the other thing that's exciting about this particular asset is that we designed it to have a shorter half-life-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... than the CMI.So our half-life is projected to be one-two days-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm
Kevin Koch
President and CEO, Edgewise Therapeutics
... instead of seven or eight days for aficamten-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... and up to 15 days for mavacamten.So although one would think, "Eh, it's not that big of a deal-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... with a smaller half-life," realistically, for the vast majority of physicians, being able to remove a drug-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... is really a competitive advantage-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... because you don't have to follow them for 6 or 7 or 8 days.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Now, a day later, anything that happens-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... can be resolved.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
I think that's an underappreciated competitive advantage-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... for our drug, and we'll be able to demonstrate that-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... in the clinic, shortly, I hope.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
No, that's very helpful.Could you maybe talk about the type of preclinical data that you have already generated and whether in these preclinical models you randomized an inhibitor as a comparator?And then if you could maybe allude to, like, what did you show, right?So as, and as a comparison, because I think a lot of investors, you know, know the clinical data and so kind of put it into perspective for the patient.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.So preclinically...And this is-- it's great that we have two of the key in vivo pharmacologists-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... from MyoKardia.So the person that ran the cat model-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
of obstructive HCM and the person that ran the non-obstructive-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
-pig model, of nonobstructive HCM, they ran mavacamten-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
through those models.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yep.
Kevin Koch
President and CEO, Edgewise Therapeutics
And they also have run our molecule-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
7500 through those same models.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
What we showed in the obstructive cat model was that we could have a decrease-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
in gradient in that obstructive cat model
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
-of 61%-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Wow!
Kevin Koch
President and CEO, Edgewise Therapeutics
with only a 2% change in ejection fraction
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm.
Kevin Koch
President and CEO, Edgewise Therapeutics
after oral dosing.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Which I think was really compelling to us-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm.
Kevin Koch
President and CEO, Edgewise Therapeutics
about the differentiation
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
of what you would see with mavacamten, and you would have a fairly-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm.
Kevin Koch
President and CEO, Edgewise Therapeutics
-dramatic change-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
in ejection fraction in that cat model.In the pig model, what we saw was in a nonobstructive HCM, what you see is thickening of the wall.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
You see a contracted volume of the-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... left ventricle, and you see an enlarged atria.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
What we're able to do, which is quite exciting, is decrease the thickening-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... of the wall, enhance the volume-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... of the left ventricle, and decrease the volume of the atria.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
So in that case, we did that all without decreasing the ejection fraction.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Now, a molecule was not mava itself-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
-it was a related molecule, and this is data that's published in a poster-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
in a presentation.Although they do see some effects on-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
-diastolic function, they don't report the ejection fraction.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
What is clear is that they can't get the diastolic effect they want-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... to see and the relaxation-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... effect you want to see without seeing this concomitant-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... change in ejection fraction.So I think again, it points to our therapeutic index-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... on both aspects of-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... of contraction and relaxation is greater than the cardiac myosin inhibitors, and that's what's unique about this mechanism.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah, that's, that's very helpful.Is there, as you guys have been able to overlay the mechanism, clients understand that there's the obstructive population and there's the non-obstructive population.Given this product profile and its unique mechanism, is there, is the likelihood to work more in non-obstructive versus obstructive, or do you expect that it could work equally well, both in both populations?How do you think about that?
Kevin Koch
President and CEO, Edgewise Therapeutics
I think it would work equally well in both populations, and what the true deficit is in non-obstructive-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
...HCM, is this relaxation?
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... so the stiff ventricle.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
I think being able to relax the ventricle to allow for-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... greater filling is something that's unique in our molecule-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... that you cannot achieve with the CMIs.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
I think we, from what we've shown pre-clinically, we should have the same or better effects-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in obstructive HCM.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
So I think it actually really fits within both-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... mechanisms.I think, you know, where probably the greatest differentiation would be in non-obstructive.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
But I feel in the obstructive space, it would be very exciting as well.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Great.Could you maybe for investors who are new, maybe remind them, when was the IND filed and when was the IND cleared, and we'll go through the design of the phase I study.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... but maybe just from a-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Um, perspective.
Kevin Koch
President and CEO, Edgewise Therapeutics
We filed the IND in the summer.We started dosing patients in September.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
These are not... normal, healthy volunteers.So one thing, we have reported the dosing schedule.So it goes from 5-15-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... to 30, 5 to 15, to 45-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... to 100-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... 200, 300.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Wow!
Kevin Koch
President and CEO, Edgewise Therapeutics
Just looking at that data itself-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... we have a broad-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... therapeutic window.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
That's the first set of studies that we're doing.That will be completed sometime this quarter.We'll initiate multiple ascending dose cohorts in normal, healthy volunteers, in the beginning of the first quarter.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We have a number of different cohorts which will be going all up.Depending on the half-life-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... we'll calculate the amount of accumulation you'll see.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We also have a set of patients who are elderly, normal, healthy volunteers with a depressed E prime.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
So they have a decrease in diastolic function.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
So we can enhance the window-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in which we can measure the diastolic effect in that-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... particular population, of normals-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... so to speak.And then, we have already written the protocol for the p hase I- B.So the way phase I- B is, we think of it in this way.We wanted to demonstrate as early as we can, a differential from the cardiac myosin inhibitors.So what they have shown is with a single dose-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... a deep decrease in gradient in an-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... obstructive HCM patient-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... but with a additional decrease-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... of over 20%-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in the ejection fraction.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We believe, as we saw in the cat model-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... that we can decrease the gradient in those obstructive HCM patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... with a single dose-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... of 60% or more without a change or minor changes in ejection fraction.And that will lead us to try to understand that, yes, this molecule-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... could be used in a fixed dose regimen.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Okay?The second part of that phase I-B study will be 28 days of dosing.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in both obstructive HCM patients-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and non-obstructive HCM patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
So there we'll see the accumulative effect-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... of the mechanism-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... in the patients.We have 28 days of dosing for the toxicology coverage.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We were so bullish on the mechanism that we decided to go to chronic tox test.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... testing immediately.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
Sometime by the end of next year-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... we'll be able to dose patients indefinitely-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Kevin Koch
President and CEO, Edgewise Therapeutics
... which will accelerate our phase II and our phase III
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Wow
Kevin Koch
President and CEO, Edgewise Therapeutics
... for both different indications.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
No, that's, that's fantastic.Let's maybe kind of like understand each segment of the design.The first segment is going to be a healthy volunteer study, right?Dose ranging, a SAD, and then a MAD.So as you guys are thinking about, could you maybe remind us, like, what is the size of the cohorts in the SAD and in the MAD?And will you share the SAD and MAD data combined and then go into the data release onto the one, one-
Kevin Koch
President and CEO, Edgewise Therapeutics
I think the goal is, we don't know where we can see this diastolic-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
relaxation effect.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
We have seen it with a single dose.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
It's a higher probability in normal healthy volunteers with multiple dosing-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... at steady state.But I think optimally, you would look at the package.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
I think the SAD and the MAD will define the safety.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
The HCM studies will define-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... the therapeutic window and the competitive advantage.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
So providing that entire package-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
...I think is more exciting.It's probably gonna be complete by the third quarter.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
So I think that's a good time to put out the entire package-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... and show distinct, clear differentiation and the potential of the mechanism.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.I don't recall going back, and I should have.I should know this, but is there any PD marker that you could track in these healthy volunteers that one could compare to the myosin inhibitors, you know, between-- Just to kind of reemphasize the therapeutic window?
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.In the—I think in the nonobstructive HCM, you can look at, certainly look at troponin, the BNP.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
You know, if you look at the timing-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... well, from the prior studies, those molecules with the long half-life and the titration-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
...they, to get the steady state-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and maximal efficacy, they have to go six weeks or so, so-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... to get there.For us, with a shorter half-life-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... we get the steady state earlier and maximal pharmacology earlier.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
I think you might be able to see-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... a biomarker response-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... in the nonobstructive relatively early-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... within three or four weeks.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.That data is coming in the third quarter?
Kevin Koch
President and CEO, Edgewise Therapeutics
Third.Third, probably the 28th day would be-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
What is the size of the total-
Kevin Koch
President and CEO, Edgewise Therapeutics
The fourth quarter.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
The total size of both the SAD and the MAD combined, do you recall?
Kevin Koch
President and CEO, Edgewise Therapeutics
Well, they're usually, and this is typical for these SAD, MADs, so they're six treated and two
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
-placebo.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah, for every cohort.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Got it.
Kevin Koch
President and CEO, Edgewise Therapeutics
It'll be quite a few patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Good.And then once that data is shared, then it will lead into the dose selection going into the 1B.Could you talk about this?The 1B is gonna be focused on the nonobstructive population first?
Kevin Koch
President and CEO, Edgewise Therapeutics
No, the obstructive patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Sorry, obstructive.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Obstructive population first.The obstructive population, what's the size of the cohort?How, how much will you try to match this cohort to maybe some of the phase II studies that we've seen with the myosin inhibitors?
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Because I think the natural thing that investors would wanna do is compare your results-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
-to the other products that are ahead.So are you guys contemplating to matching them more similarly so that-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
-comparing the?
Kevin Koch
President and CEO, Edgewise Therapeutics
That was actually really the goal of this study.We have what we call the n=9.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Which is 9 obstructive patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
three different dose levels.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
Right?So, our dose selection would be driven by our results from the SAD.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
So we have a concentration range based on the preclinical models.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... that we're looking at, and so we'll pick probably the mid dose of that-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Kevin Koch
President and CEO, Edgewise Therapeutics
... efficacious range-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Kevin Koch
President and CEO, Edgewise Therapeutics
... from the preclinical models, and look back at the SAD-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Kevin Koch
President and CEO, Edgewise Therapeutics
... and say, "Is that an effective dose?
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
We'd probably start there-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... and would go up or down-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Kevin Koch
President and CEO, Edgewise Therapeutics
... based on the results we see.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Got it.
Kevin Koch
President and CEO, Edgewise Therapeutics
Then that initial 28-day data for the non-obstructive and the obstructive would be thought really from the single dose result.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Got it.
Kevin Koch
President and CEO, Edgewise Therapeutics
also the safety from the MAD.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
In terms of baseline matching, it will be very much an inclusion/exclusion criteria, similar to what we've-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... seen with the myosin inhibitor class.
Kevin Koch
President and CEO, Edgewise Therapeutics
Right.Right, exactly.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah, and they, we'll try to match to the extent we can.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay, good.And then the data would...Basically, they would be nine patients per dose cohort, right?
Kevin Koch
President and CEO, Edgewise Therapeutics
3 patients per dose cohort.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Oh, three patients per dose cohort.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
Open, essentially open label, no placebo.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay, got it.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
That data, when do you anticipate being able to share those results?
Kevin Koch
President and CEO, Edgewise Therapeutics
The end of the third quarter, you know.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
Sometime in the third quarter, I think.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay, so that will also-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... come around the same time.
Kevin Koch
President and CEO, Edgewise Therapeutics
That protocol, that protocol is written and also already through the IRBs.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay, great.So that could also.So it would be a nice package between the SAD and the MAD and the-
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... first-
Kevin Koch
President and CEO, Edgewise Therapeutics
Right, and then the 28-day data in obstructive and non-obstructive-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... will come later.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Probably roughly the first quarter of 2025.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay, that's very helpful to actually talk about that.And it's also good that your talk package is already ongoing, so by the time 1Q comes, you actually can transition very easily.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... into a phase II study that would warrant.
Kevin Koch
President and CEO, Edgewise Therapeutics
Right.So I mean, the plan was to have continuous-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... dosing of the patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Then we can make a cut of the data-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... along the way-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... and see the benefit.And because you're largely measuring biomarkers-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
... and echo parameters.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
...I mean, I think the placebo-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Placebos aren't as-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... important in that particular-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Right
Kevin Koch
President and CEO, Edgewise Therapeutics
... study design.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
but of course, in the phase II
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... we would have a rigorous, placebo-controlled phase II.Probably very classical-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... with, three doses-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yep
Kevin Koch
President and CEO, Edgewise Therapeutics
... and a placebo group.So we would not necessarily-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
... have to titrate.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.No, that's, that's, that's gonna be really important.Do you think the one question that will come up is like, you know, I think placebo in these studies has been very minimal, even though it's an open label.I think investors are gonna get familiar, comfortable with that.Maybe just do you think the three-patient dose cohort is going to give them sufficient information?Like, what was the rationale and why not, and why not upsize it a little bit higher?
Kevin Koch
President and CEO, Edgewise Therapeutics
Well, you know, the thing about a single dose, you're at the, you know, you have the variability of the-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
of the individual
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Right
Kevin Koch
President and CEO, Edgewise Therapeutics
exposure of
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
- any individual patient.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
Data at steady state-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
- is always preferable.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Kevin Koch
President and CEO, Edgewise Therapeutics
If you look at the timelines-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
you'd be pushing out that data quite a bit if you just-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
I think
Kevin Koch
President and CEO, Edgewise Therapeutics
wanted to go 14 days and longer.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
I...
Kevin Koch
President and CEO, Edgewise Therapeutics
So I think how we viewed it as there is clear evidence...
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
- that, with a single dose, you can see-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
a change in gradient and a deep change in ejection fraction.It's, it's a comparator-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
- to the CMIs.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
That's the earliest time you can get a comparison.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Kevin Koch
President and CEO, Edgewise Therapeutics
It's not ideal-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
Because you only have nine patients.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.Yeah.No, that's-
Kevin Koch
President and CEO, Edgewise Therapeutics
You know
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... that's helpful.And then, team, I guess, so one of the differentiation, which you made clear, is higher therapeutic window, no need for dose titration, no echoes associated, which we hear is significantly the hurdle for strong adoption both of these products and for this product in the market.The other question, that also we have heard from physician is the DDIs, right?So with mavacamten, there is a significant pharmacy protocol that's in place.Could you maybe talk about if you've done any DDI work and, and what you've seen?Because I think that's the other component on just opening the bottleneck.
Kevin Koch
President and CEO, Edgewise Therapeutics
Yeah.We've done DDI work.We do not have any DDIs.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Kevin Koch
President and CEO, Edgewise Therapeutics
We do not have any issues in that case.It's very clean molecule-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
from a P450 transporter-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
- other areas.
Maybe, Behrad, let me talk a little bit about the research we've done on uptake of the molecules and, you know, what are the limiting factors-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah
Kevin Koch
President and CEO, Edgewise Therapeutics
- for the current, the, for the-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Kevin Koch
President and CEO, Edgewise Therapeutics
Current market and where we think we have an opportunity?
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah, I think, you know, you've probably done-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
similar research, right?When you speak to physicians.Actually, if you look at script data-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
Plainly, right, you see that the majority of patients are on the 5 milligram.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
Then you've got people who are actually downtitrating-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- to 2.5, and 10 is starting to pick up, but still-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
The volume isn't there.The reason is I think physicians are concerned around the-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
EF drop, right?
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
You're seeing a very conservative use of-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- the current CMI that's on the market-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- because, you know, they're getting enough of a gradient relief-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- with the five milligram dose-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- but they're not willing to push-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
because, you know-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- the consequence is quite-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
quite problematic.And I think once you let people out-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
and you don't know if, like, someone gets COVID-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
or they go get Paxlovid-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
or they have a deep, they take
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- a PPI.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
All of a sudden, you've got-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
really high levels of drug circulating, and it becomes a problem.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
So, as Kevin mentioned, we don't have that issue.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
You know, when we speak to physicians around the profile that Kevin-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
described, there's a lot of enthusiasm
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- around what we're doing, even relative to-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
You know, both of the CMIs that are out there.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.No, that's, that's very helpful.Is obviously this is a very significant value-driving program for the company, and I'm sure, you know, through our coverage of the space, strategic interest remains very-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Mm-hmm
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
... high on this.So what is your views?At what junction would you be interested in wanting to partner this asset?
Behrad Derakhshan
CFO, Edgewise Therapeutics
Sure.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
How far along-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Do you want?And obviously, you know the capital allocations needed-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
as we can map out-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Mm-hmm
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
based on other-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Mm-hmm
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
- myosin inhibitors and their past studies.
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah.So the nice thing about the way we've kind of set up-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- the program.Obviously, as you mentioned when you started-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
We have two programs.We have the skeletal program.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- but we also have 7500 for HCM.But I think, you know, base, we have $29 million in cash.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
That'll get us through 2025, maybe even into the first quarter-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Behrad Derakhshan
CFO, Edgewise Therapeutics
- of 26.With that cash, we can get well into the Phase 2s
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
for obstructive and non-obstructive.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
The nice thing is we've got a really good catalyst calendar-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
from both programs
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
to help us finance to get to that.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
I think...Personally, I think that the company's view is we're going to push these as far as we can-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
to key value inflection points, right?
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
I think we've all worked at bigger companies.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
We know what the triggers are.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
So what people are gonna be interested in.I think that the hidden aspect about this molecule is the diastolic benefit-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- that this molecule has.So we've talked about obstructive, we've talked about non-obstructive, and then there's a broader category-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- of diseases of diastolic dysfunction.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
If you think about that, you start walking into the HFpEF space-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
right?And we've seen a lot of data coming from some of the GLP-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- where, you know, you're seeing
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
some improvement in patients who have heart failure with preserved ejection fraction.If this molecule-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
diastolic benefits plays out, that's an avenue.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
that we would like to kind of pursue with the molecule, because clearly that's, that's a big issue.And that's where we would think about, okay, is there a partner who-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- we could work with in order to-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
That could go broader.
Behrad Derakhshan
CFO, Edgewise Therapeutics
That could go broader, right?
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
Because you know these trials.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
They're big trials.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
They have pretty hard endpoints.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
I think, you know, if we have conviction, and we can convince a partner-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
to work with us, that'll be a good path.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Great.No, that's, that's very helpful.And team, I know I, I don't do this fireside justice because we only focus on 7500, but given that we have about a minute left, maybe just the last place is, what are the key catalysts for the muscular programs that are going to be reading out in 2024?Obviously, the HCM data set is going to be a very important data set for many clients who are following the space.
Behrad Derakhshan
CFO, Edgewise Therapeutics
Mm-hmm.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
We're very excited for that.But if you could,
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
- talk about-
Behrad Derakhshan
CFO, Edgewise Therapeutics
There's a-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
What else is happening?
Behrad Derakhshan
CFO, Edgewise Therapeutics
It's a really exciting year for us.We'll have Duchenne data in the first half.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
The first time we'll have Duchenne data.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
It will be controlled data. 6 patients treated, 3 patients placebo-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
... for three months in multiple dose cohorts, and we'll be looking at biomarker changes-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
statistically significant biomarker changes, and-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
We will be looking at functional benefit-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
functional benefit of the drug, and all those patients will go on to an open label.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Behrad Derakhshan
CFO, Edgewise Therapeutics
That's the first half of 2024.We'll also have the 24-month data in Becker patients-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
... open label-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay
Behrad Derakhshan
CFO, Edgewise Therapeutics
- which realistically, I think is exciting because you're seeing what should see a 2.5 point change.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Okay.
Behrad Derakhshan
CFO, Edgewise Therapeutics
The hope would be that we would continue to stabilize disease…
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- which would be really outstanding-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- for those Becker patients.Later on in the year, we'll have our first controlled patient study-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- in Becker.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
3:1 randomization, 40+ patients.That'll be at the end of the year, and that has the potential of providing us the ability to file for accelerated approval if we see changes in biomarkers.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
that are statistically significant.And I think if we're directional-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm
Behrad Derakhshan
CFO, Edgewise Therapeutics
- with the North Star -
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
I think we clearly could go to the agency and say, there are no treatments for Becker.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
We have Fast Track designation.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Mm-hmm.
Behrad Derakhshan
CFO, Edgewise Therapeutics
This is a high, unmet need population.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
We should.This drug should be approved for that population.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah, we're seeing a lot of flexibility from regulators in neuromuscular, right?
Behrad Derakhshan
CFO, Edgewise Therapeutics
Mm-hmm.Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
There's some good precedents out there-
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
with Reata, Amylyx
Behrad Derakhshan
CFO, Edgewise Therapeutics
Yeah.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah.
Behrad Derakhshan
CFO, Edgewise Therapeutics
So we feel pretty good that a totality of data-
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- will be supportive of
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yeah
Behrad Derakhshan
CFO, Edgewise Therapeutics
- of early approval.
Yasmeen Rahimi
Senior Biotech Analyst, Piper Sandler
Yep.
No, that's, that's fantastic.Well, team, thank you for a great discussion.We're very much looking forward to a very busy 2024-
