Protagonist Therapeutics, Inc. (PTGX) Earnings Call Transcript & Summary

Hi, everybody. Thank you so much for joining us today. My name is Chris Howerton. I'm part of the Jefferies Biotechnology Research Team, and thanks for joining our Virtual London Healthcare conference. So just super pleased to be hosting a fireside chat with the next company, Protagonist Therapeutics. And on behalf of the company is the CEO, Dr. Dinesh Patel. So Dinesh, thanks so much for joining us.

It's a real pleasure, Chris. It would have been much better if we were all in Europe, but these are challenging times. So this should do it for now.

That's right. We'll take a raincheck on the sushi dinner, I guess, some other time or the fish and chips, I guess, let's say. Yes.

Yes.

Okay. Great. So well, maybe I think there is certainly a lot of progress that you and your team have made over the year, and I -- certainly, on 300 and other programs, but maybe before we dig in, you wouldn't mind just giving us just, I don't know, a 30-second elevator pitch or something on the company on what is it that Protagonist Therapeutics is?

Yes. No. I mean these are very, very exciting times. It's a very impressive story about persistence and going for the long haul. We started in a very rudimental manner with our technology platform, created a differentiation and we are exclusively focused on peptides. So we are one of the top-tier companies that knows how to come up with oral peptides, discover peptides in a de novo fashion against any biological target of interest or hormone mimetic, you name it. And the proof is in the pudding. We have about half a dozen different clinical assets that are in different stages of clinical development. So it has been a long, but very exciting and enjoyable journey, and here we are.

Sorry, I just had -- all my kids are crazy in the background, so I was trying to mute myself. The -- but yes, and I think we've -- I've known you for quite a bit of the -- at least the recent journey over the last 4 or 5 years or so. And it's been -- I completely agree with your characterization. So the -- let's see, so for your, I guess, lead 3 programs, 300 and then the 2 peptides for IBD, maybe why don't we start with 300 and maybe your hepcidin program just more broadly. So for PTG-300, maybe we can start with ASH. So what we're kind of -- well, maybe before we even get there, what is PV? And what is kind of the indication that you're trying to solve with PTG-300, perhaps we could start there?

Yes. No. Definitely. So PTG-300, as you know, it's a mimetic of the natural hormone, hepcidin, whose job is to really worry about iron homeostasis in the body. The absorption, the distribution, the dispersion, elimination of iron from the body, right? So that then brings with it an inclination towards various blood disorders that could be fixed through a mimetic like 300, which has much superior drug-like properties, be it the physiochemical properties or the potency or whatever it may be, right? And at the end of the day, what we are finding is like in a disease like polycythemia vera, which is a disease of excessive red blood cell production, so commonly regarded as a thick blood disease. And as you can imagine, if you are producing too many red blood cells, then there is thrombotic risk, cardiovascular risk, things of that nature. And [ right there ], we are finding amazingly strong, consistent, clear effect of our drug in terms of keeping the hematocrit levels of these patients under 45%, which is the magical and the universal benchmark for polycythemia vera.

Got it. Okay. So essentially, polycythemia vera, or PV is, these patients make too much red blood cells and PTG-300, I guess, prevents that? Or it works through iron homeostasis, which has the knock-on effect for that kind of all the risk factors? Is that kind of the right way to think about it?

Yes. I mean, what our drug does, it really balances out the process of erythrocytosis, the production of red blood cells. And one of the key ingredients that one needs in the red blood cell synthesis is iron, right? So that is where the control of iron plays a -- basically a role. And by modulating or limiting the amount of iron that makes it to the bone marrow, you basically control the red blood cell synthesis.

Okay. Got it. So it's kind of the rate limiting step to make it, so that there is not the excess of red blood cells. Okay. Makes sense. All right. So then -- so where are you at in that program with respect to the clinical program?

Yes. So we are currently doing an open-label Phase II study in polycythemia vera. And this is where, in May, we shared the data of 7 patients. Now 7 is a small number, but the data was so outstanding. I mean, 6 -- all those compliant patients, 6 out of 6 were phlebotomy-free. So phlebotomy or bloodletting is one of the main approach for this disease. Unfortunately, what happens with phlebotomy patients is like when you remove blood, you are not only removing the red blood cells, you are also removing the iron and now creating iron deficiency. And so the [indiscernible] blood, it fluctuates, iron deficiency symptoms develop. And that is why it is not a very effective approach. With our drug, we were able to showcase almost 24/7 constant control of hematocrit and keeping all patients essentially phlebotomy-free. So that was the turning point. And now, we look forward to sharing our findings, our significant findings at the ASH conference that is coming up in a few weeks in early December. As you know, we have 5 presentations at ASH. One is an oral presentation, the main one that will talk about the effect on phlebotomy and hematocrit control. And then various other posters also, one talks about how we control the iron deficiency parameters. And so there is potential for reversal of iron deficiency in these patients. We also have our own analysis of the real-world patient data that shows like how the current treatment paradigm is not effective enough because what we are finding is hematocrit is in less than 30% patients. And what is also well-known is that if you don't control hematocrit, your thrombotic and cardiovascular risks are higher. So this data is very revealing and it, again, highlights the need for an agent like 300. And then, at last but not least, we are also going to talk about our some preclinical work with oral hepcidin in one of the posters.

Very cool. Okay. Yes. So there -- and so for the -- I mean for those that perhaps didn't listen to it live, I would encourage you to view the PTG-300, what do you call it, the KOL event or market opportunity event? It was basically -- you framed both the commercial side with the unmet need and kind of what the clinical program was. So it was a great event for the program. But anyway, for -- when was that, Dinesh? It was about a month or something like that?

Yes, it was in the month of September, on September 11. And you're so right in pointing it out because investors who come to us after having reviewed the PV market opportunity data that we have on our website, both as a webcast and as a slide deck, they are now very informed investors and it's a much more meaningful and informative dialogue with them.

Yes. Well, the -- I mean, the one thing that I would point out, and I don't know if it's different than the presentation that you're planning at ASH. But I thought the portion of the discussion where it was retrospective analysis of claims, the claims database, looking at what it is that these patients are actually receiving despite the fact that they're in the highest risk factors or whatever in really kind of demonstrated, at least to me that, wow, there's really not a whole lot available for these patients that they're willing to take or that physicians are willing to prescribe.

Yes. No, totally. I mean, the current treatment paradigm is pretty straightforward in a way. Early on, you are on phlebotomy. And as we mentioned before, over there, you do not control hematocrit properly. It's kind of, you exercise control in an erratic fashion, and then you make the patients iron deficient, right? So then they have the iron deficiency, anemia symptoms. And then you move up and you have the choice of a cytoreductive, pan cytoreductive agents like hydroxyurea, which formally is not approved for PV, but it's being used. And then finally, Jakafi, which is used in the much later stages of the disease, and it is approved for hydroxyurea resistant or intolerant patients. So as you can imagine, it itself is a very small segment of people. And then our real-world analysis data shows that in spite of all this, only less than 30% of the patients have their hematocrit control under 45%. In fact, about 50% of the patients have hematocrit [ about 50% ]. And the thrombotic risk is enormous, as you start getting negligent about this hematocrit. So in short, contrast to all that, what we are doing is like we are mimicking the natural iron homeostasis mechanism that is prevailing in our body through a natural hormone, hepcidin. And the data speaks for itself. The data so far is very consistent. We are essentially able to keep all these patients phlebotomy-free by controlling their hematocrit and keeping it below 45%. And then we don't have the extra baggage of the potential side effects associated with the typical cytoreductive agents.

Sure. Yes, totally. Okay. And so you have -- what we have so far -- sorry, for those out there, I am -- we just had a little baby. So my brain is a little fuzzy with sleep deprivation here. But for the data that you displayed in May and then we just recently got the abstracts for ASH, and then we're going to have the full oral presentation for ASH. So I guess, at that final oral presentation, how many patients will we have at that point?

Yes. No, clearly, I mean, as you can see, in May, we had data on 7 patients in the abstracts, where the cutoff was early August, we have data in 13 patients. So that is a -- the study is progressing well. We are enrolling patients. So you can certainly expect data on more than 13 patients. And the beauty also is that -- as you have gathered from the abstract, there are a couple of things that are very noteworthy. And in addition to what we might have showcased in the month of May, right? So one is, now we have almost doubled the number of patients. As you see in the August abstract, we have 13 patients now instead of 7. And what you observe from the abstract is that behave -- the trend, the strong trend of hematocrit control and keeping patients phlebotomy-free, we are continuing with that trend. The other thing that is obvious, but worth pointing out is like in May, we presented the data as it was available in the month of May. In the abstract, you see the data that is as of the month of August. And now during ASH, the cutoff is mid-November. It is this way. So you will see more updated data. And so now these patients are treated over longer periods of time, right? So the durability component becomes more visible. It's like, okay, the drug worked in a few patients for a few weeks. How does it behave in more patients and over a longer period of time? So the durability part is there. The other thing you will glean from the abstract is the diversity of patients, and we just don't mean like the gender or age diversity, but it is also like there is almost a good balance of low-risk versus high-risk PV patients in the abstract. And then even in terms of the treatment regimen they have, so we have like -- of course, all patients are on phlebotomy. 6 out of the 13 also are treated with hydroxyurea. And we also have one patient with -- that is on interferon. So the whole idea is to really understand the breadth and scope of PTG-300 for PV patients. And then finally, a whole separate poster on iron deficiency reversal potential, right? We are showing improvements in very important iron biomarker parameters such as ferritin levels and then the MCH, the mean corpuscular hemoglobin and MCV, mean corpuscular volume, all those parameters are being effected and going in the right direction. So I think that it's -- when you put it all -- this together, it will clearly kind of showcase the full utility -- potential utility of the drug.

That's great. Yes. So I mean it's kind of, not only will you understand the activity in the variety of different settings and patient populations, but certainly kind of setting the stage towards what that registrational study will look like. How do you get a broad label. I think all those things are certainly very important to do from a drug development perspective, certainly.

Yes. And...

Okay. Yes, go ahead.

No, sorry, in terms of the breadth of the patient population it could be treating, it's like anywhere where hematocrit is not controlled, those patients become attractive candidates for PTG-300, as you can imagine. And that's the vast majority of the PV patient population. So yes, this could be very broad and an exciting outcome and especially for the patients to be treated with a mimetic of a natural hormone that is safe and at the same time very effective.

Absolutely. Okay. So then -- so we'll have more of kind of the open label data. And I'll point out that there is a second portion of this current Phase II study, which, I believe, is a randomized withdrawal design. And so I think some of the questions that I've gotten from investors with respect to that portion of the study is that when might we see that? I think you've given some pretty good granularity on that, so I'll let you answer that. And then I guess the other one, which I think is more speculative is if those are sufficient to support something like accelerated approval or at least to start that kind of conversation? Or like what does that look like in order to get a faster route to market potentially, if it could be even possible?

Yes. No. So the topline guidance we are giving is -- and as you know, in May, based on our exciting data, we expanded the study from 30 patients to 50 patients. So this is clearly a broader, more meaningful study. The other guidance we are giving is that we expect the enrollment of all 50 patients to be completed by the middle of next year. Having said that, though, we are not going to wait for the completion of study to -- in order for us to be in front of the regulatory authorities, both in Europe and the U.S. We expect that should happen sometime in the first half of next year. And that is where I think we will have more granularity of how the regulatory authorities look at our current study and what is the next study design that we would agree upon. As you can imagine, I mean, the randomized withdrawal portion is a very nice informative addition to our current study. As you may recall, it is blinded. So at this stage, probably at ASH, it wouldn't make much sense to be talking about it because we won't be able to put it in any particular kind of context, right? But eventually, the [indiscernible] -- but I don't think we have to wait for that phase to be completed or anything like that in order to get in front of regulatory authorities.