Protagonist Therapeutics, Inc 12th Annual Cantor Fitzgerald Global Healthcare Conference

It's a real pleasure. Thanks for inviting us.

Yeah. As you know, we have been around for a while, but all along, right from the early beginnings in 2008, we have been focused on peptide therapeutics. There has been a long and deep level of dedication and commitment, which has allowed us to build a very unique expertise. Now if you fast forward it to this year, then it has culminated in the approval of 2 drugs. One is icotrokinra, the oral IL-23, the first of its kind, partnered with J&J. The drug is doing amazingly well. It was launched a day after St. Patrick's Day, I guess, sometime in March. More recently, over the past few days, our second drug, MIMRYLO, the hepcidin mimetic for polycythemia vera, got approved, that is partnered with Takeda. We seriously could not have asked for a better, cleaner outcome.

The label is very broad and clean. We believe the drug is really poised to do incredibly well. Again, it's a first of its kind as well. Until then, there has been no erythrocytosis specific agent for polycythemia vera, and that is the hallmark of the disease. With the confidence that we gained from these two drugs, as of the end of second quarter of this year, we had around $850 million cash. The MIMRYLO approval, the combination of a milestone and the opt-out fee, it amounts to $275 million. That takes us over $1 billion in cash, that sort of thing.

It is that kind of cash position as well as the promise that we see in the two drugs, the ability to generate future revenues, that prompted us to announce the share buyback that we announced, I believe that was yesterday or the day before. Time flies, I guess. $300 million, that sort of thing. The whole idea is like, look, we have proven ourselves, we have validated ourselves with two peptidic drugs. We are all set for a repeat performance with multiple programs in our R&D pipeline. R&D is our number 1, number 2, number 3 priority. That is where money is going to go first. But we believe that we are in one of these fortunate situations where we don't see a need to go out and do an equity raise in the foreseeable future. We can fund our own R&D.

In spite of funding our own R&D, we still will be left with adequate amount of cash to do share buyback. I think from two very different directions, the whole idea is to go for repeat performance, come up with new drugs that will benefit patients, and also create tremendous shareholder value.

Yeah. I think the way the deal is structured, Takeda is in 100% charge of the commercialization, and they will be the main spokespeople about the commercial forecast and those sort of things. As you pointed out, the 1 billion-2 billion estimate they made, A, pharma companies, they are meant to be conservative. B, it was before the outstanding phase III data that was splashed as an American Society of Clinical Oncology plenary session in 2024. And C, before we got this amazingly broad and clean label. We will just have to see how they want to manage all that. Having said that, though, this is a first of its kind drug. Until now, there has not been an erythrocytosis specific drug that is out there. So there is going to be effort geared towards creating the awareness, making people aware of this kind of a new treatment that is available right now.

I would not be surprised if in the first few quarters, the takeoff could be slower than anticipated. But in terms of what happens after that initial phase, I would say you could expect a hockey stick-like phenomena because the label is just amazing. There is no black box warning, in spite of all the drama during the clinical studies and all that kind of thing. There is no issue around carcinogenicity. The phase III study, if at all anything, had more cancer events in the placebo arm compared to the treatment arm. So that is about as clean as things can get. And then, of course, it is a drug for all comers.

There are no restrictions or pre-requirements like, hey, you need a derm exam or some sort of screening, or you have to be on certain number of phlebotomies or some sort of treatment with a cytoreductive as a prior requirement. So it is all very broad utility, we would believe. The requirement being erythrocytosis, which by the way, when you look at the real-world data, it is like 78% of the patients are not controlling their hematocrit. So I would say this is a clean drug, very mechanism, erythrocytosis-specific drug. And at last but not least, this is the first drug ever that has the symptom improvement in the label, right? The fatigue improvement, which is one of the big condition that affects the quality of life of these patients. So we have got on that claim as well.

Got it. That's why I say we couldn't have asked for a better outcome, and the drug deserves it.

Yeah. I think all along what we are finding is that for indications that require long-term treatment, whether it is in obesity or in the inflammation and immunology space, or whether it is in a rare disease like polycythemia vera, the average kind of duration for a PV patient to stay with the disease is around 15 years or something like that. Whenever there is that extended utility, there is a high demand and preference for an oral pill, right? Taking an oral pill also psychologically, it doesn't remind you of having an illness or something on a regular basis. It just becomes part and parcel of the norms of daily life, so to speak. We, Protagonist, have the ability to come up with oral drugs for this kind of chronic indications.