Protagonist Therapeutics, Inc FDA announcement

Please go ahead. Thank you, Rob.

Hello, everyone, and thanks for joining us on our call today. Joining me from Protagonist are Dr. Dinesh Patel, President and CEO, Asif Ali, CFO, Dr. Arturo Molina, CMO, Dr. Ashok Bhandari, Chief Discovery Officer, and Dr. Samuel Saks, Clinical Development Advisor. On Friday, Protagonist issued a press release announcing the FDA approval of rusfertide, now known as MIMRYLO, for the treatment of erythrocytosis in adults with polycythemia vera, or PV. A copy of the release and the slides being used for this call are available on the company's website. As can be seen on this slide, we will be making forward-looking statements on this call. These may include statements relating to the safety and efficacy and the therapeutic and commercial potential of our investigational product candidates.

For further information relating to risks and uncertainties related to our business, please see the periodic reports we have filed with the Securities and Exchange Commission. This conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 31st, 2026. Protagonist undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call, except as may be required by applicable securities law. With that, I'll now turn it over to Dr. Dinesh Patel.

Go ahead, Dinesh. Thank you, Corey, and good morning, everyone.

Earlier this year, on March 18th, we had announced the U.S. FDA approval for our first drug, the first-in-class IL-23 receptor blocker oral peptide icotrokinra, in partnership with Johnson & Johnson. Today, a few months later, marks the second major drug approval milestone for Protagonist. We are very pleased to announce that MIMRYLO, which is the new brand name for rusfertide, has received FDA approval for the treatment of erythrocytosis in adults with polycythemia vera, or PV. This is a first-in-class medicine that targets the biology-driving red blood cell, or RBC, overproduction in PV. I would like to congratulate both the Protagonist team and our partner, Takeda Pharmaceutical, on this very successful outcome.

As most of you know, PV is a rare blood cancer, wherein the fundamental treatment goal for patients, as per NCCN guidelines, is to lower hematocrit, which is the ratio of red blood cell volume to total blood volume, and to maintain this hematocrit level below 45%. While PV is an erythrocytosis-driven blood disease, there has been no erythrocytosis-specific therapy available as a treatment. It is this unmet need that drove us on the path of discovering and developing MIMRYLO. How does MIMRYLO work, and what is its mechanism of action? It is a peptide mimetic of the natural human hormone hepcidin. Hepcidin is the master regulator of iron homeostasis that controls the absorption, storage, and distribution of iron in the body. MIMRYLO mimics the action of endogenous hepcidin to regulate iron availability and thereby help normalize RBC production and maintain hematocrit levels below 45%.

This erythrocytosis-specific mechanism is a very different and a more elegant therapeutic strategy compared with the current standards of care, which rely on phlebotomy and cytoreductive therapies to control the consequences of erythrocytosis. These treatments can be associated with treatment burden and adverse effects and do not specifically target the underlying iron dysregulation that fuels erythrocytosis. MIMRYLO is a first-in-class drug of its kind for PV, a first-in-class medicine marking a potential shift in the treatment paradigm for PV. We have high confidence in the long-term commercial potential of MIMRYLO and know that our partner, Takeda, is exceptionally well-positioned to maximize the global opportunity for the product. As a reminder, following our recent opt-out election, Takeda is now solely responsible for all aspects of commercialization and ongoing clinical development, and they are the ones best positioned to provide more specific details on these topics.

Before getting into the clinical studies that form the basis of the approval and the broad prescription label, let me first walk you through the discovery and development journey of MIMRYLO, since it speaks volumes about the scientific expertise of Protagonist with peptides, the in-house peptide-centric drug development accuments we have accumulated, and the future strategic vision for the rest of our peptide-dominant research and development pipeline. Going to slide 4, let's start with the historical perspective on MIMRYLO journey from concept to FDA approval and commercialization. MIMRYLO, or PTG-300, as it was known during drug discovery and early development, originated from our hepcidin mimetic program more than a decade ago. Its successful approval provides important validation for Protagonist on at least two levels.

First, it is a testament to our scientific team's innovative expertise in originating the hypothesis that a hepcidin mimetic could lead to a first-in-class medicine for iron dysregulation-related diseases such as PV. Second, it provides powerful validation of our peptide technology platform and our exceptional expertise in the emerging field of peptide therapeutics. Looking at hepcidin through the lens of a medicinal chemist, we recognized early on that the natural hormone hepcidin presented a unique challenge. It is synthetically complex, unstable, poorly soluble, and only moderately potent, making it unsuitable as a drug in its own right. There was a clear need and opportunity for creating a synthetic peptide with superior pharmacokinetic and pharmacodynamic properties in comparison to the natural hormone. We were able to utilize our peptide chemistry expertise and our proprietary platform on this project.

In particular, we applied the technique of scaffold hopping from our platform, which led to the identification of a PTG-300 scaffold, which after further optimization, led to the specific peptide PTG-300, now called MIMRYLO. As a side remark, the peptide platform is now very broad from what it was in those days, encompassing a full range of tools, including, but not limited to, computational matrix libraries, phage libraries, medicinal and peptidomimetic chemistry, formulations, and artificial intelligence. These tools are being judiciously utilized in our new discovery and development programs, which will be highlighted later on in this call. Getting back to MIMRYLO, the discovery of 300 was followed through with our phase II REVIVE clinical proof of concept study, the Takeda partnership, its successful pivotal phase III VERIFY readout, the NDA submission last year in December, and finally, U.S. FDA approval last week on Friday.

Along the way, rusfertide received orphan drug designation, fast track designation, breakthrough therapy designation, and priority review. The program also achieved broader clinical and scientific validation, including publication of the phase II REVIVE results in The New England Journal of Medicine and presentation of the phase III VERIFY results at the 2025 ASCO Plenary Session. It has been an incredible journey, and this successful outcome is deeply satisfying for the entire company, especially knowing that PV patients will now have a new treatment option attending to their unmet need of maintaining hematocrit levels and controlling erythrocytosis in a consistent manner. Let me now turn it over to our Chief Medical Officer, Dr. Arturo Molina, who will review the phase III VERIFY results and the approved label and the unmet need in PV.

Arturo? Thanks, Dinesh. Let's go to slide 5.

The phase III VERIFY study was a 32-week double-blind, placebo-controlled study which enrolled patients receiving current standard of care but requiring excessive phlebotomies because of uncontrolled hematocrit. In the placebo arm, participants continued with their ongoing therapy, whereas in the investigational treatment arm, rusfertide was added to the ongoing therapy. The primary endpoint was clinical response in the rusfertide treatment arm versus the placebo arm during weeks 20 to 32. The study met not only its primary endpoint of clinical response, but also all the four key secondary endpoints, including the patient-reported outcomes assessing fatigue and overall symptom burden, specifically the PROMIS fatigue score and the MPN-SAF symptom score. Importantly, improvement in fatigue, as measured by the PROMIS Fatigue Short Form 8a, is also incorporated into the FDA-approved label.