Protagonist Therapeutics: Unleashing The Lifechanging Power Of Peptide Therapeutics

Dinesh V. Patel, Ph.D. Director, President & CEO

The field of biotechnology is characterized by uncertainty, assumptions, and apprehensions coupled with the noble intent of dedicated employees to harness the power of science and improve lives. More often than not, an entire journey—starting from drug discovery process in a de novo fashion in the labs, to conducting clinical studies in humans, ultimately getting FDA approval, and launching a drug in the market—demands decades of unwavering dedication and billions of dollars in expenses, with the odds of success standing at less than five percent. So, who in their right mind would want to embark on such a journey?

“Interestingly enough, those in the biotech sector actually just don’t think too much about the very low probability of ultimate success,” says Dinesh V. Patel, Ph.D., director, president, and CEO of Protagonist Therapeutics. “We just accept the reality and get going with it, one day at a time. It is a challenging quest, but the one that ultimately gives people many more years or life, and better quality of life. I can’t imagine doing anything more purposeful than that.” In his own case, the journey with Protagonist Therapeutics started all the way back in 2008 as a small discovery lab, to now a publicly traded company with two novel drugs currently in advanced stages of clinical development. One of them is partnered with Janssen, the pharmaceutical arm of Johnson & Johnson, and another is being developed independently by Protagonist. If everything goes right, these drugs can get approved for market entry by 2026.

“Biotech is a marathon, not a sprint. So, we have to hold steady, pace ourselves and keep going,” says Dr. Patel.

Dr. Patel, with an extensive educational scientific background and executive, entrepreneurial, and operational experience spanning 33 years in life sciences, brings deep skill and understanding to his role at Protagonist Therapeutics. The company has a unique technology platform that enables it to discover peptides in a de novo fashion against complex biological targets spanning multiple diseases. It focuses on those pathways and diseases where the peptide approach can offer significant advantages over classical small molecule or biologics based methods of drug discovery. Protagonist has utilized this uniqueness to address unmet needs in a rare blood disease called polycythemia vera (PV), as well as in common immunological diseases like psoriasis and inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). The company has products in late stages of clinical development across these areas and has made a conscious choice of both independent drug development as well as partnering with big pharma.

From Discovery to Development

“It’s very satisfying to move your ideas from your head to discoveries in the lab and finally to clinical studies in patients, even if it takes a decade-plus and takes you and your entire team on a path filled with uncertainty,” says Dr. Patel. “The next step for Protagonist in the coming years is FDA approval and commercialization—that is, getting the drug in the hands of those who need it the most. And yes, there are no guarantees; you just continue working diligently and hope the best.”
A Promising Drug for Polycythemia Vera

Today, Protagonist has placed its focus on the development of rusfertide (PTG-300), a promising drug candidate with the potential to have transformative impact in the treatment of polycythemia vera (PV). Rusfertide is currently being evaluated in a 250-patient Phase 3 study in PV and the company is eyeing a new drug application (NDA) filing for FDA approval after completing the study, assuming a positive outcome. The study design and the various endpoints needed for approval are of similar nature to the previously conducted Phase 2 study, where the efficacy data has been very impressive. PV is a rare disease characterized primarily by excessive production of red blood cells, including abnormal red blood cells, thereby placing patients at a higher risk of cardiovascular and thrombotic events like heart attack and stroke. Phlebotomy (blood letting) is the most common treatment for PV and the patients often face challenges of severe fatigue, difficulties in concentration, and other disease-related symptoms that impede their ability to carry out daily activities. Approximately 160,000 patients in the U.S., with a similar prevalence in Europe, are affected by PV, representing an estimated multi-billion-dollar market opportunity.

Rusfertide is a synthetic mimetic of the natural hormone hepcidin, the master regulator of iron metabolic homeostasis in the body. Specifically, in PV, rusfertide appears to control RBC production by regulating the amount of iron that is supplied to the bone marrow for hemoglobin and RBC synthesis. Protagonist has worldwide rights to rusfertide and plans to finish the study with the cash runway that the company has through the end of 2024. Independent commercialization by a biotech company is not out of reach for a rare disease drug like rusfertide, although the company will evaluate all available options at any given time and act in the best interest of its stakeholders.

A Transformative Approach for Psoriasis and Inflammatory Bowel Diseases (Crohn’s disease and Ulcerative Colitis) in partnership with Janssen Pharmaceuticals

Unlike rusfertide for a rare disease like PV, PN-235 is an oral interleukin-23 receptor (IL-23r) antagonist that lends itself to blockbuster market category of common immunomodulatory diseases such as psoriasis and inflammatory bowel disease. Protagonist made a conscious decision early on to collaborate with a big pharma for a project of this magnitude, fully acknowledging that pharma has unmatched resources and experience in such areas in comparison to a biotech. The company joined hands with Janssen pharmaceuticals back in 2017, and the net result is PN-235 currently being pursued in multiple clinical studies by Janssen. Of course, Protagonist has gained a lot in the process from Janssen—$112.5 M in various payments, to be precise—but, more importantly, the comfort of realizing that this drug candidate is getting the best chance to succeed in the hands of Janssen. And with potential success of PN-235, protagonist is eyeing $800 million-plus in future payments and mid-single to 10% royalties on net sales. PN-235 is an oral peptide-based drug working on the same biological pathway that is being intervened by Janssens blockbuster injectable antibody drugs like Stelara and Tremfya. If successful, PN-235 could be providing the much-desired transition from injectables to orals to millions of patients globally suffering from these chronic diseases. “How about that for an ambitious and transformative agenda for a biotech like Protagonist” says, Dr. Patel.
It is not a bed of roses: The PN-943 Story

While being very hopeful about both Rusfertide and PN- 235, Dr. Patel asserts that not every drug discovery effort will yield the same result, referring to PN-943—another drug candidate developed in-house at Protagonist—that did not bring a roaring success. While the Phase 2b data in a 240-patient study in ulcerative colitis was determined to be positive if not outstanding by the company, and overwhelmingly recommended by key opinion leaders (KOLs) for further development, the Company has decided to peruse further development only if it can find a suitable partner for this asset. “You are going to come across such ‘winning the battle but losing the war’ kind of scenarios numerous times in the business of science. You just have to accept the reality and keep making tough but right decisions.’ This also highlights the criticality of having multiple assets and multiple shots on goal. If PN-943 was the only asset that the company had, it would have been in a miserable situation. Thanks to the versatile technology platform and the seasonded team, Protagonist intends to always have a choice of multiple assets at any given time.

The Protagonist Team: Unwavering Determination and Resilience

The entire process of drug discovery to launching a new medicine in the market is a long, complex, expensive, and uncertain path filled with high failures and severe setbacks. Besides an innovative and proprietary technology platform, it also needs brilliant minds, along with unwavering dedication and passion for the cause. Protagonist’s team has that in its DNA and has proven that over and over again by navigating around numerous unforeseen hurdles over the past fourteen years. Its constant and steady growth can be attributed to its capability to to self-evaluate and morph itself according to changing needs. “As the Company grows and transitions, so does the team. It’s a very delicate balance of not just growing, but strengthening and transforming the team and making sure it can do justice to not just the Protagonist of today, but also to the Protagonist of tomorrow,“ says Dr. Patel. A firm believer in growth from within, Protagonist relies on the continuum of self-evaluation and collective evaluation to understand the areas of improvement and achievements in the larger scheme of drug development. “As the Company grows and transforms, so can employees, and they should get every opportunity to keep scaling up along with the Company. Ultimately, you strike a balance between promoting from within and hiring from outside, while genuinely attending to the growing needs of your Company in an uncompromising way.”

Biotech is a marathon, not a sprint. So, we have to hold steady and keep going

Today, Protagonist is a publicly traded U.S.-based company with a market cap of about half a billion dollars. The opportunities it has cultivated in its pipeline can translate to billions of dollars in revenue in the future.

The Company strongly believes in the importance of life sciences education. At the management level and throughout the company, Protagonist’s team members are active sponsors, mentors, and hosts for students seeking to broaden their understanding of life sciences in the interest of advancing human health.