Product Candidates

PTG-300—Hepcidin mimetic

PTG-300 is a novel injectable compound that mimics the effect of the natural hormone hepcidin, but offers greater potency, solubility and stability. Hepcidin is a key regulator of iron equilibrium and thereby is critical to the proper development of red blood cells. We are currently developing PTG-300 as a treatment for polycythemia vera and hereditary hemochromatosis.

Polycythemia Vera overview

Polycythemia Vera (PV) is a rare myeloproliferative neoplasm characterized primarily by the overproduction of red blood cells. PV is typically caused by a form of Janus Kinase 2 (JAK2) mutation. PV is a serious chronic condition as the increased red blood cell count causes the blood to thicken and puts patients at higher risk of cardiovascular and thrombotic events such as heart attack and stroke. Patients are typically stratified as low or high risk based on age and medical history. Regardless of risk categorization, treatment guidelines for PV are consistent: to control the patient’s hematocrit (red blood cells as a percentage of whole blood) below 45% in order to reduce the risk of further cardiovascular or thrombotic events. PV may progress to myelofibrosis of leukemia.

Currently patients are typically treated with low dose aspirin and phlebotomy alone or hydroxyurea alone or in combination with phlebotomy. At later stages, patients may receive interferons or ruxolitinib (Jakafi). Jakafi is currently the only branded product in the US for PV. Cytoreductive therapies such as hydroxyurea, interferons and ruxolitinib can have challenging side effect profiles as they reduce all cell types. Current treatments are effective in some patients, but we believe there are substantial patient groups that could benefit from a new non-cytoreductive therapeutic option.

Hereditary Hemochromatosis overview

Hereditary hemochromatosis (HH) is caused by genetic mutations that leads to hyperabsorption of iron from the diet and alters its distribution in the body, leading to iron buildup in the liver, heart and other organs. Too much iron can be toxic and over time can lead to cirrhosis and cancer, heart problems, skin lesions, joint pain and diabetes. The genetic defect that causes most HH originates in northern Europe, and there are approximately 5-7 million people with this defect in the US and EU.

PV market overview

There are approximately 160,000 patients living with PV in the United States, with a similar prevalence in Europe. Approximately 15,000 new patients have been diagnosed each year since 2017. Patients are typically diagnosed between the age of 50 and 70 and median survival is approximately 20 years. Recent analysis of patient data from a large medical claims database indicates that the current treatment paradigm does not offer adequate hematocrit control below 45%. In fact, less than 30% of patients in our data set had all hematocrit test results under 45%; indicating that as many as 70,000 patients in the US alone may be at elevated risk of cardiovascular and thrombotic events.

We believe that PTG-300 has the potential to provide substantial benefit to patients by providing a tool focused entirely on managing hematocrit in a consistent and predictable manner. PTG-300 is a non-cytoreductive, first-in-class, mimetic of the natural hormone hepcidin, the master regulator of iron homeostasis in the body. PTG-300 has a unique iron regulatory mechanism which allows for persistent control of hematocrit without causing iron deficiency. It acts by redistributing iron away from the bone marrow where iron is in high demand and essential for red blood cell production, thereby limiting excess red blood cell production in patients with polycythemia vera.

Oral Peptides for Inflammatory Bowel Disease (IBD)

PN-943 is a potential first-in-class oral, alpha-4-beta-7 (α4β7) integrin-specific antagonist peptide. This product candidate is being developed initially for the potential treatment of moderate-to-severely active ulcerative colitis (UC). α4β7 integrin is considered to be one of the most GI-specific biological targets for IBD due to its binding to MAdCAM-1, an extracellular protein that resides mostly in the GI vasculature. PN-943 peptide is largely restricted to the GI as a topical approach to treat inflammatory disease.

PTG-200 is a potential first-in-class oral Interleukin-23 receptor (IL-23R) antagonist being developed initially for moderate-to-severely active Crohn’s disease (CD), and is currently in a Phase 2 study. Protagonist has entered into a worldwide agreement with Janssen Biotech, Inc. to co-develop and commercialize PTG-200 for all indications, including IBD. In addition, this collaboration was expanded resulting in the discovery and selection of two additional oral interleukin-23 receptor antagonists, PN-232 (JNJ-75105186) and PN-235 (JNJ-77242113) for advancement into clinical development. These candidates provide several strategic options for development in multiple indications.

IBD market overview

According to the Crohn’s & Colitis Foundation of America, there are more than 1.6 million IBD patients in the United States alone, an increase of approximately 200,000 patients since 2011. As many as 70,000 new cases of IBD are diagnosed in the United States each year. As of 2008, annual direct treatment costs for patients with IBD in the United States were estimated to exceed $6.3 billion, while indirect costs such as missed work days were estimated to cost an additional $5.5 billion. In 2016, GlobalData estimated that the UC market reached approximately $5.4 billion across seven major markets: United States, France, Germany, Italy, Spain, United Kingdom and Japan and is expected to increase at a compound annual growth rate of approximately 2.5% to $6.9 billion by 2026. In 2016, GlobalData estimated that the CD market reached approximately $9.6 billion, across those same seven major markets and is expected to grow approximately 3.7% per year to $13.84 billion by 2026.

The current tumor necrosis factor-alpha (TNF-α) antibody drugs approved for moderate-to-severe IBD, Humira® and Remicade®, are injectable and infused respectively. According to GlobalData, the 2013 sales for Humira and Remicade for IBD were $3.4 billion in the United States. Takeda Pharmaceuticals reported 2016 fiscal year sales for Entyvio® for IBD of approximately US $1.3 billion. Like Entyvio, which is dosed as an infusion and as an injectable antibody drug, the oral peptide PN-943 specifically inhibits α4β7 integrin. Approximately one third of IBD patients do not respond to TNF-α antibody drugs and approximately another 30% to 40% become refractory within the first year of treatment. Additionally, TNF-α antibody drugs may predispose patients to an increased risk of serious infection and the development of anti-drug antibodies (ADAs), which over time can cause loss of drug response. In a recent clinical trial Entyvio in several respects demonstrated superiority to Humira (ref).

While available treatments exist for moderate-to-severe IBD, there continues to be a significant medical need for novel, efficacious, safe and convenient treatments.