Product Candidates

Rusfertide (PTG-300)

Rusfertide (PTG-300) is a novel injectable synthetic mimetic of the natural hormone hepcidin that offers greater potency, solubility, and stability, which may translate to better in vivo PK and PD characteristics in comparison to the natural hormone. Hepcidin is a key regulator of iron absorption, storage, and distribution in the body and thereby controls the production of red blood cells (RBCs). Rusfertide is currently in an ongoing Phase 2 study in patients for the treatment of polycythemia vera (PV).

Polycythemia Vera (PV) Overview

PV is a rare myeloproliferative neoplasm characterized primarily by the overproduction of RBCs. The main underlying cause of PV is a mutation in the Janus Kinase 2 (JAK2). PV is a serious chronic condition of increased RBC count, which 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 in their recommendation to control the patient’s hematocrit (RBCs as a percentage of whole blood) below 45% in order to reduce the risk of further cardiovascular or thrombotic events. PV is a slow progressive disease with an average span of about 20 years and may ultimately progress to myelofibrosis or leukemia.

Currently, PV 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, marketed as Jakafi®; the latter currently being the only branded product in the U.S. approved for PV. There has been only one FDA-approved treatment for PV in the past 12 years. Cytoreductive therapies such as hydroxyurea, interferons, and ruxolitinib can have challenging side effect profiles as they reduce all cell types, not specifically RBCs. Current treatments are effective in some patients, but we believe there are many patients who could benefit from a new non-cytoreductive therapeutic option.

Polycythemia Vera (PV) Market Overview

PV is a rare disease affecting approximately 160,000 patients in the U.S., with a similar prevalence in Europe, representing an estimated market opportunity of approximately $1.0 billion to $2.0 billion. Since 2017, approximately 14,000 new patients have been diagnosed with PV each year since.

Patients are typically diagnosed between the ages 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 consists primarily of therapeutic phlebotomy, hydroxyurea, or a combination of hydroxyurea and phlebotomy. According to the analysis of the large data claims database, current therapies do not offer adequate hematocrit control below 45% as recommended in the NCCN Guidelines®. In fact, less than 25% of patients in our data set had all hematocrit test results under 45%, indicating that as many as 70,000 patients in the U.S. may be at elevated risk of cardiovascular and thrombotic events.

Rusfertide (PTG-300)

We believe that rusfertide has the potential to provide substantial benefit to patients by providing a tool focused on managing hematocrit in a consistent and predictable manner and dramatically decreasing the need for therapeutic phlebotomy. Rusfertide is a non-cytoreductive mimetic of the natural hormone hepcidin, the master regulator of iron homeostasis in the body. Rusfertide has a unique iron regulatory mechanism which, per early results from our ongoing Phase 2 study in PV, allows for persistent control of hematocrit without causing iron deficiency. Rusfertide controls iron metabolism by 1) preventing iron absorption in the small intestine and 2) redistribution of iron from the blood to the macrophage storage sites in certain organs and tissues leading to a restoration of an appropriate iron balance throughout the body. Specifically in PV, rusfertide appears to control RBC production by regulating the amount of iron available to the bone marrow for hemoglobin and RBC synthesis.

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 tract as a topical approach to treat inflammatory disease.

IBD Market Overview

According to the Crohn’s & Colitis Foundation of America, there are more than 1.6 million IBD patients in the U.S. alone, an increase of approximately 200,000 patients since 2011. As many as 70,000 new cases of IBD are diagnosed in the U.S. each year. As of 2008, annual direct treatment costs for patients with IBD in the U.S. 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 2019, GlobalData estimated that the UC market reached approximately $6.7 billion across seven major markets: U.S., France, Germany, Italy, Spain, United Kingdom, and Japan, and is expected to increase at a compound annual growth rate of approximately 6.1% to $12.1 billion by 2029. In 2016, GlobalData estimated that the CD market reached approximately $7.3 billion across those same seven major markets and is expected to grow approximately 5.5% per year to $12.4 billion by 2029.

For many years, tumor necrosis factor-alpha (TNF-α) antibody drugs were the primary treatment for moderate-to-severe IBD. Humira® and Remicade® are injectable and infused, respectively. 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, which over time can cause loss of drug response. More recently, antibody products focused on potentially safer mechanisms of action have been gaining market share. One such product is Takeda Pharmaceuticals’ Entyvio®, which targets the α4β7 integrin pathway. Takada Pharmaceuticals reported 2020 sales of Entyvio® of approximately $3.9 billion. Similarly, Johnson & Johnson’s Stelara®, which targets the Interleukin 12 (IL-12) and Interleukin 23 (IL-23) pathways, has gained significant traction. Johnson & Johnson global sales of Stelara® (approved for psoriasis, psoriatic arthritis, moderate-to-severe CD and UC) exceeded $7.7 billion in 2020.

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

1. Sands BE et al. N Engl J Med. 2019;381(13):1215-1226.