Product Candidates

PTG-300—Hepcidin mimetic

PTG-300 is under development for the treatment of certain disorders characterized by ineffective erythropoiesis, excessive red blood cells or iron overload. PTG-300 is an injectable compound that mimics the effect of the natural hormone hepcidin, but with greater potency, solubility and stability. Hepcidin is a key hormone in regulating iron equilibrium and is critical to the proper development of red blood cells. We are currently developing PTG-300 for β-thalassemia (non-transfusion dependent and transfusion dependent), Polycythemia Vera, Hereditary Hemochromatosis and Myelodysplastic Syndromes. PTG-300 has received an orphan drug designation from the U.S. Food and Drug Administration (“FDA”) and European Union (“EU”) regulatory authorities for the treatment of β-thalassemia. The FDA has also granted Fast Track designation to PTG-300 for the treatment of β-thalassemia.

β-Thalassemia overview

β-Thalassemia is a rare genetic blood disorder that is characterized by impaired red blood cell production that can result in life-threatening chronic anemia. Patients usually require regular and life-long blood transfusions for survival that can lead to iron overload in target organs such as the heart and liver. β-Thalassemia results from mutations in the HBB gene, which holds instructions for making beta-globin, an essential part of hemoglobin. Depending on the mutation, affected individuals have either a partial or complete reduction in beta-globin, causing ineffective erythropoiesis and red blood cell damage in turn leading to chronic anemia. β-Thalassemia is classified into two subtypes; transfusion-dependent thalassemia and non-transfusion dependent thalassemia.

β-Thalassemia is most prevalent in people of Mediterranean descent, such as Italians, Greeks or Turks and is also found in the Arabian Peninsula, Iran, Africa, Southeast Asia and southern China. The prevalence of β-Thalassemia was estimated to be approximately 300,000 patients worldwide in 2008, with at least 60,000 patients born each year with the disease, according to the CDC. In 2018, Decision Resource Group reported that while β-Thalassemia has a worldwide carrier rate of 1.5%, the disease is rare in the US, Italy, Germany, UK, Spain and France with a total diagnosed prevalence of approximately 16,307. The prevalence in the US is low, with an estimated 3,000 patients and approximately 300 patients born each year with the disease.

The greatest unmet need for β-Thalassemia is for more effective treatment for chronic anemia to decrease the burden of frequent blood transfusions and thus eliminate the complications associated with the disease and its management and costs associated with red blood cell transfusions and chelation therapy.


Polycythemia Vera overview

Polycythemia Vera (PV) is a rare chronic disease caused by a hematopoetic stem cell mutation. PV is characterized by the excessive production of blood cells and common symptoms include fatigue, headache, blurred vision, shortness of breath and an enlarged spleen. The excess of blood cells can also increase risk of serious problems such as blood clots, leading to heart attack and stroke. Over time PV may transform into myelofibrosis or leukemia. There are currently approximately 100,000 diagnosed PV patients in the US alone.


Hereditary Hemochromatosis overview

Hereditary Hemochromatosis (HH) is caused by genetic mutations that increase iron uptake 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, liver cancer, heart problems joint pain and diabetes. The genetic defect that causes most HH originates in Northern Europe, and there are approximately 5 – 7 million patients in the US and EU.


Myelodysplastic Syndrome overview

Myelodysplastic Syndromes (MDS) are a group of disorders in which blood cells do not mature properly in the bone marrow. Symptoms can include fatigue, shortness of breath, excessive bleeding or frequent infections. There are multiple MDS subpopulations; some of which are characterized by anemia, low hepcidin, and high serum iron and transferrin saturation.

PN-943 and PTG-200—oral, GI-restricted peptides for IBD

PN-943 is a potential first-in-class oral, alpha-4-beta-7 (α4β7) integrin-specific antagonist peptide product candidate that 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.

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 has completed a Phase 1 clinical trial. Protagonist has entered into a worldwide agreement with Janssen Biotech, Inc. to co-develop and commercialize PTG-200 for all indications, including IBD.

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 both injectable. 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 an injectable antibody drug, the oral peptide PTG-100 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.

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