Severe asthma proof-of-concept trial to initiate H1 2019
Fourth indication to be selected H1 2019
Biocon completed a Phase 1 study in healthy volunteers in Australia.
Graft-versus-host disease (GVHD)
Acute GVHD (aGVHD) and chronic GVHD (cGVHD) are multisystem disorders that are common complications of allogeneic hematopoietic stem cell transplants, or allo-HSCT, caused by the transplanted immune system recognizing and attacking the recipient’s body. Symptoms of GVHD include rash, itching, skin discoloration, nausea, vomiting, diarrhea and jaundice, as well as eye dryness and irritation.
GVHD is the leading cause of non-relapse mortality in cancer patients receiving allo-HSCT, and the risk of GVHD limits the number and type of patients receiving HSCT. According to the Center for International Blood & Marrow Transplant Research, there were more than 8,500 allo-HSCT’s performed in the United States in 2016. Approximately 50% of HSCT recipients develop GVHD; we estimate that the incidence of aGVHD in 2018 will be approximately 5,000 patients and the total prevalence of GVHD could be up to 25,000 patients.
GVHD results in very high morbidity and mortality, with five-year survival of approximately 53% in patients who respond to steroid treatment, and mortality as high as 95% in patients who do not respond to steroids.
GVHD is predominantly driven by T cells that express high levels of CD6. Prior clinical studies have implicated cells expressing CD6 in the development of GVHD, suggesting that CD6 is a highly relevant target to this disease. We plan to commence clinical development of EQ001 for the treatment of both aGVHD and cGVHD during the first half of 2019.
Severe Refractory Asthma
Asthma is now recognized as a heterogeneous disease with two predominant subtypes categorized by the degree of Th2-associated inflammation present in the airways. One subtype of asthma, often characterized as allergic asthma, includes patients with high levels of Th2-associated inflammation, or Th2-high, in the airways, often accompanied by high levels of eosinophils, and production of immunoglobulin E, or IgE. These Th2-high patients often respond to treatment with steroids and recently approved biologic therapies which target IgE or Th2-cytokines.
Another subtype of asthma is characterized by low levels of Th2-associated inflammation, or Th2-low, in the airways. A portion of Th2-low patients have airway inflammation caused by Th17 cytokines such as IL-17. These Th2-low patients typically do not respond to treatment with corticosteroids or recently approved biologic therapies, often have more severe disease, and have low levels of eosinophils.
Studies have shown that Th2 and Th17 cells are reciprocally regulated. As a result, if a drug only downregulates Th2 associated inflammation, then a Th2-high patient may experience increased inflammation caused by Th17 cells, and vice versa. We believe that targeting both Th2 cytokines and Th17 cytokines, such as IL-17, may maximize therapeutic efficacy for Th2-low patients with inflammation caused by Th17 cytokines by avoiding a potential increase in inflammation caused by Th17 cells.
We estimate there are between 300,000 and 650,000 of these severe Th2-low asthma patients in the U.S. who are in need of new therapeutic options.
We believe EQ001 has a unique mechanism of action by selectively inhibiting proliferation of both Th2 and Th17 cells and their associated cytokines driving Th2-low inflammation, and therefore EQ001 may be effective in treating these patients. We plan to file an IND and initiate a proof-of-concept clinical trial of EQ001 for the treatment of severe asthma in the first half of 2019.