Data to inform further GVHD development, e.g. GVHD prevention, cGVHD
Uncontrolled moderate to severe asthma proof-of-concept trial to initiate Q2 2019
lupus nephritis proof-of-concept trial to initiate in H2 2019
Data to inform further development in lupus, e.g. cutaneous lupus, SLE
Biocon completed a Phase 1 study in healthy volunteers in Australia.
Graft-versus-host disease (GVHD)
GVHD is a multisystem disorder that is a common complication of allogeneic hematopoietic stem cell transplants, or allo-HSCT, caused by the transplanted immune system recognizing and attacking the recipient’s body. Approximately 50% of HSCT recipients develop GVHD. HSCT recipients are at risk of developing either or both acute GVHD (aGVHD) and chronic GVHD (cGVHD) with approximately 30-70% of HSCT recipients developing aGVHD, 50% of which will progress to cGVHD, and another 30-70% developing cGVHD independent of aGVHD.
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 believe EQ001 has the potential to be a best-in-class treatment for this severe disease where there is a very high unmet medical need for a safe, effective and targeted treatment.
Uncontrolled moderate to severe 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 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 may 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. This may explain why many patients with this disease are refractory to both steroids and the current biologics targeting eosinophils or Th2-related pathways. Therefore a therapy with a broad mechanism targeting multiple effector T cells or cytokines may be required to adequately address this dynamic and heterogenous disease.
We estimate that 50% of the severe asthma population, or 650,000 – 1,300,000 individuals, are uncontrolled with standard-of-care long-acting beta-agonists and high-dose corticosteroids. As many as 50% – 60% of these patients likely fall within the Th2-low/non-Th2 subtype, while approximately 40-50% of this population fall within the Th2-high subtype.
We believe the unique mechanism of action of EQ001 can selectively target elements of the underlying pathogenesis of both eosinophilic (Th2-high) and non-eosinophilic (Th2-low and non-Th2) severe asthma by inhibiting both Th2 and Th17 cell proliferation and cytokine secretion, inhibiting trafficking of Th2 and Th17 cells into lung tissues, and reducing the Th2 or Th17:Treg ratio associated with uncontrolled moderate to severe asthma.
Lupus nephritis is among the most serious complications of systemic lupus erythematosus (SLE), occurring in 30-60% of SLE patients. In patients with lupus nephritis, the body’s own immune system attacks the kidneys, causing inflammation and significantly reducing kidney function over time.
Medications used to treat lupus nephritis include high-dose corticosteroids and immunosuppressive drugs; however, these therapies have multiple toxicities and as many as 50% to 75% of patients don’t respond to treatment. For patients that do respond to treatment, the majority will relapse within 5 years. Additionally, despite treatment with high-dose corticosteroids and immunosuppressive drugs, progressive loss of kidney function occurs in up to 40% of patients with severe, proliferative disease.
T cells play a central role in the pathogenesis of lupus and lupus nephritis, and we believe that EQ001, which inhibits Teff cell activation and trafficking into tissues by targeting the CD6-ALCAM pathway, represents a promising therapeutic approach for these severe patients. Targeting the CD6-ALCAM pathway in lupus nephritis is bolstered by translational research findings that have identified urinary ALCAM in lupus nephritis patients as a predictive biomarker for disease activity.
There are currently no FDA-approved drugs for lupus nephritis, underscoring the need for safe and effective therapies for these patients.