OncoArendi Therapeutics Ltd. has announced the selection of its drug candidate for asthma treatment OATD-01 for clinical development.
OATD-01 is a small molecule inhibitor of acidic mammalian chitinase (AMCase), likely the first of these type of molecules to enter development, according to the company. Acidic mammalian chitinase is an enzyme that degrades chitin, a stable and hard biopolymer present in the exoskeleton of insects and crustaceans and on the cell walls of fungi and yeast. AMCases are present in the human genome and have been found to be over-expressed and play a role in the Th2-specific and interleukin-13 –mediated pathway in pulmonary epithelial cells in human asthma. Neutralization of AMCase has been shown to decrease the Th2-inflammation and exacerbation in the airways that dominate conditions such as asthma, constituting a promising therapeutic target.
OncoArendi Therapeutics, who specializes in the development of drug candidates for neoplastic and inflammatory pathologies, is developing AMCases inhibitors under a license from Yale University, and OATD-01 constitutes its first clinical candidate. Marcin Szumowski, PhD, President and CEO of OncoArendi Therapeutics, commented on the company’s investment in this technology, “We believe that drugs against novel targets from the chitinase protein family have great potential to be transformational medicines in the treatment of several chronic inflammatory diseases. At OncoArendi, we are dedicated to researching and developing first-in-class small molecule-based therapies that could significantly advance our understanding and treatment of inflammation-based diseases such as asthma, IPF, COPD or IBD.”
OATD-01, an orally active drug, presents several promising features and biological characteristics. It presents high bioavailability (amount of unchanged drug that reaches the systemic circulation), low clearance and high volume of distribution (distribution of the drug in body tissue). Furthermore, the drug was found to be metabolically stable and does not increase or decrease cytochrome P450, important in the metabolism of many drugs in the body. Further studies confirmed a suitable one per day oral administration of the drug. When compared to montelukast (Singulair), a frequently prescribed oral drug for asthma, OATD-01 showed increased anti-inflammatory activity. It was shown to effective in two asthma mouse models and with minimal side-effects.
This clinical profile shows the great potential of OATD-01, as stated by Dr Szumowski: “We are particularly excited about the potential of our first clinical candidate as an alternative or complementary treatment to the corticosteroid-based asthma therapies such as Advair or Symbiocort. This compound has an excellent safety profile and appears suitable for once-a-day oral dosing, with a completely different molecular target and mechanism of action compared to Singulair.” The company expects to submit the drug for Investigational New Drug (“IND”) in 2017.