SOUTH SAN FRANCISCO, Calif.– Blade Therapeutics, Inc. (Blade or the Company), a biopharmaceutical company focused on developing cutting-edge treatments for fibrotic and neurodegenerative diseases, today announced that the U.S. Food and Drug Administration (FDA) has activated the Company’s Investigational New Drug (IND) application to investigate cudetaxestat in IPF. Cudetaxestat is a non-competitive autotaxin inhibitor for fibrotic diseases.
The FDA informed Blade that it has completed its 30-day safety review of the IND and indicated that the Company may proceed with its proposed clinical investigation for IPF. Blade plans to initiate the IND-opening phase 1 study (NCT04939467) in the United States to assess the effect of cudetaxestat on the pharmacokinetics of the two FDA-approved therapies for IPF (pirfenidone and nintedanib). This study in healthy subjects is projected to start in the second half of 2021 and complete in the first half of 2022. Study results will be used to inform the design of a planned phase 2 clinical trial to evaluate the efficacy and safety of cudetaxestat in patients with IPF, anticipated to start in the first half of 2022.
“We are excited about this important regulatory step that supports the development path for cudetaxestat, a highly differentiated small-molecule investigational therapy that targets a clinically validated pathway in IPF,” said Wendye Robbins, M.D., president and CEO of Blade. “We are focused on advancing cudetaxestat in pursuit of our mission to bring life-changing treatments to patients with intractable diseases.”
Blade is currently conducting two additional ongoing phase 1 studies of cudetaxestat in healthy volunteers, which remain on track and are expected to complete in the second half of 2021. One study (NCT04814472) is investigating the relative bioavailability of a new tablet formulation of cudetaxestat to the current oral solution formulation. The second study (NCT04814498) is evaluating the effect of cudetaxestat on the pharmacokinetics of a combination of probe substrates for CYP450 enzymes. The Company previously completed a single ascending dose and multiple ascending dose phase 1 study of cudetaxestat in healthy subjects (NCT04146805).
Cudetaxestat (BLD-0409), a non-competitive, reversible inhibitor of autotaxin, has demonstrated direct anti-fibrotic activity and differentiating pre-clinical and biochemical characteristics which support the potential for a treatment profile in lung and liver fibrosis. Available data from a completed phase 1 study showed that cudetaxestat was well tolerated with a demonstrated pharmacokinetic / pharmacodynamic correlation and biomarker activity, and a supportive clinical safety profile. Orphan drug designation for cudetaxestat in the treatment of IPF was granted by the FDA in February 2021. Cudetaxestat is an investigational medicine that is not approved for commercial use by the FDA or any other regulatory authority.
Pro-fibrotic processes are stimulated by autotaxin, a key enzyme responsible for generating the potent signaling lipid lysophosphatidic acid (LPA). Excessive autotaxin levels and activity play a central role in various fibrotic diseases and occur in response to epithelial cell/tissue damage, leading to elevated levels of LPA. Lysophosphatidic acid binds to LPA receptors on myofibroblasts, thereby triggering a signaling cascade that leads to myofibroblast activation/differentiation. Activated myofibroblasts produce extracellular matrix proteins that make up the fibrotic lesion (organ/tissue scarring). Increased autotaxin levels and activity are associated with liver, lung, kidney, and skin fibrosis. In addition, autotaxin levels correlate with fibrosis severity in various liver diseases (e.g., nonalcoholic fatty liver disease / nonalcoholic steatohepatitis (NASH)). Inhibition of the autotaxin pathway has been clinically validated in IPF.
Fibrosis is a complex, pathologic process involving the development of organ/tissue scarring characterized by deposition of extracellular matrix proteins that develop in response to aberrant cell/tissue damage. Excessive fibrosis disrupts normal architecture and function of organs/tissues. Later-stage fibrotic disease is marked by poor outcomes and high morbidity and mortality. Diseases characterized by uncontrolled, progressive fibrosis include IPF, interstitial lung disease, and NASH. New well-tolerated therapies that provide robust attenuation of disease progression are needed to address the high burden of fibrotic and neurodegenerative diseases.
