Blade Therapeutics Initiates Additional Phase 1 Clinical Study of Cudetaxestat, a Non-Competitive Autotaxin Inhibitor in Clinical Development for Idiopathic Pulmonary Fibrosis

• Phase 1 clinical study to assess effect of cudetaxestat on pharmacokinetics of two approved therapies for idiopathic pulmonary fibrosis (IPF)

• Company on track to initiate planned phase 2 clinical study of cudetaxestat in IPF in 1H-2022

Blade Therapeutics, Inc. (Blade or the company), a biopharmaceutical company focused on developing cutting-edge treatments for debilitating fibrotic and neurodegenerative diseases, today announced the initiation of a phase 1 drug-drug interaction clinical study of cudetaxestat, an investigational non-competitive autotaxin inhibitor in clinical development for IPF. Enrollment has opened for this study to assess the effect of cudetaxestat on the pharmacokinetics of two approved drugs for IPF – pirfenidone and nintedanib – in healthy volunteers (NCT04939467). The study is projected to be completed in the first quarter 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, which is anticipated to start in the first half of 2022.

“Blade continues to make progress advancing the clinical development program for cudetaxestat,” said Wendye Robbins, M.D., president and CEO of Blade. “We are encouraged by the recent achievement of several development milestones for cudetaxestat and look forward to executing on the planned path ahead.”

In addition to today’s announcement, the company has recently achieved the following milestones:

• Orphan drug designation granted by the U.S. Food and Drug Administration (FDA) for cudetaxestat for the potential treatment of systemic sclerosis (SSc) (click here);
• Positive data from a preclinical in vivo drug-drug interaction study of cudetaxestat when co-administered at steady state with nintedanib (click here);
• Completion of phase 1 clinical study investigating the relative bioavailability of a new tablet formulation of cudetaxestat to the oral solution formulation (click here); and
• FDA activation of an Investigational New Drug application to investigate cudetaxestat in IPF (click here).

The company is currently conducting a phase 1 study of cudetaxestat in healthy volunteers to evaluate the effect of cudetaxestat on the pharmacokinetics of a combination of probe substrates for CYP450 enzymes (NCT04814498). The study remains on track and is expected to be completed in the fourth quarter of 2021.

Cudetaxestat

Cudetaxestat (BLD-0409), a non-competitive, reversible inhibitor of autotaxin, has demonstrated direct anti-fibrotic activity and differentiating preclinical and biochemical characteristics which support the potential for a treatment profile in lung and liver fibrosis. Available data from completed phase 1 studies showed that cudetaxestat was well tolerated with a demonstrated pharmacokinetic/pharmacodynamic correlation and biomarker activity, and a supportive clinical safety profile. Cudetaxestat has been granted orphan drug designations in the treatment of IPF and SSc. Cudetaxestat is an investigational medicine that is not approved for commercial use by the FDA or any other regulatory authority.

Autotaxin

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. LPA 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

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.

Blade Therapeutics

Blade Therapeutics, Inc. is a biopharmaceutical company focused on developing cutting-edge treatments for debilitating, incurable fibrotic and neurodegenerative diseases that impact millions of people worldwide. The company has deep expertise in novel biological pathways – including autotaxin / LPA and calpain biology – that are foundational to cell- and tissue-damage responses resulting from protein deposition or aggregation associated with fibrotic and neurodegenerative diseases. Blade expects to advance a differentiated pipeline of oral, small-molecule therapies that include a non-competitive autotaxin inhibitor and inhibitors of dimeric calpains designed for potential treatment of lung, liver and cardiac fibrosis or neurodegenerative diseases. The company’s focused approach offers the potential to produce disease-modifying, life-saving therapies. Visit www.blademed.com for more information and follow Blade on LinkedIn.

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Blade Therapeutics announces initiation of phase 1 clinical study to assess effect of cudetaxestat on pharmacokinetics of two approved therapies for idiopathic pulmonary fibrosis. Study is projected to be completed in 1Q-2022.