• In Phase 1 studies, cudetaxestat displayed low potential for drug-drug interactions when dosed with approved therapies for idiopathic pulmonary fibrosis (IPF) and other commonly used medications
  • Cudetaxestat was well tolerated and showed no reports of treatment-related serious adverse events, including when co-administered with either pirfenidone or nintedanib, in healthy volunteers
  • Cudetaxestat, an investigational non-competitive autotaxin inhibitor, demonstrated robust preclinical activity on numerous fibrosis markers and regulation of key fibrotic genes
  • Blade plans to advance cudetaxestat into phase 2 clinical trial dosed either as monotherapy or co-administered with pirfenidone or nintedanib in patients with IPF

SAN FRANCISCO, CA, USA I September 04, 2022 I Blade Therapeutics, Inc., a clinical-stage biopharmaceutical company developing cutting-edge treatments for debilitating fibrotic and neurodegenerative diseases, today announced the presentation of positive data from Phase 1 and preclinical studies of cudetaxestat, an investigational non-competitive autotaxin inhibitor in clinical development for IPF and other fibrotic diseases. The data were featured in a poster (abstract #PA459) presented today at the European Respiratory Society (ERS) International Congress 2022, which is taking place in Barcelona, Spain, from September 4-6, 2022.

“Cudetaxestat is a potential first-in-class, non-competitive autotaxin inhibitor with robust preclinical antifibrotic activity and good PK/PD correlations in Phase 1 clinical trials,” said Bassem Elmankabadi, M.D., senior vice president of clinical development with Blade and lead author of the poster. “The body of available data provides a strong rationale to move forward into Phase 2 clinical development of cudetaxestat in IPF, dosed either as monotherapy or concomitantly with approved therapies.”

The poster (click here for PDF), titled “Cudetaxestat, a differentiated phase 2-ready investigational treatment for idiopathic pulmonary fibrosis,” was presented in session TP-24: Interstitial lung diseases diagnosis in the COVID-19 era: new tools for new challenges. Data analyses were included from a battery of preclinical studies that assessed the potency and activity of cudetaxestat, and four Phase 1 studies of healthy volunteers (N=216) that evaluated safety/tolerability along with pharmacokinetic (PK) and pharmacodynamic (PD) activity.

Results of analyses from preclinical studies showed that cudetaxestat maintained potency against its target in vitro regardless of substrate (lysophosphatidylcholine, or “LPC”) concentration and demonstrated significant anti-fibrotic activity in multiple in vivo preclinical models. Across the phase 1 clinical studies, there were no drug-related serious adverse events (SAE’s), including in a study where cudetaxestat was dosed concomitantly with either of the approved therapies for IPF (nintedanib or pirfenidone). Based on available data, authors of the poster made the following conclusions:

  • Non-competitive autotaxin inhibition provides differentiated characteristics with no loss of potency under high substrate (LPC) conditions;
  • Cudetaxestat demonstrated robust preclinical activity on numerous fibrosis markers and regulation of key fibrotic genes;
  • Cudetaxestat displayed low potential for drug-drug interactions when dosed with approved therapies for IPF and other commonly used medications; and
  • Multiple PK and PD parameters provide clear rationale for Phase 2 dose-selection.

For additional information about the ERS International Congress 2022, please visit the website.

About Cudetaxestat
Cudetaxestat (BLD-0409), which is Blade’s lead investigational medicine, is a non-competitive autotaxin inhibitor with direct anti-fibrotic activity and differentiating characteristics that is expected to enter a planned phase 2 clinical trial in patients with idiopathic pulmonary fibrosis. Available data from four completed phase 1 studies in more than 200 healthy volunteers showed that cudetaxestat was well tolerated with a demonstrated pharmacokinetic/pharmacodynamic correlation and biomarker activity. Cudetaxestat has been granted orphan drug designations in the treatment of IPF and systemic sclerosis. 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. LPA binds to LPA receptors on myofibroblasts 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. Inhibition of the autotaxin-LPA 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 diseases.

About Blade Therapeutics
Blade Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing cutting-edge treatments for debilitating, incurable fibrotic and neurodegenerative diseases. The company has deep expertise in novel biological pathways – including autotaxin / LPA and calpain biology – that are foundational to cell- and tissue-damage responses associated with fibrosis and neurodegeneration. Blade’s focused approach offers the potential to produce disease-modifying, life-saving therapies. Blade expects to advance a differentiated pipeline of oral, small-molecule therapies that include a non-competitive autotaxin inhibitor and an inhibitor of dimeric calpains. Visit www.blademed.com for more information and follow Blade on LinkedIn.

SOURCE: Blade Therapeutics