Blade Therapeutics Presents Data from Phase 1 and Preclinical Studies of Cudetaxestat at the American Thoracic Society 2022 International Conference
- No significant drug-drug interaction (DDI) seen with cudetaxestat in combination with either pirfenidone or nintedanib, two approved therapies for idiopathic pulmonary fibrosis (IPF)
- Cudetaxestat was well tolerated and showed no reports of treatment-related serious adverse events when co-administered with either pirfenidone or nintedanib in healthy volunteers
- In vivo pharmacokinetics study showed no significant effect of cudetaxestat on pirfenidone or nintedanib exposures when co-administered with either medication
- Company on track to start phase 2 clinical trial of cudetaxestat dosed either as monotherapy or co-administered with pirfenidone or nintedanib in patients with IPF in second quarter of 2022
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Blade Therapeutics Inc., a biopharmaceutical company focused on developing cutting-edge treatments for debilitating fibrotic and neurodegenerative diseases, today announced encouraging data from phase 1 and preclinical DDI studies of cudetaxestat, an investigational non-competitive autotaxin inhibitor in clinical development for IPF and other fibrotic diseases. These data were featured in poster presentations at the American Thoracic Society (ATS) 2022 International Conference, taking place May 13-18, 2022, at the Moscone Center, in San Francisco.
"These positive results from clinical and preclinical drug-drug interaction studies reinforce our confidence in the potential to co-administer cudetaxestat on top of currently approved IPF therapies in clinical studies of patients with IPF,” said Wendye Robbins, M.D., president and CEO of Blade. “With an extensive phase 1 clinical program now complete, we are ready to start a planned phase 2 clinical trial of cudetaxestat for the treatment of IPF in the second quarter of 2022.”
Phase 1 DDI Study with IPF Standard of Care Therapy
The phase 1 drug-drug interaction study assessed the effect of cudetaxestat 750mg on the pharmacokinetics (PK) of two approved drugs for IPF – pirfenidone and nintedanib – in 83 healthy adult volunteers who completed the study (NCT04814498). Results of the study showed:
- Neither nintedanib nor pirfenidone significantly alter the exposure of cudetaxestat;
- Cudetaxestat does not affect the PK of pirfenidone;
- Cudetaxestat does not significantly increase the exposure of nintedanib (AUC(0-12));
- Most common treatment-related adverse events were mild gastrointestinal upset (diarrhea and nausea); and
- There were no treatment-related serious adverse events.
Study data were presented along with results from three additional phase 1 clinical studies of cudetaxestat in a poster (#420 – PDF available here) titled “Clinical Evaluation of Cudetaxestat for Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Drug-Drug Interactions.” Information about the ATS poster session (B22. Emerging Management of Fibrotic ILDs) is available here.
Preclinical Evaluation of Cudetaxestat (BLD-0409) for Potential Drug-Drug Interactions
The preclinical study was designed to understand whether the plasma concentration of nintedanib, which is a P-glycoprotein (P-gp) substrate, is altered when co-administered at steady state with either cudetaxestat or GLPG-1690 (ziritaxestat), an investigational competitive inhibitor of autotaxin. Results of the study conducted in a rat model showed:
- Ziritaxestat is a potent inhibitor (single-digit micromolar IC50 values) of P-gp when either quinidine or nintedanib is used as a substrate, and cudetaxestat is a weak P-gp inhibitor under similar conditions;
- Ziritaxestat significantly increased nintedanib exposure when co-administered in vivo in rats.
- Cudetaxestat did not alter nintedanib exposure when co-administered in vivo in rats; and
Study data were presented in a poster (#P424 – PDF available here) titled “Preclinical Evaluation of Cudetaxestat (BLD-0409) for Potential Drug-Drug Interactions (DDI’s).” Information about the ATS poster session (B36. Spectrum of Fibrotic Interstitial Lung Diseases) is available here.
Toby Maher, M.D., Ph.D., professor of medicine at USC Hastings Center for Pulmonary Research, Los Angeles, said, “There is a huge unmet need for new antifibrotic therapies which can complement current treatments and potentially provide greater benefit for patients in need of new treatment options. I look forward to collaborating with Blade as it advances the clinical development of this investigational therapy.”
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 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. 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-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 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. 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.
On November 8, 2021, Biotech Acquisition Company (NASDAQ: BIOT), a special purpose acquisition company affiliated with SPRIM Global Investments, and Blade announced that they have entered into a definitive merger agreement. Upon the closing of the transaction, the combined company will be renamed Blade Biotherapeutics, Inc., and is expected to be listed on Nasdaq under the symbol “BBTX.” PIPE financing is anchored by leading institutional investors, including Deerfield Management, Pfizer Ventures, Bristol Myers Squibb, MPM Capital and Osage University Partners. Click here for the latest information about this proposed merger.
About Biotech Acquisition Company
Biotech Acquisition Company raised $230 million in its initial public offering in January 2021. The Class A ordinary shares and warrants of BAC trade on the Nasdaq Capital Market under the symbols “BIOT” and “BIOTW,” respectively. BAC is a blank check company, incorporated as a Cayman Islands exempted company, formed for the purpose of effecting a merger, amalgamation, share exchange, asset acquisition, share purchase, reorganization or other similar business combination with one or more businesses. BAC believes that a business combination with a company focused on the healthcare sector will complement the background and expertise of SPRIM Global Investments, a global investment firm in the life sciences and healthcare industries, which is an affiliate of BAC and of several members of the management team behind BAC. BAC is led by Dr. Michael Shleifer, its CEO and chairman.
Important Information and Where to Find It
This press release relates to a proposed merger between Blade and BAC. This press release does not constitute an offer to sell or exchange, or the solicitation of an offer to buy or exchange, any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, sale or exchange would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. BAC has filed a registration statement on Form S-4 with the SEC, which includes a proxy statement/prospectus, to be used at the meeting of its shareholders to approve the proposed merger between Blade and BAC and related matters. Promptly after the registration statement is declared effective by the SEC, BAC will mail the definitive proxy statement/prospectus and a proxy card to each shareholder of BAC as of a record date for the meeting of BAC shareholders to be established for voting on the proposed business combination. Investors and security holders of BAC are urged to read these materials (including any amendments or supplements thereto) and any other relevant documents in connection with the transaction that BAC has filed or will file with the SEC when they become available because they will contain important information about BAC, Blade, and the transaction. The preliminary proxy statement/prospectus, the definitive proxy statement/prospectus and other relevant materials in connection with the transaction (when they become available), and any other documents filed by BAC with the SEC, may be obtained free of charge at the SEC’s website (www.sec.gov). The documents filed by BAC with the SEC also may be obtained free of charge upon written request to Biotech Acquisition Company, 545 West 25th Street, 20th Floor, New York, NY 10001.
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Source: Blade Therapeutics, Inc.