Blade Therapeutics Presents Preclinical Data Highlighting Differentiating Characteristics of Cudetaxestat at the American Thoracic Society 2022 International Conference
- Cudetaxestat displayed direct anti-fibrotic effects on multiple biomarkers in a preclinical lung fibrosis model
- Non-competitive autotaxin inhibition by cudetaxestat maintained potency in the presence of elevated substrate concentrations found in fibrotic tissues
- Company on track to start phase 2 clinical trial of cudetaxestat in patients with idiopathic pulmonary fibrosis (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 new data from preclinical studies that highlight the differentiating characteristics of cudetaxestat, an investigational non-competitive autotaxin inhibitor in clinical development for IPF and other fibrotic diseases. These data were featured in a poster presentation at the American Thoracic Society (ATS) 2022 International Conference, taking place May 13-18, 2022, at the Moscone Center, in San Francisco.
"We are encouraged by the profile of cudetaxestat, which we believe is a clearly differentiated molecule based on its direct anti-fibrotic activity and non-competitive inhibition of autotaxin,” said Wendye Robbins, M.D., president and CEO of Blade. "We look forward to advancing cudetaxestat into the next phase of clinical development as we execute on our mission to bring life changing treatments to people with fibrotic diseases.”
Preclinical in vitro analyses assessed the potency of cudetaxestat and a competitive autotaxin inhibitor (GLPG-1690) under varying concentrations of a substrate (lysophosphatidylcholine or “LPC”) found in fibrotic tissues. Additional evaluations using mouse models assessed the impact of cudetaxestat on multiple biomarkers of lung fibrosis. Key findings include the following:
- Non-competitive autotaxin inhibition with cudetaxestat maintained biochemical potency in the presence of elevated LPC concentrations;
- In a mouse model of lung fibrosis, cudetaxestat displayed direct anti-fibrotic activity (reduced αSMA, Col1A1 expression, reduced fibrosis, and assembled collagen); and
- Inhibition of the autotaxin/lysophosphatidic acid pathway by cudetaxestat significantly reduced activation (gene expression) of several key pro-fibrotic pathways.
Study data were presented in a poster (#815 – PDF available here) titled “Differentiating Characteristics of Cudetaxestat (BLD-0409), a Non-Competitive Autotaxin Inhibitor Under Development to Treat Idiopathic Pulmonary Fibrosis.” Information about the ATS poster session (D29. Mechanisms in Lung Injury, Repair, and Fibrosis) is available here.
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.
Participants in the Solicitation
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These forward-looking statements are subject to a number of risks and uncertainties, including, the inability of the parties to successfully or timely consummate the Transaction, including the risk that any required regulatory approvals are not obtained, are delayed or are subject to unanticipated conditions that could adversely affect the Combined Entity or the expected benefits of the Transaction, if not obtained; the failure to realize the anticipated benefits of the Transaction; matters discovered by the parties as they complete their respective due diligence investigation of the other parties; the ability of BAC prior to the Business Combination, and the Combined Entity following the Business Combination, to maintain the listing of the Company’s shares on Nasdaq; costs related to the Transaction; future financial performance of the Company following the Business Combination; the ability of the Company to forecast and maintain an adequate rate of revenue growth and appropriately plan its expenses; expectations regarding future expenditures of the Company following the Business Combination; the future mix of revenue and effect on gross margins of the Company following the Business Combination; the Company’s ability to execute its business plans and strategy; the failure to satisfy the conditions to the consummation of the Transaction, including the approval of the definitive merger agreement by the shareholders of BAC, the satisfaction of the minimum cash requirements of the definitive merger agreement following any redemptions by BAC’s public shareholders; the risk that the Transaction may not be completed by the stated deadline and the potential failure to obtain an extension of the stated deadline; the inability to complete a PIPE transaction; the outcome of any legal proceedings that may be instituted against BAC or the Target related to the Transaction; the attraction and retention of qualified directors, officers, employees and key personnel of BAC and the Target prior to the Business Combination, and the Company following the Business Combination; the ability of the Company to compete effectively in a highly competitive market; neither BAC nor the Target are currently generating revenues and there can be no assurance that following the Business Combination, the Company will ever achieve revenues or profitability; the ability to protect and enhance the Target’s respective corporate reputation and brand; the impact from future regulatory, judicial, and legislative changes in the Target’s or the Company’s industry; the timing, costs, conduct, and outcome of clinical trials and future preclinical studies and clinical trials, including the timing of the initiation and availability of data from such trials; the timing and likelihood of regulatory filings and approvals for product candidates; whether regulatory authorities determine that additional trials or data are necessary in order to obtain approval; the potential market size and the size of the patient populations for product candidates, if approved for commercial use, and the market opportunities for product candidates; the ability to locate and acquire complementary products or product candidates and integrate those into the Company’s business; and, the uncertain effects of the COVID-19 pandemic; and those factors set forth in documents of BAC filed, or to be filed, with SEC. 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Source: Blade Therapeutics, Inc.