Cogent Biosciences Inc. (COGT:NASDAQ) initiated Part 2 of the Apex Phase 2 clinical trial of bezuclastinib (CGT9486) in advanced systemic mastocytosis, Wedbush analyst Dr. David Nierengarten reported in an April 17 research note.
Given the positive data from Part 1 and "the higher predicted clinical exposure of bezuclastinib's optimized formulation, we believe that Apex Part 2 is likely to succeed," Nierengarten wrote.
The analyst reiterated Wedbush's Outperform rating and US$20 per share price target on the Massachusetts-based biotech. In comparison, Cogent is currently trading at about US$10.84 per share.
Part 2 Enrollment Goals
For the main efficacy group in Apex's Part 2, about 65 patients will be enrolled, Nierengarten relayed and administered bezuclastinib. This is Cogent's selective and potent inhibitor of KIT (D816V), a common mutation in systemic mastocytosis and gastrointestinal stromal tumor.
Patients will receive 150 milligrams (150 mg) of bezuclastinib once daily versus the 100 mg twice daily administered in Part 1. The optimized 150 mg dose is expected to have greater clinical exposure than the 100 mg, the analyst wrote.
Nierengarten noted that other cohorts are planned for Part 2 as well. One will consist of up to 20 patients with systemic mastocytosis and an associated hematologic neoplasm. Another group will comprise up to 15 patients with inevaluable modified IWG disease without C-findings. A third cohort of up to 10 patients will receive bezuclastinib 300 mg daily "to assess the effect of exceeding IC90 KIT D816V engagement," wrote Nierengarten.
Completion of Part 2 enrollment is anticipated around year-end 2024.
Part 1 Results
Cogent previously reported data from the Part 1 portion of the Phase 2 study, which were positive, at the annual American Society of Hematology meeting in December 2022. Since then, efficacy and safety have remained the same.
Later this year, in H2, the company expects to present, also at a medical conference, updated Part 1 clinical data for about 30 patients.
Positive Preclinical Data
Nierengarten also discussed in his research report Cogent's recent update on some of its other inhibitor candidates. The biotech provided preclinical data for two of them: CGT3103 and CGT1786.
CGT3103 is Cogent's noncovalent, reversible inhibitor of FGFR2. Results of pharmacokinetic studies in mice and rats showed that CGT3103 covered FGFR2 for 12 hours and demonstrated greater selectivity for FGFR2 over FGFR1 than approved pan FGFR inhibitors did.
"The data suggest that Cogent's FGFR2 candidate may be able to effectively treat patients with gatekeeper and molecular brake mutations while avoiding the dose-limiting hyperphosphatemia associated with FGFR1 inhibition," Nierengarten wrote.
Cogent's CGT1786, an early inhibitor of ErbB2, or HER2, showed cellular activity against a handful of oncogenic mutations in preclinical studies. Compared to tucatinib, it demonstrated better inhibition of pErbB2 and BT474 as well as superior efficacy in terms of tumor growth inhibition.
The biotech's next generation ErbB2 inhibitors, CGT2724 and CGT4069, showed superior central nervous system penetration of about 40% and better human whole blood stability at around 24 hours.
All of the preclinical results indicate Cogent's ErbB2 inhibitors "block all key resistance (YMVA, S310F, V842I) and primary driver mutations while sparing WT EGFR, which should help avoid adverse events including diarrhea, stomatitis, and hepatotoxicity," wrote Nierengarten.
Cogent is still working toward identifying a clinical candidate for its ErbB2 program.
In the Near Term
What investors can expect soon, in H1/23, is lead-in data from Cogent's Peak Phase 3 study of bezuclastinib plus sutent in gastrointestinal stromal tumor. Wedbush expects the results to be positive, Nierengarten noted.
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Disclosures For Wedbush, Cogent Biosciences, April 17, 2023
Analyst Certification: We, David Nierengarten and Dennis Pak, certify that the views expressed in this report accurately reflect our personal opinions and that we have not and will not, directly or indirectly, receive compensation or other payments in connection with our specific recommendations or views contained in this report.
Company Specific Disclosures:
1. WS makes a market in the securities of Cogent Biosciences.
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