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Cassava Sciences updated Phase 2b results released this week are everything (and more) one could have hoped for. This study had 64 patients in a 1:1:1 triple arm randomized double controlled placebo trial for 28 days: The three arms were 50mg sumifilam BID, 100mg sumifilam BID and a matching placebo.
Biomarkers of AD (Alzheimer’s disease) pathology improved in 98% of patients on sumifilam (formerly PTI-125); compared to those on placebo. The Total Tau and PT-181 tau levels were lower on patients on sumifilam and amyloid beta (AB42) levels were higher. Note: Tau levels are higher in AD patients and AB42 levels are lower; so they moved in the desired direction with the medicine. Tau levels are higher in AD patients because as neurons die, they release Tau in the CSF (Cerebrospinal fluid). AB42 levels are lower in AD patients because AB42 binds with receptors alpha7nAChR (causing hyper phosphorylation of tau) and TLR4 (causing release of inflammatory cytokines). Besides improving on the biomarkers of AD pathology; 98% of patients on Sumifilam also had reduction in biomarkers of neurodegeneration (Neurogranin and Neurofilament light chain NfL) and of neuroinflammation (YKL-40, IL-6 and sTREM2); compared to those on placebo. There was minor (but statistically insignificant) cognition (spatial and episodic memory) improvements in patients on sumifilam; but 28 days is too short a time to make a judgement on that aspect. As a reminder of previous events, earlier Phase 2a results announced couple months ago were disappointing. However, those results were deemed to be bogus because of several factors: huge variability of biomarkers in patients on placebo; related biomarkers moving in opposite directions; and related biomarkers having no (or very little) correlation. The new results don’t have any of those issues and are deemed to be correct. The company currently has an ongoing open label study with 100 patients on 100mg BID of sumifilam; and this study is 50% enrolled. The Principal Investigator (PI) of that study mentioned minor empirical improvements in cognition in couple of patients after 2-3 months of being on the medicine. Next steps: The company is going to meet with the FDA early next year to close out the Phase2b study. They are going to continue the open label study and they have received more enrollment interest in that study since the updated Phase2b results announcement. The company is going to start preparing for Phase 3 study; which is not likely to start until late 2021 and very likely to take 3 or more years after that to have any conclusive results to report. So, any conclusive Phase 3 results (and therefore, a possible approval for the drug; if results meet the FDA requirements and expectation) is likely not going to come before end of 2024. Phase 3 study will be multi-center with a significantly larger number of patients than Phase 2b study. The company will start preparing to get medicine supply for usage in Phase 3. Phase 3 studies require large amounts of money (at least $100M); and the company will either need to raise money thru an equity or debt offering. If there is an equity offering; it would result in significant equity dilution for existing shareholders. It is also possible the company may partner with another company for Phase 3 study and it is also totally possible another company may just buy out Cassava. I need to reiterate that the pharma landscape is littered with companies that have failed drugs for the treatment of AD. Most of these companies took the approach of reducing amyloid plaque in the brain; or some variation of that approach. Cassava’s is a totally unique approach in that its molecule, sumifilam, binds to altered FLNA protein; corrects the protepoathy of FLNA; which in turn corrects the downstream effects that contribute to AD. Regarding investment in the company, investors need to ask themselves: what is the worth of a company with a promising drug for AD patients; which has had promising results in Phase 2a (single arm; 13 patients) and Phase 2b (triple arm; 64 patients). One has to remember that if the Phase 3 results are not as expected by the FDA and in which case the drug is not approved; the company’s worth (and the investment in the company) may well come down to zero. All investors have their own risk/reward appetite and profile (based on their personal overall situation) and they should consider that before making a decision to invest in the company. The company’s current market cap is roughly $270M; that includes the dilution due to outstanding warrants.
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Manish JThis page is to document my day to day thoughts on Investing in stocks. Archives
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