KMB, More reasons for Leo to sell out... Trying to develop 3 drugs with a limited budget not only erodes shareholder confidence, it allows the competition to catch up or move ahead... Why would any "potential partner" trust Leo's limited budget/staff with their shareholder's cash when Leo couldn't help it's own shareholders? Exactly why Leo has drawn blanks. Makes more sense for complete sale for all parties involved.
Thanks KMBJN, I was aware of COTI-2, but did not know about Critical Outcome's difficulties. Good, because if one trusts Critical Outcome's press, COTI-2 is the one to watch. But, isn't that always the case with press releases. I have yet to see one that would tell the drug is mediocre at best but our Co is going to push it thru regardless in hopes that some nincompoop or extra income friendly doctors will prescribe it.
Aprea 246 - Qs surrounding it Posted this article a while back
Below
As others have noted, a number of p53 drugs in trials (none further than Ph2) and I haven’t come across one that acts on both wt and mut p53 like Kevetrin, what was pointed out by Shapiro in the 2015 ASCO abstract.
Kevetrin’s true Efficacy will only really be able to be established once dosed as Oral given its half-like, PK. Do think its brightest future might be as Combo — sensitizing CRT.
Would love to see P and/or B partnered and more $ plugged into K.
PRIMA-1 acts to restore the mutant p53 by modifying thiol groups in the core domains of the protein. Its success is well documented, with many studies in different cancer models proving its effectiveness. This, however, is not unanimous, with some questions being raised about its efficacy and other aspects such as possible resistance mechanisms as well as potentially harmful degradation products.
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Other potential issues
As well as potential issues concerning resistance, the Lambert et al. (2009) study on PRIMA-1 has raised a few further possible shortcomings of the drug. At 15 min, a sample of the solution containing PRIMA-1 and its degradation products was analysed using mass spectrometry and nuclear magnetic resonance. This showed the mixture to contain three compounds, methylene quinuclidinone and two unknown compounds. (For their structures, see Lambert et al. (2009), Fig. 1). It would therefore be imperative that the effects of these unknown compounds were investigated fully, as well as those of the PRIMA itself, to ensure that the drug will be suitable for clinical use. Lambert et al. (2009) also stated that another breakdown product of PRIMA-1 is formaldehyde. Formaldehyde has been classified as a known human carcinogen by the International Agency for Research on Cancer (National Cancer Institute, 2014a); however, the potential implications of this have not yet been assessed in a PRIMA-1 study.
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