It's almost 30 months to the day that we received (to much enthusiasm) this announcement that the pre-clinical work underpinning the Sheba 2 trial had been published, showing significant synergy with Bisantrene and the other drugs in the chosen combination and a general enthusiasm to get it into the clinic. At the time the share price was ~$3.45.
Here we are finally about to get our first look at some results from this trial, and the share price is down over 75% from then - including a ~10% drop on Monday and another 10% drop today - at 83 cents.
And now we're all apparently worried that the trial has been a disaster and is going to result in a total collapse of the share price. I'm not sure how we measure sentiment but it seems to me we must be pretty close to scraping the bottom of the barrel at the moment.
Personally, I'm with
@Titans19 and feel we have reason to be positive about this trial for several reasons:
- Pre-clinical synergism in the drug combination. This synergism will hopefully help to counteract the issues around resistance and dose duration that have been mentioned.
- Dose escalation phase resulted in a 50% RR including 3 patients bridged to a transplant. Of the Sheba 1 respondees, I believe only one was bridged to a transplant.
- Further, although 6 patients were dosed in the dose escalation phase, only 5 were evaluated for a response as the 6th person unfortunately died due to infection. So actually we don't know whether the 6th person responded or not as they were not assessed for a response, but 3 out of 5 assessed patients responded (which is actually a 60% response rate from those who were assessed).
- The clinical update mentioned that "Observations in this open label protocol have been compelling". As per the Oxford dictionary -
compelling adjective evoking interest, attention, or admiration in a powerfully irresistible way; not able to be refuted; inspiring conviction.
- As at the clinical update, the decision to cease recruitment and report at the first stage decision point had been made (7 of 9 patients in that stage had been recruited). According to the trial protocol they needed 3 responses from the maximum recruitment of 17 patients in stages 1 and 2 to refute the null hypothesis. I believe that means at least 3 of those 7 patients recruited in the Simon stage 1 must have responded (so a minimum 43% response rate at that time). Had the trial instead been abandoned for futility, I think a different announcement would be warranted, and such results could hardly be described as compelling.
- The strategic update had two further AML combination trials planned. If this combination trial was a disaster, would it really make sense to pursue two more AML combo trials in quick succession?
- For the first Sheba trial, Race was provided an initial summary of results, and the publication was made at a later date. This time results are going straight to publication. Perhaps that implies that the results are more significant (academically at least).
- Has a Bisantrene AML trial ever produced what would be considered a "poor" result? Bisantrene hasn't let us down yet and surely it has seen its share of heavily treated patients in the past. Let's hope now is not the first time.
Yes of course there's also a chance that things have not panned out 100% in our favour. As with any trial there is some luck of the draw in terms of patients that can be recruited, prior lines of treatment, how they respond on the day etc. It's not an exact science. Even if the response rate is not has high as we expect, what is more significant is what that response rate means for the future of Bisantrene. For example, if the outcome of the trial is significant enough that it makes the commercial case for advancing Bisantrene as an AML treatment more "compelling", to the point where the data can be used by Race as the basis for a partnership/license/funding for future combination trials etc., that itself would be a brilliant outcome.
