Clarity's EXPANDING PIPELINE: Why I think today's Announcement was significant!
a) BREAST CANCER: That this is a really huge indication is no secret. I know that Sar-BOMBESIN is in breast cancer as well, but the absence of HER2 targetting made Cu6 look thin in the area (I felt). With the Sar-bis platform turning out to be as good as it is, it's a fantastic development.
b) The PLATFORM: This announcement is confirmation of what we have been told before: "We have a PLATFORM, from which we can develop a myriad of diagnostics and treatments ... we can develop 10, 20, 30, 40, 50 products from our platform ... we want to be broader .... "! So, it matters to me that the company is staying true by bringing out the products that the platform is capable of churning out. And, not only that: there are results from preclinical work, and it is clear that this platform is beyond what others have . Many companies or company products get bought with this kind of data!
c) TWO in Ones: This is one of those things that we might not be fully appreciating. These new products are coming in PAIRS, not singles. The diagnostic (Cu64) in Cu-64/67 SAR-trastuzumab, will have a place with or without the therapy (Cu67). As with Sar-bisPSMA, we can expect the diagnostic to be developed faster, meaning that the super-powers that 'Perfect Paring' brings as a true theranostic pair much arrive later, once the therapy is through its own trials. If this was another company, we would have had 2 separate announcements, because they can only do one at a time!
--- DELAYS Are A Bore? BUT Doing it Right now can save time later!
ONE great route to saving time is via the sample size!
HOW and WHY did COBRA finishearlier than planned? That's because of the results! They were so good that Clarity ended up needing fewer patients.
HOW come AMPLIFY requires such a smaller sample size than CLARIFY? The sample size for AMPLIFY was reached after Clarity had both PROPELLER and COBRA results! They (and the FDA) came up with a sample size that is so much smaller (220 patients versus 393 needed in CLARIFY)! While I am not privy to those discussions or the exact facts that influenced the calculation, I know that the statistics behind sample size calculations rely quite heavily on the size of the gap between treatment arms: the desired gap between what the new intervention (64Cu-Sar-bisPSMA) is projected to achieve versus the control (in our case, SOC - Pylarify, Illuccix, etc)! The bigger the gap, the fewer the number needed to show that difference, with sufficient power. So, AMPLIFY should get across the line quicker than we would have done if we hadn't done the good work before now! [I know that safety committees do stop trials early if the advantage is huge but thats not something to rely on - esp when follow up is long]!
As for the SECURE TRIAL: Determining the optimal dosing of 67Cu-Sar-bisPSMA is essential, not just for the benefits of patients, but for later time saving! We need a large enough dose to kill cancer cells but not too large to harm the human, and we want to use the right number of cycles to keep the cancer dead while minimising side effects, etc! The optimum dosage and dosing schedule will be used in the expanded cohort, and should help SECURE achieve the best possible results possible. Results of that cohort will then get factored into the design of the next trial, a Phase 3. So, on the subject of sample sizing, we can expect that the large gap in efficacy achieved, will then help lower the number (sample size requirement) for the Phase 3. Suboptimal dosing, on the other hand, creates a tiny gap, and that requires huge numbers as one tries to show a small difference. Also, as we know, suboptimal dosing has a higher risk of failing to meet endpoints! Yes, there are other considerations too, including an inflation % that gets built in to help cushion - in case some data is not analysable. There will be other issues too for generalisability, but I hope the point is made!
--- The smaller the difference, the larger the sample size required to achieve the often used 5% level of statistical significance. --- Playing around using this calculator can demonstrate - see references and links at the bottom.
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