Hi gnawkz, appreciate the candor.
Yes you are right, stable disease (SD) is a range from 29% shrinkage to 24% growth, anywhere in between. 30% - 99% shrinkage across the sum of all target lesions is a partial response (PR). No PRs and an untold number with SD at the time of yesterday's presentation for Direct trial patients. Saying how many are alive and how many have died and for how long of course gives us no indication of progression status. But when a small cap bio fails to report on PFS or SD it has been my experience that it's because those data aren't flattering. Why do you think NW failed to report it?
I would agree it's not applicable to the entire group. But it could easily be the majority are very slow progressors. Being stage IV does not automatically mean the cancer is swiftly progressing, and from MDA they had hundreds to select from. There are over 10 major indications present here. To find that probable 5% among all these in 39 patients is quite doable. It seems some of those enrolled early on (except the first handful) were also not screened with the same stringency (just >3 months life expect) and so they changed it mid stream to >6 months life expect and added the high lymphocyte count requirement also. Of course, that would cause a selection bias of longer tail survivors. I would expect the OS to look as it does.
They are certainly proceeding with scientific vigor, I agree. I only contend the slides and manner in which they are selecting which data to present and which to keep concealed, seeking to portray the therapy as being as effective as the number massaging can allow, is disingenuous and harmful to the less savvy retail investor. I'm not seeking to defend or help the retail investor but to simply state my observations. However the process is moving along as it should. If the small Ph IIs (20 patients each) show more signals or greater signals of efficacy, then a larger randomized Ph II is the next proper step with a placebo group and PFS/OS co primary end points, imo.
For life expectancy every patient has been given a specific window, and indeed it is a requirement to gain entrance into the trial (now > 6 months). With a slower progression rate, which is measured every 2 months or so, a patient can live a number of years with stage IV cancer. There are some 5%-20% depending on indication who fall into this category (2-5 years life expect or better). With the vast pool of interested patients to choose from, those running a Ph I study will seek to choose those with the best prognosis who still fit their broad trial criteria to give their experimental tx the best shot at working. It makes sense of course, but looking at Ph I data as a result is always misleading. Recall that GBM patients in IMUC's Ph I had a mOS of some 38 months, and around 40% lived over 5 years. Sounds like a miracle, doesn't it? And yet how did the randomized Ph II do? Mediocre by comparison.
I do believe the resizing is due to whole group event rates being lower than would have been anticipated by now. The trial had assumed placebo group showing a mPFS of 7 months and tx group at 13.5. That's a whole group event rate of 11.3 (2:1 allocation). If the whole group event rate is 14 months mPFS then both groups could very well be 14 months mPFS and they would increase n. It could also mean placebo is performing better than tx group or vice versa, sure. It's too variable to nail down a per group determination, especially with the low placebo group estimate (just 7 months).
If the total n is an odd number the median is rounded down. Of course with small n that becomes a larger % drop. However in the Direct Ph I the NET pancreatic cancer patient is really a separate indication with a much longer mOS. There are really just 6 of the same indication and the median for the first three passing was within 3.9 months. Therefore in this small Ph I the mOS of pancreatic cancer patients is only 3.9 months. Given how aggressive that indication usually is it would be very hard to cherry pick patients. This may be the most accurate look at how Direct stacks up in against an aggressive stage IV cancer.
Lastly it depends on your definition of "success." Do I think they will show objective response rate (ORR) this time? Actually yes I think one or two patients will show a genuine partial response. Survival endpoints will not be qualifiable without a randomized control, which these small Ph IIs will not have. But the ORR seen will be greatly overshadowed by the much higher ORR seen in checkpoint inhibitor (CI) trials, suggesting no sales upon approval of Direct were it to be granted on such data. They either have to show better ORR than CI, greater ORR in combination with CI than CI alone, or greater mOS/mPFS than CI in a large randomized study.
Jmo.
Sorry if that was hard to follow, I can't copy your text as on phone, so I just answered each paragraph in order.
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