Sorry for the lengthy post but I believe this is critical to my investment in PDS and it’s complicated but worth your time. Some of what is discussed below are facts that have been presented by the company or NCI followed by my interpretation/guess as to what it means. After you read this, you will understand why I am so excited about PDS potential, and why I believe the street is missing something incredible and why it is my largest investment.
In June 2021 we learned that 16 out of 18 HPV16++ patients were still alive at 8 months, an incredible outcome in such a difficult to treat group. This included 10/12 CPI refractory patients who are among the sickest patient population with a life expectancy of 3-4 months with current standard of care. The other 6 patients were CPI Naïve patients with a life expectancy of 7-11 months using current SoC and all of whom were still alive at 8 months. The NCI treated 7 HPV16 negative patients who did not meet the criteria for objective response, so they decided to stop treating this group. In summary, in June 2021 they reported on a total of 25 patients who were treated with the combo, 18 who are the targeted population and 7 who are not.
Last week we learned that among 37 evaluable patients (more on this below) the median survival was >12-months at 12/31/21. This is incredible when you look at the overall survival in current standard of care in this population group. Yesterday I received confirmation that the 37 patients included the 7 “off-target” HPV16 negative patients. Median means that half the patients are above a particular number and half are below. That would mean that median survival means half the patients (19) in this population survived for more than 12 months, and the other half (18) have not YET survived for at least 12 months.
At this point we don’t have the details that will come later in the year, but I believe we can infer some very important information. Here is where my speculation and interpretation of the data comes in. Please let me know if I am missing anything or not interpreting the data correctly.
The 37 evaluable patients include patients who have been treated with the combo therapy AND who have received the necessary scans to be considered evaluable, not necessarily that they were in the trial for more than 12 months at 12/31/21. This means it includes patients who were treated in 2020 AND patients who were first enrolled and treated in 2021. This is an important point to remember. Some of those who were treated and considered evaluable haven’t been in the trial for 12 months at 12/31/21 and still 19 out of 37 evaluable patients survived for more than 12 months. Think about how incredible that is but it gets even better.
When the full dataset comes out and we see the details, I believe that the >12-month survival milestone will be achieved by way more than 50% of those treated. I come to this conclusion based on the 37 patients included as evaluable. We know 7 evaluable patients were HPV16 negative. Those patients didn’t have Objective Responses to the treatment based on ASCO data and new enrollment was stopped as a result. I think since they didn’t respond we can unfortunately assume most of them did not achieve the 12-month survival milestone. This would leave 30 targeted patients included in the 37 evaluable. Remember, some of the 30 remaining were considered evaluable because they received treatment and had required scans but were first treated during 2021.
How many were first treated during 2021 and therefore couldn’t be included in the >12-month survival median? We know from ASCO that there were 18 on target patients treated for 8 months as of May 2021, meaning they were treated before 10/2020, 8 months before data cutoff for the presentation. We also know 16 out of these 18 were alive for at least 8 months and counting per ASCO.
There are 12 patients remaining in the target group (30 minus 18) that we don’t know when they were first treated. Even if we assume 1 per month for 12 months beginning 10/2020 forward, it means there were 3 patients treated in 2020 with the remaining 9 treated in 2021. If this assumption is close, that would mean that out of the 37 evaluable patients, 9 were treated in 2021 leaving 28 patients who were in the trial prior to 12/31/20.
We know 19 patients survived for more than 12 months per the HC Wainwright update where the median survival was greater than 12 months. If 19 out of 28 treated in 2020 survived for more than 12 months and 7 of the 28 were HPV16 negative, how incredible is that? Now assume most, if not all the HPV negative patients did not survive for >12 months, it would mean close to 19 out of 21 targeted patients achieved the >12-month survival milestone.
We know from the trial design that there will be 36 CPI refractory patients and 20 CPI naïve patients in the trial. The life expectancy of the refractory population is 3-4 months, and the life expectance of the naïve patients is 7-11 months. What is a reasonable assumption for the blended life expectancy of the treated group? Since there are more patients in the refractory population, using a blended average life expectancy of 5-6 months to compare to the median of > 12-months (and possibly growing) shows just how incredible the results are. This is what the street is missing.
This trial is in a very hard to treat population with a very high unmet need. When this trial completes and the data are available, how long will it take for the NCI to have meetings with the FDA for accelerated approval based on the study assuming the full data are as good as what we have seen to date? What would be a reasonable assumption for approval and more importantly, revenue coming into PDS? How is this trading at a market cap of less than a billion right now? What am I missing?
