In order to have a decent crack at assessing whether Cohort A of...

In order to have a decent crack at assessing whether Cohort A of Tacti-003 has a good shot at coming back as positive (statistically significant p < 0.05 for the primary endpoint, although you could argue the secondary endpoint of OS is more important as this is what the FDA usually bases approvals off of) I’ve had a look at what data we have available.

From Keytruda as a single treatment for 1st line HNSCC, a clinical trial was run with the following:In order to have a decent crack at assessing whether Cohort A of Tacti-003 has a good shot at coming back as positive (statistically significant p < 0.05 for the primary endpoint, although you could argue the secondary endpoint of OS is more important as this is what the FDA usually bases approvals off of) I’ve had a look at what data we have available.

From Keytruda as a single treatment for 1st line HNSCC, a clinical trial was run with the following:

- Patients were either treated with Keytruda OR Standard treatment = cetuximab (epidermal growth factor receptor inhibitor) and the chemotherapy medicines fluorouracil and a platinum-based therapy.

- There was no stratification of patient cohorts, ie everyone just had a CPS score > 1

- Patients were given 200mg of Keytruda every 3 weeks

- There were 14 out of 257 patients with a complete response, and 35 out of 257 with a partial response, to give an ORR of 19%

- Oddly enough, the standard treatment was more successful on an ORR basis, with an ORR of 35%

- However, like I said, OS is more important, and although this isn’t an OS measure the median duration of response was 20.9 months for people who received KEYTRUDA (1.5+ to 34.8+ months), compared to 4.5 months for people who received standard treatment (1.2+ to 28.6+ months).

Unfortunately, I can’t find the ORR results for patients depending on their CPS scores, but they might be out there somewhere - this is because the focus was on OS.

Now onto what IMM have done historically in 2nd line HNSCC patients:

• In Tacti-002, patients were given 200mg of Keytruda and 30mg of Efti with the following results
  • An ORR of 29.7% with an intent to treat population of 37 patients
  • An ORR of 60% for patients with a CPS score of 20 or greater (N = 15)
  • An ORR of 11% for patients with a CPS score of less than 20 (N = 17)
  • An ORR of 38.5% for patients with a CPS score of 1 or more (N = 25)

All these ORR metrics are pretty good, but we need to consider the following:

• The trial done by Merck for Keytruda was double blinded, which means that patients nor caregivers knew who was getting what. This generally enhances integrity of the trial results, because patients aren’t inclined to think they are on a certain drug therefore they should get certain results - it removes a sort of bias. Probably something to do with if you think you’ll do good, you will do good, and visa versa.
• Based on the above point, as Tacti-003 is not double blinded, maybe patients on Keytruda will feel as though they should get better - and maybe their results will be better than the historical norm? Seems outlandish but really weird stuff does happen in clinical trials - just look at AIPAC
• However, I digress in regards to my above 2 points, because I think this sort of bias is more likely to occur in subjectively measured endpoints, rather than something objective like the size of a tumour.
• The results from Tacti-002 were for 2nd line patients, but we are now moving to first line patients. This means the tumours are less tumour resistant, and theoretically should be more responsive to treatment. Therefore, could we see an overall upgrade on the ORR of 29.7%? The tumours that resulted with an ORR of 29.7% had already failed first line treatment - maybe this was after their tumours progressed on Keytruda or the standard of care noted in the Merck trial - I don’t know which one, but Keytruda is now approved for use as a mono therapy and in combination with chemo - so its either of the two
• Patient size - unfortunately for us, Tacti-002 didn’t have many patients, therefore this can go one of two ways - we got lucky with our ORR because of random bias in the patient group, or the ORR is actually understated because of random bias the other way. But again, this was for 2nd line patients, meaning we really can’t know for sure how the data will trend in 1st line patients

So, in summary and conclusion:

• If we see an ORR for 1st line patients the same as historical norms for Keytruda alone, we should see an ORR of around 19% regardless of CPS score - maybe more, maybe less. But the patient size in the Merck trial was decent, so it could be a fairer long run indicator of results
• If we see as a minimum first line patients responding the same as second line patients, we could see an ORR similar to Tacti-002, but the more patients we have, this could lead to results swinging the ORR up or down
• It would be natural to assume that as these patients are now first line patients, ORR should be higher than Tacti-002, and we would really hope so. But that patient pool in Tacti-002 is so damn small.

One thing that’s biting me though, is that in yesterday’s announcement, Marc stated that for Cohort A, data collection and cleaning needs to be conducted, which doesn’t make sense to me as the trial is open label - shouldn’t data be collected and analysed as it occurs in real time? We need to ask ourselves, do they have the data already, and is it underwhelming, therefore they are looking to identify trends in the data to swing it in a positive way?

Anyway, that’s enough from me - curious on peoples thoughts.

PS my sentiment is hold because of the binary risk involved with the upcoming result, its either going to make or break the company for years to come, and with my current holding, i'd be mad to increase it going into such an event.

Cheers