You bought on the run up even though your expertise is in clinical trials and HER-Vaxx was clearly failing to show significant difference than standard of care drugs in a crowded HER2 market?
Can you tell what it was about an 80% confidence interval that got you excited?
Darling, I'm still waiting for you to show me where I was wrong with RAC. Speaking of rehashed drugs, look what comes with it - 80% complete response rate in R/R APL patients with 8 prior therapies. Average 58.7% ORR (51% CR) in almost 150 R/R AML patients. Stop talking about Bisantrene, as you have not done your homework.
OnCarylytics is a spin-off from CF33 and really is more of a way for PH to maximise value from a less-than-average compound. There is already human data to be referring to and it clearly demonstrates CF33 has poor clinical efficacy from two clinical arms: 1) Vaxinia; and 2) CheckVACC. If you take away the cholangiocarcinoma miracle, you have a complete clinical failure.
If you are actually interested in the preclinical work, read below.
The preclinical data for OnCarlytics is showing the same as single-agent CF33 - demonstrating little efficacy in comparison to other more cytotoxic drugs. The in vivo studies below clearly demonstrate OnCarlytics is achieving stable disease at best, and bioluminescence is virtually identical between mock T cells and Oncarlytics. There is only meaningful anti-cancer activity when you add in an approved compound - Blinatumomab.
In addition, I don't think I have ever seen a weaker preclinical in vivo model than this -
~80mm^3 after 40 days of tumor injection?Here is an example of an aggressive in vivo model, where responses in this model are more likely to translate to human efficacy:
In this in vivo model,
the tumors grew to roughly 25 times the size in approximately 1/3 of the time (14 days averaged), which means they were
~75 times more aggressive. Achieving a meaningful result in this model is thus more impressive and someone like me can take away confidence that the results could translate to humans.
Putting all this information together means the likelihood of success for OnCarlytics alone or in combination with Blinatumomab is extremely low. This is evidenced by the poor responses in weak in vivo model as well as the poor clinical efficacy in humans.
I've discussed Azer-cel previously, and nothing has changed. At least you have a drug that has been shown to work.
To my understanding HER-Vaxx was never designed or intended to be a standalone treatment, rather meant to be coupled with SoC to improve efficacy with minimal toxicity. The results from HORIZON showed improved OS for those treated with HER-Vaxx combination therapy vs. SoC only. An 80% CI is just fine in clinical trials, especially Phase 2. It's simply a lever to pull to help expedite trial recruitment as a smaller sample size is needed vs. a study powered at 95%. If IMU has confidence that their drug shows promise and is willing to play it a bit riskier in the clinic by utilizing a smaller sample size and CI, then so be it. That is their gamble to take.
