Hi srsbsns
At the Melbourne presentation Yuman stated that the initial dose (Cohort 1) was just "10 to the 5th" - which is only 100,000 PFU. I think it is important to note that in some of his comments on effectiveness he was referring to the Checkvacc study (CF-33 armed with PDL1 and in trial against Triple Negative Breast Cancer). In others he was referring to the Vaccinia study in a range of solid tumours.
In Melbourne (with regard to Checkvacc) he said that "we are in teeny tiny doses... We started at a very low dose - 10 to the five - that's because the FDA said you're doing this first in man. Human beings have never seen this virus before. And they wouldn't let us start higher than that."
He also said that they didn't see any signs of toxicity in mice until they hit 10 to the 9th (1 billion PFU) - but as Yuman said in his presentation at Melbourne "That's a lot of virus to put into a tiny mouse."
For comparison - the circulating blood volume of a mouse is around 1.46 ml. The circulating blood volume of an adult human is around 5,000 ml. So although a billion PFU is "a lot of virus to put into a tiny mouse" - the same amount in a human would be diluted enormously. It I highly likely that the effective, and the toxic, doses for a human will be orders of magnitude greater than they are for a mouse.
Also in Melbourne, Yuman stated that "we were able to cure many of the tumour models" in mice at a dose of just 1,000 PFU. (See the video of his presentation from around 25:08 - link on this page:
https://www.imugene.com/investor-presentations).
But if you compare the relative sizes of a mouse and a human, an equivalent dose for a human based on blood volume would be more than 2.5 million PFU. (You get a similar result if you compare by body weight).
I have not seen anything that tells me what the dose escalation steps actually are for the Vaxinia study. ie whether we are going up arithmetically or by orders of magnitude. eg. Cohort 2 at 1 million, Cohort 3 at 10 million, Cohort 4 at 100 million etc.
However, Slide 19 of the March roadshow presentation shows a scan of one of the Checkvacc trial patients with the label "at Cohort 2 (3 x 10
5 PFU)"
So in the Checkvacc study they are certainly not going up by orders of magnitude. 3 x 10
5 PFU is just 3,000 PFU. That's only 3 times the dose that started to show a strong cancer killing effect in mice, even though a human is 2,500 times bigger than a mouse. That tells us just how cautious the FDA was being!
IMU announced first patient dosed in Cohort 3 of the Checkvacc trial way back on 10th August last year. There have been no updates since then, but Yuman seems very upbeat about progress. In Melbourne, when he was talking about the can of the Checkvacc patient, he stated that despite the "teeny tiny doses" ... "we are already seeing biologic responses that are highly highly promising."
From around 34:30 in the video of hi presentation he goes on to discuss the Vaccinia study. He notes that it is already up to Cohort 3 and he states that "we are already starting to see biologic signals that are enormously promising."
What we don't know - again - is the dose levels at each Cohort for the Vaccinia study. I would hope that based on the safety data from the Checkvacc study they have been allowed to go in at a higher dose for Cohort 1 with Vaccinia, with bigger incremental steps to Cohorts 2 and 3. But unless I have missed something, then we just don't know. (If anyone has seen more info on that - please do tell!!!)
Just based on what we do know - this is impressive. The mouse studies showed seriously good effect - a cure for mice - at 1000 PFU. But mice are tiny, and people are huge by comparison. An equivalent dose for a human would be more like 2.5 million PFU.
But Yuman said of the Checkvacc patient at Cohort 2, on just 3,000 PFU, that "we are already seeing biologic responses that are highly highly promising."
So I find that extremely positive indeed.
As always, we now have to wait for the data. My assumption is that we will see initial data from the Checkvacc study pretty soon. It could be exciting....
Cheers
Dave
(20min delay)