So for those who have followed biotechs for a long time, they...

So for those who have followed biotechs for a long time, they will know that there is usually a 'dose threshold' for a lot of cell based treatments where it suddenly starts to work more consistently and effectively. And sometimes if you give too much of a treatment, it no longer gives you the same benefit.. almost as if you've overdone it.

I'll demonstrate this with another company I hold, over two of their phase 2 trials (they went on to complete phase 3 trials which are their pivotal trials).

The first is a trial they did on chronic heart failure patients, and their phase 2 trial (equivalent to CHM's phase 1) had the aim of establishing the optimal dose to take into a pivotal/registrational/approval) trial.


So they are also a cell therapy company, with this particular treatment call mesenchymal precursor cells (MPC) and in this chart it summarises how the patients responded to the treatment at three different doses i.e. 25m , 75m and 150m. Where the lower the line goes, the more HF-MACE (Major Heart failure events, such as stroke, heart attack and cardiac death) events were seen in that patient population.

So with 25m and 75m the effect on patients tracked along with the control group. However, once they used the 150m dose ... no patients suffered any major heart failure events over three years (36 months).

So that is an example where a treatment sometimes needs to be given in a high enough dose to break through the threshold needed to result in a clinical benefit.

The next is the same company, same product but for chronic lower back pain where MPC was injected into patients with chronic lower back pain due to disgenerative disc disease.



You can see here, that the 6m dose was actually more effective than the 18m dose both at 6,12 and 24 months. So sometimes your dose can be too high.

These are just two examples of why you may not always see linear progression in patient response to a cell based treatment, but rather once the optimal dose is found.. the results will suddenly 'click' and then they will know to take that dose to the pivotal trial. Will that be the 110m dose? or will it be the 220m dose? All we know is that the lower 44m single administration and 88m dose dual administration are safe and have shown some efficacy signals but both of these are effectively a 44m dose with one into the tumor cavity at 44m dose and the second into the brain cavity at 44m dose (88m because there were two modes of administration), and now they are up to the third cohort which is 220m and then cohort 4 later this year with a 440m dose.

So arguably cohort 2 was just another baby step, with the first big step in dosage increase being cohort 3 .. which they have started to recruit and I expect them to dose their first patient shortly.

Goodluck all