Ann: CLTX CAR T PRESENTS POSITIVE INITIAL PHASE 1 CLINICAL DATA, page-64

I think it's because the announcement's scope was regarding the phase 1 clinical data so safety and efficacy readings. The other abstract seems to be more of a laboratory and scientific finding, which seems to post more of an exploratory question rather than explaining exactly what is happening so it doesn't quite fit the scope of the announcement. If the fear is that CHM is hiding or omitting information from their announcement then I think they should've omitted the cerebral edema part because I think that is more negative than the mechanism of action.

Rest assured, all clinical trials will include tumour biopsy analysis at certain points in the trial for each subject - this will allow for tumours to be extracted and to be analysed at the start and at the end of treatment as you can see from their clinicaltrial.gov listing and this will be done in all of their trials. So they will have more clarity with CLTX CAR-T's mechanism of action as it progresses. Additionally, they have to put all of these information in what you call an "Investigator Brochure" and they must continually update this every year or every time there is new information as instructed by clinical trial regulations. So they are require to actually figure this out throughout the development period of the therapy.

This missing piece of information regarding CLTX CAR-T's mechanism of action is actually not that bad and is expected. With most drugs and therapies that are developed, they are usually designed and re-engineered to hit a target in the tumour. They are optimised to be highly specific so that their mechanism of action is easily decipherable or it's already established prior to being used in humans. With CLTX it's a little different, the mechanism of action for CLTX is not optimised and engineered to hit a target because it's created by nature to act on a wide variety of living organisms. Add on the fact that we don't really know too much about how CLTX works around the body - there's actually not many papers. There's been products that have been made, but CLTX's technology is not as mature as other technological platforms. CHM and City of Hope are actually learning as we go and that's a good thing because this could actually expand the usability of CLTX to other tumours in the body.

CLTX's ability to hit other proteins in the GBM tumour is also a positive. GBM is dangerous because of its ability to migrate from its initial location via MMP2+, and also heterogeneity (many different proteins that are expressed on the surface of the tumour - it's not like blood tumours which have approved CAR-T Cell Therapies which uniformly express one protein - CD-19). If CLTX can target other proteins in the GBM area and also attack MMP2, then it could actually be an effective treatment because it will nullify GBM's cell migration and tumour escape mechanisms.

Again, all theoretical at this stage, but if it works (which is 5-10 years away), this could be good.