CHM (ASX) Comparative Analysis

Originally posted by KrushingIt: ↑

As I have mentioned previously, the closest analogue to CDH17 CART is CarsGen claudin 18.2 Satri-cel CART therapy which is also in clinical trials in China and the US.

Importantly:
a) CDH17 targets a different antigen to Satri-cel, so they are not direct competitors;
b) Satri-cel is a second generation CART, whereas CDH17 is a third generation CART;
c) CDH17 is overexpressed more in GI cancers than claudin 18.2 (which means the addressable market for CDH17 is much larger);
d) Satri-cel is showing strong efficacy data (especially for a CART in solid tumours), which highlights that CART can be effective in solid tumours;
e) Satri-cel has already been awarded RMAT designation from the FDA which is their highest designation! Better than Orphan Drug and Breakthrough Therapy.....

Now have a look at this detailed article on Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results:
https://pmc.ncbi.nlm.nih.gov/articles/PMC9205778/

Some super interesting Phase 1 results for Satri-Cel.....which are very relevant to CHM's trial.....

When you compare this data with the preliminary information for CHM CDH17, CHM's data looks quite positive.

Assumptions:
a) Patient 1 who was lost to the CDH17 trial is not evaluable;
b) CHM data is not mature enough to calculate ORR and mPFS;

Recognise there is only a very small patient sample for CDH17, but.......

In addition, when you look at the all important persistence of the CARTs for Satri Cel versus CHM CDH17 CART, things also look promising....

CHM CDH17 is showing much better persistence than Satri-Cel. Now this is in line with expectations given CDH17 is a 3rd gen cart which has specific design innovations aimed at extending persistence. This has obvious positive implications for progression free survival and may also result in some of the stable disease patients turning into partial responses or with a bit of luck complete responses!! This is despite the fact that Satri-Cel trial design had multiple infusions.......

Conclusion: Data so far for CDH17 is looking really good and the stock has been significantly de-risked from a clinical trial perspective. In fact, I will go so far as to say that is line for an RMAT designation from the FDA!

Satri Cel

CHM CDH17 CART

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Thanks, KrushingIT... comparing apples with apples with the detail to back it up is the only way to give our CDH17 CAR-T some proper perspective. I've been running a lot of questions by Grok since the webinar.

The early data results of exceptional CAR-T expansion and persistence, coupled with Stable Disease, is what we want to be seeing. In the treatment of solid tumours, early Complete Responses are often transient. In the case of NETs, relapse often involves resistant clones (e.g. SSTR-negative after PRRT), making further control harder. SD, while less dramatic, offers a stable baseline for future interventions.

As your post highlights, Satri-cel's CAR-T trial is showing success despite no CR being applicable. SD with T-cell persistence is often more significant than non-durable CR. This prompted me to run a comparison by Grok about the preclinical data of Satri-cel vs our CDH17 program which I find to be insightful and most encouraging. The response from Grok was detailed, extensive, and too lengthy to post in its entirety, but this is pretty much covers it:-

And, here's just a snippet about the interesting science that makes our 3rd-Gen CAR-T what it is:-

So, one of the many benefits of NKG2D is that it stimulates NK-cells (the innate immune system) to join the battle. The co-stimulatory rocket blasters that Dr Bec quaintly refers to.

She also states in the webinar that there were no dose-limiting toxicities or adverse effects. which supports the preclinical data. What needs to be considered, though, is that the patients receiving our therapy have advanced cancer (in the case of Patient #2, stage 4 cancer). This means that SOC drugs could compromise the immune system and our therapy. I am going out on a limb here by pointing to the collaboration with Achieve Clinics no less than 28 days after the first patient was dosed. I'd say at that juncture the AC collab was critical to of our trial, the confidence of the team, and the reason for the delay. The significance of "untainted" patient T-cells is not emphasised in the ann nearly as much as the significance of providing reach and expediency iken to "off-the-shelf" allo-cells.

"Achieve Clinics Collaboration to Expand Reach of CHM CDH17" - 25 September 2024

Does this align with your interpretation, KrushingIT? "Loss to follow up" has been bugging me all week but connecting the dots now to the Achieve collab sort of appeases me.