A very important observation there, "CHM 1101 trial has yet to...

A very important observation there, "CHM 1101 trial has yet to reach its maximal feasible dose and patient cohort."

So far, this is what CHM 1101 looks like:


https://cdn-api.markitdigital.com/apiman-gateway/ASX/asx-research/1.0/file/2924-02763677-2A1500356

Mustang Bio's trial has achieved the Disease Control Rate in a larger patient cohort, being 29/58 patients, whilst CHM so far only has released initial data for 11 patients. Very promising data, because (and I think this is something that has not been taken into consideration by @Milcom earlier):

• the above is based on a median 4th line of treatment, whilst Mustang Bio's data also includes patients that "had experienced at least one recurrence prior to enrolling in the trial. The majority were being treated for their third" (https://www.fiercebiotech.com/research/mustang-bio-and-city-hope-car-t-therapy-glioblastoma-extends-survival-phase-1-trial). Median line of treatment would therefore be below CHM's trial, and sadly, with each additional line of treatment the outlook gets worse.
• "the final cohort [in Mustang Bio's trial] with dual intratumoral (ICT)/ intraventricular (ICV) delivery and an optimized manufacturing process exhibited superior median overall survival of 10.2 months", CHM has not yet released any data of our final cohort yet, which is using the dual route of the highest dose level that is also being used in our Phase 1b trial:

Phase 1a: https://chimerictherapeutics.com/wp-content/uploads/2023/05/CHI5105_FA_Chimeric-Therapeutics_Newsletter_WEB.pdf



Phase 1b: https://chimerictherapeutics.com/our-pipeline/

• Mustang Bio's trial was targeting the IL13Rα2 receptor. However, not every tumour is the same. The tumour apppears to be changing after each treatment as well, which is why the published findings of CHM's preclinical study are worth re-reading:

"Efforts to develop CAR T cells for GBMs, therefore, must consider this high degree of heterogeneity. We have demonstrated that IL13 receptor α2 (IL13Rα2) expression is associated with a mesenchymal phenotype and poorer prognosis of GBM patients (15). For IL13Ra2-positive tumors, its expression has also been verified on tumor-initiating glioma stem-like cells, and expression is associated with tumor invasiveness (16). However, after treating with IL13Rα2-targeted CAR T cells, instances of tumor recurrence with loss and/or reduced expression of IL13Rα2 has been observed (8, 17). Similar results were also reported following EGFR variant III (EGFRvIII)-targeted immunotherapies, with the down-regulation of EGFRvIII expression in the tumors harvested post-therapy (10, 18). Indeed, GBMs are able to rapidly adapt to therapies, resulting in relapse with distinct intratumoral cellular profiles (19). Given the promising clinical results of CAR therapy against B cell malignancies by targeting CD19 which is broadly expressed by all B cell lineages (20–22), the development of more effective GBM-targeting CAR designs is expected to benefit from improving broad tumor recognition. To date, this has remained elusive due to the scarcity of antigen candidates that are both widely expressed and highly tumor-specific, especially given the extreme risk of off-tumor toxicities due to the critical location of these tumors within the brain.An opportunity to extend the repertoire of target antigens amenable to CAR T cell therapy is presented by the tumor-binding potential of some naturally-derived molecules (23). One example is chlorotoxin (CLTX), a 36-amino acid peptide isolated from the venom of the death stalker scorpion (24).
[...]
These primary brain tumor (PBT) cells were examined by flow cytometry for binding of Cy5.5-conjugated CLTX peptide (CLTX-Cy5.5) and compared with expression of IL13Rα2, HER2 and EGFR, three targets being clinically evaluated in CAR T cell therapies for GBMs (10, 17, 35). Strong CLTX-Cy5.5 fluorescence was observed for almost all patient tumors, with greater than 80% of cells binding CLTX (Fig. 1A and 1B, left panel). Across 22 tumor samples from 15 different patients, only two (PBT114 and PBT131) showed CLTX-Cy5.5 binding in less than 30% of total cells. At the same time, expression of immunotherapy targets IL13Rα2, HER2 and EGFR varied widely between patient tumors. CLTX-Cy5.5 binding appeared independent of other antigens, and was observed on tumors with both high and low expression of IL13Rα2, HER2 and EGFR (See representative flow cytometry plots in Fig. 1A). We also examined CLTX-Cy5.5 binding to low-passage patient-derived GBM tumor sphere (PBT-TS) lines expanded under conditions favoring a cancer stem cell-like phenotype (36–38). Similar to dissociated primary GBM cells, 18 out of 19 PBT-TS lines showed greater than 80% CLTX-Cy5.5 binding (Fig. 1B, right panel and Fig. S1A), including the TS lines which displayed negligible expression of IL13Rα2, HER2 and EGFR (PBT003-4-TS, PBT009-TS). To evaluate CLTX binding in engrafted tumors, GBM orthotopic xenografts were tested by fluorescent microscopy using a biotin-conjugated CLTX peptide. Consistent with the analyses of freshly resected patient tumors, CLTX displayed consistent binding to five of five engrafted PBT-TS GBM tumors, and marked a greater proportion of tumor cells as compared to the expression of IL13Rα2 and EGFR (Fig. 1C and Fig. S1B). Taken together, these studies confirmed the capacity of CLTX to bind to a high percentage of patient GBM tumors (20 of 22 freshly-dissociated GBM samples), as well as to the majority of GBM cells within each tumor."
https://www.biorxiv.org/content/10.1101/2020.01.24.918888v1.full

There is a lot more from that paper that deserves to be quotes here as it shows how versatile CLTX may be compared IL13Rα2, HER2 and EGFR.

• What both trials share is the dual delivery route, which has shown promise:

https://assets.researchsquare.com/files/rs-3117663/v1/7d12f5fe-c2bb-4719-aa70-83e2fcfdef38.pdf?c=1709885219

More information also available here: https://aacrjournals.org/cancerimmunolres/article/9/1/75/470579/The-Cerebroventricular-Environment-Modifies-CAR-T

All in all, to answer your question @brrrattt, it is too early to tell how they stack up since Mustang achieved the best outcome in their final cohort, which CHM does not yet have data for (Phase 1a and 1b). Early signs are very encouraging, albeit in a small number of patients.