Chimeric: Media Thread, page-218

Hey Freebobby, Not a dumb question mate. Same technology as in Car-T just a different target and different type of cancer.

The articles refer to Kymriah the first Car-t therapy approved by the FDA invented by Carl June out of U Penn. The same U Penn we have the exclusive license of CDH-17 (CHM-2101) target from. Kymriah is a CD-19 targeted Car-T for advanced hematological malignancies (blood cancers). Blood cancers make up only 10% of all cancers.

Kymriah® became the first CAR T-cell therapy to gain market access by the US Food and Drug Administration (FDA) in August 2017 for refractory CD19-positive B-cell ALL [27]. On August 27, 2018, the European Commission has approved Kymriah® for the treatment of pediatric and young adult patients up to 25 years of age with B-cell ALL that is refractory, in relapse aftertransplantation or in second or later relapse.

Despite CD19 targeted Car-t being an absolute game changer and clearly showing staying power in the patients immune system outlined in those recent articles, It has had it challenges. The below is from https://www.karger.com/Article/Fulltext/496870 for a real deep dive on CD-19 car-t.

Toxicities and Management

The range of toxicities associated with CAR T-cell therapy is unique and differs from those seen with traditional chemotherapies and other targeted therapies such as monoclonal antibodies and small-molecule inhibitors. The most common toxicities observed after CAR T-cell therapy are CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). Other adverse reactions include “on-target, off-tumor” recognition and anaphylaxis [34].

Cytokine Release Syndrome

CRS, also known as “cytokine storm,” is a spectrum of inflammatory symptoms due to cytokine elevations as a result of immune activation of large numbers of lymphocytes. IL-6, a pleiotropic cytokine with anti-inflammatory and proinflammatory properties, has been implicated as a central mediator of toxicity in CRS [35]. The incidence and severity of CRS in patients receiving CAR T-cell therapy appears greater in patients with higher disease burden at initiation of treatment [36]. This is probably due to higher levels of T-cell activation [35].

CRS is accompanied by constitutional symptoms such as high fever, malaise, fatigue, myalgia, nausea triggered by an increase in TNF-α at first, followed by IFN-γ, IL-1b, IL-2, IL-6, IL-8, and IL-10. In addition, any organ system may be affected, including the cardiovascular, respiratory, renal, hepatic, hematological and nervous system [35, 37-39]. In rare cases, CRS can evolve into fulminant macrophage activation syndrome [39].

Currently, research on identification of predictive biomarkers for severe toxicity is needed, as the correlation between the development of severe CRS and clinical parameters is inconclusive. The predictive values of various biomarkers (e.g., high serum levels of IL-6, soluble gp130, IFN-γ, IL-15, IL-8, and/or IL-10) seem to vary depending on the type of CAR T-cell product used [40, 41].

CRS toxicity typically develops within the first week after CAR T-cell infusion and peaks within 1–2 weeks, coinciding with maximal in vivo T-cell expansion [35, 39]. CRS should be managed in accordance with the grade of its toxicity. Patient hospitalization with close monitoring is recommended by Neelapu et al. [39] for at least 7–10 days after CAR T-cell infusion. Others have not found this to be necessary in studies using CAR T-cell constructs containing a 4-1BB costimulatory domain, including tisagenlecleucel, in both ALL and NHL populations [42].

CHM has licensed the below seen in the pipeline, which target Solid tumours (90% of the cancer market) and some blood cancers with the NK Cell programs. Our lead candidate is starting with Gioblastoma to accelerate CHM-1101’s progression due to the huge unmet need and no SOC then a basket trial of other solid tumours.. So far CHM-1101 has shown alot of promise and no signs of CRS in its Phase 1 cohort 1 trials although there was cerebral edema in one oatient which was found to be on y possibly attributed to the treatment as it is common in GBM patients. The cohort 2 trials have progressed to cohort 3 with no dose limiting toxicities. Cohort 2 results are being collated and could be released at anytime although some speculate April some June to coincide with the ASCO conference.