Novartis Unveils T-Charge™ Platform with Promising First-in-Human CAR-T Clinical Data

December 15, 2021 /BioValleyBIOON/ -- Novartis recently announced at the 63rd American Society of Hematology (ASH) Annual Meeting in 2021Next-Generation CAR-T Platform T-ChargeThe first batch of human data. T-Charge is an innovative next-generation CAR-T platform developed by the Novartis Institutes for BioMedical Research (NIBR), and will serve as the cornerstone for the development of various new investigational T-cell therapies in Novartis' pipeline. Through the T-Charge platform,NovartisThe goal is to revolutionize CAR-T cell therapy with new products.

At the meeting, Novartis announcedYTB323 (anti-CD19) and PHE885 (anti-CDMA)Phase 1 OngoingClinical TrialEarly clinical data for YTB323 and PHE885.Is the first batch developed using the T-Charge platformNovartisCAR-T Cell TherapyNotably, initial efficacy data showed that, among the 15 patients with diffuse large B-cell lymphoma (DLBCL) who received YTB3231 at dose level 2 (DL2, 12.5×10E6 CAR+ cells), at month 3,The complete response rate (CR) reached 73%.(95% CI: 44.9, 92.2). In addition, 11 patients with multiple myeloma (MM) who received the two highest doses of PHE885,The best overall response rate (ORR) reached 100%.。

T-Charge platform can preserve the stemness of T cells(T cells' ability to self-renew and mature), an important T cell characteristic closely related to their therapeutic potential, thereby generating a type ofHigher Proliferation PotentialAndLess Depletion of T Cellsproducts. By utilizing the T-Charge platform,The expansion of CAR-T cells mainly occurs in vivo, without the need for prolonged ex-vivo culture.These unique characteristics of the T-Charge platform have the potential to provide patients with better and longer-lasting relief, improve long-term outcomes, and reduce the risk of serious adverse events.

Compared with traditional CAR-T, the T-Charge platform achieves important process efficiencies and will enable rapid and reliable results by streamlining processes and optimizing quality control.It takes less than 2 days to complete the production of CAR-T cells, which can proliferate significantly after being infused into the patient's body.; In addition, compared with existing CAR-T cell products, the CAR-T cell products developed through the T-Charge platform have theirThe infusion dose can be reduced by 10 to 50 times.。

NovartisPresident of the Biomedical Research Institute Jay Bradner stated: "Through the T-Charge platform, our goal is to leverage the extensive knowledge gathered from early investments in CAR-T research and trials. We are now aiming to go beyond incremental advancements and further reimagine CAR-T cell therapy, increasing the likelihood of durable remission for patients and ultimately achieving a cure. We are encouraged by these promising early clinical data from the first CAR-T cell therapies generated using the T-Charge platform. We will accelerate their development and delivery to patients."

YTB323 is an investigational autologous CD19-directed CAR-T cell therapy developed using the T-Charge platform., in the diffuse large B-cell lymphoma (DLBCL) patient cohort from the first human multicenter Phase 1 dose-escalation study, very promising results were shown. In the trial, patients received a single infusion of YTB323 at two dose levels (DL). The median administered doses were 2.5×10E6 CAR+ cells (DL1; n=4) and 12.5×10E6 CAR+ cells (DL2; n=16). Among the 15 patients who received the DL2 dose of YTB323 at least three months prior to the data cutoff, the complete response rate (CR) was 73% (95% CI: 44.9, 92.2), including 2 patients who were already in CR before YTB323 treatment. For the 20 patients evaluable for safety, no new safety signals were observed beyond the previously known safety signals associated with CD19-directed CAR-T cell therapy.

PHE885 is an investigational autologous BCMA-directed CAR-T cell therapy developed using the T-Charge platform.In the first multicenter Phase 1 dose-escalation study in humans, very promising results were shown in patients with relapsed or refractory multiple myeloma (MM). Efficacy and safety were evaluated in 15 patients who received a fixed dose of PHE885 at 2.5×10E6 (n=4), 5×10E6 (n=10), and 14.3×10E6 (n=1) CAR-T cells, respectively. Despite the short follow-up period, PHE885 demonstrated encouraging initial clinical activity, with the best overall response rate (ORR) reaching 100% for patients receiving doses of 5×10E6 or 14.3×10E6 CAR-T cells, and responses deepened over time. At a median follow-up of 3.5 months, 8 out of 15 patients continued to show sustained responses at data cutoff. Among evaluable patients at 3 months post-infusion, by next-generation sequencing (NGS), 34% (2/6) showed MRD negativity at a threshold of 1×10−6, and 43% (3/7) showed MRD negativity at a threshold of 1×10−5.

All patients experienced CRS, with 2 patients experiencing ≥Grade 3 CRS. No patients developed Grade 4 or 5 CRS. All neurotoxicity events (n=4) were non-severe, Grades 1-2, reversible, and temporarily associated with CRS. (Bioon.com)

Source of Original Text:Novartis announces T-Charge™, next-generation CAR-T platform with first-in-human data at ASH 2021