Chimeric Antigen Receptors (CARs) and T-Cell Subtypes

Senl_1904B

  • Autologous anti-CD19 CAR-T
  • For the treatment of relapsed/refractory B-cell ALL and NHL
  • Senl_1940B overcomes the toxicity issues of conventional CAR-T therapy:
    • CAR construct contains “MND promoter”, which increases the percentage of CAR-positive cells but reduces the surface density of CAR molecules, potentially reducing the risk of CRS and CRES
    • Successfully completed a first-in-human clinical trial with a complete remission rate of 97.2% (35/36) and only 5.6% (2/36) Grade-3 CRS rate
    • Submitted Investigational New Drug (IND) to the Chinese Center for Drug Evaluation (CDE). We anticipate starting a Phase I clinical study in June 2021

Senl_H19

  • Autologous anti-CD19 CAR-T
  • For the treatment of relapsed/refractory B-cell ALL and NHL in patients who failed prior CAR-T treatment
  • Sen_H19 addresses the “immunogenicity” issue of currently approved CAR-T therapy:
    • Instead of using CD19 scFv from the murine FMC63 antibody (Novartis’ Kymriah, Gilead/Kite’s Yescarta, Bristol Myers Squibb’s Breyanzi), Senl_H19 contains a fully humanized anti-CD19 CAR to improve longevity and persistence of CAR T-cells
    • At the IND-enabling development stage and already demonstrated robust activity against CD19- positive tumor cells and xenograft animal models.

Senl_NS7CAR

Breakthrough in Treatment of T-Cell Malignancies

  • Autologous anti-CD7 CAR T-cell therapy candidate in clinical development
  • For the treatment of relapsed/refractory T-cell ALL and T-cell lymphoblastic lymphoma (T-LBL)
  • Senl_NS7CAR overcomes the poor cytotoxic effect against T-cell malignancies by conventional CAR-T therapy:
    • “Natural Selection” approach: SenlangBio discovered that T-ALL/T-LBL patients have a higher number of CD7-negative T-cells in their peripheral blood. We specifically select CD7-negative cells to make the anti-CD7 CAR-T cells
    • No need for CD7 disruption using gene editing methods such as CRISPR-Cas9
    • More memory CAR T-cells in the final product following our natural selection process, increased durability, and reduced manufacturing cost
    • In a first-in-human clinical study, 8 out of 8 R/R T-LBL patients achieved complete remission. None of the patients developed > Grade-2 CRS or CRES side effects
  • A universal (“off-the-shelf”) anti-CD7 UCAR-T is also in pre-clinical development

Senl_H19x22P

  • Autologous dual CAR T-cell therapy candidate in clinical development
  • For the treatment of relapsed/refractory B-ALL and NHL
  • This candidate contains a cocktail of H19 CAR-modified T-cells and 22P CAR-modified T-cells
  • Our proprietary “cocktail” CAR-T combination overcomes the problem of a high disease relapse rate in patients previously treated with conventional CAR-T therapy

Senl_comboCARs

  • Autologous CAR-T candidates that can be customized, engineered with a combination of anti-tumor associated antigen (anti-TAA) CAR and anti-CD22/PD-L1 CAR
  • Based on the expression of different TAAs, ScFv (TAA) can be customized and replaced to target solid tumors
  • Currently, a series of these combo CAR constructs consisting of individual or combination of TAAs have been developed, promising to potentially overcome the current shortage and limitations of CAR-T cell therapy for patients with solid tumors