▎WuXi AppTec Content Team Report

On January 6, the latest announcement was made on the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration.Novartis' Application for the New Drug PIT565 Granted Implied Permission for Clinical Trials, Intended for Development in TreatmentRecurrent and/or Refractory B-cell Malignancies。Public information shows that this is a potential "first-in-class" drug under research by Novartis.Tri-specific antibody against CD3/CD19/CD2, under development for the treatment of B-cell malignanciesAccording to the CDE official website, this is the first time the product has been approved for clinical use in China.

Screenshot source:CDE Official Website

The preclinical study results of PIT565 were previously published in 2022 inBloodJournal. It was reported that the CD19 antigen in acute lymphoblastic leukemia (ALL) andNon-Hodgkin's Lymphoma (Strong expression in NHL drivesTargeting CD19T cellsRedirective TherapyThe development, including bispecific T-cell engagers and CD19-targeted CAR-T therapies, etc. However, T-cell exhaustion often leads to treatment failure.

To address this issue, researchers have developed the IgG-like trispecific antibody PIT565.It can target CD19 on malignant B cells while binding to CD3 (a TCR signaling component) and CD2 (a co-stimulatory receptor) on T cells, redirecting T-cell cytotoxicity against CD19-positive malignant B cells.

Research shows,CD2 Signaling Is Associated with a Non-Exhausted T Cell PhenotypeThe interaction between CD2 and its ligand CD58 has been shown to play an important role in CD19 CAR-T cells killing tumor cells, while the loss of CD58 expression on lymphoma cells is associated with resistance and relapse in patients receiving CD19 CAR-T therapy.Therefore, compared with CD3 bispecific, co-stimulation of CD2 via PIT565 may overcome T-cell exhaustion and increase the depth and duration of patient response.

Preclinical study results also show that, compared with CD3 bispecific antibodies, PIT565 mediates more effective and sustained anti-tumor T-cell responses, with greater in vitro T-cell proliferation, cytokine production, and tumor cell lysis than bispecific antibodies.

Currently, PIT565 is in the international multicenter Phase 1 study stage, exploring its use forPatients with Relapsed or Refractory B-NHL and R/R CD19-positive B-ALLThe preliminary efficacy and safety. In addition,According toClinicalTrialsOfficial website, Novartis is also conducting an evaluation of PIT565 treatmentPatients with Systemic Lupus Erythematosus (SLE)A Phase 1 Clinical Study on the Safety, Tolerability, and Pharmacokinetics.

This timePIT565 has been approved for clinical trials in China, indicating that the drug will also enter the clinical development stage in China.

[1] Center for Drug Evaluation, National Medical Products Administration of ChinaWebsite. Retrieved Jan 6, 2025, from https://www.cde.org.cn/main/xxgk/listpage/da6efd086c099b7fc949121166f0130c

[2]PIT565, a First-in-Class Anti-CD19, Anti-CD3, Anti-CD2 Trispecific Antibody for the Treatment of B Cell Malignancies. Retrieved Nov 15, 2022, from https://ashpublications.org/blood/article/140/Supplement%201/3148/487267/PIT565-a-First-in-Class-Anti-CD19-Anti-CD3-Anti