ABS0200 KT501, A CD19, BCMA-DIRECTED T-CELL ENGAGER (TCE), LEADS TO DEEP B-CELL DEPLETION AND MINIMAL CYTOKINE RELEASE IN VIVO

Abstract

Background:

B cell depletion therapies targeting CD19 or BCMA, including Chimeric antigen receptor T-cell (CAR-T) therapies and Bispecific antibody such as blinatumomab and Teclistamab, had shown impressive efficacy in treating B cell malignancy. In the last few years, those therapies also showed great potential in the treatment of systemic lups erythematosus (SLE), Rheumatoid arthritis (RA), and other autoimmune diseases by inducing deep B cell depletion, and potentially repopulating and resetting the B cell population and immunoglobins, and long-lasting clinical responses in otherwise hard to treat autoimmune diseases. However, challenges exist for these therapies such as significant safety risks and logistical challenges.

Objectives:

Development of a novel IgG-like CD19XBCMAXCD3 T cell engager to target broad B cell populations.

Methods:

By antibody engineering, KT501, a novel IgG-like CD19XBCMAXCD3 T cell engager, was developed.

Results:

KT501 exhibited potent B cell killing in healthy and SLE patient PBMC. In cynomolgus monkeys, KT501 induced rapid and deep B-cell depletion in a dose responsive manner. At 0.01mg/kg, quick and deep depletion of B cells was observed but quickly rebound at day 21. At 0.1mg/kg, deep B cell depletion in peripheral blood, bone marrow and lymph nodes were observed even at day 21. At 1mg/kg, minimal cytokine releases were observed with deep B cell depletion.

Conclusion:

Those preclinical data strongly support clinical development of KT501 in autoimmune disease treatment, which is expected to move into Phase I trial in Q4, 2025.

REFERENCES:

[1] Müller F, etal. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. [2] Bucci L, etal. Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat Med. 2024 Jun;30(6):1593-1601. [3] Alexander T, etal. Teclistamab-Induced Remission in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2024 Sep 5;391(9):864-866.

Acknowledgements:

NIL.

Disclosure of Interests:

John Wang I'm a shareholder of Kalitherapeutics, I'm employed by Kalitherapeutics. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.