Novartis Advances Phase 1b Clinical Trial of PIT565, a CD19/CD3/CD2 Trispecific Antibody, for Rheumatoid Arthritis
Innovative Trispecific Antibody Mechanism Targeting Autoimmune Diseases
PIT565, currently under development by Novartis, is an innovative trispecific antibody therapy with a unique mechanism of action. This molecule targets CD19 on B cells while simultaneously binding to CD3 and the co-stimulatory receptor CD2 on T cells. Notably, it delivers signals through CD2, effectively preventing T-cell exhaustion. This mechanism aims to eliminate pathogenic B cells, providing a potential cure for autoimmune diseases.
Design and Progress of the Phase 1b Clinical Trial for Rheumatoid Arthritis
The ongoing Phase 1b clinical trial (NCT07029555) evaluates the safety and pharmacokinetics of PIT565 in patients with rheumatoid arthritis. The trial aims to enroll a total of 57 patients and is designed as an ascending dose cohort study with subcutaneous administration. Since its initiation in June 2025, the trial is currently in an 'Active, Not Recruiting' status, with treatment and analysis ongoing. The expected completion date for the primary endpoint is May 2028.
Unmet Medical Needs in the Global Rheumatoid Arthritis Market
The global rheumatoid arthritis market is estimated at approximately $35.35 billion in 2025, with TNF inhibitors such as adalimumab and JAK inhibitors such as tofacitinib being commonly used. However, existing therapies have limitations, including difficulty in achieving complete remission and the potential for adverse effects or resistance with long-term use. Therefore, B-cell depletion therapy, which targets and eliminates B cells as the root cause, has emerged as a key alternative. If PIT565 demonstrates superior safety and efficacy, it could become a new standard of care in the market.
Commercial Competitiveness Compared to CAR-T Therapies and Novartis' Strategy
CAR-T therapies, which are effective in treating autoimmune diseases, face challenges due to their high cost and complex manufacturing processes. In contrast, PIT565, being an off-the-shelf product, can be administered immediately and produced on a large scale, significantly improving patient access. Novartis is developing this molecule for multiple indications, including systemic lupus erythematosus and rheumatoid arthritis, to maximize the value of its pipeline. The data from this clinical trial will be a crucial milestone for the future entry into a large-scale Phase 2 trial.
With the global rheumatoid arthritis market reaching approximately $35.35 billion in 2025, there is intense competition to secure next-generation immunotherapies that can achieve superior remission rates compared to existing TNF inhibitors and JAK inhibitors. PIT565, a first-in-class trispecific antibody targeting CD19, CD3, and CD2, is currently in Phase 1b clinical trials by Novartis. It simultaneously induces T-cell activation and prevents exhaustion, potentially offering a new treatment option for patients who do not respond to standard therapies such as adalimumab. In the short term, the key objective is to successfully demonstrate the clinical proof-of-concept (PoC) for B-cell depletion technology targeting autoimmune diseases by securing pharmacokinetic (PK) and safety data through the completion of this trial, which is expected in May 2028. In the medium to long term, it is expected to become a core asset in Novartis' immunology pipeline as a highly efficient antibody therapy in an off-the-shelf format, which can replace high-cost CAR-T therapies in the autoimmune field. This is expected to provide a competitive advantage compared to the CD19 CAR-T pipelines of competitors such as Cabaletta Bio and Kyverna Therapeutics.
Source: ClinicalTrials.gov (api_ct)