AB-101 + Rituximab Shows Deep Responses in Refractory RA, SjD, SSc

AB-101 (AlloNK), an allogeneic, off-the-shelf natural killer (NK) cell therapy from Artiva Biotherapeutics, combined with rituximab produced clinically meaningful responses across rheumatoid arthritis (RA), Sjögren disease (SjD), and systemic sclerosis (SSc) in a Phase 2a basket study presented at the European Alliance of Associations for Rheumatology (EULAR), held June 3-6 in London, United Kingdomm by Norman Gaylis, MD, Arthritis & Rheumatic Disease Specialties.¹ Among patients with treatment-refractory RA followed through 6 months (n = 7), 71% (5/7) achieved an ACR50 response, with mean changes from baseline of -73% in swollen joint count (SJC) and -67% in tender joint count (TJC).¹ No patients discontinued the study due to adverse events or lack of efficacy as of the April 3, 2026, data cutoff.¹

Deep B-cell depletion with CAR T-cell therapy has produced durable improvements across several immune-mediated diseases but carries substantial safety risk, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).¹ AB-101 pairs an allogeneic, cord blood-derived NK cell product with rituximab to drive comparable B-cell depletion through antibody-dependent cellular cytotoxicity, without the genetic modification or inpatient monitoring CAR T-cell therapy requires.¹ The basket design allowed investigators to evaluate the regimen across 3 distinct rheumatologic diseases sharing a B-cell-driven pathology.¹

71% of Patients With RA Achieve ACR50

The Phase 2a basket study (NCT06991114) enrolled 31 patients with treatment-refractory, highly active RA, SjD, or SSc across 5 United States rheumatology sites.¹ Patients received a 3-day low-dose conditioning regimen of cyclophosphamide and fludarabine in an outpatient clinic setting, followed by 3 doses of AB-101 given 7 days apart and 2 doses of rituximab given 2 weeks apart.¹ Patients are being followed for 2 years; the reported dataset includes all patients with at least 3 months of follow-up as of the April 3, 2026, cutoff.¹

Those with RA (n = 15) had failed a median of 2 distinct biologic or targeted disease-modifying antirheumatic drug (DMARD) classes, had a mean disease duration of 13 years, and presented with high baseline disease activity (Clinical Disease Activity Index [CDAI] mean, 50.7; Disease Activity Score in 28 joints using erythrocyte sedimentation rate [DAS28-ESR] mean, 7.4).¹ Disease activity scores and joint counts improved in all patients at 3 months, with responses deepening by 6 months: mean CDAI change from baseline was -36.8 and mean DAS28-ESR change was -2.6, both exceeding established minimal clinically important improvement thresholds (≥12 for CDAI and ≥1.2 for DAS28-ESR) in every patient.¹

What Were Outcomes in Sjögren Disease and Systemic Sclerosis?

Patients with SjD (n=11) were refractory to multiple prior immunomodulators and had high baseline disease activity (Clinical European League Against Rheumatism Sjögren Syndrome Disease Activity Index [ClinESSDAI] mean, 16.1; EULAR Sjögren Syndrome Patient Reported Index [ESSPRI] mean, 8.0).¹ At 6 months (n=7), mean ClinESSDAI change was -8.6 and mean ESSPRI change was -3.0; 86% (6/7) of patients were ClinESSDAI responders (≥4-point improvement) and 57% (4/7) were ESSPRI responders (≥1-point improvement).¹ Stimulated salivary flow improved by a mean of 0.76 mL/min from baseline at 6 months.¹

Patients with SSc (n=5) were resistant to multiple prior immunomodulators, with a mean baseline modified Rodnan skin score (mRSS) of 19.8.¹ Mean mRSS change from baseline was -9.5 at 6 months (n=4); all 4 evaluable patients achieved an rCRISS25 response and 2 of 4 (50%) achieved an rCRISS50 response.¹

Across all 3 diseases, Patient Global Assessment scores fell by a mean of 52% and FACIT-Fatigue scores improved by a mean of 7.2 points at 6 months (n=19).¹ Investigators reported no cases of CRS, ICANS, or hypogammaglobulinemia, consistent with 2 prior AB-101 studies in autoimmune disease, and characterized the overall safety profile as consistent with expectations for the conditioning regimen and rituximab alone.¹ No patients discontinued the study due to adverse events or lack of efficacy, and none received new immunomodulatory drugs, as of the data cutoff.¹

“After reviewing AlloNK’s initial clinical data in refractory RA, I am encouraged by the magnitude and consistency of improvements across multiple measures of disease activity, including swollen and tender joint counts, CDAI, DAS28 and ACR responses,” Stanley Cohen, MD, adjunct professor of internal medicine at University of Texas Southwestern Medical School and program director of rheumatology at THR Presbyterian Dallas, said in a statement.² “Patients who have had an inadequate response to multiple distinct b/tsDMARDs remain difficult to treat, and there is a significant need for new therapeutic approaches that can deliver meaningful clinical benefit. I am pleased to be advising Artiva on their planned Phase 3 registrational trial of AlloNK in refractory RA.”

Artiva plans to initiate a Phase 3 registrational trial in the second half of 2026 evaluating AB-101 plus rituximab against rituximab alone in approximately 150 patients with refractory RA who have had an inadequate response to 2 or more distinct biologic or targeted synthetic DMARD classes, with ACR50 response at 6 months set as the primary efficacy endpoint.² The company expects the rituximab-alone control arm to achieve ACR50 responses of approximately 20% to 25% at 6 months.²

References

1. Gaylis N, Brionez T, Valenzuela G, et al. AB-101, an outpatient-administered allogeneic NK cell therapy combined with rituximab, generates robust clinical efficacy responses comparable with autologous CAR T in 31 patients with rheumatologic diseases. Ann Rheum Dis. 2026;85(suppl 1):LB0003. https://doi.org/10.1136/annrheumdis-2026-eular.LBA_B.19

2. Artiva Biotherapeutics. Artiva announces positive initial clinical data with AlloNK across multiple autoimmune diseases and FDA alignment to initiate Phase 3 registrational trial in rheumatoid arthritis in 2026. Published May 2026. Accessed July 24, 2026. https://investors.artivabio.com/News-and-Events/news/news-details/2026/Artiva-Announces-Positive-Initial-Clinical-Data-with-AlloNK-Across-Multiple-Autoimmune-Diseases-and-FDA-Alignment-to-Initiate-Phase-3-Registrational-Trial-in-Rheumatoid-Arthritis-in-2026/default.aspx