NKX019 Clinical Update @ ACR Convergence 2026 - NKARTA INC

Explicit Guidance:

• Cash Runway: Management expects $216 million in cash, cash equivalents, and investments to extend the operational runway into 2029 based on current plans.
• Clinical Trial Timing:
  • First Half 2027: Expected to provide additional follow-up data for both myositis and systemic sclerosis.
  • H1 2027: Anticipated completion of the process to select the registrational dose (4 billion vs. 6 billion cells).
  • 2027: Expectation to initiate pivotal trials in myositis and systemic sclerosis following FDA interactions.
• Future Data Releases:
  • Near-future: Update on safety and preliminary efficacy for three retreated patients.
  • Wednesday of the current ACR meeting: Oral presentation on overall safety data across all autoimmune indications.
  • First half of next year: Updated data on retreatment patients.
  • Next annual disclosure: Goal to present data on the 6 billion cell cohort with at least three months of follow-up for a cohort of 6+ patients.

Business-Segment Outlook:

• Therapeutic Focus: Strategic pivot to exclusive focus on myositis and systemic sclerosis for pivotal trials; other autoimmune indications (including RA) will be revisited only as time and resources permit.
• Dose Optimization: Moving forward with a compressed dosing schedule (Days 0, 2, 4) to maximize cell exposure before T-cell recovery; planning to enroll a small cohort at 6 billion cells per dose (18 billion total) to maximize efficacy potential, with the expectation that 4 billion cells may remain the preferred pivotal dose if 6 billion does not offer significant added benefit.
• Market Opportunity: Preliminary U.S. estimates identify 80,000 myositis patients (7,000 refractory) and 90,000 systemic sclerosis patients (10,000 refractory) as the addressable market; Europe represents additional untapped upside.
• Operational Model: Emphasis on outpatient administration, "on-demand" availability, and the ability to redose patients, distinguishing the product from autologous CAR-T approaches.

Market and Competitive Outlook:

• Competitive Positioning: Management asserts early efficacy data is comparable to CAR-T therapies but with a differentiated safety profile (no CRS, ICANS, IECHS, or GVHD) and superior convenience (no apheresis, no overnight stay).
• Response Rates: Pivotal success defined by reproducing initial data: TIS-40/60 response rates of 50–60% for myositis and ACRIS-25/50 response rates for systemic sclerosis are viewed as acceptable targets that would outperform current available therapies.
• Market Perception: Feedback from community rheumatologists is described as "highly favorable," with physicians eager to treat patients due to the therapy's efficacy, safety, and operational ease.

Macro / Industry Outlook:

• Regulatory Path: Upcoming FDA interactions planned to discuss the registrational path for both myositis and systemic sclerosis.
• Safety Standards: Protocol includes specific safeguards for patients with kidney impairment (reduced fludarabine doses or exclusion) to mitigate risks observed with competitors, maintaining a consistent safety standard.
• Industry Trend: Belief that cell therapy dosing and monitoring paradigms are evolving; management expects the community to become more accustomed to lymphodepletion and outpatient cell administration as education continues.

Strategic Initiatives:

• Protocol Amendment: Recently amended the Entrust protocol to compress the dosing schedule from Days 0, 3, 7 to Days 0, 2, 4 to improve PK exposure and patient convenience.
• Capacity Expansion: Plan to enroll a handful of patients at the 6 billion cell dose level on the compressed schedule.
• Real-World Evidence: Co-sponsoring the ACES companion study to capture real-world Patient-Reported Outcomes (PROs) via Zoom, with results expected next year.
• Data Collection: Increased utilization of lymph node and skin biopsies (via Dr. Valenzuela's site) to track B-cell immune reset and structural changes, serving as leading indicators for durability.

Risks and Headwinds to Outlook:

• Dose Selection Uncertainty: While 4 billion cells show strong results, there is no guarantee that 6 billion cells will provide sufficient additional efficacy to justify the higher cost; the final decision depends on rapid assessment of safety and efficacy differentials.
• Data Maturity: Lung function improvements in systemic sclerosis are currently viewed as "immature" data; pulmonary responses are expected to lag behind skin improvements, and long-term durability remains to be proven over 6–12 month periods.
• Competitor Safety News: Recent safety issues in a competitor's NK cell trial (using fludarabine) highlight the importance of the company's specific dosing and monitoring protocols for renal impairment.
• Resource Constraints: Focus on pivotal indications may delay data release for other autoimmune indications if resources are stretched.

Management Tone on the Future:

• Confidence Level: High confidence in the safety profile and early efficacy, describing the data as "impressive" and "proof-of-concept." Management believes the initial data could improve further with the compressed dosing schedule and higher dose options.
• Optimism vs. Caution: While expressing excitement about the "immune reset" mechanism and the potential to rival CAR-T efficacy, management maintains a disciplined approach, stating they will carefully monitor the 6 billion cohort before committing to a pivotal dose to avoid leaving "efficacy or durability on the table."
• Strategic Clarity: Clear shift in capital and R&D focus toward myositis and systemic sclerosis, signaling a "win now" strategy on these specific indications before expanding the portfolio.

Miscellaneous:

• Clinical Endpoints: Myositis efficacy defined by TIS-40 (moderate) and TIS-60 (major) responses; Systemic sclerosis efficacy defined by ACRIS-25 (≥25% improvement across 5 domains) and ACRIS-50 (≥50% improvement).
• Treatment Flexibility: Protocol allows for retreatment with a second cycle of lymphodepletion and infusion for non-responders; three such retreatments have been performed safely to date.
• Study Design: 40 patients treated across five autoimmune diseases as of September 18th; median treatment duration 5 months; follow-up extends up to 15 years for safety.