Tarrytown, New York, USA, November 12, 2026
Regeneron Pharmaceuticals, Inc. has announced encouraging Phase 2 results for baloncibart (REGN7544), an investigational, first-in-class monoclonal antibody designed to block natriuretic peptide receptor 1 (NPR1) in adults with postural orthostatic tachycardia syndrome (POTS). Findings from the randomized Phase 2 PINNACLE trial showed that a single subcutaneous dose of baloncibart reduced the abnormal increase in heart rate experienced by patients when moving from a lying to a standing position. The 450 mg dose also improved reported orthostatic symptoms and physical functioning through Day 29 compared with placebo. The results were presented for the first time at the American Autonomic Society’s 37th International Symposium on the Autonomic Nervous System in San Diego, California, on November 12, 2026. Regeneron plans to advance baloncibart into a potentially pivotal Phase 3 clinical trial in the first half of 2027. The findings could represent an important development for people living with POTS, a chronic condition for which there are currently no FDA-approved treatments.
Baloncibart Reduces Abnormal Heart Rate Response in POTS
POTS is a disorder of the autonomic nervous system characterized by an excessive increase in heart rate after standing. People affected by the condition may experience dizziness, palpitations, fatigue, exercise intolerance, cognitive difficulties, gastrointestinal symptoms and chronic pain. The condition can significantly interfere with everyday activities and quality of life. Although its precise cause is not fully understood, reduced circulating blood volume is considered one potential contributing factor in many patients. Baloncibart is designed to address this mechanism by blocking NPR1, a receptor involved in regulating fluid balance and blood volume. Regeneron’s therapeutic approach aims to increase circulating plasma volume, potentially reducing the exaggerated heart rate response and associated symptoms when patients stand. The Phase 2 PINNACLE study was a randomized, double-blind, placebo-controlled trial involving 82 adults with POTS. Participants received a single subcutaneous dose of baloncibart at either 150 mg or 450 mg, or placebo. The study included 27 participants in the placebo group, 27 in the 150 mg group and 28 in the 450 mg group. The primary endpoint evaluated the change in heart rate between lying down and standing (DeltaHR) at Day 8. The trial showed that the 450 mg dose reduced DeltaHR by 11.4 beats per minute compared with placebo at Day 8, with a nominal p-value of 0.0007. At Day 29, the reduction remained at 7.4 beats per minute compared with placebo. The 150 mg dose also reduced DeltaHR at Day 8, but the effect was not maintained at Day 29.
Phase 2 Data Show Improvements in Symptoms and Function
Beyond heart rate measurements, the study evaluated patient experiences using the Living With POTS Questionnaire (LWPQ), a patient-reported outcome tool being developed by Regeneron to assess symptoms and functional limitations. At Day 29, participants receiving the 450 mg dose demonstrated improvements in orthostatic symptoms and physical functioning compared with placebo. The reported least-squares mean differences were 12.9 points for orthostatic symptoms and 13.8 points for physical functioning, with nominal p-values of 0.0096 and 0.0073, respectively. The activities-of-daily-living domain showed a difference of 8.7 points, but this result was not statistically significant based on its nominal p-value of 0.1035. The lower 150 mg dose did not demonstrate an overall obvious improvement across the three questionnaire domains compared with placebo. Biomarker findings also supported the intended biological activity of NPR1 blockade. Changes included increased NT-proBNP and reductions in standing norepinephrine and hemoglobin, which the company described as consistent with plasma volume expansion. These changes provide additional evidence that baloncibart affected the biological pathway it was designed to target. However, the results remain from a relatively small Phase 2 study, and further investigation will be needed to establish the consistency and clinical significance of the observed effects.
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Safety Profile and Planned Phase 3 Development
Single doses of baloncibart up to 450 mg were generally well tolerated in the PINNACLE trial. Most treatment-emergent adverse events were mild or moderate. Such events were reported in 48.1% of placebo recipients, 66.7% of participants receiving 150 mg and 67.9% of those receiving 450 mg. Two serious treatment-emergent adverse events were reported: one headache in the 150 mg group and one case of syncope in the 450 mg group. No treatment-emergent adverse event resulted in discontinuation. Regeneron stated that the findings support continued development of baloncibart and its planned transition into Phase 3 testing in 2027. The company also highlighted the importance of incorporating patient-reported outcomes into clinical research for POTS, particularly because symptoms can affect physical functioning and daily life beyond changes in heart rate alone. Baloncibart remains an investigational medicine, and its safety and efficacy have not been evaluated or approved by any regulatory authority. The planned Phase 3 study will be important in determining whether the Phase 2 findings can be confirmed in a larger patient population and whether NPR1 blockade could become a new treatment strategy for POTS.
Source: Regeneron Pharmaceuticals press release
