POTS Phase 2 Trial Shows Baloncibart, a First-in-Class NPR1 Blocking Antibody, Reduced Orthostatic Heart Rate and Improved Orthostatic Symptoms

Rhea-AI Summary

Regeneron Pharmaceuticals (NASDAQ: REGN) reported Phase 2 PINNACLE results showing baloncibart reduced standing-related heart-rate increases in adults with postural orthostatic tachycardia syndrome (POTS). The investigational antibody’s 450 mg dose reduced the lying-to-standing heart-rate change versus placebo by 11.4 beats per minute at day 8 and 7.4 at day 29. Symptoms and physical functioning also improved at day 29. The 150 mg dose reduced the heart-rate change at day 8, but the effect was not maintained at day 29.

No formal hypothesis testing was prespecified; reported p-values were nominal. Treatment-emergent adverse events occurred in 67.9% of the 450 mg group, 66.7% of the 150 mg group and 48.1% of placebo recipients. Two serious events occurred in treated patients; none led to discontinuation. Regeneron plans a potentially pivotal Phase 3 trial in the first half of 2027.

9 points · 0 major

PositiveiHow this balance works

How this balance works

Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.

It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.

Rhea-AI Sentiment measures something else, the tone of the wording.

How the balance worksHow Sentiment works

0 major · 8 points

Hollow bars mark forward-looking points. How the balance works

Positive

• Moderate point450 mg reduced lying-to-standing heart-rate change versus placebo by 11.4 bpm at day 8; nominal p=0.0007.
• Moderate pointOrthostatic symptoms improved with 450 mg versus placebo at day 29: 12.9-point difference; nominal p=0.0096.
• Moderate pointPhysical functioning improved with 450 mg versus placebo at day 29: 13.8-point difference; nominal p=0.0073.
• Minor point450 mg maintained heart-rate benefit at day 29: 7.4 bpm below placebo; nominal p=0.0124.
• Minor point150 mg reduced lying-to-standing heart-rate change versus placebo by 9.5 bpm at day 8; nominal p=0.0045.

4 minor points

• Minor pointActivities of daily living improved with 450 mg versus placebo at day 29: 8.7-point difference; nominal p=0.1035.
• Minor pointBoth doses produced day-8 biomarker changes consistent with the intended increase in circulating plasma volume.
• Minor pointNo treatment-emergent adverse event led to discontinuation; events were mostly mild or moderate.
• Minor point. Forward-looking: it has not happened yet and may not happen.Potentially pivotal Phase 3 trial planned by Regeneron for the first half of 2027.

Negative

• Minor pointNo formal hypothesis testing was prespecified for PINNACLE; reported p-values were nominal.
• Minor point150 mg heart-rate benefit was not maintained at day 29; no obvious improvement across questionnaire domains.
• Minor pointAdverse events occurred in 66.7% with 150 mg and 67.9% with 450 mg, versus 48.1% with placebo.
• Minor pointTwo serious adverse events occurred: headache with 150 mg and syncope with 450 mg.
• Minor pointStanding systolic blood pressure rose by day 29: 8.7 mmHg with 450 mg and 5.4 mmHg with 150 mg.

3 minor points

• Minor pointInjection-site reactions occurred in 17.9% with 450 mg, 3.7% with 150 mg and 14.8% with placebo.
• Minor pointHeadache occurred in 11.1% with 150 mg and 10.7% with 450 mg, versus 0% with placebo.
• Minor pointHeavy menstrual bleeding occurred in 11.1% with 150 mg, versus 0% with 450 mg and placebo.

Key Figures

Trial arm sizes: 150 mg: n=27; 450 mg: n=28; placebo: n=27 450 mg DeltaHR difference: -11.4 bpm; nominal p=0.0007 450 mg DeltaHR difference: -7.4 bpm; nominal p=0.0124 +5 more

Trial arm sizes

150 mg: n=27; 450 mg: n=28; placebo: n=27

Randomized, double-blind Phase 2 PINNACLE trial

450 mg DeltaHR difference

-11.4 bpm; nominal p=0.0007

Versus placebo at day 8; primary endpoint

450 mg DeltaHR difference

-7.4 bpm; nominal p=0.0124

Versus placebo at day 29; secondary endpoint

150 mg DeltaHR difference

-9.5 bpm; nominal p=0.0045

Versus placebo at day 8; effect was not maintained at day 29

Orthostatic symptoms

-12.9 points; nominal p=0.0096

450 mg versus placebo at day 29 on LWPQ; baseline mean 45.5

Physical functioning

-13.8 points; nominal p=0.0073

450 mg versus placebo at day 29 on LWPQ; baseline mean 55.1

Treatment-emergent adverse events

48.1% placebo; 66.7% at 150 mg; 67.9% at 450 mg

Mostly mild or moderate events

Serious treatment-emergent adverse events

2

One case each in the 150 mg and 450 mg groups

Key Terms

monoclonal antibody, subcutaneous, least-squares mean difference, treatment-emergent adverse events

4 terms

monoclonal antibody medical

"a novel, investigational, first-in-class monoclonal antibody"

A monoclonal antibody is a laboratory-made protein designed to recognize and attach to a specific target in the body, such as a disease-causing substance or cell. It functions like a highly precise lock-and-key tool, helping to treat or detect illnesses. For investors, companies developing monoclonal antibodies can represent promising opportunities in the healthcare sector, especially as these treatments often address unmet medical needs.

subcutaneous medical

"a single subcutaneous dose of baloncibart"

Subcutaneous means situated or applied just beneath the skin. In finance, the term can describe processes or investments that are hidden or not immediately visible, much like something placed under the skin that isn't easily seen from the outside. Recognizing subcutaneous activities helps investors understand underlying factors that may influence markets or asset values over time.

least-squares mean difference technical

"with a least-squares (LS) mean difference of -11.4 beats per minute"

Least-squares mean difference is the estimated gap between two adjusted averages from a statistical model, showing how much one group differs from another after accounting for other factors. Think of it as comparing test scores between two classes after correcting for differences in prior grades; it isolates the effect of the treatment or condition. Investors use it to gauge the size and reliability of an expected outcome (for example a drug benefit) once confounding influences are removed.

treatment-emergent adverse events medical

"Treatment-emergent adverse events (TEAEs) were mostly mild or moderate"

Events or symptoms that either appear for the first time or get worse after a patient starts a treatment; think of new or intensified side effects that show up once medicine or a medical device is used. Investors watch these closely because they affect whether a therapy can gain regulatory approval, be prescribed widely, or face legal and commercial setbacks—similar to how early customer complaints can sink a new product’s prospects.

AI-generated analysis. How Rhea-AI works. Not financial advice.

See more from StockTitan in Google Search and AI answers. Adds StockTitan as a preferred source · opens Google

Add on Google Not now

Data presented today for the first time at the American Autonomic Society (AAS) annual meeting

POTS (postural orthostatic tachycardia syndrome) is a debilitating condition characterized by a marked increase in heart rate upon standing and associated orthostatic symptoms, with no FDA-approved treatments available

A single dose of baloncibart reduced the exaggerated heart rate response to standing and improved orthostatic symptoms through four weeks; biomarker changes were consistent with plasma volume expansion, the intended effect of NPR1 blockade

Potentially pivotal Phase 3 trial planned for first half of 2027

TARRYTOWN, N.Y., Nov. 12, 2026 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced results from the Phase 2 PINNACLE trial in adults with postural orthostatic tachycardia syndrome (POTS) evaluating baloncibart, a novel, investigational, first-in-class monoclonal antibody that blocks natriuretic peptide receptor 1 (NPR1). The data were presented for the first time at the American Autonomic Society’s (AAS) 37th International Symposium on the Autonomic Nervous System in San Diego, CA.

POTS is a chronic disorder in which heart rate rises abnormally upon standing. Patients may experience palpitations, dizziness, fatigue, exercise intolerance, cognitive difficulties, gastrointestinal symptoms and chronic pain. Although historically underdiagnosed, recent estimates suggest it affects between 500,000 and several million people in the U.S., and the vast majority are young women. While the cause of POTS is unknown, it is believed to be associated with low blood volume. Baloncibart is designed to increase the volume of blood in circulation in an effort to reduce the increase in heart rate and symptoms that occur in people with POTS.

“POTS causes debilitating symptoms that can profoundly disrupt daily life, and patients have no FDA-approved treatment options. In the trial, a single injection of baloncibart 450 mg reduced the exaggerated heart rate response to standing and improved orthostatic symptoms through four weeks,” said Satish R. Raj, M.D., Professor of Cardiac Science at the University of Calgary’s Cumming School of Medicine, and investigator in the trial. “The results are consistent with the rationale for NPR1 blockade in POTS, with biomarker changes pointing to an increase in blood volume alongside lower heart rate and better symptoms.”

The randomized, double-blind, Phase 2 PINNACLE trial evaluated a single subcutaneous dose of baloncibart 150 mg (n=27) or 450 mg (n=28) compared to placebo (n=27) in patients with POTS. The primary endpoint was the change in heart rate from lying down to standing (DeltaHR) at day 8; no formal hypothesis testing was prespecified. Improvements were observed with baloncibart on DeltaHR and other key measures of the disease (i.e., symptoms and function) as assessed by the Living With POTS Questionnaire (LWPQ). The LWPQ is a novel patient-reported outcome tool to assess POTS symptoms and function in clinical trials, which is being developed by Regeneron in accordance with the FDA patient-focused drug development guidance.

Baloncibart 450 mg reduced DeltaHR versus placebo at day 8 (primary endpoint) with a least-squares (LS) mean difference of -11.4 beats per minute (bpm; nominal p=0.0007), and at day 29 (secondary endpoint) with an LS mean difference of -7.4 bpm (nominal p=0.0124). Baloncibart 150 mg reduced DeltaHR versus placebo at day 8 (LS mean difference: -9.5 bpm; nominal p=0.0045), but the effect was not maintained at day 29.

Baloncibart 450 mg improved orthostatic symptoms, physical functioning, and activities of daily living versus placebo at day 29, as measured by the LWPQ. Domain scores range from 0 to 100, with lower scores indicating fewer symptoms or less impairment. The LS mean differences in change from baseline for each domain were as follows:

• Orthostatic symptoms (baseline mean: 45.5): -12.9 points (nominal p=0.0096)
• Physical functioning (baseline mean: 55.1): -13.8 points (nominal p=0.0073)
• Activities of daily living (baseline mean: 48.7): -8.7 points (nominal p=0.1035)
• Overall across the three domains, there was no obvious improvement with baloncibart 150 mg compared to placebo
  
  

Additionally at day 8, both doses of baloncibart led to changes in biomarkers consistent with the anticipated beneficial plasma volume expansion driven by NPR1 blockade, including an increase in NT-proBNP and reductions in standing norepinephrine and hemoglobin. Average standing systolic blood pressure increased for both doses, with observed mean changes from baseline at day 29 of 8.7 mmHg to a mean of 118.8 mmHg for baloncibart 450 mg and 5.4 mmHg to a mean of 114.0 mmHg for baloncibart 150 mg.

In the trial, single doses of baloncibart up to 450 mg were generally well tolerated. Treatment-emergent adverse events (TEAEs) were mostly mild or moderate and occurred in 13 patients (48.1%) receiving placebo, 18 patients (66.7%) receiving baloncibart 150 mg, and 19 (67.9%) receiving baloncibart 450 mg; one severe TEAE occurred in the trial in the placebo group. TEAEs that occurred in ≥10% of patients in any treatment group, including placebo, baloncibart 150 mg and baloncibart 450 mg, were: injection site reaction (14.8%, 3.7%, and 17.9%), headache (0%, 11.1%, and 10.7%), syncope (11.1%, 14.8%, and 3.6%), heavy menstrual bleeding (0%, 11.1%, and 0%), and nasopharyngitis (11.1%, 0%, and 0%). Two serious TEAEs were reported: one case of headache with baloncibart 150 mg and one case of syncope with baloncibart 450 mg. No TEAE led to discontinuation.

“POTS is a condition that disproportionately impacts younger women and has been under-recognized and under-served for too long, which is why it was critical to incorporate the patient experience in our trial design and measure symptoms that reflect how patients actually feel and function,” said Boaz Hirshberg, M.D., Senior Vice President, Clinical Development, Internal Medicine at Regeneron. “These initial results show the potential of baloncibart for people living with POTS and we look forward to advancing this novel therapy into a Phase 3 clinical trial in 2027.”

The safety and efficacy of baloncibart have not been evaluated by any regulatory authority.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce fully optimized human antibodies. When Regeneron’s Co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor, Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite^® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies. This includes Dupixent^® (dupilumab), Libtayo^® (cemiplimab-rwlc), Praluent^® (alirocumab), Kevzara^® (sarilumab), Evkeeza^® (evinacumab-dgnb), Inmazeb^® (atoltivimab, maftivimab and odesivimab-ebgn), Veopoz^® (pozelimab-bbfg), and Pasatru^® (garetosmab-grts). In addition, REGEN-COV^® (casirivimab and imdevimab) had been authorized by the FDA during the COVID-19 pandemic until 2024. A total of 11 antibody and bispecific products have been approved or authorized worldwide that were invented or derived using VelocImmune technologies.

About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, neurological diseases, hematologic conditions, infectious diseases, and rare diseases.

Regeneron pushes the boundaries of scientific discovery and accelerates drug development using our proprietary technologies, such as VelociSuite^®, which produces optimized fully human antibodies and new classes of bispecific antibodies. We are shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center^® and pioneering genetic medicine platforms, enabling us to identify innovative targets and complementary approaches to potentially treat or cure diseases.

For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook or X.

Forward-Looking Statements and Use of Digital Media
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. (“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,” “believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Products”) and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, “Regeneron’s Product Candidates”) and research and clinical programs now underway or planned, including without limitation baloncibart (REGN7544); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron’s Product Candidates and new indications for Regeneron’s Products, such as baloncibart for the treatment of adults with postural orthostatic tachycardia syndrome as discussed in this press release; uncertainty of the utilization, market acceptance, and/or commercial success of Regeneron’s Products and Regeneron’s Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron’s Products and Regeneron’s Product Candidates (such as baloncibart); the ability of Regeneron’s collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron’s Products and Regeneron’s Product Candidates; the ability of Regeneron to manage supply chains for multiple products and product candidates and risks associated with tariffs and other trade restrictions; safety issues resulting from the administration of Regeneron’s Products and Regeneron’s Product Candidates (such as baloncibart) in patients, including serious complications or side effects in connection with the use of Regeneron’s Products and Regeneron’s Product Candidates in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to continue to develop or commercialize Regeneron’s Products and Regeneron’s Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron’s Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement or copay assistance for Regeneron’s Products from third-party payors and other third parties, including private payor healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payors and other third parties and new policies and procedures adopted by such payors and other third parties; changes to drug pricing regulations and requirements and Regeneron’s pricing strategy, including in connection with Regeneron’s April 2026 agreements with the U.S. government; other changes in laws, regulations, and policies affecting the healthcare industry; competing products and product candidates (including biosimilar products) that may be superior to, or more cost effective than, Regeneron’s Products and Regeneron’s Product Candidates; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron’s agreements with Sanofi and Bayer (or their respective affiliated companies, as applicable), to be cancelled or terminated; the impact of public health outbreaks, epidemics, or pandemics on Regeneron's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts), risks associated with intellectual property of the Company or other parties and pending or future litigation or patent office proceedings relating thereto (including without limitation patent litigation and other related proceedings relating to Regeneron’s Products), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron’s business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2025 and its Form 10-Q for the quarterly period ended September 30, 2026. Any forward-looking statements are made based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise.

Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals).

Contacts:
Media Relations Julie Block Tel: +1 914-826-7083 julie.block@regeneron.com	Investor Relations Mark Hudson Tel: +1 914-847-3482 mark.hudson@regeneron.com

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Regeneron’s baloncibart Phase 2 POTS trial show?

Baloncibart 450 mg reduced the lying-to-standing heart-rate change versus placebo by 11.4 beats per minute at day 8 and 7.4 beats per minute at day 29. Orthostatic symptoms and physical functioning also improved at day 29. No formal hypothesis testing was prespecified, and the reported p-values were nominal.

When does Regeneron plan to start Phase 3 testing of baloncibart for POTS?

Regeneron plans a potentially pivotal Phase 3 trial in the first half of 2027.

How was Regeneron’s PINNACLE baloncibart trial designed?

PINNACLE was a randomized, double-blind Phase 2 trial comparing a single injection under the skin of baloncibart 150 mg in 27 patients or 450 mg in 28 patients with placebo in 27 patients. The primary endpoint was the change in heart rate from lying down to standing at day 8.

How did Regeneron measure symptoms and function in the baloncibart POTS trial?

The trial used the Living With POTS Questionnaire, a patient-reported tool being developed by Regeneron in accordance with FDA patient-focused drug development guidance. Domain scores range from 0 to 100, with lower scores indicating fewer symptoms or less impairment.