Rezolute Announces Phase 3 sunRIZE Study Results in Congenital Hyperinsulinism

Rhea-AI Summary

Rezolute (Nasdaq: RZLT) announced topline Phase 3 sunRIZE results in congenital hyperinsulinism on Dec 11, 2025. The study did not meet its primary endpoint assessing average weekly hypoglycemia events or its key secondary CGM endpoint.

At the top ersodetug dose (10 mg/kg) there was an approximate 45% reduction in hypoglycemia events versus a 40% improvement in placebo (not statistically significant). CGM time in hypoglycemia fell ~25% at 10 mg/kg versus a ~+5% increase with placebo. Target drug concentrations were achieved across ages. Safety was described as generally favorable; two participants had serious hypersensitivity leading to discontinuation. Rezolute intends to meet with FDA under its Breakthrough Therapy Designation; tumor HI study upLIFT topline expected H2 2026.

Positive

• Ersodetug achieved target drug concentrations across all age groups
• Majority of participants continued into the open-label extension
• Company plans meeting with FDA under Breakthrough Therapy designation

Negative

• Failed primary endpoint for weekly hypoglycemia events (not significant)
• Failed key secondary CGM endpoint for time in hypoglycemia
• Two participants had serious hypersensitivity reactions causing discontinuation
• Placebo showed a 40% improvement, narrowing treatment effect at top dose

Key Figures

Hypoglycemia event reduction (ersodetug 10 mg/kg) 45% reduction Phase 3 sunRIZE primary endpoint measure; not statistically significant vs placebo

Hypoglycemia improvement (placebo arm) 40% improvement Comparator for primary endpoint in Phase 3 sunRIZE

Time in hypoglycemia reduction (ersodetug 10 mg/kg) 25% reduction Key secondary endpoint by continuous glucose monitoring; not statistically significant

Time in hypoglycemia change (placebo) 5% increase Comparator for key secondary endpoint in Phase 3 sunRIZE

Ersodetug dosing regimen 5 and 10 mg/kg Every other week for 3 doses, then every 4 weeks over 24 weeks

Treatment duration 24 weeks Phase 3 sunRIZE treatment period

Serious hypersensitivity cases 2 participants Led to early discontinuation of study drug in Phase 3 sunRIZE

Top ersodetug dose 10 mg/kg Dose level associated with reported efficacy and safety outcomes

Market Reality Check

$10.94 Last Close

Volume Volume 2,980,745 is 1.73x the 20-day average of 1,719,758, indicating elevated trading interest. high

Technical Price at $10.94 is trading above the 200-day MA of $6.07 and within 5% of the 52-week high of $11.46.

Peers on Argus

RZLT is up 11.07% while peers show mixed, mostly modest moves (e.g., KALV +4.2%, RIGL -3.03%, VIR -2.09%), suggesting a stock-specific reaction rather than a broad biotech move.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Nov 10	Equity inducement grants	Negative	-7.5%	Inducement stock options at $9.32 with four-year vesting for new hires.
Nov 06	Earnings and update	Positive	+2.7%	Reported Q1 FY26 results and confirmed Phase 3 timelines and FDA alignment.
Nov 05	Investor event	Positive	+5.1%	Announced virtual event to discuss ersodetug Phase 3 programs and opportunities.
Oct 15	Conference participation	Positive	+6.9%	Planned appearances at multiple late-2025 healthcare investor conferences.
Oct 09	Equity inducement grants	Negative	-6.3%	Inducement equity options for new employees under Nasdaq Rule 5635(c)(4).

Pattern Detected

Recent news often triggered sizable directional moves, with equity grant filings drawing negative reactions and clinical/strategic updates generally seeing positive price responses.

Recent Company History

Over the last few months, Rezolute’s news flow has centered on clinical progress for ersodetug and corporate matters. Clinical milestones like DMC support and enrollment progress for the Phase 3 sunRIZE study previously drew positive moves up to 27.65%. Routine items such as inducement equity grants on Oct 9 and Nov 10 saw negative reactions of -6.34% and -7.48%. Today’s topline Phase 3 sunRIZE results, with primary and key secondary endpoints not met, contrast with those earlier optimistic updates.

Market Pulse Summary

The stock is dropping -87.3% following this news. A negative reaction despite the stock’s recent strength would have fit prior patterns where disappointing or non-core updates led to pullbacks. Here, the Phase 3 sunRIZE topline results show primary and key secondary endpoints were not met, in contrast to earlier supportive DMC and enrollment news that saw gains up to 27.65%. If the move were sharply negative, it would have reflected reassessment of ersodetug’s risk–reward after high expectations built through 2025.

Key Terms

monoclonal antibody medical

"relatively low compared to biologic or monoclonal antibody treatments."

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.

breakthrough therapy designation regulatory

"We intend to meet with FDA under our Breakthrough Therapy Designation to consider next steps"

A breakthrough therapy designation is a regulatory fast-track given to a drug or treatment that shows early signs of providing a major improvement over existing options for a serious condition. Think of it as a VIP lane that can speed up development and more intensive guidance from regulators, which matters to investors because it can shorten time to market, reduce development risk and potentially increase a company’s value — though it does not guarantee approval.

Phase 3 medical

"topline results from its Phase 3 sunRIZE study evaluating ersodetug"

Phase 3 is the late-stage clinical testing step for a new drug or medical treatment, where the product is given to large groups of patients to confirm effectiveness, monitor side effects, and compare it to standard care. Successful Phase 3 results are often the final scientific hurdle before regulators decide on approval and market launch—like passing a final exam before graduation—and can sharply change a company's valuation and future revenue prospects.

AI-generated analysis. Not financial advice.

Study did not meet the primary or key secondary endpoint 

45% reduction in hypoglycemia events observed at top ersodetug dose (10 mg/kg) compared to 40% improvement in placebo arm

Management to host conference call today at 8:30am ET

REDWOOD CITY, Calif., Dec. 11, 2025 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a late-stage rare disease company focused on treating hypoglycemia caused by hyperinsulinism, today announced topline results from its Phase 3 sunRIZE study evaluating ersodetug in patients with congenital hyperinsulinism (HI).

The study did not meet its primary endpoint, which assessed change in the average weekly hypoglycemia events by self monitored blood glucose. There was an approximate 45% reduction in hypoglycemia events observed at the top ersodetug dose (10 mg/kg), which was not statistically significant compared to the placebo group, which experienced a 40% improvement. Furthermore, the study did not meet its key secondary endpoint, which assessed change in average daily percent time in hypoglycemia by continuous glucose monitoring (CGM). At the 10 mg/kg dose of ersodetug, an approximate 25% reduction in time in hypoglycemia was observed, which was not statistically significant compared to the placebo, which increased by approximately 5%.

At the study dose regimens of 5 and 10 mg/kg administered every other week for 3 doses, followed by every 4 weeks over the remainder of the 24-week treatment duration, ersodetug target drug concentrations were achieved, across all age groups studied.

Safety observations from the study were generally favorable and, in the opinion of the Company, support safe use of ersodetug in pediatric and adult patients. Two of the study participants experienced serious hypersensitivity reactions which led to early discontinuation of study drug. The incidence of serious allergic reactions across the program is relatively low compared to biologic or monoclonal antibody treatments. The most commonly reported study adverse event in ersodetug treated participants compared to placebo was hypertrichosis, which was generally mild and self-limiting.

“We are disappointed that the study did not demonstrate significant improvements in glucose-related endpoints relative to placebo as well as for the patients and families living with congenital HI who urgently need new treatment options,” said Brian Roberts, M.D., Chief Medical Officer of Rezolute. “At the same time, there are aspects of the results that merit additional investigation, and we are conducting a thorough evaluation to gain a better understanding of the study outcomes, which will inform our path forward. We intend to meet with FDA under our Breakthrough Therapy Designation to consider next steps for the program. We are deeply grateful to the patients and families, the majority of whom have continued into the open label extension part of the study, as well as to the investigators and site teams who participated in this important study.”

The Phase 3 upLIFT study for tumor HI is ongoing with topline results expected in the second half of 2026.

Conference Call Information

To access the event by phone, please dial 1-877-317-6789 from the U.S. and Canada or 1-412-317-6789 internationally and ask to be joined into the Rezolute call. The live webcast can be accessed on the investor page of Rezolute’s website at https://ir.rezolutebio.com.

About sunRIZE

The Phase 3 sunRIZE study (RZ358-301) is a multi-center, randomized, double-blind, placebo-controlled, parallel arm study designed to evaluate the efficacy and safety of ersodetug in patients with congenital hyperinsulinism (HI), ages 3 months to 45 years old, who are experiencing continued hypoglycemia on currently available standard of care (SOC). Eligible participants are randomized to one of three treatment arms to receive either ersodetug (5 or 10 mg/kg) or matched placebo-control as add on to existing SOC. Study drug is administered every other week during an initial loading phase, and then every 4 weeks during the 6-month controlled pivotal treatment period. Following the pivotal treatment phase of the study, participants may roll-over into an optional open-label extension phase to continue to receive ersodetug.

The study enrolled 63 participants in more than a dozen countries around the world, inclusive of U.S. patients. The primary and key secondary efficacy endpoints in the study are the change from baseline in the average number of hypoglycemia events per week and the average percent time in hypoglycemia, respectively, over six months of treatment.

About Ersodetug  

Ersodetug is a fully human monoclonal antibody that binds allosterically to the insulin receptor to decrease receptor over-activation by insulin and related substances (such as IGF-2) in the setting of hyperinsulinism (HI), thereby improving hypoglycemia. Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any congenital or acquired form of HI. 

About Rezolute, Inc.

Rezolute is a late-stage rare disease company focused on treating hypoglycemia caused by hyperinsulinism (HI). The Company’s antibody therapy, ersodetug, is designed to treat all forms of HI and has shown meaningful benefit in clinical trials and real-world use. For more information, visit www.rezolutebio.com.

Forward-Looking Statements

This release, like many written and oral communications presented by Rezolute and our authorized officers, may contain certain forward-looking statements regarding our prospective performance and strategies within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. We intend such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 and are including this statement for purposes of said safe harbor provisions. Forward-looking statements, which are based on certain assumptions and describe future plans, strategies, and expectations of Rezolute, are generally identified by use of words such as "anticipate," "believe," "estimate," "expect," "intend," "plan," "project," "seek," "strive," "try," or future or conditional verbs such as "could," "may," "should," "will," "would," or similar expressions. These forward-looking statements include, but are not limited to the timing of future actions that we could take following the release of topline data, or the timing of the release of topline results from the upLIFT study. Our ability to predict results or the actual effects of our plans or strategies is inherently uncertain. Accordingly, actual results may differ materially from anticipated results. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release. Except as required by applicable law or regulation, Rezolute undertakes no obligation to update these forward-looking statements to reflect events or circumstances that occur after the date on which such statements were made. Important factors that may cause such a difference include any other factors discussed in our filings with the SEC, including the Risk Factors contained in the Rezolute’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, which are available at the SEC’s website at www.sec.gov. You are urged to consider these factors carefully in evaluating the forward-looking statements in this release and are cautioned not to place undue reliance on such forward-looking statements, which are qualified in their entirety by this cautionary statement.

Rezolute Contacts:

Christen Baglaneas
cbaglaneas@rezolutebio.com
508-272-6717

Carrie McKim
cmckim@rezolutebio.com
336-608-9706

FAQ

What did Rezolute (RZLT) announce on Dec 11, 2025 about sunRIZE Phase 3?

Rezolute announced the sunRIZE study did not meet its primary or key secondary endpoints for ersodetug in congenital HI.

What were the primary sunRIZE efficacy numbers for ersodetug versus placebo (RZLT)?

At 10 mg/kg ersodetug showed an approximate 45% reduction in hypoglycemia events versus a 40% improvement in placebo; difference was not statistically significant.

Did the sunRIZE Phase 3 study show improvement on continuous glucose monitoring (CGM)?

No; CGM time in hypoglycemia fell ~25% at 10 mg/kg but increased ~5% in placebo, and this key secondary result was not statistically significant.

Were there safety concerns in Rezolute's sunRIZE trial for ersodetug (RZLT)?

Safety was reported as generally favorable, though two participants experienced serious hypersensitivity that led to drug discontinuation; hypertrichosis was the most common adverse event.

What are Rezolute's next steps after the sunRIZE topline results (RZLT)?

Rezolute plans to conduct a thorough evaluation of results and meet with FDA under its Breakthrough Therapy Designation to discuss next steps.

When will Rezolute report topline results for the tumor HI upLIFT study (RZLT)?

Rezolute expects topline results from the upLIFT tumor HI study in the second half of 2026.