Biotech Company Advances Breakthrough Hyperinsulinism Treatment

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1. Ownership and Share Structure Information

The information listed above was updated on the date this article was published and was compiled from information from the company and various other data providers.

Rezolute Inc. (RZLT:NASDAQ), a late-stage company focused on treating hypoglycemia caused by all forms of hyperinsulinism (HI), reported financial results and provided a business update for the three months ended December 31, 2025, according to a February 12 release.

In December 2025, Rezolute shared topline results from the sunRIZE study, a Phase 3, multicenter, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of ersodetug for congenital HI.

The study did not meet its primary or key secondary endpoints. The company said that while reductions in hypoglycemia events were observed with self-monitored blood glucose at both ersodetug dose levels, they were not statistically significant compared to placebo due to a pronounced study effect.

A reduction in hypoglycemia time by continuous glucose monitoring (CGM) was statistically significant at the Week 16 timepoint but not at Week 24. Pharmacologic activity was observed, with target therapeutic drug concentrations achieved and decreased insulin cell signaling in the active treatment groups. All 59 participants who completed the study continued into the open-label extension, with many transitioning from standard therapies to ersodetug monotherapy.

Following the announcement of these results, the company said it is conducting an extensive analysis in preparation for an upcoming FDA meeting under Breakthrough Therapy Designation to determine next steps.

Topline Results Expected in H2

The upLIFT study, a Phase 3, single-arm, open-label trial for tumor HI, is ongoing with enrollment underway, Rezolute said. Topline results are expected in the second half of 2026.

In January 2026, the company shared data from the initial nine tumor HI patients treated under the historical Expanded Access Program (EAP), showing that 75% of patients achieved complete discontinuation of IV dextrose/TPN. This cohort was the basis for FDA granting Breakthrough Designation and agreeing to a single-arm, open-label registrational study design. The primary endpoint in upLIFT is the glucose infusion rate (GIR) assessment, measuring the number of participants achieving at least a 50% reduction in GIR.

In November 2025, Rezolute hosted a virtual Investor Event where Chief Commercial Officer Sunil Karnawat discussed the commercial opportunities for ersodetug as a treatment for congenital and tumor HI. The event featured presentations from physician experts on the disease background and unmet clinical needs in HI. A replay is available on the company’s website.

Second Quarter Fiscal 2026 Financial Results

Cash, cash equivalents, and investments in marketable securities were US$132.9 million as of December 31, 2025, down from US$167.9 million as of June 30, 2025, the company said in the release.

Research and development expenses were US$14.3 million, up from US$12.6 million a year ago, due to increased clinical trial activities and higher employee-related expenses, including severance benefits from a December 2025 reduction in force.

General and administrative expenses were US$9.9 million, up from US$4.5 million a year ago, primarily due to increased professional fees and employee-related expenses, including severance benefits, Rezolute said.

The company said its net loss was US$22.8 million, compared to a net loss of US$15.7 million a year ago.

Analyst: FDA Meeting Expected

Rezolute's Type B meeting with the FDA is scheduled for the end of the first quarter, according to an updated research note by H.C. Wainwright & Co. Analyst Douglas Tsao on February 13. The company is finalizing the analysis of the sunRIZE study, which includes other potential endpoints and patient-reported quality-of-life outcomes, in preparation for the upcoming FDA meeting under Breakthrough Therapy Designation (BTD), expected by the end of the first quarter. This meeting will help determine the next steps for the ersodetug program for congenital hyperinsulinism (cHI).

Earlier this year, the company updated its biomarker data, showing that both treatment groups (5mg/kg and 10mg/kg) experienced a reduction in insulin activity, which is the expected effect of ersodetug's mechanism, Tsao noted. Notably, all 59 participants who completed the study chose to continue receiving ersodetug in the open-label extension phase. Additionally, several children in the extension phase have successfully stopped all other therapies and are now on ersodetug as their sole treatment. One patient has been on ersodetug for as long as three years. Given the severity of the condition, it is unlikely that clinicians would keep pediatric patients on ersodetug if the drug was not providing meaningful benefits.

Having granted BTD, the analyst said his firm believes the FDA will be open to a pragmatic development path in pediatric cHI, given the disease's severity and limited therapeutic options.

"While BTD does not guarantee approval and we do not expect FDA to lower its evidentiary standards, the Agency has, in serious rare pediatric diseases, shown flexibility around endpoint selection and trial design when conventional clinical measures are noisy, behaviorally confounded, or impractical, particularly when objective, mechanistically rational, and clinically meaningful endpoints are available (e.g., dystrophin as a surrogate in Duchenne, external controls in CLN2 Batten disease)," Tsao wrote.

In this context, Tsao said the FDA could consider glucose infusion rate (GIR) as a registrational endpoint, as it offers a more objective, mechanism-aligned measure of efficacy and avoids the limitations of SMBG-based endpoints.

The company should be able to share feedback from its FDA meeting by the end of April, the analyst said. Tsao said analysts have noticed improved investor sentiment recently and are optimistic about Rezolute shares with the upcoming FDA meeting, followed by data from upLIFT in tumor hyperinsulinism in the second half of the year.

Topline results from the tumor hyperinsulinism (HI) program are expected in the second half of 2026, the analyst said. In January, the company reported data from the first nine tumor HI patients treated under its Expanded Access Program (EAP), with 75% achieving complete discontinuation of IV dextrose/total parenteral nutrition (TPN). These data supported the FDA’s decision to grant BTD and informed a revision of the Phase 3 upLIFT study to a single-arm, open-label design. The study’s primary statistical threshold requires that at least 9 of 16 patients achieve a ≥50% reduction in glucose infusion rate (GIR).

"Based on the EAP experience and objective nature of the GIR endpoint, we feel good about a positive readout in upLIFT which we think would be an important catalyst for shares in restoring investor confidence in ersodetug which was understandably shaken by sunRIZE's miss," the analyst said.

Loss Wider Than Firm's Estimate

Rezolute posted a loss per share of US$0.22 in the second quarter of fiscal 2026, wider than H.C. Wainwright's estimate of a US$0.15 loss per share and higher than the street consensus of a US$0.19 loss per share, Tsao said. The loss per share for the second quarter of fiscal 2025 was also US$0.22.

R&D expenses grew 13.4% year-over-year to US$14.3 million in the second quarter of fiscal 2026, higher than the firm's estimate of US$12 million, primarily due to increased clinical trial and personnel-related costs, including one-time severance benefits related to the December 2025 reduction in force, partially offset by lower manufacturing expenses for ersodetug. G&A expenses jumped 120% year-over-year to US$9.9 million from US$4.5 million in the second quarter of fiscal 2025, above our estimate of US$4.6 million.

The increase in G&A was mainly driven by higher professional fees and employee-related costs. At the end of the quarter, the company’s cash, cash equivalents, and investments in marketable securities balance stood at US$132.9 million, which is expected to fund planned operations for at least the next 12 months.

"Our Buy rating and US$5 price target on Rezolute are based on 5.5x our 2036 discounted risk-adjusted revenue estimate of US$99.2 million," the analyst said. "We adjust each pipeline asset for the probability of success (PoS): RZ358 for congenital hyperinsulinism (CHI) at 40%, given the strength of the RIZE data; 60% for Tumor HI, as the program is in the Phase 3 stage. Risks to price target achievement: (i) financial, because RZLT is not generating revenue and has capital needs that exceed current cash balance; (ii) dilutive, as Rezolute is likely to need to raise additional capital; (iii) commercial, due to competition; (iv) regulatory, because none of Rezolute’s products is currently approved."

The Catalyst: Drug Battles Low Blood Sugar Disease

According to Children's Hospital of Philadelphia, congenital hyperinsulinism (HI) is a genetic condition where the pancreas's insulin-producing beta cells release too much insulin. This excess insulin leads to low blood sugar levels, known as hypoglycemia.

Normally, beta cells produce just enough insulin to maintain blood sugar within a normal range. However, in children with HI, insulin secretion is not properly controlled, resulting in excessive insulin and low blood sugar levels.

The hospital said low blood sugar can be extremely dangerous, as the brain requires a constant supply of sugar. Without sufficient sugar, the brain can suffer seizures, brain damage, and potentially death. Congenital HI is a rare disorder, affecting 1 in 25,000 to 50,000 infants.

The congenital hyperinsulinism treatment market is projected to grow from US$158.91 million in 2026 to US$223.66 million by 2031, with a compound annual growth rate (CAGR) of 7.08% during this period, Mordor Intelligence reported. This growth is driven by earlier detection of cases through newborn screening, the development of a diverse pipeline that includes β-cell–selective KATP channel openers and long-acting glucagon analogs, and ongoing advancements in 18F-DOPA PET–guided pancreatectomy, which have increased focal cure rates to over 95%.

"Medication remained the dominant treatment type in 2025, yet surgical intervention is poised for faster growth as imaging precision reduces the need for near-total resections and families pursue definitive focal surgery," Mordor said. "Regionally, North America sustained leadership thanks to concentrated surgical expertise and an active investigational-drug environment, while Asia-Pacific emerged as the fastest-expanding territory on the back of newborn screening rollouts and growing access to genetic testing. Competitive intensity is moderate: generic suppliers control first-line pharmacotherapy, several venture-backed firms pursue orphan-drug approvals, and a handful of hospital-based surgical programs act as quasi-providers of last resort, collectively shaping a fragmented yet rapidly evolving competitive landscape for the congenital hyperinsulinism treatment market."

Ownership and Share Structure¹

About 90.03% of the company is owned by institutions and about 9.68% is held by insiders and management. The rest is retail.

Top shareholders include Federated Hermes Global Investment with 17.83%, Fidelity Management & Research Co. with 13.32%, Handok Inc. with 9.08%, Invus Public Equities LP with 5.25%, and The Vanguard Group with 5.16%.

Its market cap is US$336.6 million with 92.73 million shares outstanding. It trades in a 52-week range of US$1.07 and US$11.46.