IGF-2

Independent Data Monitoring Committee (the “DMC”) recommends continuation of sunRIZE trial as planned with no need to increase sample size Enrollment on track and expected to be completed in May 2025; topline data anticipated in December 2025 U.S. sites activated and enrolling patients REDWOOD CITY, Calif., April 23, 2025 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (the “Company or “Rezolute”), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, today announced the DMC’s recommendation to continue the Phase 3 sunRIZE study as planned in patients with congenital HI, without an increase in the study sample size. “We are thrilled with the DMC’s favorable recommendation, which appears to validate our initial assumptions for the design and powering of the Phase 3 sunRIZE study,” said Brian Roberts, M.D., Chief Medical Officer at Rezolute. “While we remain blinded to the partial study data and are not privy to any of the statistical outputs from the DMC, we are nevertheless encouraged by this recommendation considering past outcomes from the Phase 2 RIZE study with the same objectively measured glycemic primary endpoint, real-world observations from our Expanded Access Program, and previously announced pharmacokinetic data from the open-label arm of the sunRIZE study. With U.S. clinical sites now also enrolling patients as part of our global study, and the Company tracking to complete enrollment next month, we look forward to announcing topline results, anticipated in December of this year, and remain confident in the potential of ersodetug to be a best-in-class treatment option for people living with hyperinsulinism.” The interim analysis of the Phase 3 sunRIZE study was performed by an unblinded DMC and was based on a pre-specified analysis of the primary study endpoint (hypoglycemia events), after approximately half of enrolled patients completed the primary assessments. The analysis was intended to evaluate for study futility or otherwise to inform a potential sample size increase, for purposes of optimizing the study power and statistical confidence in the final analysis outcomes. The Company has remained blinded throughout the interim analysis and has not seen the information made available to the DMC to inform its decision making, nor received any other information from the DMC after their meeting, other than its recommendation to continue the study as planned. About sunRIZEThe Phase 3 sunRIZE study 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 HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate. The study is enrolling up to 56 participants in more than a dozen countries around the world. About ErsodetugErsodetug 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 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 Congenital HyperinsulinismCongenital HI is the most common cause of recurrent and persistent hypoglycemia in children. Patients with congenital HI typically present with signs or symptoms of hypoglycemia within the first month of life. These episodes can result in significant brain injury and death if not recognized and managed appropriately. Additionally, recurrent, or cumulative, hypoglycemia can lead to progressive and irreversible damage over time, including serious and devastating brain injury, seizures, neuro-developmental problems, feeding difficulties, and significant impact on patient and family quality of life. In cases of congenital HI that are unresponsive to medical management, surgical removal of the pancreas may be required. More than half of children with congenital HI require long-term medical treatment for hypoglycemia that is not addressed by available therapies. About Rezolute, Inc.Rezolute is a late-stage rare disease company focused on significantly improving outcomes for individuals with hypoglycemia caused by hyperinsulinism (“HI”). The Company’s antibody therapy, ersodetug, is designed to treat all forms of HI and has shown substantial benefit in clinical trials and real-world use for the treatment of congenital HI and tumor HI. For more information, visit www.rezolutebio.com. Forward-Looking StatementsThis release, like many written and oral communications presented by Rezolute and its authorized officers, may contain certain forward-looking statements regarding our prospective performance and strategies within the meaning of Section 27A of the Securities Act of 1933, as amended, 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, statements regarding the ability of ersodetug to become an effective treatment for congenital HI, statements regarding the potential regulatory approval and commercialization of ersodetug, the efficacy of the Phase 3 sunRIZE study, statements related to the Phase 3 sunRIZE study sample size, and statements regarding the timing of the completion of enrollment and release of topline data. 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 Rezolute’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, which are available on the SEC’s website at www.sec.gov. You are urged to consider these factors carefully by 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. Contacts: InvestorsChristen Baglaneascbaglaneas@rezolutebio.com 508-272-6717 MediaSarah LimaSarah@GalvinPR.com(774) 766-0200

Biologics License Application (BLA) Submission to U.S. FDA for Tralesinidase Alfa Enzyme Replacement Therapy (TA-ERT) Anticipated in 1H 2026 Spruce to Host Conference Call Today at 8:30 a.m. ET SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Apr. 15, 2025-- Spruce Biosciences, Inc. (Nasdaq: SPRB), a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need, today announced the company’s new corporate strategy and acquisition of tralesinidase alfa enzyme replacement therapy (TA-ERT) for the treatment of Sanfilippo Syndrome Type B (MPS IIIB). “This is truly a transformative moment for Spruce as we focus our expertise in rare disease on a potential near-term commercial opportunity with TA-ERT in MPS IIIB,” said Javier Szwarcberg, M.D., M.P.H., Chief Executive Officer of Spruce. “As a result of the strategic process initiated last year, Spruce acquired TA-ERT for the treatment of children with MPS IIIB, a neurodegenerative and ultimately fatal genetic disease. This new strategy opens a new chapter in our mission to provide transformative and life-changing therapies to patients affected by serious conditions with significant unmet medical need.” Dr. Szwarcberg continued, “In clinical studies, TA-ERT has been shown to significantly and durably normalize cerebral spinal fluid (CSF) heparan sulfate non-reducing end (HS-NRE) levels over a five-year period. Alignment has been achieved with the U.S. Food and Drug Administration (FDA) that HS-NRE could be used as a biomarker that may reasonably predict clinical benefit and serve as a basis for accelerated approval. Based on the existing clinical and non-clinical data, we anticipate submitting a BLA for TA-ERT to the FDA in the first half of 2026. We extend our gratitude to the patient and caregiver advocates, clinicians and industry leaders who have contributed to the TA-ERT program. With no FDA-approved treatments currently available, TA-ERT has the potential to be a groundbreaking advancement for patients and families impacted by MPS IIIB.” “The vision of the Spruce leadership team and their unrelenting commitment to serving patient communities with meaningful unmet need is on full display with the acquisition of TA-ERT,” said Mike Grey, Executive Chairman of Spruce. “The confidence and support shown by our Board underscore the immense potential of the company’s new portfolio and direction.” Corporate Strategy Seek regulatory approval and maximize the U.S. commercial potential of TA-ERT for the treatment of MPS IIIB. Spruce intends to seek U.S. accelerated approval of TA-ERT for MPS IIIB based on existing non-clinical and clinical data. As a condition of seeking such approval of a BLA from the FDA, Spruce will initiate a confirmatory trial. If the BLA is approved, Spruce intends to build a highly specialized commercial and medical affairs organization to support the commercialization of TA-ERT. Given that a relatively small number of clinicians and specialists treat most of the patients with MPS IIIB, the company believes this market can be effectively addressed with a modest-sized and targeted patient-centric field team, alongside various high-touch patient initiatives. Commercialize globally through a patient-focused organization. Spruce seeks to commercialize TA-ERT and its other investigational products throughout the developed world, including North America, the European Union (EU), the United Kingdom (U.K.), Latin America, Turkey, Asia, and other international markets. The company intends to establish its own commercial organization in the U.S., EU, and the U.K., and seek regional strategic collaborations and a network of third-party distributors in other international markets. Focus on serious diseases with significant unmet medical need and clear biology. Spruce focuses on diseases that have biology that is well understood. The company believes that developing drugs that directly impact known disease pathways will increase the probability of success of its development programs. TA-ERT for the Treatment of MPS IIIB Spruce entered into an Asset Purchase Agreement under which the company acquired an exclusive worldwide license agreement with BioMarin Pharmaceutical Inc. for TA-ERT and other enzyme replacement therapy products. TA-ERT is a fusion protein comprised of recombinant human alpha-N-acetylglucosaminidase (rhNAGLU) with modified human insulin-like growth factor 2 via an amino acid linker. TA-ERT is intended as an enzyme replacement therapy for the treatment of patients with MPS IIIB who lack rhNAGLU enzyme activity. In March 2024, in a Type C meeting with the FDA, the FDA confirmed that HS-NRE is deemed to be a surrogate biomarker reasonably likely to predict clinical benefit and could serve as a basis for accelerated approval. The FDA also confirmed that the completed clinical and non-clinical studies of TA-ERT were sufficient for a BLA submission and provided guidance around key design elements of a confirmatory trial, which must be initiated prior to potential accelerated approval of TA-ERT. TA-ERT has received fast-track designation, rare pediatric disease designation, and orphan drug designation in the U.S. and EU. Spruce intends to submit the BLA of TA-ERT for the treatment of MPS IIIB in the first half of 2026. Financial Update Spruce Biosciences also reported financial results for the year ended December 31, 2024. As of December 31, 2024, Spruce had cash and cash equivalents of $38.8 million. The company expects its cash runway to fund its current operating plan through the end of 2025. 42.2 million shares of common stock are issued and outstanding and 21.4 million shares of common stock are reserved for issuance of warrants and equity securities as of December 31, 2024. Please refer to Spruce’s 2024 Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission today for the company’s full annual 2024 financial results. Conference Call Details Spruce’s management team will host a conference call today at 8:30 a.m. ET to discuss the business update. Analysts and investors can participate in the conference call by registering here. An archived replay of the call will be available on the events section of the company’s investor relations website for approximately 90 days. About Spruce Biosciences Spruce Biosciences is a late-stage biopharmaceutical company focused on developing and commercializing novel therapies for neurological disorders with significant unmet medical need. To learn more, visit www.sprucebio.com and follow us on X, LinkedIn, Facebook and YouTube. Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the ability to seek accelerated approval of TA-ERT for MPS IIIB based on existing clinical data; the anticipated timing and conduct of our confirmatory trial for TA-ERT; the timing and likelihood of regulatory filings and approvals for TA-ERT, including our anticipated BLA Submission of TA-ERT for MPS IIIB in the first half of 2026; our ability to commercialize TA-ERT, if approved, in the United Sates and in international markets; the anticipated market opportunity and level of sales for TA-ERT for MPS IIIB, if approved; our ability to establish a commercial organization in the United States and leverage regional partnerships and a network of third-party distributors in international markets; our intended focus on serious diseases with significant unmet medical need and clear biology; and our expected future financing needs, are forward-looking statements. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “anticipate”, “continue”, “will”, “potential”, “on track”, “can”, “intend”, “expect” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Spruce’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Spruce’s business in general, the impact of geopolitical and macroeconomic events, and the other risks described in Spruce’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Spruce undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. View source version on businesswire.com: https://www.businesswire.com/news/home/20250415826256/en/ Media Katie Beach Oltsik Inizio Evoke Comms (937) 232-4889 katie.beach@inizioevoke.com media@sprucebio.com Investors Samir Gharib President and CFO Spruce Biosciences, Inc. investors@sprucebio.com Source: Spruce Biosciences, Inc.

Ersodetug, a novel, fully human monoclonal antibody for the treatment of hyperinsulinism (HI), receives Breakthrough Therapy Designation and Orphan Drug Designation Open-label arm (infant participants < 1 year old) of the sunRIZE study has been reviewed by a Data Monitoring Committee (DMC); target drug concentrations were safely reached at tested doses and infants are approved for enrollment into the double-blind portion of the study REDWOOD CITY, Calif., Feb. 12, 2025 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a late-stage biopharmaceutical company dedicated to developing transformative therapies for rare diseases with serious unmet needs, today reported financial results and provided a business update for the three months ended December 31, 2024. “We have made significant regulatory progress with ersodetug and our focus in 2025 remains squarely on advancing both Phase 3 trials for patients with congenital HI and tumor HI,” said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. “We are encouraged by our momentum and remain dedicated to providing meaningful and innovative treatments for patients with limited options.” Recent Pipeline Progress and Anticipated Milestones Congenital HI The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to ersodetug for the treatment of hypoglycemia due to congenital HI. sunRIZE, a Phase 3, multicenter, double-blind, randomized, controlled safety and efficacy registrational study, is ongoing. Enrollment of U.S. participants is anticipated to occur in the second quarter of 2025. Overall study enrollment expected to conclude in the second quarter of 2025, with topline results expected in the fourth quarter of 2025, subject to outcomes from an interim analysis. An independent Data Monitoring Committee (DMC) reviewed safety and pharmacokinetics of ersodetug in eight infant participants in the open-label arm of the sunRIZE study. Ersodetug administered between 5-10 mg/kg during a bi-weekly loading phase and a monthly maintenance phase was generally safe and well-tolerated. Observed ersodetug drug levels at peak and trough were comparable to exposures in older pediatric participants in the Phase 2b RIZE study and validate the chosen dose regimen of 5 and 10 mg/kg administered bi-weekly and monthly. Subsequent infant participants may be enrolled into the double-blind, placebo-controlled study. The DMC did not analyze efficacy and the Company remains blinded to the results. An interim analysis of the primary study endpoint (change in hypoglycemia events) is planned for this quarter, with results and study update to be announced early in the second quarter. Three possible outcomes from the analysis include: (i) futility and the study should be stopped, (ii) continue the study as is or (iii) continue the study as is but increase the sample size by 33% (18 additional patients) to enhance statistical confidence in the final outcome. Enrollment of U.S. participants is anticipated to occur in the second quarter of 2025. Overall study enrollment expected to conclude in the second quarter of 2025, with topline results expected in the fourth quarter of 2025, subject to outcomes from an interim analysis. Ersodetug administered between 5-10 mg/kg during a bi-weekly loading phase and a monthly maintenance phase was generally safe and well-tolerated. Observed ersodetug drug levels at peak and trough were comparable to exposures in older pediatric participants in the Phase 2b RIZE study and validate the chosen dose regimen of 5 and 10 mg/kg administered bi-weekly and monthly. Subsequent infant participants may be enrolled into the double-blind, placebo-controlled study. The DMC did not analyze efficacy and the Company remains blinded to the results. Three possible outcomes from the analysis include: (i) futility and the study should be stopped, (ii) continue the study as is or (iii) continue the study as is but increase the sample size by 33% (18 additional patients) to enhance statistical confidence in the final outcome. Tumor HI During the quarter, FDA granted Orphan Drug Designation to ersodetug for the treatment of hypoglycemia due to tumor HI. A Phase 3 registrational study for ersodetug in patients with tumor HI is anticipated to begin in the first half of 2025. Topline results are expected in the second half of 2026. Fiscal Second Quarter Financial Results Cash, cash equivalents and investments in marketable securities were $105.3 million as of December 31, 2024, compared to $127.1 million as of June 30, 2024. Research and development expenses were $12.6 million for the second quarter of fiscal 2025, compared with $12.0 million for the same period a year ago, with the increase primarily attributable to increased expenditures in clinical trial activities, manufacturing costs and higher personnel-related expenses, which include employee compensation. General and administrative expenses were $4.5 million for the second quarter of fiscal 2025, compared with $3.2 million for the same period a year ago, with the increase primarily attributable to professional fees and employee-related expenses as a result of increased headcount. Net loss was $15.7 million for the second quarter of fiscal 2025 compared with a net loss of $13.9 million for the same period a year ago. About Ersodetug Ersodetug is a fully human monoclonal antibody that binds to a unique allosteric site on insulin receptors to counteract the effects of insulin receptor over-activation by insulin and related substances (such as IGF-2), thereby improving hypoglycemia in the setting of hyperinsulinism (HI). Because ersodetug acts downstream from the pancreas, it has the potential to be universally effective at treating hypoglycemia due to any form of HI. About sunRIZE The Phase 3 sunRIZE study 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 HI who are experiencing poorly controlled hypoglycemia. Participants between the ages of 3 months to 45 years old are eligible to participate. The study is enrolling up to 56 participants in more than a dozen countries around the world. About Rezolute, Inc. Rezolute is a late-stage rare disease company focused on significantly improving outcomes for individuals with hypoglycemia caused by hyperinsulinism (HI). The Company’s antibody therapy, ersodetug, is designed to treat all forms of HI and has shown substantial benefit in clinical trials and real-world use for the treatment of congenital HI and tumor HI. 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 statements regarding the second quarter financial results of Rezolute, the efficacy of ersodetug in infant patient populations, the DMC approval and timeline of enrollment of infants into a double-blind and placebo-controlled study of ersodetug, the FDA’s grant of the Breakthrough Therapy Designation for ersodetug, the Phase 3 sunRIZE study of ersodetug, the ability of ersodetug to become an effective treatment for congenital hyperinsulinism, the effectiveness or future effectiveness of ersodetug for the treatment of congenital hyperinsulinism, and statements regarding clinical trial timelines for ersodetug. 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. Contact: Rezolute, Inc. Christen Baglaneas cbaglaneas@rezolutebio.com 508-272-6717 Released February 12, 2025