Insulinoma

Potential to more than double the addressable patient population living with hypoglycemia resulting from insulin receptor over-activation (tumor hyperinsulinism)REDWOOD CITY, Calif., March 06, 2024 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a clinical-stage biopharmaceutical company committed to developing novel, transformative therapies for serious metabolic and rare diseases, today announced results from a preclinical pharmacology study that validate the potential for its lead clinical compound, RZ358, to treat individuals with non-islet cell tumors (NICTs) that have uncontrolled hypoglycemia. Tumor hyperinsulinism (HI) may be caused by a variety of different tumor types, resulting in islet cell tumor hypoglycemia (ICTH) and NICTH. The Company previously reported on the successful use of RZ358 under its Expanded Access Program (EAP) to treat patients with insulin-producing pancreatic islet cell tumors (ICTs), or insulinomas, causing severe and uncontrolled hypoglycemia. The therapeutic potential of RZ358 in this setting was anticipated given that ICTH is mediated by insulin and that RZ358 is known to work at the insulin receptor to decrease excess insulin binding and activity. However, it was unknown if RZ358 would have utility in NICTH where hyperinsulinism is mediated by hormones such as insulin-like growth factor-2 (IGF-2) or its variants, which likewise cause hypoglycemia by binding to and activating the insulin receptor. To test this, the Company recently completed in vitro pharmacology studies to evaluate the impact of clinically relevant concentrations of RZ358 on insulin receptor activation by IGF-2, compared to insulin. This was tested at the relative concentrations of each ligand that activate the insulin receptor and are physiologically relevant in tumor HI caused by ICTH and NICTH, respectively. These experiments successfully demonstrated the ability of RZ358 to similarly blunt both IGF-2 and insulin-mediated insulin-receptor signaling, at levels of these ligands that are disease-relevant in humans. “These data demonstrate proof of the ligand-agnostic mechanism of action of RZ358 and therefore validate its broad utility in treating hypoglycemia resulting from any form of hyperinsulinism, including expanded tumor indications,” said Dr. Brian Roberts, Chief Medical Officer of Rezolute. “Coupled with known outcomes from our clinical trials in congenital HI and the positive outcomes seen with ICTH in our expanded access program, we are excited by the potential for RZ358 to provide dramatic therapeutic benefit to cancer patients who often have limited treatment options for managing serious and uncontrolled hypoglycemia, which can accompany their cancer and disrupt treatment plans.” The Company recently reported on its successful interaction with the U.S. Food and Drug Administration (FDA) in January 2024 regarding the potential to initiate a single registrational study in patients with hypoglycemia due to tumor HI. The Company will continue to evaluate the feasibility of a development program in this indication, with the possibility of including both ICTH and NICTH patients. The inclusion of NICTH patients in a potential addressable market for RZ358 in tumor HI would more than double the population. The Company is also currently evaluating RZ358 in a Phase 3 clinical trial in congenital HI, which is a rare pediatric condition where, similar to ICTH, children overproduce insulin creating a dangerous hypoglycemic state. About Tumor Hyperinsulinism (HI)Tumor HI may be the result of two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia due to excessive activation of the insulin receptor. Insulinomas are the most common type of functional ICT and cause hypoglycemia because of over production of insulin. NICTs can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 or related variants that bind to and activate the insulin receptor. This form of hypoglycemia can occur in more than 15 different tumor types, 60 percent of which are malignant, including hepatocellular carcinoma. The total addressable market for the combined indications causing tumor HI is estimated to be approximately 4,500 patients in the U.S. alone, including approximately 1,500 with ICTH and 3,000 with NICTH. The unique mechanism of action of RZ358 to attenuate excess insulin receptor activation mediated by insulin and related substances makes the therapy a potential universal treatment for hypoglycemia resulting from any form of hyperinsulinism. About RZ358RZ358 is a fully human monoclonal antibody that works downstream from the pancreas and other sources of insulin or related paraneoplastic substances, and instead binds to a unique allosteric site on insulin receptors in the liver, fat, and muscle. The antibody counteracts excess insulin receptor activation by insulin and other effector substances (such as IGF-2), thereby improving hypoglycemia. Because RZ358 acts downstream from the pancreas at the insulin receptor, it has the potential to be universally effective at treating hypoglycemia due to congenital HI, regardless of the causative genetic defect, as well as acquired forms of HI such as those mediated by insulinomas (ICTs) and other tumor types (NICTs). RZ358 received Orphan Drug Designation in the United States and European Union for the treatment of congenital HI, as well as Orphan Drug Designation and Pediatric Rare Disease Designation in the U.S. In the Phase 2 RIZE study, participants with congenital HI ages two and older nearly universally achieved significant improvements in hypoglycemia across multiple endpoints, including the primary and key secondary endpoints planned for the sunRIZE study. At doses and exposures that are planned for the Phase 3 study, RZ358 was generally safe and well-tolerated, and resulted in median improvements in hypoglycemia exceeding 80%. Based on the RIZE clinical trial outcomes and the evidence of benefit in this serious condition with substantial unmet medical need, RZ358 was subsequently granted a priority medicines (PRIME) designation by the European Medicines Agency (EMA) and an Innovation Passport designation by the U.K. Innovative Licensing and Access Pathway (ILAP) Steering Group for the treatment of congenital HI. RZ358 also received Orphan Drug Designation status in the European Union for the treatment of Insulinoma, the primary cause of ICTH. About Rezolute, Inc. Rezolute strives to disrupt current treatment paradigms by developing transformative therapies for devastating rare and chronic metabolic diseases. Its novel therapies hold the potential to both significantly improve outcomes and reduce the treatment burden for patients, treating physicians, and the healthcare system. Rezolute is steadfast in its mission to create profound, positive, and lasting impacts on patients’ lives. Patient, clinician, and advocate voices are integrated in the Company’s drug development process. Rezolute places an emphasis on understanding the patient’s lived experiences, enabling the Company to boldly address a range of severe conditions. 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 Innovation Passport designation, the RZ358 Expanded Access Program, the ability of RZ358 to become an effective treatment for congenital hyperinsulinism, the effectiveness or future effectiveness of RZ358 for the treatment of congenital hyperinsulinism, and statements regarding clinical trial timelines for RZ358. 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. Investors & Media:Christen BaglaneasRezolute, Inc.cbaglaneas@rezolutebio.com (508)272-6717 A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/165f8dbc-1fce-47b8-ac3f-0cf6fb4170cb

Phase 3 clinical study of RZ358 underway in patients with congenital hyperinsulinism (cHI); topline results expected in mid-2025 Benefit shown in individual patient cases with RZ358 for tumor-associated hyperinsulinism (taHI) under Expanded Access Program (EAP); drives alignment with FDA on unmet need and potential to move into late-stage clinical development to further evaluate RZ358 in this population REDWOOD CITY, Calif., Feb. 13, 2024 (GLOBE NEWSWIRE) -- Rezolute, Inc. (Nasdaq: RZLT) (“Rezolute” or the “Company”), a clinical-stage biopharmaceutical company committed to developing novel, transformative therapies for serious metabolic and rare diseases, today announced its financial results for the second quarter of fiscal 2024 ended December 31, 2023, and provided an update on recent business developments and outlook. “2024 is an exciting year of execution and milestones across our pipeline, with RZ358 continuing to demonstrate benefit to patients with hypoglycemia resulting from varying causes of hyperinsulinism, and in different indications,” said Nevan Charles Elam, Chief Executive Officer and Founder of Rezolute. “We recently initiated sunRIZE, a global, pivotal, Phase 3 clinical study in patients with congenital hyperinsulinism, and we also continue to see favorable outcomes from our Expanded Access Program with RZ358, in patients with tumor-associated hyperinsulinism caused by insulinomas, for which we are evaluating a potential development program. Additionally, we completed enrollment in the Phase 2 study of RZ402 in patients with diabetic macular edema and look forward to reporting topline data from that program in the second quarter of 2024.” Clinical and Regulatory Highlights RZ358 is a monoclonal antibody for the treatment of hyperinsulinism. cHI Rezolute initiated sunRIZE, a global, pivotal, Phase 3 clinical study in participants with cHI, in Europe and other geographies outside of the U.S. Topline results expected mid-2025. Innovation and Licensing Application Passport (ILAP) designation awarded to RZ358 for the treatment of cHI by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA). Designation was granted based on the recognition of substantial unmet medical need in this condition and the potential benefit to patients as evidenced by the Phase 2b RIZE study results in cHI, which safely demonstrated significant improvements in hypoglycemia. Supplements analogous PRIME designation status already granted by the European Medicines Agency (EMA) in E.U. taHI RZ358 has been shown to counteract excessive insulin action downstream, at the insulin-receptor on target organs. The unique mechanism of action of RZ358 makes the therapy a potential universal treatment for hypoglycemia resulting from any cause of hyperinsulinism, including neuroendocrine tumors (insulinomas). Given the unmet need in taHI and the potential therapeutic benefit of RZ358 as demonstrated in the individual case reports from the EAP, the Company met with FDA in January 2024 (January Meeting) and received a favorable opinion from the Agency on the feasibility of RZ358 being studied in a late-stage clinical trial as a new development program and second rare disease indication for RZ358. In the January Meeting, FDA indicated that current dose caps on cHI studies would not be applicable to taHI studies. Therefore, considering the indication is primarily adult, current partial clinical holds pertaining to cHI studies would be largely irrelevant in taHI. The Company remains engaged with FDA in the attempt to resolve ongoing partial clinical holds on clinical studies in the cHI indication. RZ402 is a selective and potent oral plasma kallikrein inhibitor for the treatment of diabetic macular edema (DME). Completed enrollment in Phase 2 U.S., multi-center, randomized, double-masked, placebo-controlled, parallel-arm study evaluating the safety, efficacy, and pharmacokinetics of RZ402 administered as an oral monotherapy over a 12-week treatment period in participants with DME who are naïve to or have received limited anti-VEGF injections. Topline results expected in the second quarter of 2024. Corporate Highlights Expanded leadership team with appointment of Daron Evans, M.S., M.B.A, as Chief Financial Officer. Mr. Evans has substantial experience leading public and private life science companies, with expertise in corporate finance, capital markets, and strategic transactions. He will help shepherd Rezolute through its next chapter in late-stage development. Second Quarter Fiscal 2024 Financial Results Cash, cash equivalents and investments in marketable debt securities totaled $96.0 million as of December 31, 2023, compared to $118.4 million as of June 30, 2023 Research and development expenses were $12.0 million for the second quarter of fiscal 2024, compared to $10.9 million for the same period in fiscal 2023, with the increase primarily attributable to increased expenditures in clinical trial activities and manufacturing costs General and administrative expenses were $3.2 million for the second quarter of fiscal 2024, compared to $3.4 million for the same period in fiscal 2023, with the decrease primarily attributable to lower personnel-related expenses Net loss was $13.9 million for the second quarter of fiscal 2024, compared to $13.6 million for the same period in fiscal 2023 About Rezolute, Inc. Rezolute strives to disrupt current treatment paradigms by developing transformative therapies for devastating rare and chronic metabolic diseases. Its novel therapies hold the potential to both significantly improve outcomes and reduce the treatment burden for patients, treating physicians, and the healthcare system. Rezolute is steadfast in its mission to create profound, positive, and lasting impacts on patients’ lives. Patient, clinician, and advocate voices are integrated in the Company’s drug development process. Rezolute places an emphasis on understanding the patient’s lived experiences, enabling the Company to boldly address a range of severe conditions. For more information, visit . 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 appointment of Daron Evans as Chief Financial Officer, the sunRIZE Phase 3 clinical study, Phase 2 study of RZ402, the Expanded Access Program with RZ358, the ability of RZ358 to become an effective treatment for congenital hyperinsulinism, the effectiveness or future effectiveness of RZ358 for the treatment of congenital hyperinsulinism, and statements regarding clinical trial timelines for RZ358. 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 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. Investors & Media: Christen Baglaneas Rezolute, Inc. cbaglaneas@rezolutebio.com (508)272-6717 Investors: Stephanie Carrington ICR Westwicke RezoluteIR@westwicke.com (646)277-1282 Rezolute, Inc. Condensed Consolidated Financial Statements Data (in thousands, except per share data) Three Months Ended Six Months Ended December 31, December 31, 2023 2022 2023 2022 Condensed Consolidated Statements of Operations Data: Operating expenses: Research and development $ 12,039 $ 10,945 $ 24,253 $ 18,649 General and administrative 3,155 3,447 6,855 5,961 Total operating expenses 15,194 14,392 31,108 24,610 Loss from operations (15,194 ) (14,392 ) (31,108 ) (24,610 ) Non-operating income, net 1,285 836 2,675 1,223 Net loss $ (13,909 ) $ (13,556 ) $ (28,433 ) $ (23,387 ) Basic and diluted net loss per common share $ (0.27 ) $ (0.26 ) $ (0.55 ) $ (0.46 ) Shares used to compute basic and diluted net loss per common share 51,408 51,410 51,409 50,969 December 31, June 30, 2023 2023 Condensed Consolidated Balance Sheets Data: Cash and cash equivalents $ 12,504 $ 16,036 Investments in marketable debt securities 83,446 102,330 Working capital 88,077 99,710 Total assets 102,150 123,721 Accumulated deficit (289,418 ) (260,985 ) Total stockholders’ equity 91,728 116,172

Jan. 23, 2024 -- Rezolute, Inc. (Nasdaq: RZLT), a clinical-stage biopharmaceutical company committed to developing novel, transformative therapies for serious metabolic and rare diseases, today announced that the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) has awarded the innovative medicine designation, the Innovation Passport, to RZ358 for the treatment of hypoglycemia due to congenital hyperinsulinism (HI). The Innovation Passport designation was granted based on the substantial unmet medical need in this condition and the potential for RZ358 to benefit patients as evidenced by the Phase 2 RIZE study in congenital HI, which safely demonstrated significant improvements in hypoglycemia events. The Innovation Passport designation in the U.K. is the entry point to the Innovative Licensing and Access Pathway (ILAP). The goal of ILAP is to accelerate the time to market and facilitate patient access to medicines. The Innovation Passport is the first step in the ILAP process, which activates the Medicines and Healthcare products Regulatory Agency (MHRA) and its partner agencies, including the National Institute for Health and Care Excellence (NICE), and the Scottish Medicines Consortium (SMC). “Congenital hyperinsulinism is the most frequent cause of severe, persistent hypoglycemia in newborn babies, infants and children,” said Susan Stewart, J.D., Chief Regulatory Officer at Rezolute. “The Innovation Passport opens the door for Rezolute to discuss access considerations for potential future indications for RZ358. We are thrilled to receive this designation and work closely with the U.K. and other regulatory authorities to bring this meaningful therapy to patients in need.” Congenital hyperinsulinism (congenital 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. In those with diffuse congenital HI where the whole pancreas is affected, a near-total pancreatectomy can be undertaken, although about half of these children will continue to have hypoglycemia and require medical treatment for congenital HI. RZ358 is a fully human monoclonal antibody that works downstream from the pancreas and instead binds to a unique allosteric site on insulin receptors in the liver, fat, and muscle. The antibody counteracts the effects of excess insulin binding and activity, thereby improving hypoglycemia. Rezolute believes that RZ358 is ideally suited as a potential therapy for congenital HI and other conditions characterized by excessive insulin activity (hyperinsulinism). Because RZ358 acts downstream from the pancreas, it has the potential to be universally effective at treating congenital HI, regardless of the causative genetic defect, as well as acquired forms of HI such as those mediated by insulinomas and other tumor types. RZ358 received Orphan Drug Designation in the United States and European Union for the treatment of congenital HI, as well as Pediatric Rare Disease Designation in the U.S. In the Phase 2 RIZE study, participants with congenital HI ages 2 and older nearly universally achieved significant improvements in hypoglycemia across multiple endpoints, including the primary and key secondary endpoints planned for the sunRIZE study. At doses and exposures that are planned for the Phase 3 study, RZ358 was generally safe and well-tolerated, and resulted in median improvements in hypoglycemia exceeding 80%. Based on the RIZE clinical trial outcomes and the evidence of benefit in this serious condition with substantial unmet medical need, RZ358 was subsequently granted a priority medicines (PRIME) designation by the European Medicines Agency (EMA) and an Innovation Passport designation by the U.K. Innovative Licensing and Access Pathway (ILAP) Steering Group for the treatment of congenital HI. Rezolute strives to disrupt current treatment paradigms by developing transformative therapies for devastating rare and chronic metabolic diseases. Its novel therapies hold the potential to both significantly improve outcomes and reduce the treatment burden for patients, treating physicians, and the healthcare system. Rezolute is steadfast in its mission to create profound, positive, and lasting impacts on patients’ lives. Patient, clinician, and advocate voices are integrated in the Company’s drug development process. Rezolute places an emphasis on understanding the patient’s lived experiences, enabling the Company to boldly address a range of severe conditions. For more information, visit www.rezolutebio.com. The content above comes from the network. if any infringement, please contact us to modify.