ersodetug (RZ358) / Xoma, Rezolute, Handok - LARVOL DELTA

Intermediate-Size Cohort EAP for Ersodetug in Patients With Inadequately Controlled Hypoglycemia Related to a Tumor (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Rezolute

New trial • Hypoglycemia

A Phase 3 Study of Ersodetug in Patients With Tumor Hyperinsulinism (clinicaltrials.gov) - P3 | N=16 | Recruiting | Sponsor: Rezolute | N=48 ➔ 16

Enrollment change • Hypoglycemia • Oncology

Preliminary Patient Demographics And Baseline Characteristics From A Phase 3 Study (sunrize) Of Ersodetug For Hypoglycemia Due To Congenital Hyperinsulinism: Trial In Progress (ENDO 2025) - "The trial is in progress with enrollment nearing completion. Preliminary patient demographics and baseline characteristics from at least 56 enrolled participants from the pooled treatment groups will be available for Congress presentation, using summary (descriptive) statistics."

Clinical • Late-breaking abstract • P3 data • CNS Disorders • Epilepsy • Hypoglycemia • Pediatrics • IR

A Phase 3 Study of Ersodetug in Patients With Tumor-Associated Hyperinsulinism (clinicaltrials.gov) - P3 | N=48 | Recruiting | Sponsor: Rezolute | Not yet recruiting ➔ Recruiting

Enrollment open • Hypoglycemia

Rezolute Receives Breakthrough Therapy Designation from FDA for Ersodetug in the Treatment of Hypoglycemia Due to Tumor Hyperinsulinism (GlobeNewswire) - "Rezolute, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to its investigational therapy, ersodetug, for the treatment of hypoglycemia caused by tumor HI....Rezolute plans to initiate a registrational study of ersodetug in patients with tumor HI in the middle of 2025, with topline results anticipated in the second half of 2026. In parallel and utilizing its BTD, the Company plans to engage further with FDA to discuss the registrational trial, including the necessary data package to support a BLA filing and potential approval for the tumor HI indication, as an expansion of the congenital HI indication."

Breakthrough therapy • New trial • Hypoglycemia

Global, multi-center, repeat-dose, phase 2 study of RZ358 (ersodetug), an insulin receptor antibody, for congenital hyperinsulinism. (PubMed, Med) - P2 | "Ersodetug was generally well tolerated and significantly improved hypoglycemia in participants with cHI. Ersodetug represents a novel INSR-targeted mechanism of action with the potential to be an effective therapy for all forms of cHI, alone or in combination with other therapies."

Journal • P2 data • Endocrine Disorders • Hypoglycemia • Pediatrics • IR

tHI: A Phase 3 Study of Ersodetug in Patients With Tumor-Associated Hyperinsulinism (clinicaltrials.gov) - P3 | N=48 | Not yet recruiting | Sponsor: Rezolute

New P3 trial • Hypoglycemia • Oncology

Rezolute Provides Update on its Phase 3 sunRIZE Study of Ersodetug for the Treatment of Hypoglycemia Due to Congenital Hyperinsulinism (GlobeNewswire) - "Findings from the DMC include the following: Ersodetug was generally safe and well-tolerated in participants 3 months to 1 year of age; Observed ersodetug drug levels at peak and trough were comparable to exposures in older pediatric participants in the Phase 2b RIZE study, which were demonstrated to be effective...Study start up activities in the U.S. have progressed and sites are expected to be activated and enrolling this quarter. Study enrollment completion is anticipated in the second quarter of 2025 and topline results are expected in the fourth quarter of 2025...The IA will be conducted at the end of this quarter and the Company plans to announce the conclusions of the DMC early in the second quarter of 2025 while also providing additional overall study updates....If the study sample size is increased, the Company estimates completion of enrollment would shift to the fourth quarter of 2025 and that top line results would be available in mid-2026."

DSMB • Enrollment status • P3 data: top line • Hypoglycemia

HanDok: "Related Hypoglycemia Treatment Designated as FDA Breakthrough Therapy" [Google translation] (Hankyung) - "The hypoglycemia treatment drug being developed by Handok's US affiliate has been approved as a breakthrough treatment by the US Food and Drug Administration (FDA)....Handok announced on the 8th that its affiliate Resolute received the FDA's designation of 'RZ358' (Ersodetug), a treatment drug for hypoglycemia caused by congenital hyperinsulinism, as a breakthrough treatment on the 7th (local time)."

Breakthrough therapy • Hypoglycemia

Resolute gains FDA innovative treatment designation for hypoglycemia drug RZ358 (Chosun Biz) - "Handok announced on the 8th that its US subsidiary, Resolute, has received designation as an innovative treatment for a hypoglycemia drug caused by congenital hyperinsulinemia from the US Food and Drug Administration (FDA)."

Pipeline update • Hypoglycemia

RZ358 (Ersodetug) as a Novel Therapy for Hypoglycemia due to Tumor Hyperinsulinism: Outcomes from an Expanded Access Program for Compassionate Use (NANETS 2024) - "These observations are consistent with the known mechanism of action of ersodetug, pharmacology studies, and recent results from studies in congenital HI. A global, multi-center Phase 3 study in tumorHI patients is planned."

Endocrine Cancer • Hypoglycemia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IGF2 • IR

Reduction of Overnight Hypoglycemia in Congenital Hyperinsulinism: Results from the RZ358-606 (RIZE) Study (ESPE 2024) - "In a dose-dependent manner, across all dose levels, baseline overnight hypoglycemia time (13.6% time [65 min]) improved by a median of 52% (p=0.001). Similar improvements were also observed across all dosing cohorts with a median increase of 48% (p<0.001) in cumulative 8h overnight normoglycemia exposure and a reduction in median 8h overnight cumulative exposure to hypoglycemia by 52% (p=0.03). Average overnight glucose shifted slightly from baseline median of 99mg/dL to 113mg/dL (p<0.001) at EOT."

CNS Disorders • Epilepsy • Gastrointestinal Disorder • Gestational Diabetes • Hepatology • Hypoglycemia • Sleep Disorder • Small for Gestational Age • Vascular Neurology • IR

RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients (ENDO 2024) - "Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control...Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia... RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Clinical • Metastases • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Pain • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • GAST • IR • SYP

RZ358 Therapy. A Novel Approach to Hyperinsulinemia in Metastatic Neuroendocrine Tumor Patients (ENDO 2024) - "Everolimus was started and subsequently peptide receptor radionuclide therapy (PRRT) with fair hypoglycemia control...Despite high-dose dexamethasone (up to 4 mg daily), octreotide 400 mcg every 8 hours, and high-calorie total parenteral nutrition (TPN) (over 800 grams of carbohydrates daily), she required multiple hospitalizations for persistent symptomatic hypoglycemia... RZ358 represents a novel and unique treatment option for refractory HH in patients with metastatic NETs and can improve clinical outcomes when standard interventions fail. This case underscores the potential of RZ358, a monoclonal antibody, to treat HH beyond its approved use for congenital cases, suggesting its applicability to cases of hyperinsulinemia secondary to NETs in adults.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Clinical • Metastases • Endocrine Cancer • Hepatology • Neuroendocrine Tumor • Oncology • Pain • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • GAST • IR • SYP

Refractory Hypoglycemia Secondary to Metastatic Insulinoma Treated with Novel Insulin Receptor Antibody - A Case Report (ENDO 2024) - "These medications included diazoxide, verapamil, lanreotide then changed to pasireotide, everolimus, and dexamethasone. The Insulin receptor blocking monoclonal antibody, RZ358, offers a promising approach to patients with metastatic insulinoma who have refractory hypoglycemia despite maximal medical and surgical therapy.Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference."

Case report • Clinical • Metastases • Endocrine Cancer • Hepatology • Hypoglycemia • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Solid Tumor • IR

sunRIZE: RZ358 Treatment for Congenital Hyperinsulinism (clinicaltrials.gov) - P3 | N=56 | Recruiting | Sponsor: Rezolute | Not yet recruiting ➔ Recruiting

Enrollment open

sunRIZE: RZ358 Treatment for Congenital Hyperinsulinism (clinicaltrials.gov) - P3 | N=56 | Not yet recruiting | Sponsor: Rezolute

New P3 trial

Treatment Of Severe Refractory Hypoglycemia Due To Malignant Insulinoma With A Novel Anti-insulin Receptor Antibody (ENDO 2023) - "High-dose diazoxide, everolimus, dexamethasone, glucagon, pasireotide, or enteral feeding did not produce a response. No adverse effects have been observed. In summary, the anti-insulin receptor monoclonal antibody RZ358 effectively controlled hypoglycemia refractory to multiple other therapies, allowing restoration of normoglycemia and enabling additional successful cancer therapy."

Late-breaking abstract • Critical care • Endocrine Cancer • Fatigue • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Hypoglycemia • Liver Cancer • Neuroendocrine Tumor • Oncology • Pain • Pancreatic Cancer • Severe Hypoglycemia • Solid Tumor • IR • MEN1

Results from a Global, Multi-Center, Phase 2b Study (RIZE) in Congenital Hyperinsulinism: Characterization of a High Unmet Treatment Need and Glycemic Response to RZ358 (ESPE 2022) - "Additional therapeutic interventions demonstrating clinically-meaningful hypoglycemia correction beyond what is currently available could be expected to translate to better clinical outcomes. RZ358 was generally safe, well-tolerated and demonstrated clinically-relevant dose-response improvement in glycemic measures, particularly at planned phase 3 dose levels (6, 9mg/kg)."

Clinical • P2b data • CNS Disorders • Epilepsy • Hypoglycemia • IR

Results from a Global, Multi-Center, Phase 2b Study (RIZE) in Congenital Hyperinsulinism: Characterization of a High Unmet Treatment Need and Glycemic Response to RZ358 (ESPE 2022) - No abstract available

Clinical • P2b data

An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism (clinicaltrials.gov) - P2 | N=23 | Completed | Sponsor: Rezolute | Active, not recruiting ➔ Completed

Trial completion

An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism (clinicaltrials.gov) - P2; N=32; Active, not recruiting; Sponsor: Rezolute; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2021 ➔ Jun 2022; Trial primary completion date: Dec 2021 ➔ Jun 2022

Enrollment closed • Trial completion date • Trial primary completion date

An Open-Label Multiple Dose Study of RZ358 in Patients With Congenital Hyperinsulinism (clinicaltrials.gov) - P2; N=32; Recruiting; Sponsor: Rezolute; Trial completion date: Aug 2021 ➔ Dec 2021; Initiation date: May 2021 ➔ Feb 2020; Trial primary completion date: Aug 2021 ➔ Dec 2021

Trial completion date • Trial initiation date • Trial primary completion date

An Open-Label Study of XOMA 358 in Patients With Hypoglycemia After Gastric Bypass Surgery (clinicaltrials.gov) - P2; N=20; Completed; Sponsor: XOMA (US) LLC; Recruiting ➔ Completed; Trial completion date: Oct 2017 ➔ May 2021; Trial primary completion date: Sep 2017 ➔ May 2021

Clinical • Trial completion • Trial completion date • Trial primary completion date • Hypoglycemia

[VIRTUAL] A Single and Repeat-Dose Study of RZ358 in Patients With Post-Gastric Bypass Hypoglycemia (PGBH): Results of Population Pharmacokinetic (PK) / Pharmacodynamic (PD) Modeling (ENDO 2021) - "For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021."

Clinical • PK/PD data • Diabetes • Genetic Disorders • Hypoglycemia • Obesity • IR