Our Focus

Hyperinsulinism Therapeutics

Hyperinsulinism is a disease that is characterized by the overstimulation of the insulin receptor which can lead to dangerously low blood sugar levels (hypoglycemia).

Hypoglycemia is a severe and potentially life-threatening complication of overactivation of the insulin receptor. It can result in neurological damage, coma, and even death, and it has serious implications for both pediatric and adult patients.

Congenital hyperinsulinism (HI) primarily affects infants and children, while tumor HI generally impacts adults with insulinomas or non-islet cell tumors (NICT). Despite the persistent and dangerous nature of hypoglycemia in these populations, today’s treatment options are limited, often ineffective, and poorly tolerated.

This critical gap leaves many patients vulnerable to recurrent, unpredictable hypoglycemic lows, highlighting the urgent need for innovative, effective therapies.

Forms of Hyperinsulinism

Congenital Hyperinsulinism

Congenital Hyperinsulinism (HI) is a rare pediatric genetic disorder characterized by excessive production of insulin by the pancreas. It is the most common cause of recurrent and persistent hypoglycemia in children, with symptoms typically appearing within the first month of life. If not immediately recognized and treated, congenital HI can lead to extreme hypoglycemic episodes, potentially resulting in significant brain injury or even death. Additionally, recurrent, or cumulative, hypoglycemia can lead to progressive and irreversible damage over time, including serious and devastating neurological damage, seizures, neuro-developmental problems, feeding difficulties, and a profound impact on the quality of life for both the patient and their family.

In cases of congenital HI that are unresponsive to medical management, surgical removal of the pancreas may be a choice that families make. More than half of children with congenital HI require long-term medical treatment for hypoglycemia that is not adequately addressed by available therapies.

Tumor Hyperinsulinism

Tumor hyperinsulinism (HI) is a rare disease that may be caused by two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia as a result of over-activation of the insulin receptor. Insulinomas are the most common type of ICT and cause hypoglycemia by stimulating the over production of insulin.

A variety of different NICTs, particularly hepatocellular carcinoma, can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 that bind to and activate the insulin receptor. Across both tumor types, resulting hypoglycemia is often severe, can result in serious adverse outcomes, and may prevent adjuvant tumor treatment.

With high morbidity and mortality rates within tumor HI, there remains a significant unmet need for new therapies directed at hypoglycemia treatment.

Rezolute’s Approach to Hyperinsulinism

We are developing ersodetug, a fully human monoclonal antibody, that works downstream from the pancreas to help maintain glucose in a healthy range. Ersodetug binds allosterically to the insulin receptor at target tissues in the liver, fat and muscle to modulate the binding and signaling effects of insulin to help maintain glucose values in a normalized range.

Ersodetug has the potential to be a universal treatment for hypoglycemia related to HI, whether genetic or acquired. It is currently being evaluated in two Phase 3 registrational trials for congenital and tumor HI and has demonstrated meaningful benefit in both clinical studies and real-world use. The program has also received multiple regulatory designations recognizing its promise to effectively address serious unmet needs.