# Assessment of Multiple Dose Administration ofGlucagon Receptor Blocker REMD477 in Type 1 Diabetes

> **NIH NIH R44** · REMD BIOTHERAPEUTICS, INC. · 2021 · $993,807

## Abstract

ABSTRACT
Insulin remains the mainstay treatment for type 1 diabetes mellitus (T1D); however, it is associated with
chronic iatrogenic hyperinsulinemia and life-threatening hypoglycemia events. Long term insulin treatment is
also associated with secondary hyperlipidemia, and a higher incidence of cardiovascular complications, which
tend to be more severe. Indeed, death due to cardiovascular complications is three-fold higher among insulin-
treated T1D patients than in the general public. There exists a critical need for a safe, effective add-on therapy
that reduces daily insulin requirements and, in turn, minimizes complications of chronic hyperinsulinemia.
Hyperglycemia in T1D is not only caused by deficient pancreatic β-cell, but also by exaggerated glucagon
activity. Under normal circumstances, β-cells secrete insulin that locally supresses glucagon release from
nearby α-cells. However, since patients with T1D lack intra-islet insulin, α-cells activity and glucagon secretion
are unrestrained and unopposed. Exogenous insulin administration is unable to affect this local feedback
mechanism. Consequently, glucagon receptor (GCGR) blockade has become an intriguing therapeutic target
to treat T1D.
REMD-477 is a fully human, high affinity, glucagon receptor (GCGR) antibody that blocks the hepatic GCGR
and reduces hepatic glucose and ketone production. REMD-477 exhibited a benign safety profile in animals
and in healthy volunteers in a first-in- human study. In Phase I of a recently completed Fast Track, we showed
the glucose-lowering effects of REMD-477 in three animal models of diabetes. In Phase II of the Fast Track,
we demonstrated the safety and efficacy of a single dose of REMD-477 in a small clinical study.
Based on these promising preclinical and clinical results, the current Phase IIB SBIR effort will determine
whether multiple doses of REMD-477 can safely and effectively reduce insulin requirements in patients with
T1D. In this randomized, double-blind, vehicle-controlled, Phase 2 clinical trial, we explore whether 12 weeks
treatment with REMD-477 can lower daily/average insulin use, 24h blood glucose concentration, HgbA1c, and
hypoglycemic events. We will also assess the effect of REMD-477 on alpha- and beta-cell function by
assessing glucagon and active and total glucagon-like peptide 1 (GLP-1), and c-peptide, respectively. We will
also study intrahepatic lipid content, body weight, and quality of life measures.
REMD-477 is being developed as an add-on therapy for T1DM, to substantially (>50%) reduce insulin daily
doses, leading to better glucose control, fewer and milder complications, and an improved quality of life.

## Key facts

- **NIH application ID:** 10224813
- **Project number:** 5R44DK108305-06
- **Recipient organization:** REMD BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Samuel Klein
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $993,807
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224813

## Citation

> US National Institutes of Health, RePORTER application 10224813, Assessment of Multiple Dose Administration ofGlucagon Receptor Blocker REMD477 in Type 1 Diabetes (5R44DK108305-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10224813. Licensed CC0.

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