# Anti-hIAPP for the preservation of pancreatic function in Type 2 Diabetes

> **NIH NIH R44** · CELDARA MEDICAL, LLC · 2022 · $299,896

## Abstract

Project Summary
According to the American Diabetes Association, Type 2 diabetes mellitus (T2D) affects at least 30 million
Americans and is a major unmet public health concern with an annual cost in the United States of over $300
billion dollars. Additionally, nearly 25% of the U.S. population is already considered prediabetic, or at high risk of
developing T2D. These individuals are characterized by poor glycemic control as a result of insulin resistance
combined with reduced insulin secretion in response to glucose stimulation. At the prediabetic or early diabetic
stages, insulin insufficiency is frequently managed by medications that stimulate pancreatic secretion, which is
accompanied by increased levels of human islet amyloid polypeptide, hIAPP (amylin). Native hIAPP in its
monomeric form is a hormone that inhibits glucagon secretion, delays gastric emptying, and acts as a satiety
agent. However, when hIAPP misfolds, which is common at elevated production, it results in structures called
protofibrils. These protofibrils are soluble, highly toxic, and capable of inducing cell death. The stimulated co-
secretion of hIAPP with insulin leads to a pathologic cycle of increased hIAPP, including misfolded hIAPP, that
leads to β cell toxicity in prediabetics and diabetics. The ensuing deficits in β cell function drive an increased
need for insulin secretion, which is accompanied by further hIAPP secretion. In this sense, T2D is an amyloid-
induced disease as evidenced by the presence of hIAPP plaque deposits in the pancreata of more than 90% of
T2D patients. Developing new therapeutic strategies that target toxic hIAPP protofibrils, inhibit their deposition
as toxic amylin fibrils, and ultimately preserve β cell health is a priority for addressing this major unmet need in
T2D.
Current standard-of-care in T2D is able to provide some control of blood glucose levels, but it fails to address
the ? cell decline and its contribution to T2D progression. In this application we propose to advance a novel
therapeutic platform and our lead product from that platform, CM-TS1. CM-TS1 is a monoclonal antibody that
specifically targets protofibrils, soluble conformations of hIAPP for rapid clearance prior to plaque deposition and
? cell destruction. We have already demonstrated that CM-TS1 is capable of binding to these soluble protofibrils
in peripheral blood and in the pancreata of a T2D murine model. We will continue therapeutic development by
first validating our initial finding by demonstrating that CM-TS1 can clear hIAPP in an industry standard preclinical
model leading to a reduction of T2D pathology. Following this in vivo proof-of-concept, we will then advance CM-
TS1 through humanization and into early preclinical development including manufacturability, stable cell line
construction, and non-GLP pharmacokinetic and toxicity studies ultimately culminating in a pre-IND Type B
meeting with the FDA. The milestone of ultimate success will be launching this p...

## Key facts

- **NIH application ID:** 10600613
- **Project number:** 1R44DK135154-01
- **Recipient organization:** CELDARA MEDICAL, LLC
- **Principal Investigator:** Joana M Murad
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $299,896
- **Award type:** 1
- **Project period:** 2022-09-22 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600613

## Citation

> US National Institutes of Health, RePORTER application 10600613, Anti-hIAPP for the preservation of pancreatic function in Type 2 Diabetes (1R44DK135154-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10600613. Licensed CC0.

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