# Disrupting Insulin Delivery with a Novel, Stabilized Insulin that is Ultra-rapid at U100 or U500

> **NIH NIH R44** · THERMALIN, INC. · 2020 · $1,423,451

## Abstract

Project Summary
 In this Direct-to-Phase II SBIR application we propose to advance development of a first-in-class, stabilized
insulin analog, T-1123, that has an ultra-rapid time-action profile in both U-100 and U-500 formulations. The
molecular design of T-1123 combines several synergistic stability-enhancing substitutions that enable zinc-
free, non-hexamer-based formulations. These formulations demonstrate improved resistance to both physical
and chemical degradation compared to marketed insulin products. Our preliminary studies exploited general
principles of protein design to “tune” critical molecular properties of insulin pertinent to its pharmacology:
stability, self-assembly, mitogenicity, and potency. In these studies we demonstrated (a) ultra-rapid absorption
kinetics for both U-100 and U-500 formulations of T-1123 in swine euglycemic clamp studies—results that are
comparable with U-100 Fiasp®, (b) glucose-lowering potency of T-1123 in animal models that is comparable to
human insulin and the prandial insulin analogs, (c) enhanced chemical and physical stability of T-1123, and (d)
mitogenic potency of T-1123 that no greater than human insulin. In Phase II we propose to (1) to finalize the
formulation of T-1123 in relation to established criteria for ultra-rapid PK/PD and physical/chemical stability; (2)
to finalize manufacturing scale-up conditions, transfer this technology to a contract manufacturing organization
and produce an engineering lot of T-1123 sufficient to support all IND-enabling toxicology studies; (3) to
complete pre-clinical toxicology testing of the finalized T-1123 U-100 formulation. We anticipate that
attainment of these Phase II milestones would favorably position Thermalin Inc. to initiate Phase IIb- or
investor-funded clinical safety/efficacy trials and to attract a corporate partner to further the development of T-
1123. We envision that both U-100 and U-500 formulations of T-1123 will address important, unmet needs
among people with diabetes mellitus. The U-100 formulation of T-1123 will be compatible with existing insulin
pumps, including disposable patch pumps. This is of commercial interest because T-1123’s markedly
augmented stability would enable pre-filling of tubed pump and patch pump reservoirs at the time of
manufacture. The U-500 ultra-rapid-acting formulation, enables our co-development of a miniaturized, pre-
filled and disposable closed-loop diabetes management system the size of a postage stamp—StampPump™.
Initial prototypes of this device have been developed by Thermalin with support from NIDDK (1R43DK121639-
01) and DARPA (STTR W911NF-19-C-0029). Additionally, minor modifications to existing pre-filled pen
devices could support sufficiently accurate delivery of U-500 T-1123 to patients with severe insulin resistance,
who are required to take very large and thus painful bolus doses of insulin. This latter subset of T2DM patients
disproportionately includes underserved minorities and the rural poor...

## Key facts

- **NIH application ID:** 10153108
- **Project number:** 1R44DK126613-01A1
- **Recipient organization:** THERMALIN, INC.
- **Principal Investigator:** Mervyn Dodson Michael
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,423,451
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153108

## Citation

> US National Institutes of Health, RePORTER application 10153108, Disrupting Insulin Delivery with a Novel, Stabilized Insulin that is Ultra-rapid at U100 or U500 (1R44DK126613-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153108. Licensed CC0.

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