# Novel Immunoregulatory Therapeutics for Systemic Lupus Erythematosus

> **NIH NIH R43** · BIOTHERAPEUTICS, INC. · 2021 · $300,000

## Abstract

Novel Immunoregulatory Drugs for Systemic Lupus Erythematosus
BioTherapeutics, Inc (BTI) is an emerging biotech company that synergistically combines the power of
advanced computational modeling with translational experimentation to accelerate the development of novel
products for precision medicine and health. Lead molecule, BT-11, is a new small molecule targeting the LANCL2
pathway in IBD with two open INDs, completed Phase I clinical testing and initiated a Phase II study in 2019.
Systemic lupus erythematosus (SLE) is an autoimmune disease that afflicts 1.5 million Americans. Through our
previous research on abscisic acid (ABA), we discovered the anti-inflammatory and pro-regulatory immunological
effects of its receptor, lanthionine synthetase C-like 2 (LANCL2). Using a TLR7/8, resiquimod-induced model of
SLE, we determined that the loss of LANCL2 increases susceptibility to severe disease and mortality. We have
developed next-generation LANCL2-binding chemotypes, including the gut-restricted BT-11 and systemically
distributed BT-96 that exert potent immune effects in vitro and in animal models of disease. This SBIR project
will evaluate the therapeutic efficacy, pharmacokinetics (PK) profile and safety of novel LANCL2 agonists for the
treatment of SLE.
The Specific Aims for this SBIR Phase I application are to:
(1) Evaluate the therapeutic efficacy and PK profile of BT-96 in the NZB/W F1 model of SLE. NZB/W F1
mice will be orally dosed with BT-96 at three dose levels therapeutically at 23 weeks of age. Survival,
immunological signatures in blood and spleen, anti-nuclear antibodies, proteinuria, and kidney histopathology
will be assessed as endpoints. Single and multiple dose pharmacokinetic profiles will be assessed in blood,
spleen and kidney in NZB/W F1 mice.
(2) Determine the immunomodulatory effects of BT-96 in primary human samples from SLE patients. We
will test the efficacy of BT-96 in vitro to prevent inflammatory responses in primary human peripheral blood
mononuclear cells (PBMCs) from SLE patients in response to general and nuclear antigen stimuli.
Expected successful outcomes will include: i) a significant >35% difference in survival with oral dosing of BT-96
in NZB/W F1 mice, ii) > 50% in urine protein and serum anti-dsDNA at 36 weeks of age, and iii) > 30% reduction
in IFNα, TNF and IL-6 in SLE PBMCs with BT-96 treatment.
The SBIR Phase II will elucidate the cellular mechanisms of efficacy of BT-96 in SLE, determine synergism and
comparative efficacy to current and experimental therapeutics (low-dose IL-2), characterize the role of LANCL2
in the pathogenesis of human SLE, and advance BT-96 through IND-enabling studies.
The long-term goal of this project is to develop a novel immunomodulatory therapeutic capable of serving as a
safer and more effective treatment for SLE and provide a path towards commercialization of an asset with an
unmet need and a target population of over 5 million resulting in a market of over $3 billion by...

## Key facts

- **NIH application ID:** 10138876
- **Project number:** 1R43AI156952-01
- **Recipient organization:** BIOTHERAPEUTICS, INC.
- **Principal Investigator:** Andrew Leber
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138876

## Citation

> US National Institutes of Health, RePORTER application 10138876, Novel Immunoregulatory Therapeutics for Systemic Lupus Erythematosus (1R43AI156952-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10138876. Licensed CC0.

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