# Safety and efficacy of an allergy therapeutic targeting FcERI bound IgE in human immune reconstituted mice.

> **NIH NIH R43** · SIXAL CORPORATION · 2020 · $286,656

## Abstract

PI - Andrew Saxon MD
Abstract: The goal of this SBIRI application is to accomplish key “long term” safety and efficacy time-course
studies of a novel biologic designed for the preventive treatment of all severe/IgE mediated food allergic
reactions and mastocytosis. Allergic diseases and specifically severe food allergies have increased to the
point of becoming a major worldwide public health problem, particularly in the US and other developed
countries. Currently, effective novel treatment options for such allergies remain a major unmet need; no
effective therapy is available for the broad array of severe food allergies (e.g. peanut, egg, milk etc. allergy).
Our approach uniquely employs Low-affinity Allergy Response Inhibition (LARI) in the form of a carefully
designed monoclonal antibody (LARI E59) that targets FcεRI-bound IgE on human basophils and mast cells.
The binding and release of LARI E59 functionally blocks the induction of allergic reactions by three distinct
effects. LARI treatment is designed to be pan-allergen effective and work for all IgE driven food allergies.
Additionally, LARI, because of its unique mechanism of action has been granted orphan drug designation for
mastocytosis by the FDA. We have performed extensive proof-of-concept studies that demonstrate that LARI
exhibits a potent blocking effect on allergic reactivity by rapidly inhibiting the activity of the key immediate
allergic effector cells: basophils and mast cells while far higher doses of LARI fail to trigger anaphylactic
degranulation. However, two key questions remain (1) Will repeated administration of LARI be safe? (2) What
is the time course of the therapeutic effect of LARI? This proposal is designed to specifically answer these
questions utilizing the now available complex immunodeficient mice reconstituted with human CD34+ stem
cells that make IgE. To determine the safety of repeated injections of LARI reconstituted NSG-SMS mice that
express human IgE will be injected four times with LARI over a time course that represents treatments over an
approximate 6 month time course in humans. At each time point, mice will be carefully evaluated for evidence
of allergic reactivity. To determine the time course for the efficacy of LARI, reconstituted NSG-SMS mice,
sensitized to peanut by gavage, will be treated with LARI and then challenged with peanut at day +7, +14 or
+21 after the treatment. This would test the efficacy of LARI after about one, two and three months in humans.
Having accomplished these studies proposed, we will have answered two key remaining questions as the
LARIs potential as a safe and effective therapeutic.

## Key facts

- **NIH application ID:** 9891544
- **Project number:** 1R43AI149739-01
- **Recipient organization:** SIXAL CORPORATION
- **Principal Investigator:** Andrew Saxon
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $286,656
- **Award type:** 1
- **Project period:** 2020-02-19 → 2023-02-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891544

## Citation

> US National Institutes of Health, RePORTER application 9891544, Safety and efficacy of an allergy therapeutic targeting FcERI bound IgE in human immune reconstituted mice. (1R43AI149739-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891544. Licensed CC0.

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