# IND-enabling development of MM010, a PEG-specific intervention that blocks allergic response and restores repeated dosing for select PEGylated medicines impacted by anti-PEG antibody

> **NIH NIH R43** · MUCOMMUNE, LLC · 2024 · $291,458

## Abstract

Project Summary:
 Polyethylene glycol (PEG) is routinely used in protein and nanoparticle therapeutics, with dozens of
PEGylated drugs approved to date. Although PEG itself is exceptionally safe, patients can form high titers of
anti-PEG antibodies (APA) to some PEGylated drugs. This results not only in loss of efficacy from APA-
induced rapid clearance of the drug, but also increases the risks of severe allergic responses, as exemplified
by adverse clinical experiences with Krystexxa, Oncaspar and Palynziq that leave tens of thousands of
Americans without viable treatments. Furthermore, APA induced by one drug can impact the efficacy and
safety of a second PEGylated drug. Given the increasing number of PEGylated drugs on the market (including
COVID-19 mRNA vaccines), there is an urgent need for safe and effective interventions that prevent APA
induction and PEG-allergy.
 Mucommune has in-licensed a technology that can safely and effectively overcome the impact of APA
on PEGylated medicines, without the need for broad immunosuppression or new polymers to replace PEG.
The technology is based on the use of high MW free PEG to competitively saturate circulating APA and B-cell
receptors on the surface of APA+ B-cells, thereby limiting the “hapten” effect of PEG-drugs. In published and
pilot studies, free PEG markedly suppresses APA-induction against PEG-liposomes and Krystexxa (PEG-
uricase) in immunocompetent mice and swine, and effectively restored the prolonged circulation of both in
animals with high APA titers. Importantly, repeated injection of free PEG does not simulate further APA
induction, unlike PEG-proteins or PEG-liposomes. Perhaps most surprisingly, free PEG completely eliminated
hypersensitive reactions to PEG-liposomes in swine (the gold standard model for PEG-induced pseudoallergy).
Swine receiving PEG-liposomes alone experienced strong anaphylaxis requiring immediate epinephrine
intervention and resuscitation. These findings strongly underscore the promise of using free PEG to overcome
allergic response to PEGylated medicines and to restore their efficacious use.
 Free PEG is inexpensive (pennies per dose), offers outstanding safety, and can be rapidly advanced
into late stage clinical studies. Our overarching goal in this Phase 1 SBIR proposal is to establish the
foundation to quickly advance this intervention into the clinic. We will file a pre-IND (Type B) application with
the FDA to confirm the suitability of our proposed preclinical and clinical pathway, and will develop and qualify
key assays for quantifying APA and free PEG necessary to support GLP and future clinical studies. We will
then execute a GLP tox study in rats (a common model for PEG-drugs) to support first-in-human studies.
Successful completion of these activities will allow us to file IND for MM010, putting us at the doorstep of
advancing this intervention into the clinic, potentially providing relief for the tens of thousands of Americans
suffering from respons...

## Key facts

- **NIH application ID:** 10822403
- **Project number:** 1R43AI181354-01
- **Recipient organization:** MUCOMMUNE, LLC
- **Principal Investigator:** Keiichiro Kushiro
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $291,458
- **Award type:** 1
- **Project period:** 2024-01-22 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10822403

## Citation

> US National Institutes of Health, RePORTER application 10822403, IND-enabling development of MM010, a PEG-specific intervention that blocks allergic response and restores repeated dosing for select PEGylated medicines impacted by anti-PEG antibody (1R43AI181354-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10822403. Licensed CC0.

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