# PIC1 pre-clinical formulation and optimization as a novel anti-inflammatory pharmacological agent

> **NIH NIH R44** · REALTA LIFE SCIENCES, INC. · 2020 · $578,570

## Abstract

The hypothesis for the proposed project is that inhibition of the classical complement pathway
with Peptide Inhibitor of Complement C1 (PIC1) will be neuroprotective in a rat model of
neonatal hypoxic-ischemic encephalopathy (HIE). HIE is an ischemia-reperfusion injury of the
brain that occurs around the time of birth, with up to 60% mortality and 25% of survivors left with
a significant disability. The complement system, the most potent inflammatory cascade in
humans, and a critical mediator of inflammation, phagocytic cell recruitment and direct cell lysis,
has been shown to play a major role in the pathogenesis of HIE in animal models and human
studies. Therapeutic hypothermia, the only accepted treatment for neonatal HIE, slightly
improves short-term survival and neurodevelopment in HIE, but does not significantly improve
long-term outcomes. To date, none of the tested pharmacological adjuvants to therapeutic
hypothermia have demonstrated clinical improvement. Deficiency of C1q, the initiator molecule
of the classical complement pathway, has been shown to be neuroprotective in an animal model
of neonatal HIE. Our current lead compound of PIC1 (PA-dPEG24), is the product of years of
rational drug design yielding a 15 amino acid peptide conjugated with PEG. Our compound
binds to C1q, efficiently blocking complement activation at the first step in the cascade. The
SBIR Phase I demonstrated proof of concept that PIC1 given as a rescue drug after hypoxia
and in combination with hypothermia can yield decreased brain damage. This Phase 2 proposal
will follow our PIND plan that was favorably reviewed by the FDA. We will focus on three key
objectives: 1) Drug Product and Drug Substance evaluation, 2) non-GLP pharmacokintics and
toxicology, and 3) PIC1 dosing optimization in the animal model of HIE as a rescue drug in
combination with hypothermia compared to hypothermia-alone controls, the current standard of
care. Successful completion of these studies will be used to generate a robust IND application
and provide necessary data for First in Human as well as subsequent proof of concept studies
in asphyxiated human neonates. Third-party market analysis shows the potential for healthy
sales volumes for PIC1 in HIE. Third-party regulatory analysis suggests the potential for a
stream-lined regulatory approach by seeking Orphan Drug and Breakthrough designations.

## Key facts

- **NIH application ID:** 9944444
- **Project number:** 5R44AI131764-03
- **Recipient organization:** REALTA LIFE SCIENCES, INC.
- **Principal Investigator:** NEEL KUMAR KRISHNA
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $578,570
- **Award type:** 5
- **Project period:** 2017-06-20 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944444

## Citation

> US National Institutes of Health, RePORTER application 9944444, PIC1 pre-clinical formulation and optimization as a novel anti-inflammatory pharmacological agent (5R44AI131764-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9944444. Licensed CC0.

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