# Novel bi-specific immunoprophylactics against multi-drug resistant Gram-negativebacterial infections

> **NIH NIH R01** · HACKENSACK UNIVERSITY MEDICAL CENTER · 2022 · $1,076,832

## Abstract

The Centers for Disease Control and Prevention (CDC) estimates that at least two million illnesses and 23,000
deaths annually are caused by antimicrobial-resistant bacteria in the United States. The Gram-negative (G-)
pathogens are of particular concern, as they account for roughly 99,000 deaths and $20B in health care costs a
year. More alarming, treatment options for G- infections have become increasingly limited due to rapid
emergence of multi-drug resistance (MDR) to existing and newly approved antimicrobial agents, highlighting the
need for alternative strategies to prevent MDR G- infections. Thus, an agent that leverages immunological
mechanisms to prevent infection in high risk populations from drug susceptible and MDR strains would
possess a unique advantage in addressing this need. The innovative Cloudbreak™ Antibody Drug
Conjugates (ADCs) platform, developed at Cidara Therapeutics, uses a fundamentally new immune-based
approach to prevent and treat G- infections. Similar to successful cancer bispecific agents, ADCs bind conserved
targets on pathogens via a Targeting Moiety (TM) while simultaneously engaging multiple arms of the immune
system via an Effector Moiety (EM). The TM is comprised of a dimeric peptide that binds tightly to
lipopolysaccharide (LPS) and confers broad spectrum G- coverage with potent intrinsic antimicrobial activity.
The EM is a human IgG1 Fc, which collectively activates complement dependent cytotoxicity (CDC), antibody
(Ab)-dependent cell-mediated cytotoxicity (ADCC), and Ab-dependent cell phagocytosis (ADCP) to clear MDR
G- pathogens from the host, via recognition by Fcγ receptors on host cells.!This innovative approach involving
efficient cell targeting with inherent cell killing catalyzes a robust immune response by more effectively presenting
the pathogen to immune components for clearance. CTC-026 is our lead ADC candidate and has demonstrated
highly promising properties as an immunoprophylactic agent: broad spectrum antibacterial activity that is both
intrinsic and immune-driven, acute safety in rodents, in vivo efficacy in mouse models of Escherichia coli sepsis
and Acinetobacter baumannii pneumonia, and a 67 hour plasma half-life in mice. Further optimization of potency
and spectrum and in-depth evaluation of pharmacological and toxicological properties of this lead are proposed
in this application. The overarching goal of this proposal is to identify a qualified lead development candidate
in Year 3 and an Investigational new drug (IND) candidate by the end of Year 5, that meets these criteria: 1)
acceptable stability and solubility for IV formulation, 2) MIC90s ≤1 µM against clinical isolates (including MDR) of
Klebsiella, Acinetobacter, Pseudomonas and E. coli, 3) MIC90s ≤1 µM against MCR-1, MCR-2 and other colistin-
resistant G- clinical isolates, 4) robust in vivo prophylactic efficacy against MDR G- infections in a time window
48-72h prior to infection, 5) PK/PD parameters to support once weekly or ...

## Key facts

- **NIH application ID:** 10380759
- **Project number:** 5R01AI138986-05
- **Recipient organization:** HACKENSACK UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** David S Perlin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,076,832
- **Award type:** 5
- **Project period:** 2019-03-22 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380759

## Citation

> US National Institutes of Health, RePORTER application 10380759, Novel bi-specific immunoprophylactics against multi-drug resistant Gram-negativebacterial infections (5R01AI138986-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380759. Licensed CC0.

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