# Novel bi-specific immunotherapeutic against high-threat Gram-negative pathogens

> **NIH NIH R01** · HACKENSACK UNIVERSITY MEDICAL CENTER · 2022 · $1,142,038

## Abstract

The Centers for Disease Control and Prevention 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.
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. Further, although it’s rare, MDR can potentially be a serious problem in
G- Select Agents, given the highly transmissible nature of the MDR determinants in G- bacteria and the fact that
select agents are persisting in the environment. Thus, a broad spectrum agent that leverages immunological
mechanisms to prevent as well as to treat high-threat G- bacterial infections in high risk populations
would possess a unique advantage in addressing this need. The innovative Cloudbreak™ Antibody Drug
Conjugates (ADCs) platform, developed at Cidara Therapeutics, is a broad-spectrum G- active drug candidate
that 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 high-threat 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 and
therapeutic 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 (inclu...

## Key facts

- **NIH application ID:** 10337197
- **Project number:** 5R01AI141183-04
- **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:** $1,142,038
- **Award type:** 5
- **Project period:** 2019-02-21 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337197

## Citation

> US National Institutes of Health, RePORTER application 10337197, Novel bi-specific immunotherapeutic against high-threat Gram-negative pathogens (5R01AI141183-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10337197. Licensed CC0.

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