# Preclinical Translational Studies with DRHQ

> **NIH VA I01** · PORTLAND VA MEDICAL CENTER · 2021 · —

## Abstract

Project Summary/Abstract:
Multiple Sclerosis (MS) is the most common neurologic disabling disease among young adults, affecting over
400,000 people in the United States, 2.5 million worldwide and 20,000 under the care of the Department of
Veterans Affairs. Most MS individuals are initially diagnosed with relapsing-remitting MS (RRMS) and then
eventually transition to secondary progressive MS (SPMS). When MS individuals enter SPMS, neurologic deficits
progressively worsen over time. Approximately 15% of people with MS are initially diagnosed with primary
progressive MS (PPMS) and display increasing neurologic deficits without periods of relapse. Almost all the
FDA approved therapeutics for MS are for patients with RRMS and there are very limited therapeutic options for
people with progressive MS. A key cytokine/chemokine thought to drive the early inflammatory stage of MS to
a chronic progressive phase is macrophage migration inhibitory factor (MIF). We have designed a potent
biological construct called RTL1000 and a second-generation derivative, DRhQ, that bind tightly to the MIF
receptor, CD74, and competitively inhibit MIF binding and it’s downstream signaling as well as inhibit T cell
activation and release of IL-2. RTL/DRhQ treatment was also found to promote neuroprotection and reduce the
severity of acute and chronic EAE, a mouse model of MS. RTL1000 was found to be safe and well tolerated at
doses 60 mg in a Phase I safety trial in patients with either RRMS or SPMS. However, RTL1000 contains the
extracellular domains of the MS risk factor, HLA-DR2 and as such, the FDA limited RTL1000 administration in
the clinical trial to HLA-DR2 positive patients (~50% of total MS subjects). Our second generation construct,
DRhQ, retains the potent immunomodulatory activity of RTL1000 but is HLA invariant and thus suitable for all
patients. In order to treat both DR2 positive and negative individuals with progressive MS, we are proposing
crucial preclinical studies of DRhQ and its mouse homologue, DRmQ, which will advance DRhQ towards a First-
In-Human (FIH) Phase 1 clinical trial. In this Merit Review application, we will evaluate: 1) multi-compartmental
pharmacokinetics; 2) validate relevant biomarkers, including infusion induced cytokine release, inhibition of
phosphorylated extracellular-related kinase (pERK1/2) and related cytokines, and inhibition of IL-2 secretion
induced by activated T cells; and 3) potential neutralizing activity of anti-drug antibodies against DRhQ. The data
collected during this project will be used to support the filing of an Investigational New Drug (IND) application to
the FDA for a FIH study. The previous success of RTL1000 in reaching a Phase 1 clinical trial gives us confidence
that we will achieve success in Phase 1 as well as Phase 2 and 3 clinical trials with DRhQ.

## Key facts

- **NIH application ID:** 10155078
- **Project number:** 5I01BX005112-02
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** ARTHUR A. VANDENBARK
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155078

## Citation

> US National Institutes of Health, RePORTER application 10155078, Preclinical Translational Studies with DRHQ (5I01BX005112-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155078. Licensed CC0.

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