# New Inhibitors of HIV latency reactivation

> **NIH NIH R41** · ITHAX PHARMACEUTICALS, INC. · 2021 · $298,357

## Abstract

ABSTRACT
 Company - Ithax Pharmaceutical is a new spin-off biotechnology company, located in Seattle, focused on
developing proprietary small molecule chemistry to target RNA. The experience of its founders spans virology,
drug design and RNA structure and function, and gives it a unique technological expertise in the RNA-targeting
space. Their commercial expertise includes the successful founding, and subsequent sale, of Ribotargets, an
RNA-focused small molecule drug discovery company in Cambridge, England in 1997-2001. This Phase I STTR
proposal lays out a series of experiments, beyond the scope of academic discovery, that are critical to advance
and de-risk the commercialization and pharmaceutical plans of the company. Successful completion of this
project will help Ithax improve the efficacy of exciting lead compounds, validate their activity in relevant primary
cell model systems, and obtain ADME and PK/PD data. The resulting progress would facilitate its commercial
growth by providing the data required to initiating the pre-clinical development of its lead small molecules under
a subsequent phase II SBIR project, and the acquisition of the private capital required for IND-enabling studies
that will follow.
 Technology – The existence of latent but replication competent viruses residing primarily in a very small
population of resting memory CD4+ T cells limits the long term efficacy of anti-retroviral therapy because the
virus inevitably rebounds once therapy is suspended. Escape from latency is driven by transcriptional
reactivation of the HIV provirus, which requires stimulation of RNA Pol II processivity by the host P-TEFb kinase,
which is recruited to the HIV TAR RNA through its interaction with the viral Tat protein, the only transcriptional
activator encoded by the virus. It follows that inhibition of the Tat-TAR-P-TEFb complex would lead to
suppression of viral reactivation and prevents the virus emergence from latency. This project furthers the
development of a new class of small molecule inhibitors of Tat-TAR-P-TEFb discovered by the company’s
founders that interact with TAR RNA and inhibit viral replication in cells. It will optimize the biochemical and
cellular potency of the lead using structure-based drug design; assess the lead’s pharmacological properties in
vitro and its in vivo pharmacokinetics and toxicity and evaluate its activity and mechanism of action in
sophisticated cellular models of latency. Collection of these data will allow subsequent submission of a strong
phase II SBIR project focused on pre-clinical investigations, and the parallel pursuit of private capital required
for IND-enabling studies.
1

## Key facts

- **NIH application ID:** 10208701
- **Project number:** 5R41AI152860-02
- **Recipient organization:** ITHAX PHARMACEUTICALS, INC.
- **Principal Investigator:** JONATHAN KARN
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $298,357
- **Award type:** 5
- **Project period:** 2020-07-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208701

## Citation

> US National Institutes of Health, RePORTER application 10208701, New Inhibitors of HIV latency reactivation (5R41AI152860-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10208701. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*