# Development of a small-molecule immunomodulator for the treatment of melanoma

> **NIH NIH R41** · CLARADELE PHARMACEUTICALS, INC. · 2022 · $398,242

## Abstract

SUMMARY
Melanoma is the most lethal form of skin cancer with treatment costs exceeding $3 billion each year.
Melanoma is successfully managed at early stages however, five-year survival rates for the advanced disease
are as low as 20%. Immunotherapeutic checkpoint inhibitors (ICI) including agents that target PD1/PD-L1,
have substantially improved melanoma survival rates. Unfortunately, only 35-60% of melanoma patients exhibit
complete or partial responses to ICIs. Moreover, melanoma tumors that have mutations in the Braf
protooncogene rapidly develop resistance to Braf/MEK inhibitors. Few treatment options remain for patients
who fail to respond to ICIs or have developed resistance to Braf inhibitors. To prolong the lives of these
individuals, optimized ICI regimens that are effective in ICI- and Braf-resistant melanoma are urgently needed.
Claradele Pharmacetuicals is investigating whether pretreating melanoma with the novel, small molecule
immunostimulatory endoplasmic reticulum (ER) stress inducer, 15dPMJ2, will sensitize the lesions to PD1
blockade. Our data demonstrate that 15dPMJ2 inhibited subcutaneous melanoma growth. In addition,
15dPMJ2 increased the tumor infiltration of active dendritic and memory T cells. Studies in this project will
define doses of 15dPMJ2 that are safe to administer with anti-PD1 by determining the optimal biological dose
(OBD). We will also test whether generating tumor inflammation with intratumorally administered 15dPMJ2
increases the rate at which melanoma responds to PD1 blockade. Our syngeneic murine models will be used
to examine the effects of 15dPMJ2 on melanoma that contains or is devoid of human driver Braf mutations.
Accomplishing our goals will provide proof-of-concept that optimizing the activity of ICIs with 15dPMJ2 will
allow a significant proportion of melanoma patients to benefit from these life-saving therapeutics. The
knowledge gained from this investigation will form the foundation of a Phase II STTR application that will
examine agent formulation, optimize medicinal chemistry parameters, develop a CMC package, and define key
toxicology and pharmacology properties of 15dPMJ2 to support an IND submission to the FDA.

## Key facts

- **NIH application ID:** 10379630
- **Project number:** 1R41CA261311-01A1
- **Recipient organization:** CLARADELE PHARMACEUTICALS, INC.
- **Principal Investigator:** Rukiyah Van Dross
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,242
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10379630

## Citation

> US National Institutes of Health, RePORTER application 10379630, Development of a small-molecule immunomodulator for the treatment of melanoma (1R41CA261311-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10379630. Licensed CC0.

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