# Investigational new drug enabling studies for the development of a topical fixed dose combination drug product to treat actinic keratosis and prevent cutaneous squamous cell carcinoma.

> **NIH NIH R44** · PHD SKIN CARE LLC · 2022 · $865,361

## Abstract

PROJECT SUMMARY / ABSTRACT
Actinic Keratoses (AKs) are premalignant keratinocytes that are precursors to cutaneous squamous cell
carcinoma (CSCC), which is a non-melanoma skin cancer, the second most common type of cancer, and when
metastatic, has a mortality rate comparable to that of melanoma. Non-melanoma skin cancers are a growing
public health challenge that cost the United States healthcare system in excess of $1 billion annually. Approved
topical medications only exhibit modest efficacy in treating AKs and do not offer durable protection from CSCC.
PHD Skin Care (PHD) is a clinical stage drug discovery and development company that is proposing to develop
the first U.S. Food and Drug Administration (FDA) approved fixed dose topical cream containing a combination
of calcipotriol (CPO) and 5-fluorouracil (5-FU) as a prescription drug to treat AK and prevent CSCC.
The Product of this SBIR will be a stable and well characterized fixed dose combination cream that is prescribed
to treat AK and reduce the risk of CSCC development in an immunocompetent population. The product is
innovative because it derives efficacy by inducing a CD4+ T cell mediated immune response.
The Long-Term Goal is the development of a stable and well-tolerated topical cream that harnesses the power
of the immune system to treat AKs and prevent the morbidity and mortality associated with skin cancer.
Phase I SBIR Equivalent Studies demonstrated the feasibility that just 4 (n=64) or 6 days (n=18) of treatment
with a prototype CPO / 5-FU cream was well-tolerated in AK patients, caused an AK complete clearance rate of
79.6% and reduced the risk of CSCC development for 3 years. The clinically evaluated prototype formulation is
not appropriate for commercial development because it is unstable and causes CPO to rapidly degrade.
In Aim 1 two stable and well characterized fixed dose combination creams will be developed and the delivery of
the active ingredients across human cadaver skin determined. Milestones will be the development of two stable
and well characterized formulations where one exhibits a comparable penetration profile to the prototype and a
second delivers twice the concentration of drugs into the skin. In Aim 2 the delayed contact sensitization of the
formulations will be evaluated in guinea pigs, the in vitro irritancy potential evaluated in a bovine corneal opacity
and permeability assay and FDA feedback will be solicited in a pre-IND meeting. Milestones will be finding that
the newly developed formulations will score at least as favorably as the prototype, which was already found to
be well-tolerated in AK patients.
Expected outcome: The lead formulations will be stable for at least 1 year and score as well as the prototype
when evaluated in IND-enabling assays of dermal and ocular irritation. The formulations are expected to perform
as well as the prototype when evaluated clinically and outside the scope of this SBIR. A 505(b)(2) regulatory
approval from the Foo...

## Key facts

- **NIH application ID:** 10482509
- **Project number:** 1R44AR080475-01A1
- **Recipient organization:** PHD SKIN CARE LLC
- **Principal Investigator:** Andrew B Mahon
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $865,361
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482509

## Citation

> US National Institutes of Health, RePORTER application 10482509, Investigational new drug enabling studies for the development of a topical fixed dose combination drug product to treat actinic keratosis and prevent cutaneous squamous cell carcinoma. (1R44AR080475-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10482509. Licensed CC0.

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