Re-Pharm finds new use for old drug
Antibiotic shows novel anti- inflammatory activity after five decades in service against noninflammatory conditions
CAMBRIDGE, U.K.—An antibiotic that has been in use since the 1960s may soon get a new life as an topical inflammatory medication. Re-Pharm, the drug discovery arm of computational chemistry software provider Cresset, has discovered novel anti-inflammatory activity for RP0217, a compound that is widely prescribed for other, noninflammatory conditions.
The company found the new indication for the drug as the result of an effort to use Cresset’s computational chemistry software to find a new use for an existing compound that could have strong market potential. The company began the process with an extensive review of the areas believed to have significant potential for previously developed drugs to treat unmet medical needs.
“We eventually settled on inflammatory conditions as a very broad market area that would be our focus,” Rob Scoffin, CEO of Re-Pharm, tells DDNews. “We then used Cresset’s software to go through a smart reprofiling process of existing compounds that might have anti-inflammatory activity.”
Re-Pharm used known ligands and a crystal structure as a starting point in its search, employing Cresset’s Forge software to build computational templates that would find any compounds likely to be active against the new target. Forge is a computational chemistry software program that uses the shape and electrostatic character of molecules to create qualitative and quantitative 3D models of activity. These models are calculated using Cresset’s patented ligand comparison method to align, score and compare molecules from a biological viewpoint. Re-Pharm used Forge to analyze a database of 25,000 existing molecules and narrow that list down to a small number of compounds with potential.
“The software gave us an ordered list of the compounds, with the compounds highest on the list having the highest probability of having the activity we were seeking,” says Scoffin. “So it enabled us to run through the list and easily identify the compounds with the most potential.”
Re-Pharm eventually identified RP0217 as the compound with the most potential as an effective new anti-inflammatory agent. Re-Pharm has filed patents on RP0217 for a variety of disease indications.
“We are delighted that this new activity has been identified as a direct result of work using Cresset software,” says Dr. Mark Mackey, Cresset’s chief scientific officer. “Cresset’s software codifies the electrostatics and shape of compounds in a way that makes it computationally viable to search databases of thousands of compounds to find new chemical series with similar biological activity. This work highlights the immense value of Cresset’s approach for finding new drug activity.”
Compounds are usually narrowly tested against one disease indication in the traditional drug development process, with compounds often achieving approval for a particular medical need without ever having been tested for other indications. But such marketed drugs can often represent a valuable source of medications for other indications due to their well-established safety profiles. This process is generally referred to as reprofiling or repurposing.
Reprofiling an existing drug for new use can have significant advantages over the conventional drug development pathway. Most notably, reprofiling can be a much quicker process. It took Re-Pharm about two months to identify the new indication for RP0217, for example, in contrast with the years-long process that drug development typically involves. “In the context of normal drug discovery, going from identifying your target biology of interest to identifying an active compound in two months is pretty quick,” Scoffin tells DDNews. “The hope with reprofiling is to be able to go down an expedited development path, significantly shortening Phase 3.”
There are disadvantages to reprofiling as well, however. “The downside with reprofiling is that you’re dealing with existing compounds, and intellectual property is always going to be an issue,” says Scoffin. “While the development process may be quicker, you spend more time working through the IP issues.”
In the case of RP0217, Re-Pharm hopes to overcome intellectual property barriers by establishing the anti-inflammatory indication for the compound as an area of unmet medical need. Additionally, Scoffin says the company hopes to be able to establish a new use position based on the topical delivery of the compound for this indication, since it has previously been delivered orally for its other indications.
If its patent applications are successful, Re-Pharm anticipates developing RP0217 for new non-steroidal approaches to the treatment of a variety of disease indications.
“We are delighted with the discovery of RP0217 and look forward to its progression through clinical trials,” says Dr. Alan Rothaul, chief scientific officer at Re-Pharm. “Cresset’s software made it possible to analyse the potential activity of thousands of existing drugs so that we could pinpoint those that were likely to be active against the new enzyme target. Cresset software is a key part of our re-purposing pipeline, and I look forward to many similar future successes.”