Harmonic platform

Harmonic Pharma’s «pharmacological rediscovery ©» platform uses spherical harmonic based molecular representations to process molecules.

Since inception in 2009, Harmonic Pharma has developed a unique platform to characterize polypharmacology profiling of safe drugs and drug candidates. Assets have been patented upon in vivo proof of principle.

A molecule of interest is compared to the company’s proprietary collection of 15,000 safe drugs and drug candidates classified according to selected parameters. A polypharmacology profile of putative biological targets is generated which is consolidated with in vitro assays. This methodology has proven to be highly reliable with a success rate of at least 30% from modeling outcome to experimental assessments. The subsequent newly identified indication is validated with relevant in vivo models mimicking the pathophysiology conditions of the selected disease. Considering that safety of the molecule has already been thoroughly investigated in man, early clinical trials may therefore be carried out sooner and safer by pharma or biotech companies.

1- Spherical harmonics as a molecular shape comparison method

Harmonic Pharma has developed a proprietary software called HPCC (Harmonic Pharma Chemistry Coefficient) able to describe a molecule by a shape with associated surface properties characterizing the chemical nature of its atoms.

The HPCC software is also able to compare pairs of molecules through spherical harmonics. HPCC performance was evaluated and validated with the international reference dataset DUD (Directory of Useful Decoys) that includes more than 100,000 compounds spread over 40 protein targets [Karaboga et al. 2013].

2 – A proprietary database of safe molecules

Harmonic Pharma has built a proprietary database that contains more than 15000 safe drugs. They are transformed in the HPCC format to enable subsequent comparisons with a reference molecule. In addition, each drug has associated information related to its cognate target(s) protein(s), mechanism of action, therapeutic indication, stage of development, etc …

3, 4 – Building and assessing a polypharmacology profile

Harmonic Pharma has developed a method called quantitative GES (Gaussian Ensemble Screening) capable of predicting new protein targets for a given molecule using the HPCC software. The principle and the performance of the method have been described by Perez-Nueno et al. 2014¹. This study included 5,000 compounds, spread over 800 different protein targets. Thus, a list of target proteins is generated with significant similarity probability. These predictions are then assessed with in vitro assays specific to each target protein and the resulting ensemble of proteins characterize the experimental polypharmacology profile of the active ingredient.

¹ Journal of Chemical Information and Modeling 2014 54, 720-734 J. Chem. Inf. Model.

5- In vivo proof of principle

The polypharmcology profile will give rise to the identification of new therapeutic indication(s) for the molecule. Its mechanism of action is then assessed with relevant animal models mimicking the pathophysiology conditions of the targeted human disease(s). Institut Curie possesses a genetically documented human tumors collection and has developed a unique expertise in Patient-Derived Xenograft models that are predictive of clinical outcome. At this stage, Harmonic Pharma files a patent application to protect the novel therapeutic use of the molecule.

6- Quick access to an early clinical trial

At this stage, we are open to discussions about licensing and/or partnering. Considering that safety of the query molecule has already been thoroughly investigated in man, early clinical trials may therefore be carried out sooner and safer by pharma or biotech companies.