ION Channel Program

Program Overview:

Hydra Biosciences is a leader in the field of novel ion channels. In particular, the Transient Receptor Potential (TRP) family of ion channels offers numerous drug discovery opportunities. We are utilizing our state of the art high throughput screening facility and expertise in ion channel physiology to develop novel modulators of TRP channel.

Scientific Rationale:

Ion channels are transmembrane proteins that facilitate the flow of ions (positively and negatively charged molecules) into and out of the cell. They are critically important not only for normal cellular homeostasis, but also for transmission of information into and out of the cell.

The Transient Receptor Potential (TRP) channel family comprises a novel group of non-selective cation channels that are distinct from classical voltage gated ion channels. Recent work indicates that TRPs respond to a variety of stimuli including changes to specific ligands, temperature, acid, salt concentration, and second messenger signaling. As such, TRPs act as multimodal signal integrators. This gene family represents ~20% of all ion channels found in the body. Since TRP channels are only distantly related to voltage gated channels, they present an opportunity to identify selective "First in Class" drugs. In addition, homology among TRP family members is quite low, allowing specific modulators to be more readily identified in this family than in other ion channel families, limiting the potential for off-target effects, which have plagued other ion channel families. Hydra is at the forefront of efforts to develop novel drugs that target these channel.

Clinical Opportunity:

Ion channels have been implicated in many diseases, including hypertension, cardiac arrhythmias, gastrointestinal disorders, cystic fibrosis and pathological pain. Many drugs on the market today act on ion channels, either directly or indirectly, including calcium channel blockers such as Norvasc® for hypertension and angina, and sodium channel blockers such as Lidocaine for pain.

Hydra's TRP discovery program has identified numerous TRP channel modulators predicted to impact diseases such as pain and inflammation and hypertension. Many of these modulators have been shown to be efficacious in animal models of disease. We have assembled a world class team of experts to advise us on the best and most direct paths forward to assess these promising molecules in clinical trials.

In addition to the TRP family of ion channels, Hydra has also focused on the CatSper (Cation Channel of Sperm) family of ion channels. CatSpers are found specifically in the tail of mature sperm, and functional CatSper channels are required for fertilization. This program has the potential to yield "First in Class" non-hormonal contraceptives that could be used by either gender on an "as needed" basis.

Commercial Opportunity:

Ion channel have been successful drug targets, with modulators of ion flux representing up to 17% of world pharmaceutical sales. Commercial opportunities around the Transient Receptor Potential (TRP) and CatSper families are numerous. Indications for Hydra Biosciences' first TRP channel blocker is for the treatment of pain, representing an area of significant unmet medical need associated with various conditions such as arthritis, acute and chronic pain. The market opportunity for pain therapy drugs is projected to have annual global sales of greater than $20 billion. Modulators of other TRP channels could be used to treat diseases such as hypertension, chronic heart failure, kidney disease and inflammation.