Closely-held Hydra Biosciences expects to complete Phase 1 trials of its HX-100 inhibitor of the Transient Receptor Potential (TRPA1) ion channel as a treatment for painful diabetic neuropathy and allergic asthma by the end of this year.
“We expect to file regulatory documents by the end of December to initiate Phase 2 trials in patients with allergic asthma and painful diabetic neuropathy in the first half of 2016,” president and CEO, Russell Herndon, says in an interview with BioTuesdays.com.
“Data from the allergic asthma trial should be available in the second half of next year and for painful diabetic neuropathy, data should be available either late this year or in early 2017,” he adds.
Mr. Herndon explains that TRPs are membrane-bound proteins that play a role in controlling cellular calcium levels and excitability in response to a variety of stimuli. For example, when someone eats wasabi, it activates TRPA1, causing a burning sensation in the mouth.
TRPA1 is believed to be involved in chronic pain and inflammation. In addition, there is the potential for pipeline expansion in treating dermatology and pulmonary disorders. Other TRP ion channels have been implicated in diseases affecting the central nervous system and some metabolic disorders, he added.
Unlike other ion channels, Mr. Herndon suggests that TRPs do not require cellular voltage to open and close in response to stimuli. There is also significant amino acid diversity with TRPs, which helps provide for better selectivity, reducing the potential for off-target effects, he adds.
“The takeaway is that we can identify very potent molecules that are very selective, with the potential for better efficacy and fewer side-effects,” he contends.
“We’ve been at this for about 10 years, and we’re now at the point with our selective compounds where we can test to see if blocking these channels has a clinical and statistically significant effect in chronic disease states.” Hydra has raised more than $51-million in non-dilutive capital to finance its research.
According to Mr. Herndon, Hydra’s lead molecule, HX-100, is a highly selective pill that has demonstrated promising safety and efficacy in animal studies. “We believe there is a strong causative link between known TRPA1 agonists and human disease.”
He points out that the targets for existing treatments of neuropathic pain, such as Lyrica, Cymbalta, Neurontin and opioids, are all found in the brain. As a result, they require penetration of the blood-brain-barrier and activation of certain sites in the brain to produce a clinical effect. Side-effects with these treatments can lead to weight gain, nausea and somnolence.
On the other hand, he contends that TRPA1 has not been found to be expressed in the brain, so there are no issues with tolerance and addiction. “There is a huge need to adequately treat neuropathic pain without the societal issues connected to abuse of opioids.”
Some seven million people now suffer from painful diabetic neuropathy, with forecasts climbing to nine million people by 2022. The disease is often associated with reduced quality of life, including pain and loss of function of hands and feet, and is often accompanied by depression.
In asthma, Mr. Herndon notes that known disease triggers, such as cigarette smoke, ozone and industrial irritants, all activate TRPA1. “That’s why we believe there is a direct link between that activation and asthma.” TRPA1 also plays a major role in the neural control of cough, he adds.
Asthma affects some 300 million people worldwide. The global asthma market is expected to reach $21.6-billion by 2019, according to RNR Market Research, from $16.6-billion in 2013.
There are no oral asthma products on the market, with the exception of Singulair, which generated annual sales of $5-billion before going generic in mid-2012. Singulair worked in a small patient population but was very safe and highly prescribed, Mr. Herndon says.
Big Pharma’s asthma research is largely focused on developing steroids for inhalation and antibodies that require infusion at a hospital. “Our product candidate is an orally-active compound that would be used as a preventative to reduce the number of asthma exacerbations,” he says.
Mr. Herndon points out that the Phase 2 asthma trial next year will be modeled closely on earlier animal studies, specifically where HX-100 reduced allergic asthma in sheep. The primary endpoint will be lung resistance, including late airway response.
“Based on our animal data, we are anticipating a strong positive correlation in human patients,” he adds.
In addition to its sponsored Phase 2 trials in painful diabetic neuropathy and allergic asthma, the company is evaluating additional Phase 2 pulmonary and pain trials, targeting TRPA1.
Hydra also has signed two global partnerships with Boehringer Ingelheim to study other TRP ion channels as possible treatments for CNS diseases and disorders, and renal disease.
Hydra’s IP is protected by more than 70 patents and pending applications worldwide, of which 30 cover the HX-100 TRPA1 program, including composition of matter and method of treatment. “As the leader in the TRP space, we’ve built a nice picket fence around our technology,” Mr. Herndon points out.