DUBLIN and PERTH, Australia – Sensorion SA is teaming up with Cochlear Ltd. to explore the potential for combining drug therapy with cochlear implant surgery to improve patient outcomes. The two companies will spend next year evaluating Sensorion's clinical-stage drug candidate, SENS-401, with Cochlear's implantable devices in a number of preclinical models. If that work is successful, clinical trials could follow in 2019.

Montpelier, France-based Sensorion is receiving a €1.6 million (US$1.9 million) equity investment from Sydney-based Cochlear. Should the collaboration progress, the other terms will be agreed at a later point. "They have first right of negotiation," Sensorion CEO Nawal Ouzren told BioWorld. But she wanted to see the preclinical data before making a judgment on the potential value of SENS-401 in the combination setting.

SENS-401 demonstrated good safety and tolerability in a phase I trial as a monotherapy, she said, and it will move into phase II studies in sudden sensorineural hearing loss and cisplatin-induced ototoxicity in the first and second halves of 2018, respectively.

The drug is a member of the "setron" class of serotonin receptor subtype 3 (5HT-3) antagonists. But it has a second mechanism of action that sets it apart from its stable mates. It also acts as an inhibitor of calcineurin, a calcium-regulated protein phosphatase implicated in a number of biological pathways. Excessive noise leads to an increase in the concentration of calcium in the sensory hair cells of the inner ear, leading to calcineurin activation and hair cell loss through apoptosis.

"When you inhibit calcineurin, you actually inhibit that apoptotic process," Ouzren said. Preclinical data show that SENS-401 mediates that effect. Its action is evident at a histological level – synaptic organization is maintained in the inner ear in preclinical models; whereas it is disrupted in the drug's absence.

"The other setrons did not have the same protective effect on hair cells," she said. "These data were the foundation of the conversation with Cochlear," she said.

"SENS-401 has been shown to preserve function in models of noise-induced and chemotherapy-induced hearing loss (NIHL/CIHL), and may improve outcomes in individuals undergoing cochlear surgery," said Lifesci Capital analyst David Sherman in a research note.

In teaming up with Cochlear, Sensorion will be working with the global market leader in cochlear implants – about 450,000 people have been fitted with one of its devices over the past five decades. The devices bypass the damage to the inner ear's hearing apparatus by sending coded electronic signals – derived from an externally fitted speech processor – directly to the brain through the auditory nerve.

The procedure does not result in a complete restoration of hearing and, indeed, the procedure can destroy the user's residual hearing ability, according to FDA guidance.

Even so, patients who have been implanted with the devices have reported up to an 80 percent improvement in sentence understanding, compared to 10 percent improvement in hearing aids, Cochlear said.

There have been some previous efforts at marrying drug therapy to cochlear implantation in academic settings, and Stevenage, U.K.-based Autifony Therapeutics Ltd. conducted a pilot trial of AUT-00063, a voltage-gated potassium channel modulator, as an add-on therapy for cochlear implant users. None of those efforts has yielded convincing data, Ouzren said.

Cochlear's first biopharma equity investment

"As part of its general R&D program, Cochlear has undertaken more than 100 collaborative research projects focused on improving hearing outcomes in patients with cochlear implants, including in the area of potential combination therapies," Cochlear's chief technology officer, Jan Janssen, told BioWorld.

"However, this collaborative project involves the company's first equity investment into a biopharmaceutical company," she said.

When asked what patient population would likely benefit the most from the combination therapy, Janssen said the collaboration is still early stage, and patients for whom any related therapies may be most effective will depend on the outcome of the study.

She said the trial is also designed to investigate the potential for SENS-401 to enhance long-term functional stability of the implant and improve hearing outcomes for patients undergoing cochlear implant surgery. The proposed study will evaluate combination therapy for the potential to enhance survival and functional integrity of hair cells in the inner ear.

For most cochlear implant recipients, there are regularly scheduled follow-up appointments after the initial programming visit. The technology is maximized when coupled with adequate follow-up appointments so adjustments can be made to provide the best hearing performance for each patient, the company said.

Last month, the FDA approved Cochlear's remote feature to allow follow-up programming sessions for its Nucleus cochlear implant system through a telehealth platform. The approval is the first in the cochlear implant industry, and it opens the door for many implant patients who have trouble accessing continued care because they can't travel to an implant center.

Cochlear's company's market cap is A$10.12 billion. Shares (ASX:COH) were A$176.985 on market close Monday.

Sensorion reported cash and equivalents of €9.2 million at June 30. The company is funded through the completion of the upcoming phase II trials of SENS-401 and the read-out from an ongoing phase IIb trial of SENS-111, an oral histamine 4 receptor, in unilateral vestibulopathy, an acute form of spinning vertigo.

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