FDA Allows Phase 2 Study for Sound Pharmaceuticals’ Novel Drug to Prevent Chemotherapy Induced Hearing Loss.

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SEATTLE, Aug 07, 2008 /PRNewswire via COMTEX/ — Sound Pharmaceuticals (SPI) has received FDA notification that it may proceed with its Phase II study to prevent chemotherapy induced hearing loss. The Ph-II study will enroll 80 patients with advanced head and neck, and non-small cell lung cancer at the National Center for Rehabilitative Auditory Research at the Veterans AdministrationHospital and the Oregon Health and Science University in Portland, Oregon.

Hearing loss due to ototoxic medications such as chemotherapy, antibiotics or loop diuretics often results in permanent and progressive disability. Furthermore, the combined use of these ototoxicagents is contraindicated, often limiting their clinical utility. Symptoms of ototoxicity include hearing loss, tinnitus, dizziness, vertigo and difficulty understanding speech. Historically, the incidence ofcisplatin or carboplatin-induced hearing loss was widely under estimated or reported due to inadequate testing or a lack of reporting. Recently, a new behavioral audiometric protocol has been developed and employed to test an individual’s sensitive range for ototoxicity (SRO). This involves pure-tone audiometry at very specific steps within a person’s upper range of hearing. With the SRO protocol, several studies now report an incidence of ototoxicity of 85-92% for cisplatin and carboplatin receiving cancer patients, an incidence that is much greater than previously reported. One of the goals of this Ph-II study is to reduce the incidence and severity of the ototoxicity in platinum receiving cancer patients as measured by pure-tone audiometry using the SRO protocol, distortion productotoacoustic emissions (DPOAEs) and the tinnitus handicap inventory. DPOAEs are a measure of outer hair cell function in the inner ear and are another sensitive and specific measure of ototoxicity.

In several preclinical studies, SPI has showed that its novel chemoprotectant drug product, a small molecule that mimics and induces Glutathione Peroxidase activity was critical in preventing ototoxicity while not interfering with the chemotherapy treatment. In one rodent model of cancer, the chemoprotectant enhanced the tumoricidal activity of cisplatin.

Sound Pharmaceuticals, Inc. is a privately held biopharmaceutical company with a focus on developing the first drugs for hearing loss and brain injury. For more information please contact Jonathan Kil, MD, President and CEO, 206-634-2559 or http://www.soundpharma.com.

SOURCE Sound Pharmaceuticals, Inc.

Copyright (C) 2008 PR Newswire. All rights reserved

VentureWire Lifesciences story covers Sound Pharma’s start of Ph-II clinical trials of SPI-1005 to prevent and treat noise induced hearing loss. 

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Drug Start-Ups Take Aim At Hearing Loss

A handful of venture-backed companies are striving to introduce the first drugs to treat or prevent hearing loss, a problem that affects more than 32 million Americans.

The only treatments today are hearing aids and, in severe cases, cochlear implants. Neither treats the underlying condition, which is so complex that few pharmaceutical companies, or venture investors, have considered the idea of a drug therapy.

Sound Pharmaceuticals Inc. may be among the first to find out. The Seattle company, which recently began Phase II trials to test an oral capsule for hearing loss, has raised $10 million from individuals and an undisclosed hearing-aid company. It hopes to secure up to $20 million more in Series B financing this year for additional clinical studies.

Promising results could shift more investor attention to a field sure to expand as the nation grays. While venture firms have funneled billions of dollars into treatments for diabetes, heart disease, and other maladies of aging, hearing loss barely registers.

“A lot of people just can’t believe that a drug could prevent or treat hearing loss,” said Jonathan Kil, Sound Pharma’s chief executive. “It hasn’t been done, so it’s not on people’s radar.”

Hearing begins when sound vibrations bounce against the eardrum, causing it to vibrate. The eardrum, along with three tiny, middle-ear bones, amplifies the vibrations as they travel to the cochlea, an organ of the inner ear that houses a system of membranes, fluids, neurons and sensory hair cells. These sensory, or auditory, hair cells convert vibrations to electrical signals, which are transmitted to the brain by the auditory nerve.

While a punctured eardrum can be repaired, most hearing loss stems from irreversible injury to auditory hair cells or the auditory nerve. This “sensorineural” hearing loss can be caused by aging and certain drugs, but the principal culprit is noise. About 22 million Americans aged 20 to 69 have permanent damage to their hearing from excessive noise, according to the National Institute on Deafness and Other Communication Disorders, an NIH institute.

The 100-decible roar of a chainsaw, for instance, can injure auditory hair cells in an hour. Since a decline in hearing often creeps along, it may go unnoticed for years. “By the time people think they have a hearing-loss problem, they need a hearing aid,” Kil said.

The problem looms especially large for soldiers returning home. Over 800,000 veterans receive disability compensation for service-connected hearing disability, according to the U.S. Department of Veterans Affairs. That’s why the military seeks help from companies like Sound Pharma, whose lead drug might prevent hearing loss if taken just before noise exposure or treat it if given just after.

In one Phase II trial, U.S. servicemen will take Sound Pharma’s lead drug, SPI-1005, or a placebo before conducting live-fire drills. Even with ear protection, those exposed to the 150-decibel din of gunfire risk harm. This study is being run by Naval Medical Center San Diego.

SPI-1005 mimics glutathione peroxidase — an enzyme that reduces metabolic stress in the cochlea — and encourages genes to make more of it. If the drug earns regulatory approval, the defense department and the veterans affairs agency could be big customers. Phase II trials in noise-induced hearing loss will be completed by midyear, and Phase III studies could commence later this year or in early 2009.

Oncologists may be another customer for Sound Pharma, which also is conducting a Phase II trial to see if a glutathione-peroxidase mimic it calls SPI-3005 will protect against hearing loss caused by cisplatin, a widely used chemotherapy. That trial, which is being run by National Center for Rehabilitative Auditory Research of the Portland (Ore.) Veterans Affairs Medical Center, should be completed next year, Kil said.

Platinum-based cancer drugs such as cisplatin can damage auditory hair cells — which do not regenerate — and leave patients dependent on hearing aids, which amplify sounds, or cochlear implants, which stimulate the auditory nerve. Though helpful, neither device restores natural hearing.

A competitor, publicly held Adherex Technologies Inc., may introduce a protective therapy as soon as 2011. Its drug, sodium thiosulfate, or STS, binds and inactivates cisplatin metabolites to reduce the drug’s side effects. In one study conducted by Oregon Health & Science University, STS reduced the need for hearing aids to treat high-frequency hearing loss to 5% from 50%.

Phase III trials in children with hepatoblastoma, a type of liver cancer, are enrolling in Europe, and a pivotal study of children with five different cancers is getting underway in the U.S. Adherex also plans a Phase III trial in adults with head and neck cancer, said CEO William P. Peters.

Since hearing loss makes speech and learning difficult, children are hit especially hard by cisplatin’s side effects. Another company trying to help them is privately held Quark Pharmaceuticals Inc., which has raised over $70 million from Tako Ventures, and others. The Fremont, Calif., concern develops RNA-interference drugs that quell disease genes.

One of its experimental medicines, AHLi-11, temporarily silences p53, which causes cell death in the inner ear following cisplatin treatment. The company is preparing to test AHLi-11 in a trial of 70 children receiving high doses of cisplatin, said Gavin B. Samuels, senior vice president, business development.

Hearing loss itself isn’t the only opportunity. Swiss start-up Auris Medical AG aims to relieve a symptom of lost hearing: tinnitus, a persistent ring, roar or hiss in the ear. Over 50 million in the U.S. are affected, 12 million of them enough to seek medical attention, according to the American Tinnitus Association.

No drugs are approved for tinnitus, though a few therapies cleared for other uses may help, including some antihistamine, anticonvulsant and anti-anxiety medications.

Auris aims to quiet tinnitus by blocking a receptor in the inner ear called NMDA, said Managing Director Thomas Meyer. In particular, its therapy may help acute-stage patients — those with tinnitus for less than three months — whose condition originates in the periphery of the ear. Auris ran its initial human trial in 24 German subjects, but may conduct the next one in the U.S., depending on results of talks with the Food and Drug Administration.

Interest in this potential remedy is far-reaching. “I’m receiving emails every week from Argentina, U.S., Hong Kong, it’s incredible,” Meyer said. “It’s clear confirmation there is demand.”

In February Auris rounded up a CHF11 million Series B ($10.9 million) led by AGF Private Equity. The round will enable it to run Phase IIb studies for this therapy, called AM-101, and to test another drug, AM-111, in a 200-person Phase IIb trial for the treatment of acute noise-induced hearing loss, Meyer said. AM-111 works by blocking an intracellular peptide in the inner ear called JNK, he said.

While the military is a natural audience for Auris and others, civilians are of course the larger opportunity. Small companies could begin reaching them by marketing to doctors who concentrate on ear, nose and throat conditions, just as ophthalmology upstarts have targeted retinal physicians. To expand beyond the specialists, they will likely need help from a corporate partner, but big drug companies have proceeded cautiously, said Sound Pharma’s Kil.

The lead product Sound Pharma is developing was originally tested as a stroke treatment in Japan. That didn’t pan out, but Kil and others saw its potential to treat hearing loss by protecting auditory hair cells. After much work, Sound Pharma showed that SPI-1005 is safe in a Phase I study of 32 subjects completed in late 2006.

Now, it is close to finding out if the compound can help people who have lost their hearing. Getting this far has not been easy. “It’s been almost six years from idea to a Phase II,” Kil said. “Once Sound shows some positive Phase II data, the tide will turn.”

USPTO issues Notice of Allowance for Novel Patent on Hair Cell Regeneration in the Inner Ear. 

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SEATTLE, WA—Sound Pharmaceuticals, Inc. (SPI) announced that its patent “Stimulation of cellular differentiation and regeneration in the inner ear” has received a notice of allowance from the United States Patent and Trademark Office.

SPI is developing antisense oligonucleotides, RNAi duplexes, and expressed shRNA modalities to antagonize p27Kip1 at the mRNA level. Normally, p27Kip1 functions at the level of the nucleus by binding and thus inhibiting certain proliferation inducing Cyclin/CDK complexes.

Recent publications from researchers at both the House Ear Institute in Los Angeles (White et al., Nature 2006) and the Kresge Hearing Research Institute in Michigan (Kanzaki et al., Hearing Research 2006) continue to validate the importance of p27Kip1 in proliferative regeneration of the cochlea as previously described (Lowenheim et al., PNAS 1999).

“Sound Pharmaceuticals is developing a unique approach towards cellular regeneration in the cochlea by focusing on cell cycle control. This allows new cell production to occur locally with reduced potential for side effects” says Jonathan Kil, MD, President & CEO. This patent protected methodology will enter pre-clinical toxicology in the next year.

Sound Pharmaceuticals, is a drug development company focused on developing drugs to treat hearing loss and brain injury. For more information please visit http://www.soundpharmaceuticals.com

CONTACT: Dr. Jonathan Kil, President & CEO, Sound Pharmaceuticals, Inc., 4010 Stone Way N Suite 120, Seattle WA 98103, jkil@soundpharmaceuticals.com, 206-634-2559.

New Drug for Hearing Loss Enters Clinical Testing

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New Drug for Hearing Loss Enters Clinical Testing June 12th, 2006 – Seattle, WA Sound Pharmaceuticals initiates clinical testing of SPI-1005 for the prevention and treatment of noise induced hearing loss. Sound Pharmaceuticals has started a 32 patient Phase 1 study of SPI-1005 in normal healthy volunteers. SPI-1005 is an oral capsule, and contains as its active ingredient a selenium based small molecule mimic of the enzyme glutathione peroxidase. In multiple preclinical studies, low oral doses of SPI-1005 have been shown to be effective in preventing and treating noise induced hearing loss. “These animal studies have been replicated by three independent labs, all demonstrating that the active ingredient in SPI-1005 is effective in reducing both the temporary and permanent hearing loss associated with exposure to loud noise,” said VP and Director of Research, Eric Lynch, PhD. “This dose escalation safety study will lay the ground work for our Phase 2 safety and efficacy trials with the US Army and Navy later this year,” stated VP and Director of Clinical Operations, Bret MacPherson. The goal of the current study is to comfirm the known adsorption, distribution, metabolism, excretion and pharmacokinetic profile and to determine the safety of SPI-1005 at high doses. According to OSHA and the CDC, 30-40 million Americans are exposed to hazardous sound levels on a daily basis. Combined with a burgeoning population of war veterans and the dangerous listening habits of the MP3 generation, the societal costs for hearing devices and compensation awards have soared into the billions. There are currently no drugs for the prevention and treatment of hearing loss despite the vast and increasing need. Sound Pharmaceuticals hopes to address this need with its first in class first in indication drug, SPI-1005. Sound Pharmaceuticals, Inc., is a privately held biopharmaceutical company with a focus on developing the first drugs for hearing loss and brain injury. For more information please contact Jonathan Kil, MD, President and CEO 206-634-2559. Website: http://soundpharmaceuticals.com/