PPIF

SEATTLE--( BUSINESS WIRE )--Sound Pharmaceuticals is pleased to announce that the pivotal Phase 3 clinical trial involving SPI-1005, a novel anti-inflammatory compound (ebselen), for the treatment of Meniere’s Disease (STOPMD-3), achieved its co-primary endpoints for efficacy involving improvements in hearing loss and speech discrimination. Meniere’s disease (MD) is an inner ear disorder that involves fluctuating hearing loss and tinnitus, and episodic vertigo and/or dizziness. There are no FDA-approved medical treatments for MD, nor for the treatment of hearing loss, tinnitus, vertigo, or dizziness. SPI-1005 is an oral capsule containing 200 mg ebselen that has shown safety and efficacy in several Phase 2 clinical trials involving multiple hearing loss and tinnitus indications including MD. STOPMD-3 enrolled adult subjects (N=221) with a history of definite MD and active symptoms into a randomized double-blind placebo-controlled trial (RCT) in which subjects received 28 days of either SPI-1005 (400 mg twice daily) or placebo treatment with monthly follow-up assessments of auditory and vestibular function through 84 days. Compliant patients could immediately enter an open label extension (OLE) of SPI-1005 treatment for up to 12 months. During OLE, subjects continued to receive SPI-1005 and had their auditory and vestibular function reassessed every 3 months. In both the intent-to-treat and per-protocol RCT analysis, the SPI-1005 group showed higher rates of improvement in low frequency hearing loss (≥10 dB gain at one low frequency from baseline) using pure-tone audiometry (LFPTA) and speech discrimination (≥4-word increase from baseline) using the words-in-noise (WIN) test than the placebo group at day 28, 56, and 84 of follow-up. On day 84, the SPI-1005 group showed a significant rate of LFPTA improvement over placebo (57.9% vs 36.5%, an increase of 58.6% over placebo, p-value=0.0037). When LFPTA criteria were increased to require a ≥10 dB gain at two adjacent low frequencies from baseline, the SPI-1005 group showed a significant rate of improvement of 204.4% over placebo (41.1% vs 13.5%, p-value <0.0001). On day 84, the SPI-1005 group showed a significant rate of WIN improvement of 54.4% over placebo (42.1% vs. 27.1%, p=0.0336). During OLE, responder rates involving LFPTA and WIN continued to improve, and patient reported outcome measures for tinnitus, vertigo, aural fullness, and dizziness severity all improved significantly from baseline (≥30% on average, p-value <0.001). “We would like to thank all of our investigators and study participants for contributing to this pivotal Phase 3 trial success involving SPI-1005,” said Dr. Jonathan Kil, MD, CEO of Sound Pharmaceuticals. A presentation of the full RCT/OLE data analysis as well as additional post-hoc analysis will occur at the Association for Research in Otolaryngology Midwinter Meeting in Orlando FL, February 22-26. About Meniere’s Disease (MD) MD is diagnosed by episodic vertigo or dizziness, fluctuating low frequency hearing loss, and intermittent or constant tinnitus, and is thought to be due to a swelling of the inner ear involving the endolymphatic duct. Patients are typically diagnosed between 40-65 years of age, and the auditory symptoms of hearing loss and tinnitus often involve only one ear. Some patients experience aural fullness or pressure in the affected ear that can also contribute to dizziness. As patients age, the hearing loss and tinnitus become worse resulting in severe to profound hearing loss and intractable tinnitus. For the definite diagnosis of MD, the American Academy of Otolaryngology-Head & Neck Surgery guidance requires audiometric documentation of low frequency hearing loss (i.e., ≥30 dB) in at least one ear using pure tone audiometry. Loss of speech discrimination, especially in noisy environments or when tinnitus is present, is common in MD and other forms of sensorineural hearing loss. MD is currently managed with low salt diets, thiazide diuretics, and oral or locally injected steroids. Unfortunately, this standard of care has not proven effective and is not FDA-approved for the treatment of MD. About the STOPMD-3 trial STOPMD-3 screened 254 participants for eligibility at 11 sites, including some of the leading academic centers in the US. Eligible participants (221) were randomized to either SPI-1005 treatment (400 mg twice daily for 28 days) or matching placebo treatment and followed up to day 84. 201 participants continued on to SPI-1005 OLE for 1-6-months (153 completed) and 107 participants continued on to 7-12-months (82 completed). To our knowledge, STOPMD-3 is the longest continuous treatment trial involving an investigational new drug ever completed for a hearing loss or tinnitus indication including MD. STOPMD-3 was led by Dr. Paul Lambert, Distinguished University Professor and Chair Emeritus of the Dept. of Otolaryngology-HNS at MUSC in Charleston, SC, and the past President of the American Neurotologic Society. Dr. Lambert, Dr. Shaun Nguyen, director of clinical trial research in the Dept. of Otolaryngology-HNS at MUSC, and their colleagues also led the successful Phase 2b RCT involving SPI-1005 and MD patients. About SPI-1005 SPI-1005 is an investigational new drug that contains ebselen, a new chemical entity. Ebselen is a selenorganic compound that mimics and induces glutathione peroxidase (GPx) activity and is effective in reducing neuroinflammation across the central and peripheral nervous system. GPx activity is critical to several cell types and tissues in the inner ear, retina, prefrontal cortex of brain, lung, and kidney, and is often reduced during exposures to environmental insults or aging. Loss of GPx activity has been shown to result in sensorineural hearing loss in multiple animal models. SPI-1005 is being developed for several neurotologic indications including noise-induced hearing loss and two types of ototoxicity (hearing loss, tinnitus, dizziness, or vertigo) caused by aminoglycoside antibiotics (such as tobramycin or amikacin) or platinum-based chemotherapy (such as cisplatin or carboplatin). To date, no significant drug-drug interactions have been observed across multiple study populations including bipolar mania and treatment-resistant depression. About Sound Pharmaceuticals A privately-held biotechnology company is testing SPI-1005 under five other active Investigational New Drug Applications involving several neurotologic indications including the prevention and treatment of aminoglycoside-induced ototoxicity co-funded by the CF Foundation and hearing preservation in cochlear implant patients co-funded by MED-EL. Details of the SPI-1005 clinical trials can be viewed online at www.clinicaltrials.gov or www.soundpharma.com . Please contact info@soundpharma.com for further information.

STEVENAGE, United Kingdom, Feb. 22, 2023 (GLOBE NEWSWIRE) -- NRG Therapeutics, Ltd., an innovative neuroscience company targeting mitochondrial dysfunction, is pleased to announce that it has been awarded a second $500,000 grant from The Michael J. Fox Foundation for Parkinson’s Research (MJFF), to support its lead drug discovery programme and the development of a novel treatment for Parkinson’s. NRG Therapeutics is applying breakthrough science in the field of mitochondrial biology to develop first-in-class treatments for Parkinson’s. Its approach is based on inhibiting the mitochondrial permeability transition pore (mPTP) in brain cells, which has been shown to be neuroprotective in several preclinical models of Parkinson’s and other neurodegenerative diseases. Having met the goals of the grant it received from MJFF in 2021, this second grant will support experiments to validate a novel mitochondrial drug target for Parkinson’s. The work will determine whether genetic deletion of this mitochondrial protein in vitro and in vivo protects brain cells, and therefore, whether drug modulation of this protein has the potential to improve Parkinson’s symptoms. The overall goal of the programme is to develop drugs that block the opening of the mPTP, an event which is triggered by high concentrations of calcium ions, leading to the death of dopamine-producing brain cells. NRG Therapeutics’ co-founder and CEO Dr Neil Miller said, “We have made great progress with our research funded by MJFF and we are delighted to have received a second award to fund further research to validate the molecular target for our mPTP inhibitors. There is a significant unmet medical need as all current treatments for Parkinson’s control symptoms but do not halt or slow progression of disease. Truly disease-modifying treatments for Parkinson’s and other neurodegenerative diseases remain the holy grail. It is our hope that our work could lead to new treatments that could positively change the lives of individuals with neurodegenerative disorders.” Classical ‘first-generation’ inhibitors of the mPTP, such as cyclosporin A, inhibit cyclophilin D (CypD), a protein that is believed to regulate the pore. However, all historical attempts to develop CypD inhibitors that can cross the blood-brain barrier have been unsuccessful. NRG has discovered novel ‘second-generation’ mPTP inhibitors that are small drug-like molecules, orally bioavailable and brain penetrant, and therefore have the potential for use in the treatment of chronic neurodegenerative disorders. NRG’s lead assets were identified through phenotypic screening in isolated mitochondria and have been shown to act independently of CypD. “Our mission is to support development of life-changing treatments to fulfill the unmet needs of people with Parkinson’s disease, and we are pleased to provide funding for a second project with NRG toward that goal,” said Alexandra Vaiana, PhD, MJFF’s Associate Director of Research Programs. Details of the MJFF’s most recently funded programs can be found HERE. These include NRG’s funded study ‘Validation of a Novel Mitochondrial Drug Target for Parkinson’s Disease’ HERE. Media enquiries (for NRG Therapeutics) Sue Charles, Charles Consultants - +44 7968 726585 sue@charles-consultants.com About NRG Therapeutics – NRG Therapeutics is a neuroscience drug discovery company building a pipeline of disease-modifying mitochondrial therapeutics to slow or halt the progression of neurodegenerative disorders such as Parkinson’s and Amyotrophic Lateral Sclerosis (ALS), also known as motor neurone disease (MND). The company’s pre-clinical pipeline of small molecule assets is based on inhibiting the mitochondrial permeability transition pore (mPTP) through a novel mechanism of action. Inhibition of the mPTP has been shown to protect neurones, reduce neuroinflammation and extend survival in pre-clinical disease models. Based at the Stevenage Bioscience Catalyst (SBC), UK, NRG Therapeutics is a private company with equity investment from Parkinson’s UK, Omega Funds and Brandon Capital. The company has also received grant funding from The Michael J. Fox Foundation, Innovate UK (Biomedical Catalyst Award), and is the industrial partner for a FightMND Drug Discovery grant awarded to WEHI (Walter and Eliza Hall Institute of Medical Research). Follow us on Twitter and LinkedIn.

Courtesy Jason Armond/Los Angeles Times/Getty Images VBI Vaccines and Hepion Pharmaceuticals received Orphan Drug Designations from the U.S. Food and Drug Administration Friday for their experimental cancer drugs. Orphan Drug Designations are granted for drugs that show promise for treatment, prevention or diagnosis of orphan diseases, which in the U.S. is defined as affecting fewer than 200,000 people. It comes with certain incentives, including tax credits for qualified clinical trials, user fees exemption and potential seven years of market exclusivity after approval. Based in Cambridge, MA, VBI received its designation for a bivalent cytomegalovirus gB/pp65 enveloped virus-like particles (VLPs) designed to treat glioblastoma, a type of brain cancer. The company focuses on developing VLPs, leveraging a proprietary enveloped VLP (eVLP) platform technology. These are so-called cancer vaccines that act by mimicking viruses with the intention of stimulating the human immune system. Earlier this month, the company presented new tumor response and overall survival (OS) data from the ongoing Phase IIa trial of VBI-1901 in recurrent glioblastoma. It was included in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. David E. Anderson, Ph.D., chief scientific officer of VBI, said at the time, “We continue to be motivated by the data seen in this Phase IIa study of VBI-1901 as we endeavor to provide new treatment options to patients with very few available to them. Considering the high mortality rate among GBM patients, particularly in the recurrent setting, median overall survival of approximately 13-15 months seen in our two study arms suggests an additional survival benefit of nearly six months in comparison with historical control data in the recurrent population after treatment with a monotherapy.” He added, “Moreover, the correlation of tumor responses and clinical response benefit observed in tandem is very encouraging. We remain in close discussion with our study investigators and scientific advisors as we move toward the next stages of development in both the recurrent and frontline GBM settings, and look forward to advancing this development program as diligently as possible.” Hepion received the designation for rencofilstat for hepatocellular carcinoma. Rencofilstat is the company’s lead oral drug candidate for nonalcoholic steatohepatitis (NASH) and viral hepatitis-induced liver disease. The drug binds to Cyclophilin A, which blocks it from binding to specific inflammatory cell receptors. This decreases the infiltration of the inflammatory cells into the tissue and lessens harmful inflammatory responses that can cause damage to the liver. It also blocks the actions of Cycophilin B, which regulates collagen production in stellate cells, causing fibrosis (scarring) in the liver. And it binds to Cyclophilin D, preventing or reversing the formation of pores in the mitochondrial membrane that causes the mitochondria to rupture. This allows the mitochondria to resume normal energy production and helps liver cells survive. In January, Hepion, headquartered in Edison, NJ, announced the results of a nonclinical research study of rencofilstat that decreased liver tumor growth and extended mouse survival when combined with an anti-PD-1 antibody, or immune checkpoint inhibitor. The effects were seen in fatty livers, which may be associated with less ant-PD-1 efficacy in hepatocellular carcinoma (HCC). This suggests that the drug may improve the treatment potential of anti-PD-1 treatment in human liver cancer. Examples of anti-PD-1 drugs include Merck’s Keytruda (pembrolizumab) and Bristol Myers Squibb’s Opdivo (nivolumab). At the time, Daren Ure, Ph.D., Hepion’s chief scientific officer, noted, “Anti-PD-1 therapies that stimulate immune cell attack on cancer cells are approved and effective in many types of cancer, but they have had limited success in HCC clinical trials. The lack of clinical outcomes success may be partly due to the occurrence of HCC in individuals that also have non-alcoholic fatty liver disease (NAFLD) or the more advanced form of the disease, NASH." He added, "NAFLD and NASH are both highly prevalent across the globe, and recent reports indicate that a fatty liver environment blocks the efficacy of anti-PD-1 drugs, and perhaps other checkpoint inhibitors. In addition, as successful treatments for viral hepatitis have been implemented, NASH has been quickly becoming the leading cause of HCC."