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Akouos Inc. raised $50 million in a tranched series A financing co-led by 5AM Ventures and New Enterprise Associates (NEA), which first committed to the newly formed gene therapy firm in a $7.6 million seed round in November 2017. Existing seed investor Partners Innovation Fund and new investors Sofinnova Ventures, RA Capital Management and Novartis Venture Fund joined the series A.

Boston-based Akouos is developing targeted adeno-associated viral vector (AAV)-based gene therapies for sensorineural hearing loss, which results from dysfunction or damage to sensory cells and/or nerve fibers of the inner ear. The condition – the most common form of hearing loss and one of the most common sensory disorders – mostly occurs at either end of the lifespan, affecting newborns as well as adults over the age of 65 and has no FDA-approved therapies. Akouos initially is focused on monogenic forms of sensorineural hearing loss, in which mutations in individual genes lead to profound deafness – a strategy that resonated with the seed investors and attracted others to the syndicate, according to Manny Simons, co-founder and CEO.

"We've taken a very focused approach in bringing what we believe is the first precision genetics medicine approach to hearing loss," Simons told BioWorld MedTech. "We're focusing on forms of hearing loss that are well characterized and genetically driven where the etiology is clear."

That tactic differentiates Akouos from other contenders in the somewhat unwieldy hearing loss space that are working on "more complex, heterogeneous" indications whose pathophysiology is not well understood, Simons pointed out.

Within its targeted forms of hearing loss, Akouos – the company's name derives from the Greek word for acoustics – will focus on "making sure that we can deliver healthy copies of genes to the right target cells in the ear to maximize the impact on affected patients," Simons explained. The effort to provide one-time administration of gene therapy to treat hearing loss encompasses both the surgical procedure as well as the identification of suitable vectors "that allow access to the right target cells of the inner ear," he said.

Proceeds from the series A, which included $25 million in the initial tranche and the remainder on the occurrence of milestones that Simons declined to disclose, will allow it to advance its lead program to first-in-human studies and to accelerate the development of multiple pipeline programs addressing other forms of sensorineural hearing loss with validated mechanisms and gene targets. The proposed development timetable includes initial interactions with the FDA in the next 12 months and an IND filing in the next two to three years.

'Dozens of cell types within the inner ear'

The initial gene therapy candidate is derived from the ancestral AAV (Anc-AAV) gene therapy platform exclusively licensed by Akouos in November 2017 from Lonza Group Ltd., of Basel, Switzerland, and the Massachusetts Eye and Ear (MEE) to treat hearing and balance disorders. The Anc80 gene therapy vector is the lead Anc-AAV in a portfolio of nearly 40,000 capsids.

Anc-AAVs are in silico-designed AAVs first developed in the laboratory of Luk Vandenberghe, assistant professor at Harvard Medical School and director of the Grousbeck Gene Therapy Center at MEE, who co-founded Akouos and chairs the company's scientific advisory board. Vandenberghe's laboratory published the first work describing Anc-AAV technology, using computational and evolutionary methods to predict novel conformations of the AAV particle. The approach yielded Anc80, a putative ancestor of AAV1, 2, 3, 6, 7, 8, rh.10 and AAV9, subsequently shown in preclinical mice and non-human primates to be a safe and potent therapeutic gene delivery vector. The researchers also showed that Anc80 targeted auditory hair cells in an efficient manner that could lead to functional correction of hearing loss in mice.

Vandenberghe is a listed inventor on Anc-AAV intellectual property initially licensed to Lonza and Akouos, according to Cortellis Competitive Intelligence.

Last year, when the technology was in-licensed by Akouos, the companies said the agreement was designed to accelerate the AAV gene therapy, built around the existing Anc-AAV partnership between MEE and Lonza, by giving Akouos the berth to marshal experts and resources in auditory science R&D, clinical research and AAV manufacturing.

Simons was engaged in the hearing research space for more than two decades and had known co-founders Michael McKenna and William Sewell for more than 15 years. Two years ago, Simons said, the three began to talk about tackling "unsolved problems" in the hearing loss space and assembling a team well-positioned to achieve those goals.

Simons previously held leadership roles in business and corporate development at Voyager Therapeutics Inc. and Warp Drive Bio LLC. Earlier in his career, as an entrepreneurial fellow at Flagship Ventures, he was a member of the founding team of Seres Therapeutics Inc. McKenna, newly named chief medical officer, is chair and director of the division of otology and neurotology at MEE and professor of otolaryngology at Harvard Medical School. McKenna, whose lab focuses on the molecular pathophysiology of otosclerosis, and colleagues were the first to show an association between the COL1A1 gene and clinical otosclerosis. Sewell, who sits on the scientific advisory board, is professor of otolaryngology at MEE and Harvard Med, where his research focuses on the identification and characterization of neurotransmitters and their receptors in the cochlea.

Co-founder Richard Smith is founding director of the Iowa Institute of Human Genetics and the Molecular Otolaryngology and Renal Research Laboratories (MORL) at the University of Iowa, where he also serves as professor of otolaryngology, pediatrics, medicine and molecular physiology and biophysics. Smith and collaborators at the MORL have mapped and/or cloned about one-fifth of the genes implicated in non-syndromic hearing loss.

The establishment of Akouos represented validation of the scientific discoveries by the founding team, which has decades of experience in the hearing loss field, Simons said.

As to the push toward the clinic, "the specifics will become clear" after the company meets with regulators, but "there is an opportunity for the first program to be in a pediatric population," he added. "In many of these forms of hearing loss, the greatest benefit is when children are treated earlier."

Moreover, "there's now precedent for gene therapy in pediatric populations for a wide range of disorders," Simons noted, alluding to last year's approval of Luxturna (Spark Therapeutics Inc., voretigene neparvovec-rzyl), the gene therapy to treat RPE65 mutation-associated retinal dystrophy.

Tellingly, Jennifer Wellman, who joined Akouos as senior vice president of regulatory, was a co-founder of Spark, where she led the regulatory strategy for Luxturna from pre-IND through BLA acceptance.

Although the technology from MEE and Lonza will serve as the foundation for the company's initial program, "we will be active in licensing, as well," Simons insisted. "There are dozens of cell types within the inner ear, and we expect that there will be different vectors and different technologies that will be employed to access the different target cells for future indications."

Potential applications encompass a range of monogenic and acquired hearing disorders. Researchers have detected more than 150 forms of genetically defined hearing loss, and additional genes continue to be implicated.

The decision to remain opportunistic underlies the desire by co-founders to build "a long-term, independent, integrated biotechnology company," Simons confirmed. Although Akouos will seek broad academic and industry collaborations to advance the science of hearing loss, "we don't see that as an exit strategy but as an opportunity to build more value and reach more patients," he said.

In conjunction with the series A, Arthur Tzianabos, president and CEO of Homology Medicines, and Christopher Smith, former CEO of Cochlear Ltd. were named as independent directors on the Akouos board, joining Simons, Kush Parmar, managing partner at 5AM Ventures, and Ed Mathers, NEA partner.

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