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Akouos Presents Nonclinical Data Supporting the Planned Clinical Development of AK-OTOF and Strategies for Regulated Gene Expression in the Inner Ear at the American Society of Gene and Cell Therapy 25th Annual Meeting- Nonclinical data demonstrate that a single intracochlear administration of an AAVAnc80 vector led to durable restoration of auditory function and was well tolerated, supporting planned clinical development of AK-OTOF for the treatment of OTOF-mediated hearing loss - MicroRNA target site (miR-TS)-incorporation in AAV vectors is shown to have potential benefits for de-targeting transgene expression in the inner ear, supporting future BOSTON, May 19, 2022 (GLOBE NEWSWIRE) -- Akouos, Inc. (NASDAQ: AKUS), a precision genetic medicine company dedicated to developing potential gene therapies for individuals living with disabling hearing loss worldwide, presented nonclinical data at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting. The company gave two nonclinical presentations at the meeting: one that supports the planned clinical development of AK-OTOF, a gene therapy intended for the treatment of OTOF-mediated hearing loss; and another that supports the potential use of microRNA target site (miR-TS) in adeno-associated viral (AAV) vectors for regulated gene expression in the inner ear. “We are excited to present these nonclinical data, which highlight our precision genetic medicine platform and the potential of genetic medicines to address a broad range of inner ear conditions, to the gene and cell therapy community. The AK-OTOF nonclinical data demonstrate durable restoration of auditory function and show that the product candidate was systemically and locally well tolerated in two translationally relevant animal species,” said Manny Simons, Ph.D., founder, president, and chief executive officer of Akouos. “As we continue to progress toward planned IND submissions for AK-OTOF in the first half of 2022 and AK-antiVEGF in 2022, we are encouraged by the growing body of evidence supporting these filings, as well as by our efforts to advance preclinical development of other potential gene therapies for inner ear conditions, such as GJB2-mediated hearing loss, and to develop platform capabilities that can be applied to regenerative medicine approaches in the inner ear.” Nonclinical In Vivo Expression, Durability of Effect, Biodistribution/Shedding, and Safety Evaluations Support Clinical Development of AK-OTOF (AAVAnc80-hOTOF Vector) for OTOF-mediated Hearing Loss AK-OTOF is an AAV vector-based gene therapy intended for the treatment of patients with otoferlin gene (OTOF)-mediated hearing loss by delivering transgenes encoding OTOF to inner hair cells (IHCs). Following intracochlear delivery, and subsequent co-transduction of IHCs by each component vector, the two transgene products recombine to generate a full-length otoferlin mRNA transcript and subsequently a full-length otoferlin protein. Results from this presentation show:
Together, these nonclinical studies further support the planned clinical development of AK-OTOF for the treatment of OTOF-mediated hearing loss. The digital presentation is located at https://akouos.com/gene-therapy-resources/. Evaluating miR-Target Sites as a Strategy to Allow AAV Vector-based De-targeting of Gene Expression in the Inner Ear In the development of AAV gene therapy vectors, a goal is to generate safe and effective product candidates that deliver targeted transgene expression. Ubiquitous promoters can drive strong widespread expression in the inner ear in mice and NHPs. This expression can be well tolerated across the inner ear, as is the case for Akouos’s first two programs, AK-OTOF and AK-antiVEGF. Addition of selective cis-regulatory elements may be needed for some transgenes, such as GJB2, where expression in a portion of nontarget cells is not well tolerated. This nonclinical study explored the potential use of miR-TS incorporation in AAV vectors for de-targeting transgene expression in different cell types of the cochlea. Using an in vitro model, expression of transgene mRNA and protein in the presence or absence of the target sites was evaluated. Akouos identified multiple microRNA target sites to drive various differential expression patterns demonstrating that a combination of AAVAnc80 and miR-TS can drive expression in supporting cells, while limiting expression in hair cells in cochlear explants. Future work will focus on evaluating miR-TS regulation in vivo and identifying combinations of different miR-TSs to enhance de-targeting in specific cell types where, for example, expression driven by ubiquitous promoters is not well tolerated. The digital presentation is located at https://akouos.com/gene-therapy-resources/. About Akouos Forward-Looking Statements Contacts Investors: |