Akouos presents non-clinical data demonstrating the potential applicability of the precision genetic medicine platform for a wide range of inner ear conditions at the Association for Oto Research’s 45th Annual Mid-Winter Meeting -rhino-laryngology

– Data from two nonclinical studies evaluating protein expression and tolerability support future clinical development of AK-antiVEGF for the treatment of vestibular schwannoma

– AAVAnc80 and a supportive cell-selective promoter can lead to widespread spread GJB2 expression in supporting cells, while limiting hair cell expression and loss in mice

– AAV-mediated RNAi gene silencing and CRISPR/Cas9 gene editing methods demonstrate promising reduction in expression of proteins of interest, extending the capabilities of Akouos’ Genetic Medicine Platform

BOSTON, 07 Feb. 10, 2022 (GLOBE NEWSWIRE) — Akouos, Inc. (NASDAQ: AKUS), a precision genetic medicine company dedicated to developing potential gene therapies for people living with disabling hearing loss around the world, has presented undisclosed data. clinics at the Association for Research in Otorhinolaryngology (ARO) 45and Annual mid-winter meeting that supports the future development of gene therapies targeting inner ear conditions. The company shared the data in two podium presentations and a poster.

“We are pleased to present these data, which further demonstrate the potential of our precision genetic medicine platform comprised of proprietary ancestral adeno-associated viral (AAV) vectors, a novel delivery approach and multiple vector-mediated modalities. to treat a wide range of inner ear disorders. conditions, including those that are monogenic and of complex etiology,” said Manny Simons, Ph.D., Founder, President and CEO of Akouos. “As we progress towards planned IND submissions for AK-OTOF in the first half of 2022 and AK-antiVEGF in 2022, we also continue to advance the preclinical development of 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.

Demonstration of expression levels of secreted proteins after intracochlear administration of AK-antiVEGF (AAVAnc80-antiVEGF vector) at multiple doses in non-human primates
Speaker: Michelle D. Valero, Ph.D.
Podium session: 11

AK-antiVEGF is a gene therapy candidate in preclinical development for the potential treatment of patients with vestibular schwannoma (VS). Published data from previous clinical trials of systemic VEGF inhibitor treatment show reduction in VS tumor volume and improved hearing in some participants with VS due to mutations in the NF2 uncomfortable. However, the associated toxicity may limit long-term systemic administration of VEGF inhibitors as a viable treatment option for VS. Local expression of anti-VEGF protein after intracochlear administration of AK-antiVEGF is robust and well tolerated in non-human primates (NHPs), an anatomically relevant model for assessing delivery parameters. Data from two non-clinical studies evaluating multiple doses demonstrate that systemic exposure to anti-VEGF protein is limited. Computational modeling supports the potential for diffusion of reported biologically active anti-VEGF protein levels at the typical location of early VS tumors. Together, these data support the future clinical development of AK-antiVEGF for the potential treatment of SV.

The digital presentation can be found at https://akouos.com/gene-therapy-resources/.

Adapting regulatory elements in gene therapies for hearing loss
Speaker: Danielle R. Lenz, Ph.D.
Podium session: 11

Ubiquitous promoters can drive safe expression of several transgenes and are used in commercially approved and development-stage gene therapies. In mice and NHPs, AAVAnc80-hOTOF with a ubiquitous promoter enabled robust and well-tolerated expression of hOTOF.FLAG. However, depending on the gene of interest, tailored regulation of the expression pattern may be preferred. The inclusion of a selective promoter was evaluated in the case of GJB2, where expression in hair cells is not well tolerated. Akouos has developed a method to guide the customization of regulatory elements based on bioinformatics efforts; regulatory elements to drive various differential expression patterns have been identified and cell-selective promoters have been evaluated in mice in vivo. Non-clinical data demonstrate that a combination of AAVAnc80 and a supportive cell-selective promoter can result in widespread spread GJB2 expression in supporting cells, while limiting hair cell expression and loss in mature cochlea in wild-type mice. Future work will include customization of regulatory elements where this can be beneficial.

The digital presentation can be found at https://akouos.com/gene-therapy-resources/.

In vitro characterization of gene silencing methods with the potential to treat autosomal dominant hearing loss
Speaker: Katherine D. Gribble, Ph.D.
Poster number: 574

The development of AAV vectors as an intra-cochlear drug delivery platform presents a unique opportunity to treat genetic forms of hearing loss, including autosomal dominant hearing loss (ADHL), by developing precision-designed drugs selectively to target affected genes. To treat the affected genes, one approach based on genetic medicine is to reduce the expression levels of both alleles and simultaneously deliver a functional copy of the gene. AAV vector-mediated biallelic RNAi gene silencing and CRISPR/Cas9 biallelic gene editing were assessed, with the simultaneous addition of a functional copy of the gene of interest. Modified microRNA constructs and CRISPR/Cas9 constructs were evaluated for their efficacy in knocking down the target gene. With the microRNA and CRISPR/Cas9 constructs, a promising reduction in protein expression for the target ADHL gene was observed. The data show no measurable decrease in the protein product of a codon-altered add-back target gene, suggesting that the microRNA and CRISPR/Cas9 constructs are selective for the predicted endogenous sequence. The findings reinforce fundamental platform capabilities that can be used to develop potential AAV vector-mediated therapies for many types of ADHL and other inner ear conditions.

The digital poster can be found at https://akouos.com/gene-therapy-resources/.

About Akouos
Akouos is a precision genetic medicine company dedicated to developing gene therapies with the potential to restore, improve and preserve high-acuity physiological hearing for people living with disabling hearing loss worldwide. Leveraging its precision genetic medicine platform that incorporates a proprietary adeno-associated viral (AAV) vector library and novel delivery approach, Akouos is focused on developing precision therapies for forms of sensorineural hearing loss. Boston-based Akouos was founded in 2016 by leaders in the fields of neurotology, genetics, inner ear drug delivery and AAV gene therapy.

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