Alcyone Presents Preclinical Data on Gene Therapy Programs with the Center for Gene Therapy at the Abigail Wexner Research Institute (AWRI) at ASGCT 2022

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May 18, 2022, 08:00 ET

– X-reactivation gene therapy is safe and well-tolerated in Rett syndrome mouse model –

– Preclinical safety and efficacy data presented on ACTX-401, a gene replacement therapy for the treatment of IGHMBP2-related disorders, validates current Phase 1/2 study –

– Data validate productivity for AAV9 gene therapy manufacturing through platform upstream process –

LOWELL, Mass., May 18, 2022 /PRNewswire/ -- Alcyone Therapeutics Inc. ("Alcyone"), a biotechnology company pioneering next-generation precision gene-based therapies for complex neurological conditions, today presents preclinical data showing the Company's partnered novel adeno associated virus serotype 9 (AAV9) gene therapy vector ACTX-101 safely and effectively reactivates the inactive X chromosome in a Rett syndrome mouse model and is safe in a preliminary nonhuman primate study at the American Society of Gene & Cell Therapy (ASGCT) 25th Annual Meeting.

Alcyone also presented data from its partnered gene therapy program for ACTX-401, a gene replacement therapy currently in a Phase 1/2 clinical study for the treatment of IGHMBP2-related disorders (IRDs), and on the Company's internal AAV manufacturing process and platform.

"X-reactivation is a novel gene therapy approach to correcting mutations in X-linked dominant disorders such as Rett syndrome," said Ottavio Vitolo, M.D., M.M.Sc., Chief Medical Officer and Global Head of R&D at Alcyone. "The Rett mouse model preclinical data produced thus far by Dr. Kathrin Meyer's lab at the Abigail Wexner Research Institute at Nationwide Children's Hospital and by Dr. Sanchita Bhatnagar, formerly with the University of Virginia, currently at the University of California Davis School of Medicine, demonstrate that activation of the silenced X chromosome has the potential to be a safe and effective approach, which mitigates the risk of MECP2 overexpression typical of gene replacement therapies."

"Based on our growing body of preclinical data, we are pioneering a vectorized therapeutic X-reactivation platform that has the potential for clinical application to address Rett syndrome and other X-linked dominant disorders," said PJ Anand, Chief Executive Officer of Alcyone. "Alcyone's differentiated gene therapy combines the X-reactivation platform with Falcon^TM, our proprietary intrathecal CNS precision drug delivery and dosing technology platform, to optimally address the current challenges of treating people living with severe neurological disorders."

Highlights from Alcyone's 2022 ASGCT Presentations

Rett Syndrome

Oral presentation, A Novel Gene Therapy for Rett Syndrome through Reactivation of the Silent X Chromosome:

ACTX-101 is a novel, vectorized gene therapy approach to X-reactivation for the treatment of Rett syndrome.
Data from a mouse model of Rett and preliminary nonhuman primate data suggest that the X-reactivation gene therapy is safe, efficacious, and well-tolerated.
Administration of the X-reactivation gene therapy improved MeCp2 expression and respiratory patterns, behavioral indicators of Rett syndrome, bodyweight, and survival time in a severe Rett syndrome mouse model.

This abstract received the Excellence in Research Award in recognition as one of the top 18 abstracts submitted to the ASGCT 25th Annual Meeting by a postdoctoral fellow or student.

SMARD1/CMT2S

Oral presentation, Multicenter AAV Gene Therapy Studies for SMARD1/CMT2S Establishes Safety and Efficacy in Multiple Animal Models and poster presentation, Evaluation of AAV9 Gene Therapy for SMARD1/CMT2S in Different Mouse Models Reveal Differences in Efficacy Dependent on Promoter Choice:

ACTX-401 is a gene replacement therapy for the treatment of IGHMBP2-related disorders (IRDs) including SMARD1/CMT2S.
Data from mouse models of IRDs and preliminary nonhuman primate data suggested that the gene replacement therapy is safe and well-tolerated.
Administration of the gene replacement therapy improved behavioral and physiological indicators of IRDs and weight gain in a dose-dependent manner in three mouse models of the disease.
Construct testing on multiple model systems helped identify the optimal gene therapy vector and establish dose-rationale critical in the development of clinical trials for SMARD1/CMT2S.
The safety and efficacy data led to the successful approval of an investigational new drug (IND) application.
The gene replacement therapy clinical Phase 1/2 study is actively enrolling patients and has been well-tolerated to date.

Manufacturing

Poster presentation, Development of an Upstream Process and Analytics for AAV Manufacturing:

Development and optimization for dosing (vg) and potency assays are critical to ensure optimal process development and continued robustness of process and critical quality attributes (CQA).
Development and optimization of an upstream process is critical and must meet the criteria for productivity and scalability with a line of sight to regulatory and economic challenges for commercialization.
We have developed an upstream process that is flexible, versatile, and scalable with continuous process improvements for productivity.
Optimization of chemistry manufacturing and controls (CMC) can accelerate a therapeutic candidate through the regulatory process and to the clinic.

About Alcyone Therapeutics
Alcyone Therapeutics is a biotechnology company pioneering next-generation precision gene-based therapies for complex neurological conditions. The company integrates innovation in neuroscience, precision dosing platforms, and manufacturing capabilities to deliver transformative therapies to patients. Alcyone leverages the synergy between Falcon^TM, the company's proprietary intrathecal precision dosing and biodistribution platform that incorporates deep knowledge of cerebral spinal fluid (CSF) dynamics, computational modeling, and bioengineering, and four novel gene-based therapeutics platforms developed at the Abigail Wexner Research Institute at Nationwide Children's Hospital (AWRI). This comprehensive approach allows for the optimization of central nervous system (CNS) dosing and delivery to better target the pathophysiology and anatomy specific to various neurological diseases. Alcyone's lead programs utilize X chromosome reactivation for X-linked disorders and targets the treatment of Rett syndrome, and gene replacement for the treatment of IGHMBP2-related disorders including spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot Marie Tooth disease type 2S (CMT2S). For more information, visit www.alcyonetx.com.

About Alcyone's Strategic Collaboration with the Abigail Wexner Research Institute at Nationwide Children's Hospital
Alcyone works closely with scientists from the Center for Gene Therapy at the Abigail Wexner Research Institute at Nationwide Children's Hospital (AWRI) in Columbus, Ohio, where four discrete gene therapy platform technologies, each with novel and differentiated mechanisms of action, including X-reactivation, conventional transgene replacement, vectorized exon skipping and promoter modulation are designed, developed, and advanced towards the clinic. Through the collaboration with AWRI, Alcyone is exploring the potential for the clinical application of these therapeutics using Falcon^TM, its proprietary CNS precision drug delivery and dosing technology platform, to improve the lives of people impacted by severe neurological conditions. The research is led by Kathrin Meyer, Ph.D., and Nicolas Wein, Ph.D., Principal Investigators in the Center for Gene Therapy at AWRI. Both Dr. Meyer and Dr. Wein are members of Alcyone's Scientific Advisory Board (SAB), with Dr. Meyer serving as Chief Scientific Advisor and Chair of Alcyone's SAB.

SOURCE Alcyone Therapeutics