Astellas Announces FDA Update on the FORTIS Clinical Trial of AT845 in Adults with Late-Onset Pompe Disease

Press Release
Astellas Announces FDA Update on the FORTIS Clinical
Trial of AT845 in Adults with Late-Onset Pompe Disease
TOKYO, June 27, 2022 - Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji
Yasukawa, Ph.D., “Astellas”) announced that the US Food and Drug Administration (FDA) has
placed a clinical hold on the FORTIS Ph1/2 trial following the occurrence of a serious adverse
event (SAE) of peripheral sensory neuropathy in one of the trial participants. FORTIS is a
clinical trial evaluating AT845, an investigational adeno-associated virus (AAV) gene
replacement therapy in adults with Late-Onset Pompe Disease.

The FDA informed Astellas that it did not have sufficient information to assess the risks to
subjects and requires additional information about the recently reported SAE. To date, the
SAE has been classified by the site investigator as Grade 1 (mild in severity) and deemed
serious due to medical significance. A written explanation for the basis of the hold will be
issued by the FDA and sent to Astellas within the next 30 days.

Astellas is working with the site investigator to closely follow the patient's clinical course and
will continue to gather and review all relevant data. All currently enrolled participants will
continue to be monitored closely per the study protocol.

“Patient safety is our top priority, and we are working closely with the FDA to determine
appropriate next steps,” explained Weston Miller, M.D., Senior Medical Director, Clinical
Development at Astellas Gene Therapies. “We remain committed to the safe and effective
development of AT845 and will keep the scientific and patient communities informed with
updates as we learn more.”

Astellas is focused on developing genetic medicines and working alongside its world-
renowned partners to build a portfolio of potentially life-changing gene therapies. Astellas
strives to identify, develop and deliver therapies for patients with genetic diseases who
currently have few or no effective treatment options.

Astellas is reviewing potential financial impacts of this matter for the fiscal year ending March
31, 2023.

About Pompe Disease
Pompe disease is a rare, severe, autosomal recessive metabolic disease characterized by progressive muscular
degeneration. The overall incidence is estimated to be approximately 1 in 40,000 births 1, although frequency and
disease progression varies with age of onset, ethnicity and geography.2 The disease is caused by mutations in the
alpha-glucosidase (GAA) gene that prevent the production and function of a protein called acid alpha-glucosidase
(GAA). GAA is responsible for metabolizing glycogen, and dysfunction or absence of this protein results in the
accumulation of glycogen in tissues, primarily in the skeletal and cardiac muscles, where it causes damage to
tissue structure and function. Currently, the only approved treatment for Pompe is enzyme replacement therapy
(ERT), which is a chronic treatment delivered in bi-weekly infusions and relies solely on tissue uptake of GAA from
plasma.


About AT845 for the treatment of Late-Onset Pompe Disease (LOPD)
Astellas is developing AT845, a novel gene replacement therapy using an AAV8 vector under a muscle-specific
promotor to deliver a functional copy of the GAA gene, for the treatment of LOPD. AT845 is being investigated to

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determine whether it can deliver a functional GAA gene that is efficiently transduced to express GAA directly in
tissues affected by the disease, including skeletal and cardiac muscle.

About FORTIS
FORTIS (NCT04174105) is a multicenter, open-label, ascending dose Phase I/II first-in-human clinical trial to
determine if AT845 is safe and tolerable in adults with LOPD. The primary endpoints of the trial are safety and
tolerability, as well as efficacy measures, including change in muscle GAA protein expression and enzyme activity
from baseline. Secondary endpoints evaluate improvements in respiratory, endurance and quality of life measures.

About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the
world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous
creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality.
Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that
combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through
these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for
patients. For more information, please visit our website at https://www.astellas.com/en.

About Astellas Gene Therapies
Astellas Gene Therapies is an Astellas Center of Excellence developing genetic medicines with the potential to
deliver transformative value for patients. Based on an innovative scientific approach and industry leading internal
manufacturing capability and expertise, we are currently exploring three gene therapy modalities: gene
replacement, exon skipping gene therapy, and vectorized RNA knockdown and will also advance additional
Astellas gene therapy programs toward clinical investigation. We are based in San Francisco, with manufacturing
and laboratory facilities in South San Francisco and Sanford, N.C.

Cautionary Notes
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other
statements that are not historical facts are forward-looking statements about the future performance of Astellas.
These statements are based on management’s current assumptions and beliefs in light of the information currently
available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual
results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not
limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical
markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to
market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and
develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’
intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development) which is included in this
press release is not intended to constitute an advertisement or medical advice.

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Contacts for inquiries or additional information:
Astellas Portfolio Communications
Cassie Hogenkamp
+1-847-942-0980
cassie.hogenkamp@astellas.com

Astellas Pharma Inc.
Corporate Advocacy & Relations
+81-3-3244-3201

References
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1 Kishnani, PS, et al. Pompe disease diagnosis and management guideline. Genetics in medicine: official journal of
the American College of Medical Genetics, 2006. Available from:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110959/

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Ausems MG, et al. Frequency of glycogen storage disease type II in The Netherlands: implications for diagnosis
and genetic counselling. European Journal of Human Genetics, 1999. Available from:
https://www.nature.com/articles/5200367.pdf?origin=ppub; Lin CY, et al. Pompe's disease in Chinese and prenatal
diagnosis by determination of alpha-glucosidase activity. Journal of Inherited Metabolic Disease, 1987. Available
from: https://pubmed.ncbi.nlm.nih.gov/3106710/; Hirschhorn R, et al. Pediatric Research, 2004; Bashan N, et al.
Glycogen storage disease type II in Israel. Israel Journal of Medical Sciences, 1988. Available from:
https://europepmc.org/article/med/3132435; Meikle PJ, et al. Prevalence of Lysosomal Storage Disorders. JAMA,
1999. Available from: https://jamanetwork.com/journals/jama/article-abstract/188380