AnGes : Notice on the Filing of an Application for Manufacturing and Marketing Approval of Zokinvy for the Treatment of Premature Aging Syndrome

May 12, 2023

Company Name: AnGes Inc.

Presentative: Ei Yamada, President & CEO

Notice on the Filing of an Application for Manufacturing and Marketing Approval of

Zokinvy for the Treatment of Premature Aging Syndrome

AnGes announced that it filed an application with the Japanese Ministry of Health, Labour and Welfare for manufacturing and marketing approval of Zokinvy (lonafarnib) for the treatment of Hutchinson-Gilford-Progeria syndrome, a form of infant premature aging syndrome and processing- deficient progeroid laminopathies.

Eiger BioPharmaceuticals Inc. (Headquarters: California, USA; President: David Corey; hereinafter referred to as "Eiger") received approval and began marketing Zokinvy in the U.S. in November 2020.

In May 2022, we entered into an exclusive distribution agreement with Eiger for Zokinvy in Japan, and in March 2023, the Ministry of Health, Labour and Welfare granted orphan drug status to the drug.

For more information on Zokinvy please see the attached document.

Although this matter will have a negligible impact on the consolidated earnings forecast for the fiscal year ending December 31, 2023, we believe that it will contribute to the improvement of our mid- to long-term business performance. We plan to promptly announce any further events that should be disclosed in the future.

(Note)This document has been translated from the Japanese original for reference purposes only.

In the event of any discrepancy between this translation and the Japanese original, the original shall prevail.

About Zokinvy

Eiger received approval and began marketing Zokinvy(lonafarnib), for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS) and processing-deficient progeroid laminopathies (PL) in the U.S. in November 2020 by the U.S. Food and Drug Administration (FDA), and approved by the European Union in July 2022, and by the United Kingdom in August 2022 .

Zokinvy inhibits the accumulation of farnesylated mutant proteins that impair nuclear membrane structure and function (inducing nuclear instability and premature aging) in children and young adults with HGPS and processing-deficient PL. Zokinvy is a first-in-class (Note 1) disease modifier that has been studied for its efficacy in HGPS and processing-deficient PL in children and young adults.

Results showed that in patients with HGPS, Zokinvy reduced mortality by 60% (p=0.0064) and prolonged mean survival by 2.5 years (p<0.0001). Many patients continued Zokinvy treatment for more than 10 years, with the most commonly reported side effects being gastrointestinal (vomiting, diarrhea, nausea), most of which were mild or moderate (grade 1 or 2).

We estimate that the number of patients expected to use Zokinvy in Japan is only a few.

About HGPS and PL

Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathy (PL) are each a very rare and lethal genetic premature aging disease with an accelerated mortality rate from a young age. HGPS is caused by a point mutation in the LMNA gene that produces a farnesylated (Note 2) mutant protein, progerin. PL is caused by mutations in the LMNA and ZMPSTE24 genes, which produce a farnesylated protein similar to progerin and accelerate aging. Both forms of the disease cause premature aging symptoms such as severe growth retardation, scleroderma-like skin, generalized lipodystrophy, alopecia, joint contractures, skeletal dysplasia, accelerated atherosclerosis, and death at a young age due to atherosclerotic disease (myocardial infarction or stroke), and the average age of HGPS is reported to be 14.5 years. The average life expectancy of HGPS is reported to be 14.5 years.

AnGes Initiatives

On May 10, 2022, we entered into an exclusive distribution agreement with Eiger for Zokinvy (lonafarnib) for the treatment of HGPS and PL indications in Japan. In March 2023, Zokinvy was designated as an Orphan Drug (Note 3) by the Ministry of Health, Labour and Welfare.

Our business objective is to contribute to the improvement of people's lives and the standard of medical care through the development of innovative drugs for diseases for which there is no cure, intractable diseases, and rare diseases, etc. To this end, we aim to deliver innovative, internationally accepted drugs to patients as quickly as possible, and this application for manufacturing and marketing approval of Zokinvy is also in line with this objective.

We have contracted to screen newborns for rare genetic disorders at the the AnGes Clinical Research Laboratory (ACRL), a health laboratory opened in 2021, and are preparing to offer genetic

(Note)This document has been translated from the Japanese original for reference purposes only.

In the event of any discrepancy between this translation and the Japanese original, the original shall prevail.

testing to determine if they are HGPS and PL in addition. The Company will also consider new indications for Zokinvy, which is expected to benefit from its mechanism of action of inhibiting the accumulation of farnesylated mutant proteins.

(Note 1)

First-in-class: An original drug that is highly novel and useful, differs from conventional drugs in its chemical structure from the basic framework, and significantly changes the conventional therapeutic system.

(Note 2)

Farnesylation: A type of modification performed on proteins. Farnesylation enzymes attach hydrophobic prenyl groups to the ends of proteins. The hydrophobic end of the protein inserts its hydrophobic portion into the plasma membrane, thus anchoring the protein to the inner membrane of the cell or nuclear membrane. This means that the farnesylated protein can exist unmetabolized on the cell or nucleus.

(Note 3)

Orphan Drug: Orphan drugs are designated on the condition that the number of eligible patients in Japan is less than 50,000 and that there is a particular medical need for the drug as a means of treating a serious disease. Once a drug is designated as an Orphan Drug, it receives priority review and other benefits and support measures, such as a 10-yearre-examination period if the drug is approved for the designated indication.

(Note)This document has been translated from the Japanese original for reference purposes only.

In the event of any discrepancy between this translation and the Japanese original, the original shall prevail.