Genovate Announces Plans to Submit a New Drug Application for PMR to the
U.S. Food & Drug Administration in the Second Half of 2025

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TAIPEI, May 28, 2024 /PRNewswire/ — Genovate Biotechnology Co., Ltd. (TPEx: 4130), a Taiwan-based
specialty pharmaceutical company, today announced its plans to submit a New Drug Application (NDA)
with the United States Food and Drug Administration (US FDA) for PMR, an investigational once daily
extended-release form of cilostazol for the treatment of Intermittent Claudication, in the second half of
2025.In the written responses to the pre-NDA meeting package, the FDA confirmed that the clinical studies
conducted are sufficient to support the submission of a marketing application under the 505(b)(2)
regulatory pathway. The key study in the submission package, GBL23-001 (NCT06167265), is a
randomized, fully replicate crossover study designed to evaluate the bioequivalence and within-subject
variability between PMR 145 mg once daily and the immediate-release tablet of cilostazol 100 mg twice
daily. This study is expected to be completed in mid-2024, and the top-line results have shown that the
primary endpoints of the study were achieved, and the decision to submit the application was made
following the successful outcome of study GBL23-001. Furthermore, Genovate has been improving the
PMR formulation and its manufacturing processes in order to address additional FDA comments. All
clinical study and manufacturing data are expected to be included in the final submission package.

“We are pleased to share what we believe is an efficient regulatory pathway for PMR with the goal of
bringing a new treatment option to the people who suffer from intermittent claudication and recurrence
of cerebral infarction, from the US to the globe.” said Chia-Chen Chu, General Manager of Genovate.

About PMR (Cilostazol Extended-Release Tablets)
PMR, a novel extended-release (ER) formulation of cilostazol, was designed to reduce the concentration-
dependent side effects associated with immediate-release (IR) tablet form of cilostazol. Cilostazol is
currently available in IR tablet form at 50 and 100 mg strengths administered twice daily. The IR
formulation of cilostazol, marketed as Pletal’ in the US (Pletaal’ in Taiwan and other Asian countries),
was first available in Japan in 1988 for the treatment of peripheral arterial diseases and the prevention of
recurrence of cerebral infarction and later approved by the US FDA in 1999 for the treatment of
intermittent claudication (IC). Cilostazol is a specific PDE III inhibitor that can cause reduced platelet
aggregation and increased vasodilatation. Cilostazol showed good efficacy in preventing secondary
strokes, notably reducing the rates of ischaemic stroke recurrence. Nevertheless, the results from eight
placebo-controlled clinical trials indicated that 15.4% of patients withdrawn from cilostazol treatment
were as a result of adverse reactions. Headache, palpitations, and diarrhea were the most frequently
reported adverse reactions among these patients. These adverse reactions were attributable to the peak
concentration of cilostazol. Genovate is developing an ER tablet form of cilostazol, PMR, to be
administered once daily aiming to improve adherence and to reduce the side effects associated with the high peak-to-trough variation of the concentration of cilostazol IR.

About Intermittent Claudication
Peripheral arterial disease (PAD) affects over 200 million people globally and around 8.5 million
Americans over the age of 40. PAD occurs as a result of the narrowing or blockade of blood vessels that
carry blood from the heart to the legs. The main symptom of PAD observed in approximately 70% of
patients is intermittent claudication (IC), a condition that presents as pain and cramping in the lower
extremities (thigh, calf, hip and buttock muscles), as a result of limited blood flow. IC is commonly viewed
as a signal of substantial atherosclerosis, suggesting a higher likelihood of heart attack or stroke. The
symptoms of IC are intermittent, exacerbated when walking or during exercise, and are alleviated with
rest, but reoccur when activity resume; as a result, IC can be very debilitating, drastically affecting the
quality of life of those affected. In severe cases, IC may require surgical intervention, but in general, it can
be treated and managed with a combinational approach including medication, life style changes that
modify or eliminate risk factors, and exercise program. Drugs improving blood flow such as anti-clotting
agents (aspirin), anti-hypertensives, statins, and phosphodiesterase (PDE) III inhibitors such as cilostazol
are currently used to treat IC.

About Genovate Biotechnology Co., Ltd.
Genovate Biotechnology Co., Ltd. is a Taiwan-based, fully integrated specialty pharmaceutical company
focusing on the new drug development in new formulation, new active ingredient, new treatment
modality in cardiovascular, autoimmune, neurodegenerative, and liver diseases. Genovate is equipped
with PIC/S GMP manufacturing, marketing, and distribution capabilities.

Forward-Looking Statements
All statements other than statements of historical facts contained in this press release are forward-
looking statements, including statements regarding the timing of any regulatory process or ultimate
approvals for PMR for the treatment of IC. These forward-looking statements speak only as of the date of
this press release and are subject to a number of risks, uncertainties and assumptions, including the risks
and uncertainties associated with the projected timeline of our NDA submission, whether FDA will agree
with our interpretation of the data or the adequacy of data to support an NDA, the FDA’s review of our
NDA, market conditions, as well as risks and uncertainties inherent in Genovate’s business. The events
and circumstances reflected in the company’s forward-looking statements may not be achieved or occur
and actual results could differ materially from those projected in the forward-looking statements. Except
as required by applicable law, the company does not plan to publicly update or revise any forward-
looking statements contained herein, whether as a result of any new information, future events, changed
circumstances or otherwise.

Corporate Contact: Willie Chiang, Senior Director, Department of Administration, +886.3.598.2221 ext. 118,
Email: williechiang@genovate-bio.com

Following the Technology Licensing and Co-Development Agreement for NCE New Drug DBPR108 in Mainland China Signed between Genovate Biotechnology Co., Ltd. and CSPC Pharmaceutical Group Limited in 2012, New Drug Application for DBPR108 for the Treatment of Diabetes Mellitus has been Filed and Accepted by the National Medical Products Administration (NMPA) in Mainland China.

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[Apr 28, 2023] Genovate Biotechnology Co., Ltd. has signed a technology licensing and development contract with CSPC Pharmaceutical Group Limited (CSPC) for the joint research, registration, promotion, sales, and production of the new chemical entity (NCE) drug DBPR108 in China in 2012. CSPC has completed Phase III clinical trials and held a pre-New Drug Application (NDA) meeting with the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA). CSPC has completed the preparation and submission of the NDA clinical data, which has been officially accepted by the NMPA.
Market Status:
According to the 10th edition of the IDF Diabetes Atlas, published by the International Diabetes Federation on World Diabetes Day 2021, there are currently 537 million adults worldwide living with diabetes, representing a prevalence rate of 10%, meaning one in every 10 adults has the disease. Notably, China has about 141 million people with diabetes, ranking first globally, followed by India (74.2 million), and Pakistan (33 million); the United States ranks fourth with 32.2 million people. In 2021, the global diabetes-related health expenditure for adults aged 20-79 years was approximately USD 966 billion, growing by 316% over the last 15 years. On a country level, the United States has the highest diabetes-related health expenditure (USD 379.5 billion), followed by China and Brazil (USD 165.3 billion and USD 42.9 billion, respectively). Experts estimate that by 2030, the number of people with diabetes will increase to 643 million (783 million by 2045), while the total diabetes-related health expenditure will reach USD 1.03 trillion, presenting considerable business opportunities.
DBPR108 is an NCE DPP4 inhibitor with the advantages of fewer side effects compared to other leading drugs acting on DPP-4 and patent protection. The short-term goal is to market it in China and capture a large market share.

Genovate’s Investigational New Drug GVX171 Approved by the U.S. FDA for First-in-Human Clinical Trial for the Treatment of Antiphospholipid Syndrome

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[Sep 12, 2022] Antiphospholipid syndrome (APS) is a disorder caused by an abnormal autoimmune response to phospholipids in cell membranes, resulting in the production of autoantibodies. The diverse signs of APS include arterial and venous thrombosis, stroke, pulmonary hypertension, thrombocytopenia, and pregnancy-related complications such as recurrent miscarriage, premature birth, stillbirth, and preeclampsia. The prevalence of APS is about 40-50 patients per 100,000 people, with an incidence rate of approximately 2-5 new cases per 100,000 people each year. Women are about five times more likely than men to have APS. The recurrence rate of APS within five years is approximately 20%-30%, and the mortality rate of catastrophic APS is as high as 50%. Currently, there are no drugs or therapies approved specifically for the treatment of APS. Clinical treatment of APS mainly focuses on medications to prevent thrombosis, such as aspirin, anticoagulants, or hydroxychloroquine (HCQ). Studies have shown that HCQ can effectively prevent thrombosis formation in patients with APS.GVX171 is an enantiomer of HCQ, known as (S)-(+)-HCQ, developed by Genovate. This enantiomer is safer for long-term medication use compared to other commercially available HCQ products. Advantages include smaller fluctuations in the blood concentration, longer efficacy, and fewer side effects.HCQ has immunomodulation activity and is an important medication for the treatment of lupus and chronic rheumatoid arthritis. According to a market report by Vantage Market Research, the sales of HCQ in 2021 were approximately USD 900 million, with an estimated compound annual growth rate of 5.7%, and are projected to reach about USD 2.6 billion in 2028. Genovate intends to focus on APS as the entry point for GVX171, providing an effective alternative for the immunomodulation drug market.

Genovate’s Investigational New Drug GVX171 Approved by the U.S. FDA for First-in-Human Clinical Trial for the Treatment of Antiphospholipid Syndrome

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[Sep 12, 2022] Antiphospholipid syndrome (APS) is a disorder caused by an abnormal autoimmune response to phospholipids in cell membranes, resulting in the production of autoantibodies. The diverse signs of APS include arterial and venous thrombosis, stroke, pulmonary hypertension, thrombocytopenia, and pregnancy-related complications such as recurrent miscarriage, premature birth, stillbirth, and preeclampsia. The prevalence of APS is about 40-50 patients per 100,000 people, with an incidence rate of approximately 2-5 new cases per 100,000 people each year. Women are about five times more likely than men to have APS. The recurrence rate of APS within five years is approximately 20%-30%, and the mortality rate of catastrophic APS is as high as 50%. Currently, there are no drugs or therapies approved specifically for the treatment of APS. Clinical treatment of APS mainly focuses on medications to prevent thrombosis, such as aspirin, anticoagulants, or hydroxychloroquine (HCQ). Studies have shown that HCQ can effectively prevent thrombosis formation in patients with APS.GVX171 is an enantiomer of HCQ, known as (S)-(+)-HCQ, developed by Genovate. This enantiomer is safer for long-term medication use compared to other commercially available HCQ products. Advantages include smaller fluctuations in the blood concentration, longer efficacy, and fewer side effects.HCQ has immunomodulation activity and is an important medication for the treatment of lupus and chronic rheumatoid arthritis. According to a market report by Vantage Market Research, the sales of HCQ in 2021 were approximately USD 900 million, with an estimated compound annual growth rate of 5.7%, and are projected to reach about USD 2.6 billion in 2028. Genovate intends to focus on APS as the entry point for GVX171, providing an effective alternative for the immunomodulation drug market.

Genovate Biotechnology Co., Ltd. Granted Patent for New Formulation New Drug PMR in China

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[Nov 9, 2020] PMR, a new drug developed by Genovate Biotechnology Co., Ltd. for the treatment of intermittent claudication, has been granted a patent by the China National Intellectual Property Administration. The patent is titled ‘Novel Formulation of Cilostazol, a Quinolinone-Derivative Used for Alleviating the Symptom of Intermittent Claudication in Patients with Peripheral Vascular Disease.’
PMR has completed the pivotal trial required for a New Drug Application (NDA) in the U.S. and is currently undergoing NDA registration, following the U.S. FDA’s 505(b)(2) regulatory pathway. PMR, a novel extended-release formulation of cilostazol administered once daily, is safer and has fewer side effects compared to the intermediate-release formulation of cilostazol. The indications for PMR’s active pharmaceutical ingredient, cilostazol, can be potentially extended to therapeutic areas such as anti-thrombosis and stroke prevention, which are prevalent in China.

Genovate Biotechnology Co., Ltd.’s New Active Ingredient New Drug GX17 for the Treatment of Lupus Erythematosus Received a Response from the U.S. FDA Regarding the pre-IND Meeting

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[Sep 7, 2020] Genovate Biotechnology Co., Ltd. and UniPharma Co., Ltd. are jointly developing a new active ingredient new drug, GX17, for the treatment of lupus erythematosus. Genovate recently received a response from the U.S. FDA regarding the pre-Investigational New Drug (IND) meeting application. The FDA provided recommendations on the preclinical data, clinical trial design, and efficacy endpoints required for the IND and New Drug Application (NDA) filing. Based on the FDA’s recommendations, Genovate will establish a 505(b)(2) new-drug development strategy and proceed with the relevant work for the IND application.Market Status:
The active pharmaceutical ingredient of GX17 is hydroxychloroquine (HCQ), a key drug for treating lupus erythematosus and chronic rheumatoid arthritis. GX17 is an enantiomer of HCQ, known as (S)-(+)-HCQ. Research conducted by Genovate and existing literature suggests that this enantiomer has a better safety profile for long-term use, with lower blood concentration fluctuations, longer efficacy, and fewer side effects compared to commercially available racemic HCQ products. The preparation of (S)-(+)-HCQ crystalline raw material uses a patented method for the new drug’s development in terms of formulation and indication. The sales of HCQ in 2019 were approximately USD 1.6 billion. Due to HCQ’s potential efficacy against COVID-19, the market for HCQ is expected to grow at a compound annual growth rate of 5.3%, reaching an estimated USD 2.7 billion by 2029. GX17 will provide a better option for patients with lupus erythematosus and potentially for those with COVID-19.

Genovate Biotechnology Co., Ltd.’s New Diabetes Drug, DBPR108, Enters Phase III Clinical Trials in China

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[Mar 2, 2020] Genovate Biotechnology Co., Ltd. and CSPC Pharmaceutical Group Ltd. (CSPC) have signed a technology licensing and development contract in 2012 for the joint research, registration, promotion, sales, and production of DBPR108 in China. CSPC recently received approval from the Biomedical Research Ethics Committee of the lead units (Peking University First Hospital and Peking Union Medical College Hospital) to conduct the ‘Phase III, multicenter, randomized, double-blind, double-dummy, active-comparator, placebo-controlled clinical trial of DBPR108 tablets as monotherapy for type 2 diabetes’ and the ‘Phase III, multicenter, randomized, double-blind, parallel controlled clinical trial of DBPR108 tablets combined with metformin hydrochloride tablets for type 2 diabetes.’
Market Status:
According to the 9th edition of the IDF Diabetes Atlas published by the International Diabetes Federation on World Diabetes Day 2019, there are currently 463 million adults worldwide living with diabetes, representing a prevalence rate of 9.3%, meaning one in every 11 adults has the disease. Notably, China has about 114.4 million people with diabetes, ranking first globally, followed by India (72.92 million) and the United States (30.2 million). In 2019, the global expenditure for diabetes-related treatment drugs was approximately USD 95.6 billion, and experts expect it to grow to $124 billion by 2022. In China, the amount was USD 36 billion in 2019, and it is predicted to increase to USD 43.7 billion by 2022, presenting considerable business opportunities. DBPR108 is a new chemical entity (NCE) DPP4 inhibitor with the advantages of fewer side effects compared to other leading drugs acting on DPP-4 and patent protection. The short-term goal is to market it in China and capture a large market share.

Genovate Biotechnology Co., Ltd. Has Completed the Pivotal Clinical Trial in the United States for Its New Formulation New Drug PMR for the Treatment of Intermittent Claudication Caused by Peripheral Arterial Occlusive Disease

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[Jun 13, 2019] Genovate Biotechnology Co., Ltd. has completed the pivotal clinical trial of PMR that is required for a New Drug Application (NDA) in the United States. The Pharmacokinetic Statistical Analysis Report showed that the blood concentration of people taking PMR once daily is bioequivalent to the US-approved reference drug, Cilostazol Tablets, taken twice daily, and achieved the primary efficacy endpoint. Genovate will proceed with the NDA filing per the FDA’s 505(b)(2) regulatory pathway.
Market Status:
According to Evaluate’s market analysis, the global market for cilostazol (PMR’s active pharmaceutical ingredient [API]) is about USD 250 million. Otsuka Pharmaceutical’s Pletaal contains the same API and currently dominates the market. PMR’s formulation uses a new technology to continuously release the drug over 24 hours, achieving the required therapeutic concentration while reducing the incidence and severity of adverse reactions, thereby improving overall treatment efficacy. PMR’s once-daily administration with milder side effects will offer patients a better option than the current comparable drug on the market. Cilostazol Tablets have been approved for the treatment of peripheral arterial occlusive diseases and the prevention of recurrent cerebral embolism in major Asian countries (such as China, Japan, and Taiwan). Therefore, the indications for PMR can be further expanded to the field of stroke, offering immense future potential.

Genovate Biotechnology Co., Ltd.’s New Indication New Drug Mycocep Approved for the Treatment of Lupus Nephritis by the Ministry of Health and Welfare for

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[Sep 25, 2018] Today, Genovate Biotechnology Co., Ltd. received a letter from the Ministry of Health and Welfare approving an additional indication for Mycocep. It reads: ‘In combination with corticosteroids, Mycocep is indicated as induction and maintenance therapy for adult patients with lupus nephritis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III, IV, or V.” The new indication has also been granted a 5-year administrative protection period from the date of approval, following Article 54 of the Regulations for Registration of Medicinal Products.
Market Status:
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ in the body, with the kidneys being one of the most commonly affected organs. Severe lupus nephritis (LN) can progress to end-stage renal disease and even death if not properly treated. In recent years, the immunosuppressant mycophenolate mofetil (the active pharmaceutical ingredient of Mycocep), originally used to reduce organ rejection in transplant patients, has shown good results in the induction or maintenance therapy for patients with proliferative LN, becoming the first-line treatment for maintenance therapy in LN.According to statistics from the Ministry of Health and Welfare in 2015, there were about 30,000 patients with SLE in Taiwan, and the 10-year incidence rate of nephritis is approximately 50%-60% according to epidemiological reports. At the end of 2014, in response to a request from the Taiwan Rheumatology Association and the recommendation of the Taiwan Food and Drug Administration (TFDA), Genovate initiated human clinical trials to study the potential new indication for Mycocep to meet the medical needs of LN patients in Taiwan and reduce the economic burden. After nearly four years, this effort was successful. The clinical trial data gathered locally will allow the drug to provide LN patients and physicians with a better treatment option once it is on the market.

Genovate Biotechnology Co., Ltd. Passed the On-Site GMP Inspection for Aseptic Preparations by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan

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[Sep 6, 2018] Genovate Biotechnology Co., Ltd. was contracted by a Japanese pharmaceutical company to produce sterile formulation drugs for export to Japan. The Ministry of Health, Labour and Welfare of Japan authorized its Pharmaceuticals and Medical Devices Agency (PMDA) to conduct an on-site inspection at Genovate’s plant from March 13 to 16, 2018. Today, Genovate received the ‘Drug Conformity Investigation Result Notice’ from PMDA, confirming compliance with the regulations regarding the quality, efficacy, and safety of pharmaceuticals and medical devices in Japan.

The Clinical Study Report for the New Indication New Drug Mycocep Submitted by Genovate Biotechnology Co., Ltd. has been Approved for Registration by the Ministry of Health and Welfare of Taiwan

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[Feb 21, 2018] Following the on-site GCP inspection at the clinical trial center by the Ministry of Health and Welfare of Taiwan, Genovate Biotechnology Co., Ltd. received a letter approving its Clinical Study Report for the new indication new drug Mycocep. The efficacy and safety results of Mycocep in treating lupus nephritis have met the study endpoints. Genovate will submit a New Drug Application for the new indication in accordance with the Taiwan Food and Drug Administration’s (TFDA) regulations.

Genovate Biotechnology Co., Ltd. Signed a Joint-Venture Agreement with NaviFUS Corporation, Agreeing to Establish a Joint-Holding Company to Together Develop Innovative Medical Device,  Neuronavigation-Guided Focused Ultrasound System (NaviFUS System), for Central Nervous System Diseases in Europe, Australia, and New Zealand

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[Jan 19, 2018] Genovate Biotechnology Co., Ltd. and NaviFUS Corporation signed a joint venture agreement to establish a holding company at a 50:50 investment ratio. The company will engage in the development, manufacturing, registration, sales, and licensing of innovative neuronavigation-guided focused ultrasound (NaviFUS) medical devices and services for central nervous system diseases, such as Alzheimer’s disease, epilepsy, and Parkinson’s disease, excluding tumors, in the Europe, Australia, and New Zealand. A wholly-owned subsidiary will first be established in Australia to execute the necessary clinical development and sales.