First commercialization, strong progress in drug pipeline, and innovative approach to engaging eye health community in China

·        Self-developed innovative drug CsA Ophthalmic Gel for dry eye disease (DED) passed regulatory onsite inspections in January 2023, with expected commercialization as early as 2024.

·        NVK002, our blockbuster innovative drug for myopia progression control, crossed multiple critical milestones.

o   Our partner Vyluma successfully concluded their global phase III study a significant step in the lead-up to a U.S. FDA NDA submission.

o    Zhaoke Ophthalmology completed patient recruitment for its two Phase III trials in China significantly ahead of schedule last summer

·        Bimatoprost Timolol (晶贝莹®), a glaucoma treatment, obtained marketing authorization from the NMPA, with the first prescription issued on 8 March 2023 in Guangzhou.

·        A new presbyopia partnership with Visus enabled Zhaoke Ophthalmology to become the first ophthalmic pharmaceutical company in China with innovative drugs in advanced clinical development (Phase III or later) covering three major front-of-the-eye diseases namely DED, myopia and presbyopia.

·        The launch of our 堡得视® flagship store on Tmall with category 2 medical devices and a continued rapid growth in physician engagement via our Boshi public account heralded the beginning of a comprehensive omnichannel approach towards brand building and commercialization.

·        Solid progress was made in establishing a global footprint, with the Company reaching an exclusive distribution and supply agreement with Kwangdong Pharmaceutical to commercialize NVK002 in South Korea.

·        Continued our disciplined approach towards capital expenditure, with cash, cash equivalents and time deposits of approximately RMB1,725.2 million as at end of 2022, providing strong support for our clinical programs and product launches in the coming few years.

HONG KONG, 27 March 2023 – Zhaoke Ophthalmology Limited (“Zhaoke Ophthalmology” or the “Company”, SEHK: 6622), a leading ophthalmic pharmaceutical company dedicated to the research and development, manufacturing and commercialization of therapies that address significant unmet medical needs, today announced its annual results for the year ended 31 December 2022 (“Reporting Period”).

Zhaoke Ophthalmology is strategically focused on treatments that cover a wide range of ophthalmic diseases, with one of the largest and most comprehensive drug portfolios of innovative and generic treatments covering the six major eye diseases across both the front-and back-of-the-eye, including dry eye disease (“DED”), myopia, presbyopia, wet age-related macular degeneration (“wAMD”), diabetic macular edema (“DME”) and glaucoma. The Company’s portfolio includes several potential blockbuster innovative drug candidates.

Dr. Li Xiaoyi (Benjamin), Chairman of the Board, Executive Director and CEO of Zhaoke Ophthalmology, said, “2022 was a milestone year in which we accomplished a series of significant achievements, maximizing our shareholder value by focusing on our twin engines of growth: Early commercialization combined with innovation in our R&D and business model, ensuring our success both in the near to medium term and for years to come.”

Xinyan Feng (Lisa), Chief Business Officer and Chief Financial Officer of Zhaoke Ophthalmology, commented, “We have launched many initiatives this year, but I want to emphasize the focus we give to exercising diligence and great discipline with respect to cash management. This is critical given the continuing rapidly changing market dynamics and allows us to successfully develop and commercialize our products.”

In 2022, the Company achieved significant progress in the clinical programs of several drugs. The NDA (New Drug Application) for CsA Ophthalmic Gel for DED was accepted for review by the National Medical Products Administration (NMPA) in June 2022. Around six months later, in January 2023 the drug also passed the on-site regulatory and clinical trial inspections by the NMPA, as well as the Good Manufacturing Practices (GMP) compliance inspection by the Guangdong Medical Products Administration.

Dr. Li continued, “Passing the onsite inspections and the GMP inspection was an important step towards the final approval of CsA Ophthalmic Gel. We hope to bring the drug to the market as early as 2024, to provide a new and best-in-class treatment solutions to DED patients, alongside our heat compress eyepatch.”

Another highlight for the Reporting Period is the progress the Company made in bringing NVK002,  an innovative drug for myopia progression control for children, closer to market. Vyluma, Zhaoke Ophthalmology’s partner for NVK002, announced the successful Phase III clinical results in October 2022, which strengthened its leading position in low-dose atropine globally and brought this drug a step closer toward a U.S. FDA NDA submission. At the same time, in July 2022, Zhaoke Ophthalmology completed the recruitment for its concurrent two-year Phase III clinical trial (“China CHAMP”) and one-year Phase III bridging trial (“Mini-CHAMP”). The former completed enrolment on 21 July 2022, two months ahead of schedule, while the latter completed enrolment on 28 July 2022, three months ahead of schedule. Furthermore,

Dr. Li added, “We are excited by our partner Vyluma’s clinical results for NVK002 in the U.S. and Europe. With a U.S. NDA submission by Vyluma expected within a relatively short order, NVK002 is thought to become the first clinically proven and approved pharmaceutical product for treating myopia progression globally. We also expect to complete our Mini-CHAMP clinical trial for NVK002 this summer. Assuming consistent and positive results and support from the Center for Drug Evaluation (CDE), we plan to make an NDA submission in China using the combined global CHAMP and Mini-CHAMP studies.”

NVK002 also helped lay the foundation for Zhaoke’s global footprint. In March 2023, Zhaoke Ophthalmology entered into an exclusive distribution and supply agreement with Kwangdong Pharmaceutical to commercialize NVK002 in South Korea. The Company is working hard to globalize NVK002 and other relevant drugs in the pipeline in other territories including Southeast Asia, Europe and/or the United States.

Another new partnership was announced in May 2022 with Visus, a U.S. pharmaceutical company, to license BRIMOCHOL™ PF and Carbachol PF, innovative drugs for presbyopia. The introduction of the two innovative assets enabled Zhaoke Ophthalmology to become the first ophthalmic pharmaceutical company in China with innovative drugs in advanced clinical development (Phase III or later) covering the three major front-of-the-eye diseases – dry eye, myopia, and presbyopia. Also, TAB014, the Company’s first drug for the treatment of back-of-the-eye diseases, initiated a Phase III clinical trial and the first patient was enrolled for wAMD in June 2022. At the same time, our research and clinical teams have conducted several Phase II studies and one IIT and continue to determine the direction for the development of our ZKY001 asset, which has broad applications in the healing of corneal wounds and can potentially be used in multiple corneal repair indications.

Turning to Zhaoke Ophthalmology’s equally important other engine of growth, the Company achieved a key milestone in drug commercialization. In February 2023, Bimatoprost Timolol eye drop (晶贝莹®), a generic drug researched, developed and manufactured by Zhaoke Ophthalmology for the treatment of glaucoma, obtained marketing authorization from the NMPA. The first prescription for Bimatoprost Timolol was issued on 8 March in Guangzhou.

Dr. Li said, “The Bimatoprost Timolol eye drop is our first drug authorized by the NMPA and marks the beginning of a new chapter for Zhaoke Ophthalmology. We anticipate making several additional abbreviated new drug application (ANDA) submissions in 2023.”

Lisa Feng continued, ”As the Company has evolved from a pure R&D institution to a commercial pharmaceutical company, we have not only innovated in R&D but also in our approach to commercialization. We have made great strides in our omnichannel efforts targeting both physicians and patients/consumers, initiating this approach with our highly successful Boshi public account (with over 11,000 followers and more than 60 active KOL’s and ophthalmologists contributing content) and our Tmall flagship where we launched  Zhaoke Ophthalmology’s first commercialized product, 堡得视® the Heat Compress Eyepatch, a category 2 medical device for reducing symptoms of mild cases of dry eye. We also just launched on Tmall another eyepatch for children.”

Lisa Feng continued, “The Eyepatch launch has not only accelerated the Company’s efforts to establish an omnichannel commercial strategy, but also helps to increase the public’s awareness and knowledge of eye diseases and treatment solutions in China. Digital engagement drives dialogue between drug companies, physicians, and patients/consumers in China. In addition, it establishes our digital sales presence and promotes the brand reputation for Zhaoke Ophthalmology in the market.”

In anticipation of the commercial launch of Bimatoprost Timolol and other innovative and generic products to follow, the Company has started to expand its sales and marketing team under the leadership of John Feng, formerly Allergan with a strong command of the Chinese ophthalmology market, and expects its size to grow from shy of 50 people at the end of 2022, to around 100 by the end of 2023. In addition, in March 2022, Zhaoke Ophthalmology signed strategic partnership agreements with three of China’s leading pharmaceutical supply chain service companies, Sinopharm, Shanghai Pharma and China Resources Pharma to collaborate in areas including procurement models, logistics management, market developments, joint projects and information communication.

Turning to financial performance: at the end of the Reporting Period, Zhaoke Ophthalmology recorded cash, cash equivalents and time deposits of approximately RMB1,725.2 million. The Company recorded a total loss of approximately RMB 407.3 million for the year ended 31 December 2022, compared to approximately RMB2.1 billion for the year ended 31 December 2021. During the year, the Company’s R&D expenses reached approximately RMB296.4 million, compared to approximately RMB220.1 million for the year ended 31 December 2021. The Company continues to maintain its focus on prudent capital expenditure given overall financial market conditions.

Looking forward, Dr. Li said, “2023 will be another landmark year for Zhaoke Ophthalmology. We will continue investing in our omnichannel ecosystem so that we are fully prepared for the upcoming launches of our key drug assets, starting with CsA ophthalmic gel. We will continue to progress our clinical programs in 2023, including the completion of Mini-CHAMP, completion of patient recruitment for TAB014 for wAMD, and IND filing for BRIMOCHOL™ PF and Carbachol PF for presbyopia.”

Dr. Li concluded by saying, “We are encouraged to see ophthalmology as a key focus area for the Chinese government as part of the overall development of the healthcare sector. This was evidenced in the National Eye Health Plan included as part of the ‘Fourteenth Five-Year Plan for National Economic and Social Development of the PRC and the Outline of Vision Goals for 2035. (中華人民共和國國民經 濟和社會發展第十四個五年規劃和2035年遠景目標綱要)’, The Chinese government has also designated three geographic areas as future centers of excellence for healthcare, including the Greater Bay Area (GBA), home to Zhaoke Ophthalmology’s state-of-art manufacturing facility. We are committed to being a leader in the GBA region and will benefit from new supportive measures from the regional and local governments. We will continue pursuing our goal to address significant unmet medical needs across different eye diseases in China and globally, to improve public visual health through scientific research as quickly as possible.” 

Zhaoke Ophthalmology highlighted several pipeline updates as a part of the results announcement:

CsA Ophthalmic Gel for DED (self-developed)

Overview

CsA Ophthalmic Gel is an innovative drug being developed by Zhaoke Ophthalmology for the treatment of DED. It is a single, daily dose hydrogel that eliminates daytime administration and the associated discomfort and inconvenience, and aims to dramatically improve patients’ treatment compliance and quality of life. The proprietary hydrogel formulation is protected with patent approval in China and internationally. This novel formulation enhances the pharmacokinetic profiles of CsA on the ocular surface, allowing efficacy similar to that of Cyclosporine A products currently available for DED. However, unlike the current treatment, CsA Ophthalmic Gel’s unique formulation stays on the eye for longer, requiring only once-a-day dosing (compared with traditional twice-a-day dosing). In Phase III clinical trial, the treatment also showed a faster onset of action by demonstrating efficacy at around the two-week time period.

Updates during the Reporting Period and up to the date of this announcement

On June 8, 2022, the NDA submission for CsA Ophthalmic Gel was accepted for review by the CDE.

On January 31, 2023, CsA Ophthalmic Gel passed the on-site regulatory and clinical trial inspections by the NMPA, and the GMP compliance inspection conducted by the Guangdong Medical Products Administration.

Zhaoke Ophthalmology continues to target regulatory approval and commercialization of CsA Ophthalmic Gel in China in early 2024. Given the prevalence of DED globally and the differentiated profile of CsA Ophthalmic Gel, the Company is also exploring opportunities outside of China. Specifically, the Company will continue the dialog with the FDA regarding a clinical development pathway for CsA in the U.S. with the aim of getting into the position for U.S. IND filing around the end of 2023.

NVK002 (Atropine) for Myopia (partnered with Vyluma)

Overview

To date, low concentration atropine has been widely studied and demonstrated to be effective in myopia progression control among children and adolescents. Zhaoke Ophthalmology’s NVK002 is currently positioned as the first clinically proven pharmaceutical product approved for treating the progression of myopia globally. This treatment has a proprietary formulation that successfully addresses the instability of low concentration atropine, with patent protection in the U.S. as well as in China, and is preservative-free with an expected shelf life of over 24 months.

Zhaoke Ophthalmology’s licensing partner for NVK002 is Vyluma Inc., a wholly owned subsidiary of U.S.-based Nevakar Inc. Vyluma has successfully completed the Phase III clinical trial for NVK002 in the U.S. and Europe and announced encouraging top-line results of the three-year trial in October 2022.

In September 2021, Zhaoke Ophthalmology received approval from the CDE to initiate two concurrent Phase III clinical trials, including a two-year Phase III clinical trial (China CHAMP) and a one-year Phase III bridging trial (Mini-CHAMP) in China.

The China CHAMP trial is led by Professor Wang Ningli from Beijing Tongren Hospital as the principal investigator and involves 19 centers and 777 patients. The Mini-CHAMP trial is jointly led by Professor Qu Xiao Mei from the Eye and ENT Hospital of Fudan University and Professor Yang Xiao from the Zhongshan Ophthalmic Center of Sun Yat-Sen University as principal investigators and involves 18 centers and 526 patients.

Combined with global data from Vyluma’s Phase III clinical trial (CHAMP) in the U.S. and Europe, the overall CHAMP trial for NVK002 will be one of the largest, longest and most comprehensive Phase III clinical trials for low dose atropine use in the world.

Updates during the Reporting Period and up to the date of this announcement

Patient recruitment was completed significantly earlier than expected across both NVK002 trials in China, giving our Company a strong head start in moving towards its goal of becoming one of the first companies to commercialize myopia progression treatment in China and beyond, despite the challenging COVID-19 environment in 2022.

The China CHAMP trial completed enrolment on 21 July 2022, two months ahead of schedule; while the Mini-CHAMP trial completed enrolment on 28 July 2022, three months ahead of schedule.

In March 2023, we entered into a distribution and supply agreement on NVK002 with Kwangdong Pharmaceutical Co., Ltd. (“KDP”), a Korean-based company principally engaged in the manufacturing and distribution of pharmaceutical products. Under the terms of the agreement, KDP was granted exclusive rights to import, promote, distribute, market, and sell NVK002 in South Korea. This partnership marked a concrete step towards expanding our global footprint, while creating new business opportunities as well as developing new revenue streams for our Company.

We expect to complete the one-year Mini-CHAMP bridging trial of NVK002 in the second half of 2023, and the two-year China CHAMP trial in the second half of 2024. Zhaoke Ophthalmology is well-positioned as one of the first companies to commercialize a myopia drug in the mainland China market, with an expanded lead, particularly if we are able to combine the data from Mini-CHAMP and those from the successful Phase III clinical study conducted by our partner Vyluma for NDA submission.

BRIMOCHOL™ PF and Carbachol PF (partnered with Visus)

Overview

BRIMOCHOL™ PF and Carbachol PF are pupil-modulating eye drops designed to be once-daily, preservative-free therapeutics to correct the loss of near vision associated with presbyopia. BRIMOCHOL™ PF is a fixed-dose combination of carbachol (a cholinergic agent) and brimonidine tartrate (an alpha-2 agonist). Carbachol PF is a proprietary, preservative-free formulation of carbachol monotherapy. Both investigational therapies reduce the size of the pupil resulting in a “pinhole effect” so that only centrally focused light rays are able to enter the eye, thereby sharpening both near and intermediate images.

Zhaoke Ophthalmology’s licensing partner for Brimochol is Visus, a clinical-stage pharmaceutical company focused on developing innovative ophthalmic therapies with offices in Seattle, Washington, and Irvine, California. In Visus’ Phase II study, VIVID, both formulations met primary and secondary endpoints, demonstrating a three-line improvement in near visual acuity with no loss of distant vision for up to nine hours. Both BRIMOCHOL™ PF and Carbachol PF were well tolerated with no serious adverse events. Visus is currently conducting Phase III pivotal trials with results from the first Phase III trial expected in Q2 2023.

Concurrent with the ongoing Phase III clinical studies of BRIMOCHOL™ PF and Carbachol PF in the U.S., Zhaoke Ophthalmology plans to file IND for a Phase Ib/II study in China in late 2023 which, if successful, will be followed by a Phase III study.

TAB014 (Bevacizumab) for wAMD (partnered with TOT BIOPHARM)

Overview

TAB014 is the first clinical-stage bevacizumab-based antibody indicated for wAMD in China. Bevacizumab is a clinically validated anti-VEGF drug. Globally, bevacizumab is approved for oncology treatment through intravenous infusion. However, there has been increasing off-label use of bevacizumab via intravitreal injection for the treatment of wAMD.

Updates during the Reporting Period and up to the date of this announcement

In March 2022, Zhaoke Guangzhou, a wholly-owned subsidiary of the Company, and TOT BIOPHARM Co., Ltd., a wholly-owned subsidiary of TOT BIOPHARM, entered into a supplemental agreement, pursuant to which Zhaoke Guangzhou full control in the execution of clinical trials and the ultimate decision-making power in the development and commercialization of TAB014 in China, Hong Kong and Macau. Zhaoke Guangzhou has also been given the right to develop TAB014 for other ophthalmic indications besides wAMD and/or novel formulations for ophthalmic indications.

We recruited the first patient for the Phase III clinical trial on 28 June 2022, and expect to complete patient recruitment before the end of 2023.

The Phase III clinical trial of TAB014 is a randomized, double-blind and non-inferiority study. The main objective of the study is to evaluate the change from baseline in best corrected visual acuity at week 52 in TAB014-treated subjects group compared with the Lucentis®-treated subjects group. The study involves approximately 60 centres and a total of 488 patients, led by Professor Chen Youxin from Peking Union Medical College Hospital as the principal investigator.

ZKY001 (self-developed)

Overview

ZKY001 is a seven-amino acid peptide derived from the functional fragment of Thymosin β4 that binds actin, a type of protein that plays a central role in cell structure and movement. ZKY001 has broad applications in the healing of corneal wounds and can potentially be used in multiple corneal repair indications. Zhaoke Ophthalmology has been exploring multiple indications for ZKY001, including corneal epithelial defect (CED), transepithelial photorefractive keratectomy (TPRK), a surgical treatment for myopia; pterygium, a growth in the cornea or the conjunctiva; and neurotrophic keratitis (NK), a rare degenerative corneal disease.

Zhaoke Ophthalmology has conducted Phase II clinical trials of ZKY001 for CED, TPRK and Pterygium and an investigator-initiated trial (IIT) for NK. The research and clinical teams aim to analyze all the results across these studies to determine the direction for development of this asset and next steps.

NTC010 (Partnered with NTC)

Overview

NTC010 is a fixed dose combination of antibiotics and steroids to prevent infection and inflammation for patients undergoing cataract surgery. The drug belongs to a new generation of antibiotics, which increase efficiency and cover a wider range of bacteria. The drug also shortens the duration of the treatment by half — from 14 to seven days — making it beneficial to patients’ overall health and helping to prevent antibiotic overuse.

The drug has already been approved across the EU countries and in 15 countries/areas outside of EU and is expected to be further rolled out across extra-Europe countries. According to the information from China Insights Consultancy, NTC010 is the first eye drop product marketed in the EU that combines a quinolone antibiotic with an anti-inflammatory steroid. 

The Company submitted an NDA in conjunction with a clinical trial exemption based on the existing European clinical data to the NMPA in November 2022.

PAN-90806 (VEGFR2 inhibitor) for wAMD and DME (partnered with PanOptica)

Overview

PAN-90806 is an innovative drug indicated in the treatment of wAMD, as well as DME, the leading cause of blindness in diabetic patients worldwide.

PAN-90806 is a novel eye drop formulation. The goal is to be applied as a maintenance therapy in order to reduce the frequency of intravitreal injections and other treatment issues associated with mainstream anti-VEGF therapies while at the same time maintaining visual stability. If successful, the use of PAN-90806 is expected to significantly reduce treatment discontinuation and therefore slow underlying disease progression through improved patient comfort, acceptance, convenience and compliance.

Zhaoke Ophthalmology is currently focused on optimizing the formulation of PAN-90806. The Company plans to file an IND for patient trials after the completion of requisite animal studies.

Generic drugs

We follow a balanced approach in designing our drug pipeline. In addition to innovative drug candidates, our Company has several generic drugs in the pipeline. The market potential for the management and treatment of ocular disease in China is unmatched globally. Generic drugs address a substantial portion of current ophthalmic medical needs in China. From a market demand perspective, our generic pipeline complements our innovative pipeline and positions us to provide total solutions to ophthalmologists and patients.

We made meaningful progress across our generic programs in the Reporting Period. In particular, we obtained marketing authorization from the NMPA in February 2023 for Bimatoprost Timolol eye drop, known as 晶贝莹® in the PRC, and researched, developed and manufactured by Zhaoke Ophthalmology for the treatment of glaucoma.

Bimatoprost Timolol eye drop (晶贝莹®) is used to lower the intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension who do not respond sufficiently to β-blockers or prostaglandin analogues (PGA). It is the first generic drug of Bimatoprost Timolol eye drop for the treatment of glaucoma or ocular hypertension in China.

Bimatoprost Timolol eye drop (晶贝莹®) is also our Company’s first drug approved for commercialization. The first prescription for this drug was written on 8 March 2023 in Guangzhou. The launch of this product will help expand brand recognition of Zhaoke Ophthalmology to support the future commercial launch of our innovative drugs.

We also aim to file additional ANDA submissions for a number of candidates in our generic drug pipeline this year in glaucoma and other areas.

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