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 interim results for the six months ended 30 June 2023 (the “Reporting Period”).
Dr. Li Xiaoyi (Benjamin), Chairman of the Board, Executive Director and Chief Executive Officer of Zhaoke Ophthalmology, said, “Zhaoke Ophthalmology has begun an exciting new chapter. During the first half of this year, we recorded meaningful sales revenue for the first time while making significant progress in our R&D programs, including NVK002, as well as in our commercialization activities through both traditional and new digital channels. Altogether our results demonstrate the significance of the year 2023 for the Company.”
In the reporting period, out of a total of RMB11.3 million of revenue, RMB2.3 million was derived through the commercialization of our generic drug for glaucoma, Bimatoprost Timolol eye drop (晶贝莹®), and RMB3.6 million was derived through our Baodeshi (堡得视®) series of eyepatches. The revenue came from both traditional hospital and new digital and physical channels. This proves Zhaoke’s ability to generate sales from an innovative mix of offline and online sales channels supported by multi-faceted brand building initiatives. In addition, the Company recorded RMB5.4 million from an upfront payment following its distribution and supply agreement for NVK002 in South Korea.
Zhaoke Ophthalmology also continued to consolidate its leadership position in R&D activities by advancing its late-stage programs which address significant market opportunities in major front- and back-of-the-eye diseases.
One major highlight for Zhaoke Ophthalmology during the Reporting Period concerned NVK002, its treatment for myopia progression control for adolescents and children. The Company’s US partner Vyluma, Inc. (“Vyluma”) announced that its New Drug Application (“NDA”) for NVK002 was accepted by the US FDA, who has assigned it a Prescription Drug User Fee Act (PDUFA) goal date of 31 January 2024. Zhaoke’s own NVK002 trials in China are progressing well, with the last patient last out for Mini Champ, its Phase III bridging clinical trial, completed on 3 August 2023. In addition, China CHAMP, the Company’s two-year study, passed the half-way mark of its trial period with good patient compliance. With plans to make an NDA submission for NVK002 to the Chinese regulator, the Company is now positioned favorably as a frontrunner in the low-dose atropine space in China.
The Company also recorded a range of other achievements during the Reporting Period across its R&D programs. For example, CsA Ophthalmic Gel passed the on-site regulatory and clinical trial inspections by China’s National Medical Products Administration and a Good Manufacturing Practice review conducted by the Guangdong Medical Products Administration. Alongside this, it concluded several Phase II clinical trials and an investigator initiated trial for ZKY001 and selected an indication to progress in a Phase III trial next year. ZKY001 was developed by the Company in-house and has broad applications in corneal wound healing.
With these and the Company’s other R&D programs making impressive progress, Zhaoke Ophthalmology has grown its sales and marketing organization to 80 employees and further developed its omni-channel sales and marketing model to support the upcoming commercialization activities.
During the Reporting Period, the Company expanded its presence on China’s two major e-commerce platforms by launching its second product on Tmall (堡得视® Far Infrared Eye Heat Compress) and its first commercialized drug on JD Health (晶贝莹® Bimatoprost Timolol eye drop). It has also continued to grow brand awareness through its content-driven WeChat platform, Zhaoke Boshi (兆科博視). As of the date of this announcement, Zhaoke Boshi has over 13,800 followers, representing approximately one quarter of the ophthalmologist community in China. This rapid growth is matched by the impressive engagement and resoundingly positive feedback the Company receives on the platform from leading ophthalmologists.
These successes in the Company’s digital activities prove its ability to connect with the medical community in China and build brand awareness directly amongst consumers. They also validate the Company’s strategy of combining traditional and innovative methods to maximize its success as a commercial pharmaceutical company.
In addition to its own sales and marketing efforts in China, Zhaoke Ophthalmology has established revenue-generating partnerships with leading companies outside China as an initial step to build out its global footprint. For example, during the Reporting Period, it signed a distribution and supply agreement with Kwangdong Pharmaceutical Co., Ltd. (“KDP”), one of Korea’s leading companies, for NVK002. In addition to an upfront payment, Zhaoke Ophthalmology is eligible to receive additional payments based on achieving certain regulatory milestones and royalty payments.
Underpinning the success of the company’s activities during the Reporting Period is Zhaoke Ophthalmology’s continued strong financial health. As of 30 June 2023, it had a cash balance of RMB1,674.7 million which comfortably provides the resources required to support its clinical and R&D programs. Gross margin was 89.8%. R&D expenses of RMB205.3 million reflect the extent and advanced clinical stage of the Company’s programs. Sales and marketing costs were RMB23.1 million, while general and administrative expenses were RMB42.6 million. Again, these numbers are in line with the latest development stages of the Company’s various programs as well as with the overall transition of the Company from a pure R&D-focused company to one with dual focuses on R&D and commercialization.
In conclusion, Dr Li said, “The success of our early commercialization activities demonstrates the potential of our innovative sales approach as our R&D programs advance and more products reach the commercial stage. Alongside the hard work and commitment of our people and partners, the updates we have made today all indicate an exciting future for the company. We look forward to announcing more developments over the rest of this year and during the course of 2024.”
Zhaoke Ophthalmology highlighted several pipeline updates as a part of the results announcement:
Innovative Drugs
CsA Ophthalmic Gel for DED (self-developed)
Overview
Cyclosporine A (“CsA”) Ophthalmic Gel is an innovative drug being developed by Zhaoke Ophthalmology for the treatment of dry eye disease (“DED”).
· It is a single daily dose hydrogel which eliminates the need for daytime administration and the associated discomfort and inconvenience, whilst aiming 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 which need to be applied twice daily. However, unlike these current treatments, CsA Ophthalmic Gel’s unique formulation stays on the eye for longer, requiring only once-a-day dosing.
· In the Phase III clinical trial (COSMO), the treatment also showed a faster onset of action by demonstrating efficacy at around the two-week period, while traditional CsA drugs often take around seven to eight weeks for onset of action.
Updates during the Reporting Period
On January 31, 2023, Zhaoke Ophthalmology announced that CsA Ophthalmic Gel passed the on-site regulatory and clinical trial inspections by the NMPA, and the Good Manufacturing Practice review conducted by the Guangdong Medical Products Administration.
· Zhaoke Ophthalmology continues to target regulatory approval and commercialization of CsA Ophthalmic Gel in China in 2024.
· Given the prevalence of DED globally and the differentiated profile of CsA Ophthalmic Gel, the Company is also progressing its plans for CsA Ophthalmic Gel globally including in the U.S. We had one pre-IND meeting with the FDA in February 2023 and are working towards an IND filing in the US in 2024.
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 well-positioned as the first clinically proven pharmaceutical product approved for slowing 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 US 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, a wholly owned subsidiary of US-based Nevakar, Inc. Vyluma successfully completed its Phase III clinical trial for NVK002 across the U.S. and Europe, which involved nearly 600 children and adolescents in a three-year study period.
· Zhaoke Ophthalmology is conducting two concurrent Phase III clinical trials in China: a two-year Phase III clinical trial (China CHAMP) and a one-year Phase III bridging trial (“Mini-CHAMP”). Combined with global data from Vyluma’s Phase III clinical trial (“CHAMP”) in the US 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.
· The China CHAMP trial involves 18 centers and 777 patients and is led by Professor Wang Ning Li from Beijing Tongren Hospital as the Principal Investigator. The Mini-CHAMP trial involves 16 centers and 526 patients and is led by Principal Investigators 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.
Updates during the Reporting Period
In June 2023, Vyluma received FDA acceptance of its NDA for NVK002, supported by positive results from its landmark three-year placebo-controlled international Phase III CHAMP clinical study. A PDUFA goal date of 31 January 2024 has been assigned by the FDA.
On 3 August 2023, the last patient last visit was completed for the Mini-CHAMP of NVK002 in China. This is an important step forward towards the Company’s submission of an NDA in China.
· Zhaoke Ophthalmology will become one of the first companies in China to commercialize approved low-dose atropine product, particularly if we are able to make an NDA submission with the combined data from Mini-CHAMP and those from the CHAMP study conducted by our partner Vyluma.
· At the same time, we continue to progress the two-year China CHAMP study and expect to complete the trial in the second half of 2024.
In March 2023, Zhaoke Ophthalmology entered into a distribution and supply agreement for NVK002 with KDP, a leading Korean pharmaceutical company.
· Under the terms of the agreement, KDP was granted exclusive rights to import, promote, distribute, market and sell NVK002 in South Korea. With this partnership we have taken a concrete first step towards monetizing NVK002 outside of China and expanding our global footprint via strategic partnerships.
· We are also in active dialogue with potential partners in the SEA region.
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 can enter the eye, thereby sharpening both near and intermediate images.
· Zhaoke Ophthalmology’s licensing partner for BRIMOCHOL PF™ and Carbachol PF is Visus, a clinical-stage US pharmaceutical company focused on developing innovative ophthalmic therapies. Visus is currently conducting Phase III pivotal trials.
Updates during the Reporting Period
In April 2023, Visus announced positive topline results from its Phase III pivotal BRIO-I trial. BRIMOCHOL PF successfully met the pre-specified visual acuity primary endpoints for both the US and EU/UK against its active comparators carbachol and brimonidine. In the trial, BRIMOCHOL PF™ demonstrated highly statistically significant improvements in near and distance binocular visual acuity at multiple timepoints over carbachol and brimonidine.
· BRIMOCHOL PF achieved highly statistically significant near vision improvements over 8 hours and was well-tolerated.
· An additional Phase III safety trial, BRIO-II, is underway with results expected to be announced during 2024.
· The clinical development plan in China will be a Phase I study followed by a Phase III study. We are actively progressing a China IND application and expect to formally file an IND application before the end of this year.
TAB014 (Bevacizumab) for wAMD (partnered with TOT BIOPHARM Co., Ltd.)
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.
· 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 (“BCVA”) at week 52 in TAB014-treated subjects group compared with the Lucentis®-treated subject group.
· The study involves up to approximately 60 centres and a total of 488 patients and is led by Professor Chen Youxin from Peking Union Medical College Hospital as the Principal Investigator.
· We are currently recruiting patients for the Phase III clinical trial of TAB014. We completed the First Patient In (“FPI”) in June 2022, and 370 patients have been recruited across 50 centres as of June 30, 2023. We aim to complete patient recruitment before the end of 2024.
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 conducted several Phase II clinical trials and an investigator initiated trial of ZKY001 for multiple potential indications, including CED (“corneal epithelial defect”); TPRK (“transepithelial photorefractive keratectomy, a surgical treatment for myopia); pterygium (a growth in the cornea or the conjunctiva”); and NK (“neurotrophic keratitis”, a rare degenerative corneal disease).
· Following the analysis of all the results across these studies, the research and clinical teams have decided to focus on TPRK, specifically the treatment of corneal epithelial defects after eye surgery as the indication for a Phase III trial to be initiated in 2024.
· Once approved for a first indication, we believe the adoption of ZKY001 will expand quickly into other corneal repair applications.
Generic Drugs
We follow a balanced approach in designing our drug pipeline. In addition to innovative drug candidates, our Company is working on several generic drugs. The market potential for the management and treatment of ocular disease in China is unmatched globally. Generic drugs address a substantial portion of current unmet ophthalmic medical needs in China. From a market demand perspective, our generic pipeline complements our innovative pipeline and positions us to provide a full range of solutions to ophthalmologists and patients.
· In February 2023, Bimatoprost Timolol eye drop, known as 晶贝莹® in the PRC – a drug researched, developed and manufactured by Zhaoke Ophthalmology for the treatment of glaucoma – obtained marketing authorization from the National Medical Products Administration (NMPA).
· 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/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 it was written on 8 March 2023 in Guangzhou. The eye drop will help expand brand recognition of Zhaoke Ophthalmology to support the future commercial launch of our innovative drugs. In May 2023, Bimatoprost Timolol eye drop (晶贝莹®) was also launched on JD Health, where a wider audience of glaucoma patients are able access the drug.
· As of the date of this announcement, we have also filed 2 additional ANDA submissions to the NMPA for Travoprost (one of the most frequently prescribed PGAs for open-angle glaucoma in China), and Travoprost Timolol.
