We are an ophthalmic pharmaceutical company dedicated to the research, development and commercialization of therapies that address significant unmet medical needs in China. Leveraging our deep domain expertise, we have built a comprehensive ophthalmic drug pipeline of 25 candidates that covers most major ocular indications affecting the front and the back of the eye, through either in-house development or in-licensing. We have also established an advanced ophthalmic manufacturing facility and are assembling an experienced marketing team in anticipation of near-term product launch. Our goal is to become a leader in China and the neighboring ASEAN marketplace.
China has a large and underserved ophthalmic patient population. In 2019, the total prevalence of ocular diseases and disorders in China was significantly higher than the United States, yet the ophthalmic pharmaceutical market was only one-sixth as large, according to CIC. This suggests significant growth potential. According to CIC, the Chinese ophthalmic pharmaceutical market is forecast to grow from US$2.6 billion in 2019 to US$20.2 billion in 2030, at a CAGR of 20.6%. However, the market is fragmented, lacking a leader with ophthalmic-focused expertise that can provide a comprehensive solution for this specialty therapeutic area.
To address this attractive market opportunity, we have built an ophthalmic drug pipeline comprising 13 innovative drugs and 12 generic drugs as classified under NMPA drug registration regulations. Our innovative pipeline includes 8 drug candidates which have the potential to be market-leading products in China if approved. Our generic pipeline includes 6 potential first-to-market generics in China, which we believe will bring us near-term cash flows and significant first-mover advantages in commercial-scale manufacturing and marketing. According to CIC, we have one of the most comprehensive ophthalmic drug pipelines in China.
In designing our pipeline, we have initially placed strategic emphasis on five major ophthalmic indications in China in terms of market potential, including dry eye disease, or DED, wet age-related macular degeneration, or wAMD, diabetic macular edema, or DME, myopia and glaucoma. Most ocular conditions present at variable stages of disease severity, often driven by multiple pathological processes that affect local microenvironments with specific tissue responses. Hence most conditions are heterogeneous in nature. Therefore, for each of the major indications, we typically develop multiple drug candidates with different mechanisms of action. We expect our multi-targeted approach to give physicians access to an arsenal of different drugs and the therapeutic flexibility to administer them as mono- or combination therapies, helping them formulate an optimal regimen for each patient and serve a broader group of patients in each of the ophthalmic sub-specialties. Through this pipeline strategy, we aim to become the essential one-stop solution.
We have developed internal capabilities in key aspects of ophthalmic drug development. Our specialized in-house research, development, clinical and regulatory capabilities have enabled us to concurrently advance multiple innovative and generic drug candidates through the preclinical and clinical phases. We have a solid track record in business development, having in-licensed a number of drug candidates across major indications with high growth potential from international partners. Setting us apart from competitors in China, we have established a commercial-scale advanced manufacturing facility, which is designed and built for ophthalmic drugs in compliance with cGMP requirements of China, the United States and the European Union. We are also assembling a commercial team with extensive experience covering various nationwide sales channels and ophthalmologists in China. We believe these established capabilities will help us bring innovative and comprehensive ophthalmic therapies to market and become the partner of choice of multinational pharmaceutical companies.
We are led by an international management team with decades of industry experience and a track record of research and development, clinical operations, manufacturing, regulatory communications, business development and commercialization of ophthalmic therapies. In addition, we have received strong endorsement from blue-chip investors, including GIC, Hillhouse, TPG, Loyal Valley Capital, Orbimed and Aier Eye Hospital.
Our Pipeline of Innovative Drugs
Our DED Drug Pipeline
Cyclosporine A (CsA) ophthalmic gel, our late-stage Core Product and an eye gel indicated for DED based on the CsA compound. Compared with Restasis, the first CsA ophthalmic drug approved in the United States, which is an oil-based emulsion, our CsA drug is in an innovative hydrogel formulation. It diffuses faster on the ocular surface and stays longer. In an ex vivo preclinical study, our CsA ophthalmic gel demonstrated significantly greater local bioavailability in the tear film and ocular surface tissues compared to Restasis. In a Phase II exploratory study in moderate-to-severe dry eye patients, once-daily dosing of our CsA ophthalmic gel was able to deliver similar efficacy and safety compared to the twice a day dosing of Restasis. These clinical findings are supported by the higher exposure delivered in the front of the eye by our CsA ophthalmic gel compared to Restasis in preclinical experiments. In addition, studies have shown that the most common reason for which patients discontinue Restasis is the transient burning sensation immediately after topical application of the drug. By eliminating all daytime administrations and the associated discomfort and inconvenience, our CsA ophthalmic gel, administered once every night, is expected to significantly improve patients’ compliance and quality of life. See “Business—Our Pipeline of Innovative Drugs—Our DED Drug Pipeline—Cyclosporine A (CsA) ophthalmic gel—Summary of Clinical Trials” for details of the clinical trial results.
We commenced research and development of CsA ophthalmic gel in 2006. We initiated a Phase II clinical trial in December 2017 and completed this trial in November 2019. We are conducting a Phase III clinical trial in China to evaluate the efficacy and safety of CsA ophthalmic gel in patients with moderate-to-severe DED, and expect to complete the trial in the third quarter of 2021. We plan to submit an NDA to the NMPA in the fourth quarter of 2021.
RGN-259, an eye drop indicated for moderate-to-severe DED. This is a therapeutic peptide (Thymosin 4), with cellular and tissue protective as well as repair and regeneration enhancement properties. RGN-259 has a novel mechanism with dual effects of corneal repair and anti-inflammation. Studies suggest that it has fast onset efficacy in multiple outcomes of signs and symptoms. It has also shown a statistically significant reduction in ocular discomfort and corneal fluorescein staining compared to placebo in one of the completed Phase III trials in the United States. RGN-259 has also demonstrated a satisfactory safety profile in such trials. We obtained from RegeneRx an exclusive license to manufacture and sell, and a non-exclusive license to develop, RGN-259 and any other Thymosin 4-based drug candidates developed by RegeneRx in Greater China. RegeneRx has completed a Phase II/III clinical trial and two Phase III clinical trials in the United States. Leveraging the results of such clinical trials, we plan to submit an IND application to the NMPA in the second half of 2022, and initiate a Phase III trial in China in 2023.
CsA/rebamipide ophthalmic gel, an innovative combination eye gel with dual mechanisms of anti-inflammation and tear film stabilization, with potentially better efficacy for patients having inadequate response to topical CsA (estimated to account for 20% to 30% of all moderate-to-severe DED patients globally, according to CIC). In the preclinical studies, the CsA/rebamipide ophthalmic gel showed meaningful improvement in DED signs and symptoms in a rabbit DED model. We plan to submit an IND application to the NMPA for the CsA/rebamipide ophthalmic gel candidate in the first half of 2022 and commence a Phase I clinical trial in China in the second half of 2022.
IC-265, an eye drop composed of highly selective and potent Syk tyrosine kinase inhibitor with broad anti-inflammatory effects which has also shown general efficacy in reducing signs of allergic conjunctivitis. We obtained an exclusive license from IACTA to develop, make and sell IC-265 in Greater China and certain Southeast Asia countries. A Phase II clinical trial for the treatment of allergic conjunctivitis was completed. We plan to initiate a Phase II clinical trial for IC-265 in China in the first half of 2022, and we also intend to develop IC-265 for the treatment of uveitis.
Our wAMD Drug Pipeline
PAN-90806, an anti-VEGF agent for wAMD and DME, in a novel eye drop formulation. PAN-90806 is a small-molecule compound with optimal physicochemical properties to allow for topical delivery. If approved, it will bring significant convenience and provide a less invasive treatment alternative for patients as a maintenance therapy, reducing the frequency of intravitreal injections and other associated treatment burden of mainstream anti-VEGF therapies while maintaining visual stability. We obtained an exclusive license from PanOptica to develop and commercialize PAN-90806 in Greater China, South Korea and certain other Southeast Asian countries. We plan to file an IND application with the NMPA for PAN-90806 in the first half of 2022.
TAB014, the first clinical-stage bevacizumab-based antibody indicated for wAMD in China. Bevacizumab is a clinically validated anti-VEGF drug. Globally, although bevacizumab is only approved for oncology treatment through intravenous infusion, there has been increasing off-label use of bevacizumab via intravitreal injection for treatment of wAMD. We obtained an exclusive license from TOT BIOPHARM to commercialize TAB014 for neovascularization-related eye diseases in China. We expect the Phase III clinical trial of TAB014 to be initiated in the second quarter of 2021 and be completed in 2023. We plan to submit an NDA to the NMPA for TAB014 by 2024.
Our DME Drug Pipeline
ZK002, a protein with a novel mechanism of action to contain inflammation (i.e., anti-inflammation effect) and vascular flood leakage (i.e., anti-permeability effect), which has potentially better efficacy advantages over existing mainstay treatments for DME. ZK002 is expected to lower treatment burden by reducing the number of intravitreal injections required and improve treatment compliance. ZK002 also has anti-angiogenesis effect in addition to anti-permeability and anti-inflammatory properties. As such, we believe ZK002 has the potential to be a foundational agent, either as monotherapy or in combination with anti-VEGF agents, to address proliferative diabetic retinopathy in addition to DME. We plan to submit an IND application to the NMPA for ZK002 for DME in 2023.
PAN-90806, in addition to the wAMD indication, we are also developing PAN-90806 for DME.
Our Myopia Drug Pipeline
NVK-002, a potential novel topical ophthalmic solution to control myopia progression. NVK-002 has a proprietary formulation that successfully addresses the instability of low-concentration atropine. It is preservative-free with an expected shelf life of as long as 24 months. According to CIC, NVK-002 is one of the most advanced atropine drug candidates globally for myopia progression control, and targets the broadest patient group, covering children and adolescents from 3 to 17 years old. We obtained an exclusive license to develop, manufacture, register, import and commercialize NVK-002 in Greater China, South Korea and certain countries in Southeast Asia. We plan to submit an IND application to the NMPA in the second quarter of 2021. Subject to IND approval from the NMPA, we plan to commence a Phase III bridging clinical trial in China in the fourth quarter of 2021, and submit an NDA to the NMPA in 2023.
Other Innovative Drug Candidates
ZKY001, one of our Core Products, an eye drop targeting corneal epithelial defects, or CED, through anti-inflammatory effects plus stimulation of epithelial cell migration. Compared to widely prescribed growth factor therapies, such as rh-EGF and rb-bFGF drugs, which stimulate angiogenesis and may cause edema and inflammation, ZKY001 showed better in vivo efficacy in reducing corneal swelling and suppressing abnormal ocular vessel growth in preclinical animal models. ZKY001 also has a favorable safety profile, well tolerated at all concentrations in one of our Phase I clinical trials. We believe ZKY001 has the potential to be a foundational therapy for a broad range of corneal epithelial diseases.
We commenced research and development activities for ZKY001 in January 2013. We have completed two preclinical studies to evaluate the efficacy of ZKY001. The first study compared the efficacy of ZKY001 against rh-EGF, levofloxacin lactate and saline on the treatment of CED after laminectomy, a surgery which removes a layer in the cornea and, inevitably, creates damages to the cornea. ZKY001 showed faster onset effects than rh-EGF and levofloxacin lactate. The second study compared the efficacy of ZKY001 at three concentrations against rh-EGF and saline on the repair of CED after corneal alkali burns, serious damages to the cornea after contact with alkaline chemicals. The study showed that cell migration in the ZKY001 treatment groups was signicantly higher than that in the control groups, with 20 g/ml ZKY001 and 40 g/ml ZKY001 being more efcacious than the other groups.
In addition, we completed a Phase I clinical trial in December 2018 which evaluated safety, tolerability and systemic pharmacokinetics of ZKY001 in healthy subjects. ZKY001 was well tolerated in all concentrations during the trial. Among the 34 subjects who received ZKY001, only three mild AEs were reported. We are conducting another Phase I clinical trial evaluating the ocular pharmacokinetics and safety of ZKY001 and a Phase II clinical trial evaluating the safety and efficacy of ZKY001 for the treatment of CED after endothelial keratoplasty. See “Business—Our Pipeline of Innovative Drugs—Other Innovative Drug Candidates—ZKY001—Summary of Clinical Trial Data” and “—Summary of Preclinical Studies” for details. We plan to initiate a Phase III clinical trial in the second half of 2022 and target to submit an NDA to the NMPA in 2024.
Resolv ER, an intravitreal injection of liposome-loaded urea for the treatment of vitreomacular traction, or VMT. By using Resolv ER, patients suffering from VMT may avoid invasive surgery and preserve vision. We obtained an exclusive license from Kato Pharmaceuticals to develop, make and sell Resolv ER in Greater China and certain countries in Southeast Asia. We plan to submit an IND application to the NMPA for in the second quarter of 2021 and initiate a Phase II clinical trial in the fourth quarter of 2021.
IC-270, a fixed-dose combination of IC-265, a Syk tyrosine kinase inhibitor, and an antihistamine agent for the treatment of allergic conjunctivitis. IC-270 has the potential to be a treatment for allergic conjunctivitis that addresses not only itching but also redness and inflammation associated with allergic conjunctivitis. We obtained an exclusive license from IACTA to develop, make and sell IC-270 in Greater China and certain Southeast Asia countries. We plan to commence a Phase III clinical trial in 2023 and submit an NDA to the NMPA in 2024.
ZK002, a protein with anti-angiogenesis and anti-inflammation effects, and therefore is an ideal drug candidate for pterygium, in which vascular angiogenesis and inflammation play prominent roles. We plan to submit an IND application to the NMPA for pterygium in the second half of 2022.
Our Pipeline of Generic Drugs
Bimatoprost, a potential first-to-market generic in China targeting glaucoma and potentially the only bimatoprost eye drop without any preservatives. We submitted an abbreviated NDA to the NMPA in August 2019 and expect to receive approval in the fourth quarter of 2021.
Bimatoprost timolol, a potential first-to-market generic bimatoprost timolol in China targeting glaucoma. We submitted an abbreviated NDA to the NMPA in October 2020 and expect to receive approval in the first half of 2022.
Latanoprost, one of the most frequently prescribed PGAs for open-angle glaucoma in China. We plan to submit an abbreviated NDA to the NMPA in the first half of 2022 and expect to receive approval in 2023.
Latanoprost timolol, a PGA and blocker combination eye drop targeting glaucoma. We plan to submit an abbreviated NDA to the NMPA in the first half of 2022 and expect to receive approval in 2024.
Travoprost, one of the most frequently prescribed PGAs for open-angle glaucoma in China. We plan to submit an abbreviated NDA to the NMPA in the first half of 2022 and expect to receive approval in 2023.
Travoprost Timolol, a potential first-to-market generic travoprost timolol in China targeting glaucoma. We plan to submit an abbreviated NDA to the NMPA in the second half of 2022 and expect to receive approval in 2024.
Levobetaxolol HCl, a potential first-to-market generic levobetaxolol hydrochloride in China targeting glaucoma. We plan to submit an abbreviated NDA to the NMPA in the first half of 2022 and expect to receive approval in 2023.
Epinastine HCl, a potential first-to-market generic in China targeting allergic conjunctivitis with a dual mechanism of action of anti-histamine and mast cell stabilization. We submitted an abbreviated NDA to the NMPA in June 2020 and expect to receive approval in the first half of 2022.
Natamycin, an antifungal ophthalmic eye drop used to treat fungal infections around the eye. We plan to submit an abbreviated NDA to the NMPA in 2022 and expect to receive approval in 2024.
Proparacaine HCl, a single-dose preservative-free proparacaine HCl eye drop for short-acting surface anesthesia. We plan to submit an abbreviated NDA to the NMPA in the fourth quarter of 2021 and expect to receive approval in 2023.
Povidone iodine, a single-dose preservative-free eye drop for skin disinfection before and after surgery. We plan to submit an abbreviated NDA to the NMPA in the third quarter of 2021 and expect to receive approval in 2023.
Fluorescein Sodium, a potential first-to-market generic in China and potentially the first fluorescein sodium in eye drop formulation. We plan to submit an abbreviated NDA to the NMPA in 2023.
As of the Latest Practicable Date, we owned eight issued PRC patents and one issued EU patent, and had filed six PRC patent applications, two patent applications under the PCT, and three patent applications in other jurisdictions. Among our patents and patent applications, (i) two patents were in relation to ZKY001, one of our Core Products, and were material to our business and (ii) one patent and two patent applications were in relation to CsA ophthalmic gel, our other Core Product, and were material to our business.
Source: Zhaoke Ophth-B (06622) Prospectus (IPO Date : 2021/04/16) |