The earliest use of topical medicines in human history dates back to the ancient Egyptian period around 2000 B.C., when doctors used ointments made from oils and plant extracts to treat skin diseases and burns. By the medieval period, topical medicines had become one of the main treatments for diseases in many parts of the world. With the development of modern pharmacology, a variety of topical medicines for different conditions have emerged, such as antibiotic ointments, steroid creams and eye drops, which have greatly improved human health.

"At present, the demand for topical medicines is increasing day by day. For example, skin diseases, where topical medicines are widely used, are showing an elevated incidence and consultation rate as China's economy develops and people's living standards improve, and patients begin to pay attention to and seek treatment for skin diseases that were previously often ignored." Dr. Du Yunlong, Chief Executive Officer (CEO) and Chief Medical Officer (CMO) of PrimegeGene, said, "In the face of the expanding demand for treatments, the development of new drugs in the field of topical medicines has become more and more urgent. It is against this backdrop that PrimegeGene was founded, and the company is now primarily focused on topical drug development to meet the unfinished medical needs of a wide range of patients."

At present, PrimegeGene has established a product pipeline featuring topical drugs around immunomodulatory and inflammatory targets, with indications covering a wide range of dermatological diseases such as atopic dermatitis (AD), nodular itchy rash, herpetic epidermolysis bullosa, and psoriasis, as well as other diseases such as allergic rhinitis, peripheral neuralgia, and glaucoma. Among them, PG-011 gel, a JAK inhibitor, has recently initiated a multi-center Phase 2b/3 clinical study in China to evaluate the efficacy and safety of its topical route of administration for the treatment of mild to moderate atopic dermatitis. Since its inception, PrimegeGene has completed several rounds of financing, including over 100 million yuan of Series A+ financing, with investors such as K2 Venture Partners, Lapamcapital, Sunland Fund, and Tongxi management.

What are PrimegeGene's unique advantages in the field of topical drug development? What are the current challenges in disease treatment that the company's pipeline is expected to address? What new changes are expected in the field of topical drugs in the next 10 years? With these questions in mind, WuXi AppTec's content team recently interviewed Dr. Yunlong Du. Dr. Du has more than 20 years of experience in global pharmaceutical companies, with experience in early development, clinical research, medical affairs, drug safety management, and marketing applications in the areas of dermatology, metabolism, and neurology.

WuXi AppTec Content Team: What are some of the key challenges facing current therapeutic modalities or clinical solutions in the areas of dermatology and ophthalmology that PrimegeGene is working on?

Dr. Yunlong Du: PrimegeGene focuses on topical drug development. Compared to the traditional oral route of administration, topical drugs are safer and more suitable for the long-term treatment of chronic diseases, especially in the areas of dermatology, allergic rhinitis and ophthalmology. The Company focuses closely on the development of immunomodulatory and inflammatory targets, and focuses on unmet clinical needs in the fields of dermatology, rhinology, ophthalmology, rare diseases, etc. There are several therapeutic challenges in these fields as follows: 1) Currently, domestic and overseas clinical use of medicines is still dominated by generics, and there is a lack of innovative topical medicines, especially Class 1 innovative medicines; 2) For many years, traditional hormones have still been used as the main means of treatment in the field, and their safety and efficacy cannot effectively meet clinical needs; 3) with China's economic development and improvement of people's living standards, patients have started to pay attention to and seek treatment for skin diseases that were often neglected in the past, and the incidence and consultation rate of such diseases have shown a rising trend; 4) compared with oncology, cardiovascular and other medicines, the listing of overseas innovative topical drugs in China is also relatively lagging behind.

WuXi AppTec Content Team: Will PrimegeGene's new technology and R&D pipeline help address these challenges?

Dr. Yunlong Du: PrimegeGene is committed to developing innovative topical drugs for the treatment of inflammatory and immune-related diseases to fill the existing gaps in the field. The company has developed a new generation of JAK/ROCK dual-target inhibitors for skin, which can inhibit multiple immune-inflammatory factors by inhibiting JAK protein kinase, thereby effectively relieving disease-induced inflammation and improving skin repair, addressing the problems of unsatisfactory results and many side effects of traditional treatments.

Currently, the Company's fastest progressing product under development, pumecitinib (PG-011) gel, has completed an exploratory clinical phase 2 trial for the treatment of adult atopic dermatitis and nodular itch, and is in the process of further optimizing the treatment protocol. We are also further developing the product in adolescent atopic dermatitis subjects, including pharmacodynamics and safety evaluation. We hope to advance the product to market as soon as possible to meet the clinical demand for non-glucocorticoid topical innovations for the treatment of atopic dermatitis in adults and adolescents.

WuXi AppTec Content Team: Why did you choose to join PrimegeGene, which specializes in topical innovator drugs?

Dr. Yunlong Du: Based on the unmet clinical needs, areas such as oncology have made major breakthroughs in recent years, and different types of innovative therapies such as immune checkpoint inhibitors like anti-PD-1 antibodies, CAR-T therapies, and Antibody-Coupled Drugs (ADCs) have been launched on the market, and at the same time there are a lot of Biotech companies that are developing new medicines in these areas. In contrast, specialized segments such as dermatology, rhinology, ophthalmology, etc. have seen very few new drugs come to market in the last 10 years, and patient demand is far from being met, especially for specialty formulations with a higher safety profile. We hope to bring a variety of innovative therapies to these disease areas with our team's exploration and efforts. We also believe that the development of innovative drugs in these disease segments that PrimegeGene specializes in will also see a prosperous spring in the future.

WuXi AppTec Content Team: What are the biggest internal and external challenges you and your team have encountered since starting your business? How do you plan to solve them?

Dr. Yunlong Du: For PrimegeGene, the biggest challenge the company has encountered is the lack of talents, especially professionals in the R&D of topical drug formulations. Taking transdermal drug delivery as an example, as the third largest drug delivery system after oral and injection, it solves the problems of first-pass metabolism, peaks and valleys, and poor adherence of the traditional drug delivery methods of oral and injection to a certain extent, and at the same time reduces the gastrointestinal and other side effects, and improves the convenience, adherence, and safety of drug delivery for special groups such as children, the elderly, and pregnant women. However, due to the complex structure of the surface layer of the skin, including the thickness of the stratum corneum and lipid content, the number of capillaries, the distribution of sweat glands and hair follicles, body temperature and other factors will have an impact on the drug from the epidermis into the circulatory system. This makes the development of such drugs difficult, and the scarcity of international expertise in this area poses a challenge to the development of drug formulations and processes.

For this reason, PrimegeGene has gathered a team of experts from home and abroad to explore this field in practice. After years of development and accumulation, the company has established a complete new drug R&D system from front-end R&D to back-end clinical development, and has set up a number of distinctive platforms for precise screening of drug targets, chemical synthesis process and formulation development, and clinical protocol design, thus improving the success rate of the company's products under development and shortening the drug development cycle. In overcoming these challenges, we have also built certain technical barriers for PrimegeGene. Currently, the company's core team has rich experience in the fields of new drug development, clinical research and product launch.

WuXi AppTec Content Team: How do you view the current innovative drug development environment in China?

Dr. Du Yunlong: In recent years, China's pharmaceutical industry has been developing rapidly under the guidance of China's pharmaceutical innovation policy and the support of the capital market. It is inevitable and a general trend for biopharmaceutical companies to make innovation breakthroughs. Under this situation, the strength of Chinese innovative drug companies has been gradually strengthened, the number of new drug clinical trial projects has been increasing rapidly, the number of innovative drug submissions has been growing year after year, and the degree of internationalization has been greatly improved and gained more recognition. It is undeniable that the rapid development of innovative drugs in China has been accompanied by some problems in the industry. Therefore, it is important to differentiate the layout as early as possible, look for truly unmet clinical areas, and make innovative drugs with real clinical value in order to enable the company to stand higher and go farther.

WuXi AppTec Content Team: How do you see the role and influence of "collaboration" in the current biopharmaceutical innovation ecosystem?

Dr. Du Yunlong: Drug R&D is a complex and systematic work. No innovative drug company can do everything in terms of new drug R&D and commercialization, but generally need to complement each other's strengths and weaknesses through cooperation, so as to reduce costs and improve efficiency. PrimegeGene also cooperates with CROs and CDMOs in the development of new drugs, so that the projects can be fast-tracked and both parties can realize win-win cooperation. Through the cooperation, PrimegeGene has also initially established a complete organizational structure for Biopharma, laying the foundation for the strategic layout of commercial production and product promotion at a later stage.

WuXi AppTec Content Team: In the field of topical drugs, what new changes do you think will come in the next 10 years?

Dr. Du Yunlong: In recent years, the application of topical medicines, especially topical medicines for dermatological diseases, has become more and more important outside of hospitals, especially the increasing demand for medicines purchased through online pharmacies. With the popularization of Internet hospitals and pharmaceutical e-commerce, the development prospect of topical drugs will be even more promising in the future. In the next 10 years, it is believed that under the continuous development of science and technology, the field of topical drugs will usher in these changes: 1) more drugs with new targets will be developed, including monoclonal antibodies and topical small molecule innovators; 2) more topical improved new drugs will emerge, including the expansion of listed products to new topical indications; 3) there will be greater breakthroughs and upgrading of topical drug delivery preparation technology; 4) some topical drugs will be developed from prescription to (OTC), providing patients with more accessible, convenient and easy-to-accept personalized treatment options.

In addition, dermatologic diseases, as a large category of diseases, contain more than 2,000 types of diseases, and we are convinced that there are certain differences between these diseases. New drugs developed for different types of diseases are also different, with differences in suitable targets, types of molecular structures, modes of formulation, sites of drug action and depth of the dermis. Only when these are thoroughly researched can we make differentiated, high-quality clinical therapeutic drugs.