-Lead compound selectively and directly inhibits XBP1s-Supported by research funding for two years, advancing to an oral first-in-class anticancer drug candidate-Expected to show antitumor effects in patients resistant to standard hormone therapy-Discovered through AI-based R&D platform CLOVER, continuously generating new drug candidates in oncology and immunological diseases June 2024 JW Pharmaceutical (CEO Shin Young-seop) announced on the 25th that its subsidiary, C&C Research Laboratories (CEO Park Chan-hee), has been selected for the "2024 1st National New Drug Development Project for Building a New Drug R&D Ecosystem" to develop a treatment for hormone-resistant and non-responsive prostate cancer. The National New Drug Development Project is an interagency national R&D initiative launched to strengthen the global competitiveness of the domestic pharmaceutical and biotechnology industries. The National New Drug Development Project Team (led by Director Park Young-min, hereafter referred to as 'the team') aims to support all phases of new drug development from 2021 to 2031, enhancing the domestic new drug R&D ecosystem, creating globally practical outcomes, and generating public health benefits. Over the next two years, C&C Research Laboratories will receive research funding from the team to optimize a lead compound that directly inhibits XBP1s and develop an oral first-in-class anticancer drug candidate. XBP1s is a protein that is highly expressed in various solid tumors, playing a crucial role in cancer proliferation. Specifically, XBP1s increases the activity of genes related to cancer cell survival, diminishing the efficacy of standard treatments and enabling cancer cells to evade immune responses. The lead compound selected for this project was discovered through the institute's proprietary data science platform, CLOVER, which combines chemical and biological informatics big data with AI and deep learning technologies. This lead compound demonstrated excellent anticancer effects by directly binding to and inhibiting the XBP1s protein in cell experiments, and showed tumor suppression effects. It also exhibited superior antitumor efficacy in drug response measurements in prostate cancer animal models compared to control groups. C&C Research Laboratories plans to conduct structural optimization research on the XBP1s-targeted anticancer lead compound and derive a preclinical new drug candidate by 2025. A representative from JW Pharmaceutical stated, "Prostate cancer, the second most common cancer in men, has a high demand for innovative drugs with new mechanisms of action due to resistance and non-responsiveness to first-line standard hormone therapies. We aim to develop the lead compound targeting XBP1s into an innovative anticancer drug that can overcome the limitations of existing treatments not only for prostate cancer but also for various solid tumors." C&C Research Laboratories, established in 1992 as the first Korea-Japan joint venture bioventure by JW Pharmaceutical and Chugai Pharmaceutical, a member of the Roche Group, became a 100% subsidiary of JW Pharmaceutical in 2020. Since 2010, C&C Research Laboratories has been discovering innovative drug candidates through its R&D platform, CLOVER, which integrates AI and deep learning technologies with chemical and biological informatics big data. It currently holds a pipeline of over 10 new drug candidates for oncology and immunological diseases, including gout treatment 'Epaminurad (URC102)', atopic dermatitis treatment 'Ezzofrant (JW1601)', and STAT3-targeted anticancer drug 'JW2286', all of which have been licensed to JW Pharmaceutical. The institute is also focusing on developing new drugs targeting STAT proteins that regulate cell growth, mutation, and proliferation, alongside its XBP1s-targeted research. C&C Research Laboratories' new drug pipeline has been continuously recognized as a national project by the team. In 2021, the institute was selected for the lead compound optimization research for a STAT3-targeted atopic dermatitis treatment, in 2022 for the preclinical research of the STAT3-targeted anticancer drug JW2286, and in 2023 for the lead compound optimization research for a STAT5/STAT3 dual-targeted acute myeloid leukemia treatment. 

About Prostate Cancer and the Market

Prostate cancer is a malignant tumor that develops in the prostate gland cells and is the second most frequently diagnosed cancer in men worldwide. Its incidence increases with age, and while early-stage disease progresses slowly with a five-year survival rate of 97.1%, the survival rate for metastatic prostate cancer drops sharply to 34.1%. Prostate cancer is often asymptomatic in its early stages, making detection difficult, but as it progresses, symptoms such as urinary abnormalities, testicular pain, and erectile dysfunction may appear. The primary treatment, hormone therapy, is initially effective but most patients develop resistance within 18-24 months, leading to recurrence. This creates a high unmet medical need for new therapies. Globally, while the incidence of prostate cancer is decreasing or stabilizing, the number of diagnosed patients is expected to increase due to population aging. According to "Datamonitor Healthcare" in 2023, approximately 597,440 people were diagnosed with prostate cancer worldwide in 2022, and this number is projected to rise to about 681,600 by 2032. The global prostate cancer treatment market is expected to grow from $10.667 billion in 2022 to over $19.998 billion by 2032, reflecting a compound annual growth rate (CAGR) of 6.5%. 

About XBP1s

XBP1s (X-Box-binding Protein 1 splicing form) is a protein activated by endoplasmic reticulum (ER) stress and androgen receptor (AR) signaling, known to play a critical role in the proliferation of various solid tumors. High ER stress and increased expression of XBP1s are common in patients resistant to standard treatments, making it a major cause of drug resistance. XBP1s increases the activity of genes related to cancer cell survival, rendering standard treatments ineffective and further weakening the efficacy of drugs by inhibiting immune cells' anticancer responses, allowing cancer cells to evade immune attacks. Currently, there are no clinically developed XBP1s inhibitors as anticancer drugs worldwide. Therefore, JW Pharmaceutical expects that C&C Research Laboratories' XBP1s inhibitor will be developed as a new targeted therapy providing both anticancer effects and immune modulation for patients resistant to standard treatments.

 -STAT3 Inhibitor JW2286 Developed as a First-in-Class Global Innovative Drug-Expected to Address Unmet Medical Needs in Various Solid Tumors-Progression to Clinical Phase with In-House R&D Platform Targeting Wnt and STAT June 2024 JW Pharmaceutical announced on the 19th that it has received approval from the Ministry of Food and Drug Safety for the clinical phase 1 IND for its STAT3 inhibitor 'JW2286', which is being developed as a treatment for solid tumors. JW2286 is a novel mechanism-based first-in-class candidate that selectively inhibits STAT3. It is being developed as an oral drug, targeting triple-negative breast cancer, gastric cancer, and colorectal cancer. This clinical trial aims to evaluate the safety, tolerability, and pharmacokinetic properties of JW2286 in approximately 70 healthy Korean and Caucasian adults at Seoul National University Hospital. STAT3 is a protein (transcription factor) that promotes the expression of various genes within cells. Abnormal activation of STAT3 is deeply involved in the growth, proliferation, metastasis, and drug resistance of cancer cells, and it is also known to cause inflammatory diseases and autoimmune disorders such as atopic dermatitis. According to preclinical pharmacological evaluation results presented by JW Pharmaceutical at the 2021 American Association for Cancer Research (AACR) Annual Meeting, JW2286 demonstrated higher efficacy and safety compared to standard therapies in several solid tumors with high STAT3 activity as a biomarker, showing particularly strong efficacy in triple-negative breast cancer. Triple-negative breast cancer is a type of breast cancer that is not affected by female hormones or epidermal growth factor (HER2), with very high unmet medical needs. A JW Pharmaceutical representative stated, "The IND approval is a significant milestone in the development of JW2286, recognizing its potential to address unmet medical needs in oncology and immunological disorders. We will continue to develop JW2286 as the first innovative drug that selectively inhibits STAT3." JW2286 was selected as a supported project in the '2022 2nd National New Drug Development Project'. With funding from the National New Drug Development Project, JW Pharmaceutical completed the GLP (Good Laboratory Practice) toxicity evaluation and production of the clinical drug for JW2286. 

About STAT and JW Research

The JAK-STAT pathway is a representative intracellular signal transduction system involved in cell development, differentiation, growth, survival, and various immune responses. STAT proteins consist of seven different types (STAT1~4, STAT5A, STAT5B, STAT6) with distinct functions, activated by the upstream protein JAK. While the JAK-STAT pathway is typically controlled within a normal range, abnormal activation (overexpression or hyperactivation) of the proteins can lead to various diseases. Pharmaceutical companies, including global big pharma, are focusing on developing treatments for immune and tumor diseases by targeting JAK to inhibit the JAK-STAT signaling pathway. However, to date, no new drugs have been developed globally that directly inhibit STAT. JW Pharmaceutical is developing specific small molecule inhibitors that directly bind to and inhibit the activity of STAT3, STAT5, STAT6, aiming to achieve powerful effects and overcome the side effect issues of JAK inhibitors. JW Pharmaceutical's subsidiary, C&C New Drug Research Institute, is focused on discovering new drugs targeting STAT proteins, currently securing a pipeline of over 10 new drug candidates for tumor and immune disorders. C&C's new drug pipeline has been continuously recognized as a national project. In addition to the preclinical research on the STAT3-targeted anticancer drug JW2286 (2022), the optimization research for the lead compound of the STAT3-targeted atopic dermatitis treatment (2021), and the optimization research for the lead compound of the STAT5/STAT3 dual-targeted acute myeloid leukemia treatment (2023) were each selected as national projects. 

About AI and Data Science Platform-Based Innovative Drug Development Targeting Wnt and STAT

JW Pharmaceutical is continuously generating new drug candidates in oncology, immunological diseases, and regenerative medicine by leveraging its in-house data science platforms 'JWELRY' and 'CLOVER', targeting Wnt and STAT. Recently, JW has been enhancing and differentiating its R&D platform by integrating AI (artificial intelligence) and deep learning technology with chemical and biological informatics big data and actively pursuing open innovation with external AIDD (AI-based Discovery) platforms. JW's new drug research center is utilizing 'JWELRY (JW Excellent LibraRY)', specialized in the Wnt signaling pathway, as a core technology. JWELRY is based on a library of tens of thousands of compounds involved in the Wnt pathway and drug evaluation and mechanism research technologies that distinguish inhibition and activation of the Wnt pathway. CLOVER (C&C Research Laboratories Omics serVER) is the R&D platform of C&C New Drug Research Institute, a research subsidiary of JW Pharmaceutical, actively engaged in developing new drugs targeting STAT proteins. JW is accelerating the development of its new drug pipeline targeting Wnt or STAT, with plans to initiate clinical trials for the Wnt-targeted hair loss treatment 'JW0061' and the STAT3-targeted anticancer drug 'JW2286' in 2024. Additionally, JW is continuously striving to enhance translational research to reduce the gap between preclinical and clinical stages and increase the likelihood of clinical success by integrating R&D platforms such as AI, organoids, and zebrafish (open innovation).

 -First Efficacy Evaluation on Human Skin Organoids and Androgenic Alopecia Animal Model Revealed at the Society of Investigative Dermatology-Demonstrated Excellent Hair Follicle Proliferation and Hair Growth Compared to Standard Treatments-Innovative First-in-Class Drug Activating Wnt, First to Elucidate Hair Growth Mechanism-Developed as a Global New Drug that Can Complement and Replace Existing Hair Loss Treatments, Suitable for Both Men and Women' May 2024 JW Pharmaceutical announced on the 20th that it had presented the superiority of Wnt-targeted hair loss treatment ‘JW0061’ in hair follicle formation and hair growth compared to existing treatments at the Society of Investigative Dermatology, held from May 15 to 18 in Dallas, Texas. At this conference, JW Pharmaceutical revealed for the first time the efficacy of JW0061 evaluated on human skin organoids (organ-like structures) and an androgenic alopecia animal model. The study using skin organoids differentiated from human induced pluripotent stem cells was designed to predict whether JW0061 generates hair follicles on the actual human scalp. Organoids can replace animal testing and are a next-generation drug development technology that can assess drug efficacy without direct human trials. When JW0061 and the standard treatment were applied to skin organoids, the number of hair follicles in the JW0061-treated organoids significantly increased compared to the standard treatment. Specifically, JW0061-treated organoids had 7.2 times and 4.0 times more hair follicles on the 5th and 10th days of drug application, respectively, than the standard treatment. Notably, JW Pharmaceutical’s skin organoid research presentation was the only result in the poster session at this conference, drawing significant attention from participants. In addition, the hair growth effect was confirmed in an androgenic alopecia animal model induced by the male hormone testosterone. The androgenic alopecia animal model was divided into four groups: low-dose JW0061, high-dose JW0061, standard treatment (SoC), and placebo. Both low-dose and high-dose JW0061 groups showed faster hair growth promotion compared to the standard treatment. On the 17th day of administration, low-dose and high-dose JW0061 showed 18% and 39% efficacy improvement, respectively, compared to the standard treatment, demonstrating dose-dependent responses. The efficacy presented at this conference resulted from JW0061 directly binding to the GFRA1 protein in dermal papilla cells and activating the Wnt signaling pathway. JW Pharmaceutical previously gained attention by presenting JW0061 as the first low-molecular-weight drug to elucidate the hair growth mechanism at the ‘Wnt 2022’ conference. JW0061 is an innovative first-in-class drug candidate that promotes hair follicle proliferation and hair regeneration by activating the Wnt signaling pathway. This substance was discovered through JW Pharmaceutical’s AI-based data science platform, 'JWELRY.' The Wnt signaling pathway plays a crucial role in skin development and hair follicle formation during embryogenesis and body growth, promoting hair follicle differentiation of skin stem cells. It is particularly involved in the proliferation of dermal papilla cells, located at the base of hair follicles, regulating hair growth and maintenance. Based on the various preclinical results, including those presented at this conference, and the toxicity evaluations completed according to GLP (Good Laboratory Practice) at overseas institutions, JW Pharmaceutical plans to initiate Phase 1 clinical trials within this year. A representative from JW Pharmaceutical stated, “We expect JW0061 to emerge as a promising treatment option that can complement or replace existing hair loss treatments in the global market through this conference presentation. We will develop JW0061 into a global innovative hair loss treatment that is safe and effective for both male and female hair loss patients.” Meanwhile, JW0061 was selected as a project supported by the National New Drug Development Institute last year and received funding for preclinical research. 

About Hair Loss Disorders and Treatment Market

Hair loss can be caused by various factors, including genetic predisposition, autoimmune diseases, and mental stress, leading to a rapid increase in patient numbers. Currently, the main first-line treatments for hair loss are finasteride, dutasteride, and minoxidil. Finasteride and dutasteride are prescribed for male patients and can cause mechanism-specific side effects. Minoxidil is primarily prescribed for female patients, but its hair growth mechanism is unclear, and hair loss recurs soon after discontinuation. Therefore, there is a significant unmet need for a hair loss treatment with a clear mechanism of action that is safe for both men and women. According to the National Institutes of Health, hair loss affects 42% of men worldwide, with approximately 80 million people (25% of the total population) affected in the United States. The Korean Hair Society estimates the domestic hair loss population to be around 10 million (20% of the total population). Market research agencies estimate the global hair loss treatment market to be valued at 10 trillion KRW as of 2021, growing at an annual rate of 8.2%. The market is projected to reach nearly 16 trillion KRW by 2028 (Research and Markets, 2021). 

About the Wnt Signaling Pathway

The Wnt signaling pathway is present across all species, from nematodes and fruit flies to mammals, and plays a crucial role in cell proliferation, differentiation, organ development, and morphogenesis, as revealed by various studies over the past 40 years. Inhibiting the Wnt pathway suppresses the formation, proliferation, and metastasis of cancer cells within various tissues. Conversely, activating the Wnt pathway promotes tissue regeneration by stimulating stem cells and inducing cell proliferation. Despite its influence on many human diseases, there are currently no drugs targeting the Wnt pathway. 

About the Development of Innovative New Drugs Targeting Wnt and STAT Based on Data Science Platforms

Since the 2010s, JW Pharmaceutical has been building AI and deep learning-based data science platforms ‘JWELRY’ and ‘CLOVER,’ in addition to chemical and bioinformatics big data. Through these platforms, JW Pharmaceutical continues to generate new drug candidates targeting Wnt and STAT for cancer, regenerative medicine, and immune diseases. Since the early 2000s, JW Pharmaceutical has focused on developing new drugs targeting the Wnt signaling pathway. Currently, the company utilizes 'JWELRY' (JW Excellent LibraRY), a core proprietary technology specializing in the Wnt signaling pathway. JWELRY is based on a library of tens of thousands of compounds involved in the Wnt pathway, along with drug evaluation and mechanism research technologies for distinguishing inhibition and activation of the Wnt pathway. Through JWELRY, JW Pharmaceutical has identified various new drug candidates, including JW0061, and is generating new projects. In addition, JW Pharmaceutical is actively developing new drugs targeting the STAT protein through ‘CLOVER’ (C&C research Laboratories Omics serVER), established by the research subsidiary C&C New Drug Research Institute. The company focuses on discovering innovative new drug candidates targeting each subtype of the STAT protein, such as the STAT3-targeted anticancer drug JW2286, a STAT3 atopic dermatitis treatment, a STAT5-targeted anticancer drug (for hematologic cancers), and a STAT3-ADC anticancer drug (for solid tumors). Furthermore, JW Pharmaceutical is conducting joint research incorporating AI and organoid platforms from domestic and international biotech companies to explore new indications for its drug candidates and validate their development potential.

 -Discovered through the new drug development platform ‘JWELRY,’ targeting the Wnt signaling pathway for hair loss treatment-First efficacy evaluation on human skin organoid model revealed at international dermatology research conference May 2024 JW Pharmaceutical announced on the 7th that it will present the preclinical results of its Wnt-targeted hair loss treatment ‘JW0061’ through a poster presentation at the Society of Investigative Dermatology conference, which will be held from May 15 to 18 in Dallas, Texas. JW0061 is an innovative new drug (First-in-Class) candidate that promotes hair follicle proliferation and hair regeneration by activating the Wnt signaling pathway. This substance was discovered through JW Pharmaceutical’s AI-based data science platform, ‘JWELRY.’ The Wnt signaling pathway plays a crucial role in skin development and hair follicle formation during embryogenesis and body growth, promoting hair follicle differentiation of skin stem cells. It is particularly involved in the proliferation of dermal papilla cells, which are located at the base of hair follicles and regulate hair growth and maintenance. JW0061 directly binds to the GFRA1 protein in dermal papilla cells, activating the Wnt signaling pathway. JW Pharmaceutical previously garnered attention by presenting JW0061 as the first low-molecular-weight drug to elucidate the hair growth mechanism at the ‘Wnt 2022’ conference. At this year’s Society of Investigative Dermatology conference, JW Pharmaceutical will reveal efficacy evaluation results on various models, including human skin organoids. Organoids are next-generation drug development technologies that can replicate the structural and functional characteristics of patient organ tissues. They can replace animal testing and predict clinical trial results without directly conducting human trials. Based on preclinical research results, JW Pharmaceutical plans to initiate Phase 1 clinical trials within this year. The company has already completed toxicity evaluations according to GLP (Good Laboratory Practice) at overseas institutions and is producing clinical-grade drugs. A JW Pharmaceutical representative stated, “Various preclinical tests have confirmed JW0061’s excellent hair growth and hair follicle regeneration effects. Through this conference presentation, we aim to establish the potential of JW0061 as an innovative treatment option that can complement and replace existing hair loss treatments internationally.” Meanwhile, JW0061 was selected as a project supported by the National New Drug Development Institute last year and received funding for preclinical research. 

About Hair Loss Disorders and Treatment Market

Hair loss can be caused by various factors, including genetic predisposition, autoimmune diseases, and mental stress, leading to a rapid increase in patient numbers. Currently, the main first-line treatments for hair loss are finasteride, dutasteride, and minoxidil. Finasteride and dutasteride are prescribed for male patients and can cause mechanism-specific side effects. Minoxidil is primarily prescribed for female patients, but its hair growth mechanism is unclear, and hair loss recurs soon after discontinuation. Therefore, there is a significant unmet need for a hair loss treatment with a clear mechanism of action that is safe for both men and women. According to the National Institutes of Health, hair loss affects 42% of men worldwide, with approximately 80 million people (25% of the total population) affected in the United States. The Korean Hair Society estimates the domestic hair loss population to be around 10 million (20% of the total population). Market research agencies estimate the global hair loss treatment market to be valued at 10 trillion KRW as of 2021, growing at an annual rate of 8.2%. The market is projected to reach nearly 16 trillion KRW by 2028 (Research and Markets, 2021). 

About the Wnt Signaling Pathway

The Wnt signaling pathway is present across all species, from nematodes and fruit flies to mammals, and plays a crucial role in cell proliferation, differentiation, organ development, and morphogenesis, as revealed by various studies over the past 40 years. Inhibiting the Wnt pathway suppresses the formation, proliferation, and metastasis of cancer cells within various tissues. Conversely, activating the Wnt pathway promotes tissue regeneration by stimulating stem cells and inducing cell proliferation. Despite its influence on many human diseases, there are currently no drugs targeting the Wnt pathway. 

About the Development of Innovative New Drugs Targeting Wnt and STAT Based on Data Science Platforms

Since the 2010s, JW Pharmaceutical has been building AI and deep learning-based data science platforms ‘JWELRY’ and ‘CLOVER,’ in addition to chemical and bioinformatics big data. Through these platforms, JW Pharmaceutical continues to generate new drug candidates targeting Wnt and STAT for cancer, regenerative medicine, and immune diseases. Since the early 2000s, JW Pharmaceutical has focused on developing new drugs targeting the Wnt signaling pathway. Currently, the company utilizes 'JWELRY' (JW Excellent LibraRY), a core proprietary technology specializing in the Wnt signaling pathway. JWELRY is based on a library of tens of thousands of compounds involved in the Wnt pathway, along with drug evaluation and mechanism research technologies for distinguishing inhibition and activation of the Wnt pathway. Through JWELRY, JW Pharmaceutical has identified various new drug candidates, including JW0061, and is generating new projects. In addition, JW Pharmaceutical is actively developing new drugs targeting the STAT protein through ‘CLOVER’ (C&C research Laboratories Omics serVER), established by the research subsidiary C&C New Drug Research Institute. The company focuses on discovering innovative new drug candidates targeting each subtype of the STAT protein, such as the STAT3-targeted anticancer drug JW2286, a STAT3 atopic dermatitis treatment, a STAT5-targeted anticancer drug (for hematologic cancers), and a STAT3-ADC anticancer drug (for solid tumors).Furthermore, JW Pharmaceutical is conducting joint research incorporating AI and organoid platforms from domestic and international biotech companies to explore new indications for its drug candidates and validate their development potential.

 -DSMB's primary evaluation based on safety data from gout patients is positive-Accelerating Phase 3 trials in five Asian countries, including Korea... Evaluating uric acid reduction efficacy and safety-hURAT1 inhibition mechanism promotes uric acid excretion... Expected to be a 'Best-in-Class' global gout treatment February 2024 JW Pharmaceutical announced on the 14th that the U.S. Drug Safety Monitoring Board (DSMB) has positively assessed the primary results of the multinational Phase 3 trial of their gout treatment, Epaminurad (code name URC102), and recommended the continuation of the trial. The DSMB, composed of experts in rheumatology, pharmacology, nephrology, and statistics, reviewed the Phase 3 clinical data of Epaminurad on January 31 (local time) to discuss the trial’s continuation. The board unanimously recommended continuing the trial based on the review of safety data from currently enrolled gout patients. Following this first DSMB decision, JW Pharmaceutical plans to accelerate the Phase 3 trial of Epaminurad, which is being developed as a Best-in-Class new drug. Epaminurad, an oral medication, selectively inhibits hURAT1 (human uric acid transporter-1), promoting uric acid excretion. It is an effective candidate for treating hyperuricemia and gout, conditions characterized by abnormally high uric acid levels in the blood. The Phase 3 trial of Epaminurad involves 588 gout patients across five Asian countries, including Korea, and evaluates its efficacy (uric acid reduction) and safety compared to febuxostat. Alongside the Phase 3 clinical trials, JW Pharmaceutical is pursuing global technology licensing (License-Out) for Epaminurad. In 2019, they out-licensed the development and sales rights for China, Hong Kong, and Macau to Simcere Pharmaceutical Group. A JW Pharmaceutical representative stated, “The recommendation from the first DSMB to continue the global clinical development of Epaminurad positively reflects the drug’s competitiveness, patient safety, and data reliability. We plan to accelerate the development of Epaminurad as a global gout treatment to address significant unmet medical needs.” 

About Gout Treatments

Gout is classified into two types: the first is the 'underexcretion type,' where uric acid is not excreted effectively, unlike in healthy individuals, and the second is the 'overproduction type,' where the body produces more uric acid than normal. Currently, medications that decrease uric acid production are available, but treatments that promote uric acid excretion for underexcretion-type gout are not widely prescribed due to safety concerns for the kidneys and liver, despite the large number of patients. Additionally, allopurinol, a uric acid production inhibitor commonly prescribed as a first-line treatment, has weak effects at initial doses, and febuxostat is excluded as a first-line treatment in the US due to safety concerns. Therefore, the need for 'safe' gout treatments is greater than ever. In Phase 2 trials, Epaminurad met all primary and secondary efficacy endpoints and demonstrated excellent safety and tolerability in gout patients. 

Gout Disease and Market Size

Known for causing extreme pain even with the slightest touch, gout is a representative intractable disease. With the westernization of dietary habits, the incidence rate among younger people has significantly increased, with the number of patients in Korea rising sharply from 334,705 in 2015 to 509,699 in 2022 (according to the Health Insurance Review and Assessment Service’s Healthcare Big Data Open System). Gout is a metabolic disease that occurs when uric acid produced in the body is not excreted through urine and accumulates. Uric acid remains in the blood or joint fluid in crystal form and deposits in cartilage, tissues around joints, or subcutaneous tissues, causing inflammation and pain. Common causes include regular meat consumption, excessive drinking, and overeating. Recently, it has been occurring across various age groups without age specificity. Like hypertension or diabetes, once it develops, it is considered a chronic intractable disease that requires continuous treatment. With the increasing number of patients, the gout treatment market is also growing significantly. According to a report by Grand View Research, the global gout treatment market, currently valued at approximately 3 trillion KRW, is projected to grow to about 10 trillion KRW (8.3 billion USD) by 2025.

 -Phase 3 IND approvals completed in 5 Asian countries, including Korea... Efficacy in reducing blood uric acid and safety to be rigorously evaluated-hURAT1 inhibition mechanism promotes uric acid excretion... Expected to be a 'Best-in-Class' global gout treatment January 2024 JW Pharmaceutical announced on the 15th that it has received approval from Malaysia’s National Pharmaceutical Regulatory Agency (NPRA) for the Phase 3 clinical trial (IND) of its gout treatment, Epaminurad (code name URC102). The Phase 3 trial of Epaminurad will evaluate its efficacy (blood uric acid reduction) and safety compared to febuxostat in a total of 588 gout patients across five Asian countries, including Korea. With this approval, JW Pharmaceutical has now received all necessary multinational Phase 3 IND approvals for Epaminurad. In Korea, the IND was approved in November 2022, and patient enrollment and dosing began in March last year. In Taiwan, the IND was approved in August 2023, with the first patient registered by December. Subsequently, IND approvals were obtained in Thailand and Singapore in September. Epaminurad, developed as an oral medication, selectively inhibits hURAT1 (human uric acid transporter-1), promoting uric acid excretion and is an effective candidate for hyperuricemia and gout, conditions characterized by abnormally high uric acid levels in the blood. In the domestic Phase 2b clinical trial, completed in March 2021, JW Pharmaceutical confirmed Epaminurad's excellent tolerability and safety, meeting all primary and secondary efficacy endpoints. Alongside the Phase 3 clinical trials, JW Pharmaceutical is also pursuing global technology licensing (License-Out) for Epaminurad. In 2019, it out-licensed the development and sales rights for China, Hong Kong, and Macau to Simcere Pharmaceutical Group. A JW Pharmaceutical representative stated, “With the Malaysia IND approval, we can now proceed with Phase 3 clinical trials of Epaminurad across five Asian countries. Given the confirmed tolerability and safety in the previous Phase 2b trial, we aim to proceed with Phase 3 trials without setbacks to develop a Best-in-Class treatment for the significant unmet medical need in the global gout market.” 

About Gout Treatments

Gout is classified into two types: the first is the 'underexcretion type,' where uric acid is not excreted effectively, unlike in healthy individuals, and the second is the 'overproduction type,' where the body produces more uric acid than normal. Currently, medications that decrease uric acid production are available, but treatments that promote uric acid excretion for underexcretion-type gout are not widely prescribed due to safety concerns for the kidneys and liver, despite the large number of patients. Additionally, allopurinol, a uric acid production inhibitor commonly prescribed as a first-line treatment, has weak effects at initial doses, and febuxostat is excluded as a first-line treatment in the US due to safety concerns. Therefore, the need for 'safe' gout treatments is greater than ever. In Phase 2 trials, Epaminurad met all primary and secondary efficacy endpoints and demonstrated excellent safety and tolerability in gout patients. 

Gout Disease and Market Size

Known for causing extreme pain even with the slightest touch, gout is a representative intractable disease. With the westernization of dietary habits, the incidence rate among younger people has significantly increased, with the number of patients in Korea rising sharply from 334,705 in 2015 to 509,699 in 2022 (according to the Health Insurance Review and Assessment Service’s Healthcare Big Data Open System). Gout is a metabolic disease that occurs when uric acid produced in the body is not excreted through urine and accumulates. Uric acid remains in the blood or joint fluid in crystal form and deposits in cartilage, tissues around joints, or subcutaneous tissues, causing inflammation and pain. Common causes include regular meat consumption, excessive drinking, and overeating. Recently, it has been occurring across various age groups without age specificity. Like hypertension or diabetes, once it develops, it is considered a chronic intractable disease that requires continuous treatment. With the increasing number of patients, the gout treatment market is also growing significantly. According to a report by Grand View Research, the global gout treatment market, currently valued at approximately 3 trillion KRW, is projected to grow to about 10 trillion KRW (8.3 billion USD) by 2025.

 -Optimization of Lead Compounds for Direct STAT6 Inhibition-Utilization of XtalPi’s AI Drug Development and Automated Synthesis Platforms December 2023 C&C Research Laboratories, a subsidiary of JW Pharmaceutical, announced on the 18th that it has entered into a collaborative research agreement with XtalPi, a US-based AI-driven drug development company, to develop small molecule therapeutics targeting STAT6 Through this agreement, C&C Research Laboratories will utilize XtalPi’s quantum physics-based AI drug development platform and automated robotic system to optimize lead compounds for STAT6-targeted small molecule therapeutics. STAT6 is known as a key protein that regulates the inflammatory immune response of type 2 helper T cells (Th2). These cells are activated by inflammatory cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13), which are implicated in conditions like asthma and atopic dermatitis. Currently, biological agents targeting IL-4, IL-13, and their receptors, as well as JAK inhibitors, which target upstream proteins of STAT, are used as anti-inflammatory treatments. However, there are no successful examples of developing small molecule therapeutics targeting STAT6 to date. Founded in 2015 by quantum physics experts from MIT, XtalPi is an AI drug R&D platform company. It possesses core technologies in quantum mechanics-based AI drug development and automated synthesis platforms, aiming to reduce the time and effort required for drug development and transform the existing drug research ecosystem. Previously, C&C Research Laboratories secured lead compounds with direct binding affinity to STAT6 through collaborative research with XtalPi. The current joint research aims to optimize these lead compounds to develop a STAT6-targeted drug candidate. A representative from C&C Research Laboratories stated, "There is a high medical demand for new targeted therapies due to resistance and side effects associated with existing anti-inflammatory treatments. We aim to develop a STAT6-targeted anti-inflammatory therapeutic for patient groups with high unmet needs in existing treatments." About C&C Research Laboratories C&C Research Laboratories is the first Korea-Japan joint venture bio-venture established by JW Pharmaceutical and Chugai Pharmaceutical of the Roche Group in 1992. It became a wholly-owned subsidiary of JW Pharmaceutical in 2020. Since 2010, C&C Research Laboratories has been conducting its own research projects, leveraging its R&D platform 'CLOVER,' which integrates chemical and biological informatics big data with AI and deep learning technologies, to discover innovative first-in-class drug candidates. The institute currently has over ten new drug pipelines targeting oncology and immune diseases. Notable projects include the gout treatment 'Epaminurad (code name URC102),' and the STAT3-targeted anticancer agent 'JW2286,' both of which have been licensed to JW Pharmaceutical. Epaminurad is undergoing multinational phase 3 clinical trials, and JW2286 aims to start phase 1 clinical trials in 2024. The institute is also focused on discovering new drugs targeting STAT proteins (STAT1-6) that regulate cell growth, mutation, and proliferation. Prior to the development of STAT6-targeted therapeutics, C&C Research Laboratories has been developing STAT3-targeted atopic dermatitis treatments and dual inhibitors of STAT5/3, which were selected for national new drug development projects in 2021 and 2023, respectively. Additionally, the institute actively engages in joint research with domestic and international biotechs by integrating AI and organoid platforms to explore and validate new indications for its proprietary drug candidates. About XtalPi XtalPi is an innovative drug development company focused on AI and robotic automation synthesis. Established in 2015 by quantum mechanics experts from MIT, XtalPi leads digital transformation in the life sciences and new materials industries. The company provides various technological solutions, services, and products to life sciences and new materials companies through its cloud-based quantum physics and AI platforms, and large-scale robotic automated synthesis systems. About STAT Proteins The JAK-STAT pathway is a representative signaling system in the body involved in cell development, differentiation, growth, survival, and various immune responses. STAT proteins consist of seven types with different functions: STAT1-4, STAT5A, STAT5B, and STAT6, activated by upstream proteins JAK. While JAK-STAT pathways are normally regulated within a physiological range, abnormal activation (overexpression or hyperactivation) of these proteins can lead to various diseases. JW Pharmaceutical and C&C Research Laboratories aim to overcome the side effects of JAK inhibitors and achieve powerful effects by developing specific small molecule inhibitors that directly bind to and inhibit STAT3, STAT5, and STAT6.

 -Supplying 'WINUF Central 736·1085ml' through Mongolian pharmaceutical company AsiaPharma LLC-First WINUF export in the Asia region, with expectations of expanding exports to other countries November 2023 JW Holdings has announced that it will officially start exporting the Total Parenteral Nutrition 'WINUF Central 736·1085ml' (hereafter, WINUF) to AsiaPharma LLC in Mongolia. JW Holdings, responsible for JW Group's global business, signed an exclusive supply agreement for WINUF in the Mongolian market with AsiaPharma LLC in December 2021. AsiaPharma LLC is a top local pharmaceutical company in Mongolia established in 2001 with extensive experience for 21 years and specialized in distributing parenteral nutrient solutions. AsiaPharma LLC received product approval for WINUF from the Mongolian Ministry of Health in December last year and officially entered local sales starting this month. WINUF is a total parenteral nutrition developed by JW Life Science. It separates one container into three chambers to easily mix essential nutrients, including four types of lipids, amino acids, glucose, and fish oil. It is characterized by its high content of Omega-3 and Omega-6, which promote immune system enhancement and recovery more effectively than single nutrient solutions. In the domestic market, JW Pharmaceutical is responsible for its sales. Since its release in 2013, it has maintained the top position in the total parenteral nutrient solution market. This is the first time that JW Holdings is exporting WINUF to the Asian market. With the export of WINUF to Mongolia, the company expects to gain momentum for exports to other Asian countries. A representative of JW Holdings stated, "JW's product development and production competitiveness for high-value total parenteral nutrient solutions have been recognized in the global market." They added, "Now that WINUF has taken its first step into Asian countries, we will further strengthen our position as a global nutrition company by expanding to more countries." Meanwhile, JW Life Science, an affiliate of JW Holdings, completed the expansion of the automated production facility 'TPN 3 Chamber' for domestic exclusive-volume total parenteral nutrient solutions in its production facility located in Dangjin, Chungcheongnam-do in October last year. With the full operation of 'TPN 3 Line,' the annual maximum production capacity of JW Life Science's total parenteral nutrient solutions has increased by 37% from the previous 10.2 million units to 14 million units. The annual maximum production capacity for all intravenous solutions, including total parenteral nutrient solutions, has become the largest in South Korea, totaling 180 million units.

-Wnt pathway activation via GFRA1 receptor binding is a key action mechanism of hair regeneration…First reported case of synthetic small molecule-The excellent efficacy to growth in hair shaft and hair follicles was confirmed…Verification of equivalent or higher effects compared to the standard of care drug 2022. 11 JW Pharmaceutical announced on the 21st that JW researchers unveiled action mechanism of the newly identified Wnt-modulating small molecule, "JW0061" and demonstrated preclinical efficacy for hair regeneration at the "Wnt 2022" conference. The WNT signaling is playing a critical role in the differentiation of skin stem cells into hair follicles. In particular, Dermal Papilla (DP) cells as a dermal organizing center are well known for providing inductive signals to promote growth and differentiation of surrounding cells during hair growth, which mainly relies on an intracellular WNT signaling. JW0061 is a first-in-class drug candidate that promotes hair regeneration by activating the Wnt pathway in skin and hair follicle stem cells. According to the preclinical data, JW0061 activates the Wnt signaling pathway by directly binding to the GFRA1 protein in the dermal papilla cells. JW researchers further demonstrated that JW0061 induces anagen phase in hair growth cycle and hair regeneration that are highly correlated with WNT activation in various efficacy models. In detail, the hair growth cycle is made up of three phases: anagen, catagen and telogen. The anagen is also referred to as the active phase of hair growth whose defects mostly cause hair loss. JW0061 was shown to make the entry of anagen earlier by more than 15 days, which takes 50 days on average in mice, and be efficacious to growth in hair shaft and new hair follicles in 34 days after application, which are comparable to or higher than that of the standard of care (SoC) drug. Moreover, the combination therapy of JW0061 with the SoC drug synergized the maximum hair growth effect.  JW Pharmaceutical plans to develop JW0061 as a new topical drug supplementing and replacing existing hair loss treatments in the future. Currently, GLP toxicological evaluation is being conducted, aiming at a clinical trial of JW0061 in the first half of 2024, and collaboration research is also underway with a key opinion leader in dermatology field in the USA. Chan-hee Park, chief technology officer (CTO) of JW Group, said, “Among standard treatments on the market and various clinical trials for androgenic alopecia, there is no drug that clearly identifies the action mechanism of hair growth and its binding target protein.” He also said, “The JW0061 data will draw attention as an innovative drug candidate targeting GFRA1 for hair loss treatments.” Meanwhile, the Wnt international conference has an important objective to bring together various researchers for exchanging cutting-edge information, leading to advance of the Wnt research area. The year of “2022” marks the 40th anniversary of the discovery of the Wnt protein, and the in-person conference was held in Awaji, Japan for the first time in three years after last meeting. Researchers gathered from academia, pharmaceutical and bio companies in Asia, Oceania, the US as well as Europe.◎ Wnt Signaling PathwayVarious studies have shown over the past 40 years that the Wnt signaling pathway exists across all species, from nematodes to mammals, and plays an essential role in cell proliferation and differentiation, organ generation, and morphogenesis. Impeding the Wnt pathway inhibits the formation, proliferation, and metastasis of cancer cells in various tissues. Conversely, the Wnt pathway activation is involved in tissue regeneration through stem cell promotion and cell proliferation. Likewise, the Wnt pathway affects many human diseases, but so far, no new drug is available to control this pathway. ◎JW Pharmaceutical Wnt Targeted First-In-Class R&DJW Pharmaceutical has been focusing on development of new drugs controlling Wnt signaling pathway since the early 2000s. "JWELRY," a data science platform specialized in the Wnt signaling pathway, is being used as a core technology where we screen drug candidates from tens of thousands of compound libraries and conduct mechanism studies associated with Wnt signaling pathway. Currently, various new drug candidates were nominated in the fields of anticancer, regenerative medicine, and immune diseases. In addition, joint research is being conducted by harmonizing domestic and foreign Biotech's AI (Artificial Intelligence) platforms in order to explore new indications of own drug candidates in JW pharmaceutical. ◎ Hair Loss and Treatment MarketHair loss is caused by various causes such as genetic factors, autoimmune diseases, and mental stress, and the number of patients is rapidly increasing. Currently, primary hair loss treatments include Finasteride, Dutasteride, and Minoxidil. Finasteride and Dutasteride are prescribed to male patients, and there is a possibility of on-target side effects. Minoxidil can be prescribed to both male and female patients, and its disadvantages are that the mechanism is unclear and hair loss recurs soon after stopping medication. Altogether, there is a great demand for hair loss treatments which have a clear mechanism of hair growth and can be safely used by both genders. The global market is worth 8 trillion won as of 2020, and the related market is growing by 8% every year. According to Global View Research, a global market research company, it is expected to be worth of 15 trillion won by 2028.

- ‘First in Korea', it has formed a partnership with Venture Capital firm ARCH Venture Partners of U.S. to establish relationships with biotechnology companies and research institutions overseas.- Targeting global open innovation and expanding from medical centers and research institutes to bio companies- Searching for joint research partners and technology concepts in six fields, including pharmaceuticals and biopharmaceuticals, through the ATS program 2022. 7 JW Group announced on the 6th that it has signed a agreement with ARCH Venture Partners, a U.S. venture capitalist (VC), to strengthen the promotion of open innovation strategies with global buyer companies. Under the agreement, JW Group will receive ATS (ARCH Technical Service) programs from ARCH Venture Partners. ATS provides promising technology concepts and biotech information to strategic investors interested in business cooperation with venture companies around the world. ARCH Venture Partners invests in advanced technology companies and is one of the largest early-stage technology venture firms in the United States. The firm is a recognized leader in commercializing technologies developed at academic institutions, corporate research groups and national laboratories. ARCH invests primarily in companies it co-founds with leading scientists and entrepreneurs, bringing innovations in life sciences and physical sciences to market. ARCH recently announced the closing of ARCH Venture Fund XII, with $2.975 billion to invest in the creation, development and funding of early stage biotechnology companies. This is the first time ever that a domestic pharmaceutical company has joined hands for open innovation in the field of basic research (discovery stage) with a VC specializing in bio and healthcare in the U.S. JW Group is planning to expand its open innovation partners to global bio companies by utilizing ATS programs. Until now, overseas open innovation targets have been centered on hospitals, medical schools, and research institutes. JW Group plans to search for joint research partners regarding △Synthetic molecules (Small Molecule) △Biologics △New modality △ Data science (AI/ML) △ Medical devices △ Nutrition in consideration of each company's R&D areas such as, JW Pharmaceuticals, C&C Research Laboratories, JW Life Sciences, JW Bioscience, JW CreaGene, etc. Keith L. Crandell, co-founder of ARCH Venture Partners, said “ARCH Technical Services (ATS) is an ARCH Venture Partners, program for Strategic Investors that enables the strategic groups to successfully build their venture and business development practice around the world, By working with JW as part of this program we hope to enable the success of such efforts with JW and build a strong relationship” Chan-Hee Park, CTO (Chief Technology Officer) of JW Group said, "JW aims to build a sustainable cooperation model that creates synergy by combining it with its own platform and to create R&D results." He also said, "We will achieve successful open innovation results by cooperating with ARCH Venture Partners and discovering leading biotech technologies overseas.” Meanwhile, JW Group is focusing on generating profits, establishing research organizations, and securing differentiated technology based on the specialized business structure of each affiliate. It is focusing on developing new global innovative drugs, developing IV fluids technologies and improving services, and developing advanced precision in vitro diagnostic devices. In particular, JW Pharmaceutical is promoting an open innovation strategy in order to expand a new modality for new drug candidates under development. This is to secure the next-generation new innovative drug pipeline by combining JW's own R&D platform (JWELRY, CLOVER) and promising bio companies' R&D platform.