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Xgene Pharmaceutical Announces Positive Top-Line Results from Phase 1b/2a Trial of Topical Gel XG004 for the Treatment of Osteoarthritis (OA) Pain of the Knee

April 26,2023

Patients had acceptable safety and good tolerability to all regimens tested
Compared with placebo, 5% and 10% XG004 topical gel BID and TID treatment for one week resulted in substantial pain relief and improvement in physical function and sleep quality

Cayman Island, April 26, 2023: Xgene Pharmaceutical today announced the results of a multiple dose-escalation Phase 1b/2a study in patients with painful knee osteoarthritis (OA), evaluating the safety and exploratory efficacy of topical administration of XG004, an investigational drug of a patented new chemical entity with dual-action to treat both nociceptive and neuropathic pain (NCT05454020).

The study tested 5% and 10% XG004 topical gel applied once (qd), twice (bid) or thrice (tid) daily for 7 consecutive days, respectively, in 32 OA patients with moderate to severe pain and Kellgren-Lawrence grade of II-IV.

All patients demonstrated good tolerability and acceptable safety profile. There were no serious adverse events, nor discontinuations from the study drug or the study.

All treatment regimens improved the exploratory efficacy measures. On top of the placebo effect, the twice and thrice daily drug applications resulted in symptom relief in Western Ontario and McMaster Universities (WOMAC) pain, physical function, stiffness, total score and daily walking pain with standard effect sizes of 0.639, 0.444, 0.528 0.508, and 0.343 by the end of 7 days treatment, respectively. Furthermore, these treatment regimens improved pain-induced sleep interference with an effect size of 0.752. Numerically greater reduction of rescue medication use was observed in the XG004-treated patients than in placebo-treated patients. Assessed with Patient Global Impression of Change (Minimally worse + No Change + Minimally improved + Much improved + Very much improved), 72.2% patients with XG004 BID and TID treatment reported at least “minimally improved” and 27.8% reported “no change”, while 50% reported at least “minimally improved” and 50% reported “no change” or “minimally worse” in the placebo-treated patients.

Although active comparator was not tested in this study, to better understand the effective size, a previously published study demonstrated that “Topical diclofenac sodium 1% gel (four times a day: qid) demonstrated therapeutic efficacy after 12 weeks topical treatment in knee OA patients with Kellgren-Lawrence grade of I-III (lighter joint damage than the patients enrolled in XG004 study), with standard effect sizes of 0.311, 0.303 and 0.227 in WOMAC pain, function and movement pain, respectively (Baraf et al. Safety and Efficacy of Topical Diclofenac Sodium 1% Gel in Knee Osteoarthritis: A Randomized Controlled Trial. THE PHYSICIAN AND SPORTSMEDICINE • ISSN – oo91-3847, June 2010, No. 2, Volume 38.). In another published study, intra-articular injection of corticosteroids or hyaluronic acid demonstrated effect size of 0.32 or 0.34 compared with placebo at 12 weeks post treatment (Bannuru et al., Annals of Internal Medicine. 2015; 162:46-54.). “We are extremely encouraged by these early study results, which show the potential of topical XG004 as a non-oral, non-invasive treatment option for pain reduction and improvement in physical function and quality of life in osteoarthritis patients. Topical therapeutics are still the first line recommendation of various OA treatment guidelines for pharmacological management of OA.” said Leon Jiang, Chief Medical Officer at Xgene Pharmaceutical.

“There is a substantial need for innovative safer new treatment options for osteoarthritis, as many patients are unable to get sufficient relief with currently available medicines with intolerable side effects. We are pleased that the results from this trial showed the positive therapeutic effect of topical gel XG004, with the potential to be a better treatment option compared to the current therapies. Today’s data are a culmination of a persistent team effort within our organization and its collaborators. As fast-growing aging population continues to burden the healthcare systems across the globe, safer and cost-effective treatments will be needed for chronic pain. Xgene is proud to continue its efforts on this unique product aiming for various chronic pain conditions, moving forward with great confidence.” Said Gene Hsu, CEO of Xgene.

About the Study

The exploratory Phase 1b/2a OA study (NCT054540200) was a 1-week randomized, double-blind, placebo-controlled, single-center, parallel-group trial evaluating the safety and efficacy of topical administration of XG004 compared to placebo in patients with OA of the knee. The trial included an additional 1-week safety follow-up period following dosing completion. In the study, patients were enrolled with moderate to severe OA pain who had experienced inadequate pain relief with other treatment options for OA pain or were unable to take other pain medications. The patients were randomized to six treatment groups in a 3:1 ratio to receive 3 mL of 5% or 10% topical gel of XG004 qd, bid, tid or placebo over the 1-week period. Patient safety and tolerability was monitored as the primary endpoint. The exploratory efficacy of XG004 vs. placebo was measured by changes from baseline in the WOMAC Total score, Pain, Stiffness and Physical Function subscales, daily walking pain, sleep interference and the patient’s Global Assessment of OA.

About Topical XG004

XG004, a novel molecule possesses dual functions of anti-inflammatory and anti-neuropathic pain therapeutic potential. It is a potential first-in-class, topical treatment being evaluated for OA pain. XG004 works by absorption through skin, followed by carboxyl esterase cleavage in the dermis to release two active drugs into the local tissues. By inhibiting local COXs enzymes and modulating peripheral a₂d subtype calcium ion channels simultaneously, XG004 is postulated to reduce inflammation in synovial membrane and knee joint and prevent pain signals produced by muscles and the skin from reaching the spinal cord and brain. Topical XG004 could minimize the gastrointestinal and central nervous systems side effects associated with these classes of drugs to improve side effects in a long term use.

About Xgene Pharmaceutical: Transforming Medicine for Better Lives

At Xgene, we apply new clinical findings, science and innovative technology to bring therapies to people to extend and significantly improve their lives. We strive for quality, safety and value in our new products. Our goal is to deliver the world’s best medicine to patients worldwide. Xgene’s drug discovery areas include pain and CNS diseases, finding treatments and cures to unmet medical needs. We collaborate with health care providers, governments, and local communities to identify patient needs and deliver reliable, affordable medicines around the world.

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Xgene Pharmaceutical secures $40m in Series C

November 04,2021

Clinical-stage drug developer Xgene Pharmaceutical Group announced on November 4 that it has garnered $40 million in its Series C round of financing.

The fresh round was co-led by state-backed SAIC Capital’s fund of funds platform Hengxu Capital, CITIC Securities and Neovision Capital.

GSR United Capital, Tao Capital and Yijing Capital joined the round along with return backer Ping An Ventures.

The company will use the proceeds for R&D and clinical trials in China and the US.

Reference：

-Deal street Asia

NDA Application of XG005 will follow a 505(B)(2) regulatory pathway based on FDA’S feedback

April 22, 2020

Xgene Pharmaceutical Inc., a clinical development stage biopharmaceutical company, today announced that it recently held a pre-Investigational New Drug (pre-IND) meeting with the U.S. Food and Drug Administration (FDA) to discuss the regulatory pathway for the development of XG005, a drug conjugate of naproxen and pregabalin for the management of acute pain. The company has previously competed two phase 1 clinical studies in Australia.

”Following this informative meeting with the FDA, we confirm the initial IND for XG005 oral will not require any additional nonclinical or clinical data to support a Phase 2/3 study which will serve as one of the two pivotal studies for new drug registration with FDA. This enables us to enter the clinic study promptly with a fast-track development path to market, which is consistent with our platform of repurposing or rediscovering high-impact prescription medications for unmet or underserved needs in pain patients. We are on track to evaluate XG005 in postoperative pain for bunionectomy surgery patients in the fourth quarter of 2020.” said Gene Hsu, Ph.D., President and CEO of Xgene.

”Utilizing the multimodal analgesia, XG005 potentially provides the maximum pain relief with reduced adverse events and opioid use. The development of XG005 will be partly based on the available information on naproxen and Lyrica, therefore the New Drug Application (NDA) application of XG005 will follow a 505(b)(2) regulatory pathway based on FDA’s feedback.” noted Dr. Gene Hsu.

The 505(b)(2) pathway allows FDA to rely on previous findings of safety and effectiveness for Reference Listed Drugs (RLDs). XG005, a prodrug-like New Chemical Entity (NCE), has been shown to be stable in gastrointestinal (GI) tract, but cleaved rapidly upon absorption by esterase to release naproxen and pregabalin. In the nonclinical studies in several species, XG005 showed superior GI safety when compared to the equivalent doses of naproxen. The results from the Phase 1 studies in healthy subjects also suggest that XG005 produced less Central Nervous System (CNS)-related adverse events compared to the similar doses of Lyrica.

”We are pleased that the FDA recommended that we are only required to carry out ‘two adequate, well-controlled trials’, i.e., one Phase 2b study plus one Phase 3 study, to show the superiority of XG005 over naproxen and its contribution to Lyrica, for the NDA submission!” said Dr. Gene Hsu. ”We look forward to working with the FDA to bring this much-needed treatment option to patients who suffer from pain as rapidly as possible.”

Dr. Hsu added ”XG005 got a lot of potential, a topical XG005 formulation Phase 1 trial (SAD+MAD) in Australia has been kicked off in late 2019 and we are planning to evaluation XG005 oral on chronic pain applications, such as chemotherapy-induced neuropathic pain and low back pain, in Greater China area in 2021!”

September 22,2021

Xgene Pharmaceuticals Co. Ltd. (A subsidiary of Xgene Pharmaceutical Inc.; Head Office: Hong-Kong; CEO: Ching-Hung Hsu, Ph.D.; hereinafter “Xgene”) and RaQualia Pharma Inc. (Head Office: Nagoya, Aichi, Japan; President & CEO: Hirobumi Takeuchi; hereinafter “RaQualia Pharma”) have entered into a licensing agreement for a novel TRPM8 blocker discovered by RaQualia Pharma.

TRPM8 is a discovery-stage, temperature-sensitive ion channel expressed in sensory neurons, which is activated by cold stimuli below 28 degrees Celsius or by menthol (an ingredient of mint). There is a growing scientific evidence suggesting that TRPM8 channel plays a role in multiple conditions, including pain. RQ-00434739, a TRPM8 channel blocker discovered by RaQualia Pharma, has demonstrated efficacy in validated animal models of pain supporting a novel　mechanism of action that differs from those of currently utilized analgesics. RQ-00434739 has a potential to become first in its class to address an unmet need in treatment of chronic pain.

Under the terms of the agreement announced today, Xgene obtained exclusive global rights (excluding Japan) to develop, manufacture, and commercialize RQ-00434739. RaQualia Pharma will receive an upfront fee, success-based milestone payments, and sales-based royalties. Xgene is planning to promptly complete preclinical studies required by regulatory authorities and to advance the program into phase I trials.

“We are excited to add RQ-00434739 to Xgene’s portfolio. With its novel mechanism of action that has a potential to address a substantial unmet clinical need in treatment of pain, this asset is a great strategic fit to leverage our Company’s expertise in this therapeutic area.” said Xgene’s CEO Dr. Gene Hsu.

“We are very pleased to announce the license agreement for TRPM8 blocker.” said Mr. Hirobumi Takeuchi, President and CEO of RaQualia Pharma. “We hope that Xgene, with its strong focus and expertise in the development of pain therapeutics, will advance the development of RQ-00434739 to bring an innovative analgesic drug to patients in the world in the near future.”

Through the license agreement, Xgene and RaQualia Pharma will strive to further strengthen the pipeline of drugs for pain treatment, an area of focus for both companies, and contribute to improving the quality of life of patients by providing new treatment options.

XGene Pharmaceutical Closed the B Plus Round Financing

May 4, 2019

Xgene Pharmaceutical has completed B Plus financing round successfully.

The financing round was participated by Taiwania Captial, a famous venture capital company in Taiwan. Xgene plans to promote its pipeline product development through this round of investment and help the company to become a world-class pharmaceutical company.

XGene Pharmaceutical Closed US$20 Million B Round Financing

October 25, 2018

Xgene Pharmaceutical raised $20 million in series B financing round led by Ping An Ventures. Xgene’s lead product, a combination of naproxen and pregabalin (Lyrica®) for chronic pain, is in Phase II trials in the US. Founded in 2015 Q4, Xgene Pharmaceutical develops small-molecule drugs for chronic pain, infectious diseases and tumors. Also participating in the funding were Zhongtai Investment, a subsidiary of Indonesia’s Asia Pulp & Paper Group (Sinar Mas Group), and existing investors Morningside Venture Capital and TF Capital.