News - Xgene Pharmaceutical Inc.

Xgene Pharmaceutical Inc. Announces Dosing of First Patient in a Phase 2b/3 Trial of XG005 for the Treatment of Pain Following Bunionectomy Surgery.

August 23,2023

Taipei, Taiwan (or other office location) Aug. 25, 2023. Xgene Pharmaceutical, a clinical-stage pharmaceutical company focusing on pain and other central nervous system (CNS) conditions, today announced the dosing of the first patient in the Phase 2b/3 study in the United States – a randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of XG005 oral tablet in subjects undergoing bunionectomy.

The XG005 trial, conducted in the US with Lotus Clinical Research LLC, has a planned enrollment of approximately 450 patients undergoing bunionectomy in a randomized, double-blind, placebo-controlled, 3-day treatment, evaluating the pharmacokinetic profile, safety, and analgesic efficacy of two doses of XG005 compared to placebo. In addition, the company will assess the reduction in post-surgical consumption of opioid analgesics.

“The dosing of the first patient in this important study represents a significant milestone in the ongoing late-stage development program of XG005 oral tablet for treatment of acute and chronic pain,” said Dr. Leon Jiang, Chief Medical and Senior Vice President of Xgene Pharmaceutical. “The clinical development of XG005 includes a Phase 2 trial in chronic pain of the osteoarthritis of the knee which is ongoing in China and a trial in cancer pain which is currently in a planning stage,” said Dr. Jiang.

XG005 is a non-opioid new chemical entity (NCE) with novel dual-mechanism of action targeting an anti-inflammatory and neuropathic components of pain. When released into the blood stream, by inhibiting the pain signals due to inflammation and nerve injury simultaneously, XG005 can further enhance the analgesic effect and improve the safety profile while reducing the use and side effects of opioids in a post-operative setting.

About XG005
XG005, a new chemical entity (NCE) and a novel non-opioid dual-action prodrug conjugate of an NSAID and a calcium channel inhibitor, is simultaneously targeting an anti-inflammatory and neuropathic pathways of pain. Through its unique multi-modal analgesic mechanism, XG005 can inhibit pain signals more effectively and achieve better clinical efficacy in a wide range of painful conditions.

About Xgene Pharmaceutical, Inc.

Xgene Pharmaceutical Inc. is a clinical stage, venture capital-backed, international company utilizing their proprietary linker technology to create novel, multimodal, conjugated molecules for treatment of pain and other neurological disorders. Xgene’s proprietary linker technology, tailored to the recognized profiles of specific existing and newly discovered drugs, overcomes the challenges of the multimodal drug combination approach and offers potentially better, safer, and more efficient treatments. Current programs are focused on improving the efficacy and tolerability of pain therapeutics with a pipeline comprising late-stage clinical programs as well as assets in discovery and preclinical development. Since its establishment, Xgene has been recognized and supported by Morningside Capital, TF Capital, Ping’an Venture Capital, Hengxu Capital, CITIC Securities and other investment institutions.

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Xgene XG005 phase 2b/3 trial FPI announcement

Xgene Pharmaceutical Announces Positive Topline Results from Late Phase Trial of XG005 Tablet for Post-surgical Pain

Dec 12,2024

– XG005 treatment resulted in statistically significant as well as a clinically meaningful pain relief in the bunionectomy randomized controlled trial –

– The Primary Efficacy Endpoint of Summed Pain Intensity (SPI) over 48 hours for high dose (1250 mg BID) of XG005 versus placebo was statistically significantly lower (P< 0.0001), with Least-Squares Means (LSM) ± SE of 132.63±8.004 and 285.99±8.183, respectively –

– The Key Secondary Efficacy Endpoint of SPI over 48 hours for low dose (750 mg BID) of XG005 versus placebo was statistically significantly lower (P< 0.0001), with LSM ±SE of 157.86±8.345 and 289.50±8.5, respectively –

– Additional Secondary Efficacy Endpoints showed that: The high dose of XG005 was statistically significantly more analgesic than low dose of XG005 in SPI48 (P= 0.0374).

– XG005 was safe and well tolerated –

Shanghai, China December 12th, 2024: Xgene Pharmaceutical today announced the positive results of a multiple-center, placebo-controlled, dose-ranging Phase 2b study (registration number: NCT06017999) in patients undergoing bunionectomy, evaluating the safety and efficacy of the XG005 oral tablet on acute pain.

XG005 is a non-opioid, new chemical entity with dual mode of action in blocking both nociceptive and neuropathic pain signals. The placebo, 750 mg or 1250 mg of XG005, was administered twice a day (bid) for 72 hours to patients undergoing bunionectomy. The study was collaborated with Evolution Research Group and Lotus Clinical Research at multiple sites in USA. A total of 450 subjects were enrolled into the trial with 1:1:1 randomization ratio. The drug was well tolerated with an acceptable safety profile. There were no drug-related serious adverse events.

Per the prespecified analysis plan, the primary and the key secondary efficacy endpoints of SPI over 48 hours for the 1250 mg and 750 mg dose group versus placebo were statistically significantly different, respectively. And 1250 mg was statistically significantly more analgesic than 750 mg.

Other efficacy endpoints are briefly listed below :

• The pain intensity score was statistically lower in both active arms than placebo over 72 hours post-surgery (P< 0.0001); the maximum pain was mild (< 4.0 NRS) in severity in the high dose arm, in contrast to up to severe pain (> 7.0 NRS) scored in the placebo arm during the same period (see figure below).

• The time to first use of rescue medication was delayed up to 8-fold in the high dose arm compared with placebo, the median times to first use of rescue medication for high dose, low dose and placebo were 31.47, 12.24 and 4.03 hours, respectively, with Hazard Ratios of 0.18 and 0.24 (P< 0.0001).

• Total opioid consumption over 72 hours was statistically significantly less in active arms than in placebo (P< 0.0001), with Morphine Equivalent Dose (MEQ) of 6.72, 9.38 and 23.86/24.68 mg for the high, low dose of XG005 and placebo, respectively.

• Total acetaminophen use (rescue medication) over 72 hours was statistically significantly less in the active arms than in the placebo (P< 0.0001), with means of 1586.03, 1975.89 and 4812.7/4892.74 mg for the high dose, low dose of XG005 and placebo, respectively.

• Patient Global Assessment (PGA) on pain control was statistically greater in XG005 arms than in the placebo arm over 72 hours (P< 0.0001).

• Patients’ sleep post-surgery was significantly better in the XG005-treated arms compared with placebo as assessed with Sleep Interference Score (P< 0.0001).

Dr. Richard Evanson, DO, one of the principal investigators and an orthopedic surgeon, from Legent Orthopedic Hospital, Texas, commented, “As a grateful participant in this phenomenal study, I can honestly say that we finally have a better alternative to narcotic pain medicine. This new medicine will revolutionize the world of peri-operative pain management”.

“I have not seen any analgesics showing such great efficacy in well-controlled multiple center trials. Mean pain severity was mild at the most in high dose group versus severe in placebo group. The amount of rescue medication used including opioids was less than 1/3 in the high dose arm compared with placebo. The standard effect sizes for the primary (high dose) and the key secondary (low dose) efficacy endpoints are 1.55 and 1.28, respectively. This compelling efficacy of XG005 overwhelmingly distinguishes it from other analgesics and we are extremely encouraged to expedite the development for early delivery to patients.” said Leon Jiang, Chief Medical Officer at Xgene Pharmaceutical.

“There is a substantial need for more efficacious, safer, non-opioid treatment for acute pain, as many patients are unable to get sufficient relief with currently available medicines due to intolerable side effects. We are pleased that the results from this trial showed the excellent therapeutic effect of XG005, with the potential to be a better treatment option compared to current therapies,” said Gene Hsu, CEO of Xgene. “Xgene is proud to continue its efforts on this unique product, moving forward with great confidence.”

About Acute Pain：

Acute pain is defined as pain lasting less than 3 months. In 2023, the acute pain market was valued at approximately USD 50.03 billion and project to reach around USD 78.36 billion by 2032. Due to limited non-opioid treatment options, there is an unmet need in acute pain management to improve the patient experience and reduce the economic and societal burden. (Acute Pain Market Size, Share, Trends & Report | 2032 )

About XG005

XG005, a novel molecule possesses dual functions of anti-nociceptive and anti-neuropathic pain therapeutic potential. It is a potential first-in-class oral treatment in development for treatment of acute and chronic pain conditions. Due to its dual mechanism of action, XG005 is potentially able to provide greater inhibition of the pain signal transmission achieving better analgesic outcomes while providing good safety profile.

A positive phase 2b trial of XG005 on osteoarthritis was recently reported, and a Phase 2 trial of XG005 on cancer-induced bone pain is also ongoing in Taiwan and Mainland of China.

About Xgene Pharmaceutical: Transforming Medicine for Better Lives

At Xgene, we apply new clinical findings, science, and innovative technology to bring therapies to patients 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 conditions focusing research on 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. Visit our website at www.xgenepharm.com.

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Xgene XG005 BUN trial results announcement

Xgene’s Osteoarthritis Study Accepted as Late-Breaking Abstract to Present at the American College of Rheumatology (ACR) Convergence 2024 Conference

Oct 25,2024

October 25, 2024, Xgene Pharmaceutical Inc., a clinical-stage company developing transformational treatments for various pain conditions with high unmet medical needs, today announced that its Phase 2b osteoarthritis trial has been accepted as a Late-breaking Abstract for presentation at the ACR Convergence 2024 Conference, taking place on November 14–19 at the Walter E. Washington Convention Center in Washington, D.C. The presentation will highlight the findings from the Phase 2b study which evaluated safety and efficacy of XG005 – a dual action conjugate analgesic – in 331 patients with painful osteoarthritis of the knee.

Key findings of the study：

• Statistically Significant Analgesic Effect：XG005 demonstrated a significant reduction in pain, which is a crucial outcome for patients suffering from osteoarthritis.
• Beyond Pain Relief：Notably, XG005 exhibited benefits beyond pain management. It positively impacted other symptoms associated with osteoarthritis and improved quality of life and sleep quality.

Details for the presentations are as follows：

Poster Number：L08

Submission Number：1922387

Title：A Phase 2b, Randomized, Double-blind, Placebo-controlled, Dose-ranging and Parallel-group Study to Evaluate the Safety and Efficacy of XG005 in Subjects with Painful Osteoarthritis of the Knee

Session：Poster Session C, (L01–L14) Late-Breaking Posters

Date：Monday November 18, 2024

Presentation Time：10:30 AM – 12:30 PM

Weblink：https://acr24.eventscribe.net/SearchByBucket.asp?f=CustomPresfield55&bm=Late-Breaking%20Abstract&pfp=LBA

“The acceptance of this study as the Late-Breaking Abstract at this prestigious global conference reflects the recognition of the impact of XG005 by world-class key opinion leaders and experts. We are extremely pleased and honored. 52% of patients had at least 50% and/or 70% reduction from Baseline in Daily Walking Pain, and 64.8% patients had such reductions in WOMAC pain sub score. Other efficacy measures also consistently supported each other, showing that XG005 had dose-dependent pain reduction accompanied with improvements in joint stiffness and function along with prompt onset of effect. The compelling effect of XG005 may distinguish it from other currently available therapies and further benefit patients.” said Leon Jiang, Chief Medical Officer at Xgene Pharmaceutical.

About XG005

The company’s lead product candidate, XG005, is a dual-MOA non-opioid oral tablet targeting inflammatory and neuropathic pain pathways. It is in active development for acute pain – completed Phase 2/3 in the US in post-surgical clinical model – and for chronic pain with a completed Phase 2 trial in OA and an ongoing cancer pain trial in China. The positive top line results of the OA trial demonstrated analgesic effect and improvement in function News – Xgene Pharmaceutical Group. The company is finalizing the analysis of the data from the completed phase 2/3 acute pain trial and anticipates the top line results to be available by the end of 2024. XG005 has a potential to be highly effective in and safe in chronic pain conditions as well as delaying/eliminating the use of opioids in a post-surgical and an oncology setting.

About Xgene

Xgene Pharmaceutical Inc. is a clinical stage, venture capital-backed, international company utilizing linker technology to create novel, multimodal, conjugated molecules for the treatment of pain and other neurological disorders. Xgene’s linker technology is tailored to overcome the challenges of the multimodal therapy approach, and offers potentially better, safer, and more efficient treatments. Current programs are focused on dual-action NCEs with improved analgesic efficacy and tolerability with the pipeline comprising late-stage clinical programs as well as assets in discovery and preclinical development. Xgene has gained recognition and support from leading investment institutions such as Morningside Capital, TF Capital, Ping’an Venture Capital, Hengxu Capital, CITIC Securities and other investment institutions.

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Xgene XG005 OA ACR abstract announcement

Xgene Pharmaceutical Announces Positive Topline Results from Phase 2b Trial of XG005 Tablet for Treating the Symptoms of Osteoarthritis of the Knee

Aug 08,2024

– The Primary Efficacy Endpoint of pain improvement from baseline was statistically significant for the 750 mg arm compared to placebo at Week 4 in mITT population (P=0.0055). The result was consistent with ITT and PPS analysis populations and was confirmed with observed data and multiple input sensitivity analyses –

– All Key Secondary Efficacy Endpoints achieved statistical significance compared with placebo for both 500 mg and 750 mg arms, including WOMAC Pain subscore and KOOS Pain subscore –

– Other Statistically Significant Efficacy Endpoints at Week 4 for 750 mg group versus placebo included WOMAC Stiffness, Function and Total scores (also positive for 500 mg group); KOOS subscores; Sleep Interference Score; both Patient and Clinician Global Impression of Change (PGIC) (also positive for 500 mg group); OMERACT-OARSI responder rate and proportion of patients with ≥ 30%, 50% or 70% improvement of Walking Pain –

– XG005 was safe and well tolerated–

Shanghai, China, August 8th, 2024: Xgene Pharmaceutical today announced the positive results of a multiple-center, placebo-controlled, dose-ranging Phase 2b study (registration number: 2021LP01217) in patients with painful knee osteoarthritis (OA), evaluating the safety and efficacy of the XG005 oral tablet.

XG005 is a new, non-opioid, investigational chemical entity with dual action in treating both nociceptive and neuropathic pain. The 750 mg, 500 mg or placebo dose was administered twice a day (bid) for 4 weeks to patients with painful knee due to OA. The study was conducted at multiple sites in China. A total of 331 OA patients suffering moderate to severe pain of the knee, with Kellgren-Lawrence grade of II-III, were enrolled in the trial. The drug was well tolerated with an acceptable safety profile. There were no drug-related serious adverse events.

The primary efficacy endpoint and WOMAC pain, stiffness and function sub-scores are shown in the figures below .

Professor Li ZhanGuo, the lead principal investigator from Beijing Renmin Hospital of Beijing University commented, “Thanks to the enormous efforts from our team of investigators. We are very pleased with the outcomes of this Phase IIb trial. The data showed that XG005 can not only significantly reduce arthritis pain, but also improve functions. It is a promising additional means to treat OA patients without resorting to opioids”.

“We are extremely encouraged by the robustness of the study results; the broad efficacy measures consistently supported each other, showing that XG005 had dose-dependent pain reduction accompanied with improvements in joint stiffness and function along with prompt onset of effect. Currently, no pain treatment for OA has earned the joint stiffness or function improvement on an approved label. The compelling effect of XG005 may distinguish it from other currently available therapies and further benefit patients.” said Leon Jiang, Chief Medical Officer at Xgene Pharmaceutical.

“There is a substantial need for safer, more innovative treatment options for osteoarthritis, as many patients are unable to get sufficient relief with currently available medicines due to intolerable side effects. We are pleased that the results from this trial showed the excellent therapeutic effect of XG005, with the potential to be a better treatment option compared to current therapies,” said Gene Hsu, CEO of Xgene. “Xgene is proud to continue its efforts on this unique product aiming for various chronic pain conditions, moving forward with great confidence.”

About Osteoarthritis

Osteoarthritis (OA) is a painful, irreversible, and debilitating chronic degenerative joint disease affecting approximately 595 million people globally. Cases of OA are projected to increase 49-95% for various joints by 2050 as population ages (GBD Osteoarthritis Collaborators. Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Rheumatol 2023; 5: e508–22). The direct medical costs of OA in US are estimated at $72 billion. The economic burden of OA accounts 1-2.5% of GDP in countries with established market economies (Leifer VP, Katz JN, Losina E. The burden of OA-health services and economics. Osteoarthritis and Cartilage 30(2022)10e16).

About XG005

XG005, a novel molecule possesses dual-acting functions of anti-inflammatory and anti-neuropathic pain therapeutic potential. It is a potential first-in-class, non-opioid oral treatment in development for the treatment of chronic and acute pain conditions.

A pivotal trial of XG005 on acute surgical pain is rapidly enrolling in the USA, and a Phase 2 trial of XG005 on cancer-induced bone pain is also ongoing in Mainland China and Taiwan.

About Xgene Pharmaceutical: Transforming Medicine for Better Lives

At Xgene, we apply new clinical findings, science, and innovative technology to bring therapies to patients 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 conditions focusing research on 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. Visit our website at www.xgenepharm.com.

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Xgene XG005 phase 2b OA trial results announcement

Xgene Pharmaceutical Pty Ltd. Announced the Enrollment of the First Cohort in the Phase I clinical trial of XG2002 capsules, a novel selective TRPM8 channel blocker.

May 08,2024

On May 8,2024, Xgene Pharmaceutical Pty Ltd. announced the enrollment of the first cohort in the phase I clinical trial of XG2002 capsules, a novel oral small molecule selective blocker targeting the pain channel TRPM8, at the CMAX Research Center in Australia.

This single-dose escalation study aims to evaluate the safety, tolerability, pharmacokinetic profile and the maximum tolerated dose of XG2002 in healthy volunteers.

About TRPM8

TRPM8 is an ion channel expressed in peripheral sensory neurons. Upon activation, it allows the influx of Na+ and Ca2+ ions into the cell, leading to depolarization and the generation of electrical currents that transmit signals into neurons, ultimately resulting in the sensation of pain. Numerous studies have shown high expression of TRPM8 ion channels and increased channel sensitivity in various painful conditions, such as neuropathic pain, chemotherapy-induced pain, complex regional pain syndrome, bladder pain syndrome, and many others. Additionally, TRPM8 ion channels are also highly expressed in various cancer cells. It is an androgen-dependent Ca 2+ channel that is closely associated with the survival of prostate cancer cells, making it a promising potential target for cancer therapy.

XG2002, licensed from RaQualia Pharma, Inc., Japan, via inhibiting TRPM8 channels, exhibits pain suppressing effects in various animal model of pain with good safety profile. This Phase I clinical study aims to assess the safety, tolerability, and pharmacokinetic profile of XG2002 in healthy subjects, laying the groundwork for subsequent trials and potential tests across various pain-related conditions.

Dr. Leon Jiang, Chief Medical Officer and Senior Vice President of Xgene Pharmaceutical Pty Ltd emphasized the significant clinical unmet need for safe and effective analgesic treatments. Various painful pathways are activated to various extent in different pathological processes, thus, drugs targeting different modes of action are needed to precisely address corresponding pathogenesis including different stages of a painful condition. The enrollment of the first subject marks a significant milestone in XG2002’s clinical development, enabling exploration of additional treatment options for acute and chronic pain management.

Dr. Feng Xu, Co-founder, Chief Operating Officer and Chief Scientific Officer of Xgene Pharmaceutical Pty Ltd, highlighted the pivotal role of TRPM8 in pain sensation and its association with various physiological pathologies. He expressed confidence in XG2002 as a novel TRPM8 channel blocker with favorable safety and efficacy profile, paving the way for its future clinical applications.

Dr. Gene Hsu, Founder and CEO of Xgene Pharmaceutical Pty Ltd, reaffirmed the company’s patient-centric approach and commitment to addressing clinical needs in pain management. He emphasized the company’s focus on developing safe and effective treatments for a wide range of acute and chronic pain conditions, leveraging the unique drug conjugation platform and exploring novel therapeutic targets.

About Xgene
Xgene Pharmaceutical Pty Ltd.is a subsidiary of the Xgene parent company, registered in Australia. Xgene Pharmaceutical Inc. is a clinical stage, venture capital-backed, international company utilizing linker technology to create novel, multimodal, conjugated molecules for the treatment of pain and other neurological disorders. Xgene’s linker technology, is tailored to overcome the challenges of the multimodal therapy approach, and offers potentially better, safer, and more efficient treatments. Current programs are focused on dual-action NCEs with improved analgesic efficacy and tolerability with the pipeline comprising late-stage clinical programs as well as assets in discovery and preclinical development. Xgene has gained recognition and support from leading investment institutions such as Morningside Capital, TF Capital, Ping’an Venture Capital, Hengxu Capital, CITIC Securities and other investment institutions.

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Xgene XG2002 phase 1 trial FPI announcement

Xgene Pharmaceutical Pty Ltd. Receives HREC’s approval to initiate a First-In-Human (FIH) trial of its innovative analgesic product XG2002

March 11,2024

Xgene Pharmaceutical Pty Ltd. today announced that the Company has received approval from Bellberry Human Research Ethics Committee (HREC) to conduct a First-In Human Trial in Healthy Volunteers.

XG2002, , shows compelling pain suppression effects in multiple animal pain disease models, demonstrating clean safety profile including in the cardiovascular, central nervous and respiratory systems in various toxicology studies. This novel analgesic holds great potential for treating various acute and chronic pain disorders, including neuropathic pain such as migraine, diabetic neuropathy, etc.

The Phase I dose-ascending trial will assess XG2002’s tolerability and pharmacokinetic properties in healthy volunteers, providing crucial data for subsequent clinical trials.

Dr. Leon Jiang, Chief Medical Officer and Senior Vice President of Xgene Pharmaceutical Pty Ltd explained that given the substantial unmet clinical needs for acute and chronic pain management, XG2002, an analgesic on a novel target, is expected to have its unique responding population for various painful disorders, thus complementing the analgesic pipelines such as XG005 and XG004 that Xgene is developing.

Dr. Feng Xu, Co-founder, Chief Operating Officer and Chief Scientific Officer of Xgene Pharmaceutical Pty Ltd, emphasized the scarcity of innovation in pain management compared to oncology, despite the 20% global population affected by pain disorders. The company’s product pipeline focuses on oral and topical non-opioid analgesics, aiming to enhance compliance in both inpatient and outpatient settings while circumventing clinical challenges associated with opioid use, such as addiction and appetite suppression. Dr. Xu expressed anticipation for high-quality clinical data from the company’s analgesic pipeline, aiming to fulfill the fundamental need of pain relief for patients.

Dr. Gene Hsu, Founder and CEO of Xgene Pharmaceutical Pty Ltd, highlighted the increasing emphasis on patients’ quality of life in clinical practice. The company remains dedicated to analgesic product development, striving to offer economically efficient and safer options for clinicians, thereby contributing to advancements in pain management.

About Xgene

Xgene Pharmaceutical Pty Ltd.is a subsidiary of the Xgene parent company, registered in Australia. Xgene Pharmaceutical Inc. is a clinical stage, venture capital-backed, international company utilizing proprietary linker technology to create novel, multimodal, conjugated molecules for the treatment of pain and other neurological disorders. Xgene’s proprietary link technology, tailored to the recognized profiles of specific existing and newly discovered drugs, overcomes the challenges of the multimodal drug combination approach, and offers potentially better, safer, and more efficient treatments. Current programs are focused on improving the efficacy and tolerability of pain therapeutics with a pipeline comprising late-stage clinical programs as well as assets in discovery and preclinical development. Xgene has gained recognition and support from leading investment institutions such as Morningside Capital, TF Capital, Ping’an Venture Capital, Hengxu Capital, CITIC Securities and other investment institutions.

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Xgene XG2002 FIH announcement

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 XG004 phase 1b/2a results announcement

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 dual-targeting prodrug conjugate of an NSAID and a gabapentinoid for pain, is in Phase II trials in the US. Founded in 2015 Q4, Xgene Pharmaceutical develops small-molecule drugs for acute and chronic pain. 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.

Xgene Pharmaceutical Inc. announced achievement of the target patient enrollment in the phase II clinical trial of XG005 oral tablet in the treatment of pain associated with Osteoarthritis

April 08,2024

On April 8,2024, Xgene Pharmaceutical Inc. (hereinafter referred to as Xgene) announced that the phase II clinical trial of XG005 oral tablet in osteoarthritis pain of the knee has completed its target enrollment of 325 subjects. The last patient’s visit is expected in May with top line results expected to be reported in August 2024. The trial is led by the Peking University People’s Hospital and involves 26 hospital cites in China.

Dr. Leon Jiang, Chief Medical Officer and Senior Vice President of Xgene Pharmaceutical Inc. emphatically points out that the enrollment of all subjects was successfully achieved due to unremitting efforts of the Xgene’s team despite the COVID-19 restrictions in China at the time of the initiation of the project. “In the future, XG005 will not only be used to treat OA patients and cancer pain patients but is also expected to provide an effective and safe clinical treatment for a wide range of painful conditions.” – said Dr. Jiang.

Dr. Feng Xu, Co-founder, Chief Operating Officer, and Chief Scientific Officer of Xgene Pharmaceutical Inc. emphasized that XG005 is a new non-opioid oral analgesic that has the characteristics of treating both inflammatory and nerve pain. “For most kinds of acute and chronic pain, XG005 can more effectively inhibit pain signals and achieve better clinical efficacy through its dual-action analgesic effect” – said Dr. Xu.

Dr. Gene Hsu, Co-founder and CEO of Xgene Pharmaceutical Inc., express thanks to Xgene’s team for their great efforts and stressed that” Xgene has taken a big step forward to global commercialization by pursuing simultaneous late stage of clinical development of XG005 in China and the United States”. Furthermore, the team is also actively progressing with other pipeline products, completing the Phase 1b/2a clinical trial of XG004 topical gel in the Royal Adelaide Hospital in Australia and initiating the Phase I clinical trials for XG2002, a novel oral small molecule selective antagonist targeting the TRPM8 receptor. “The company will continue to focus on the research and development of innovative analgesic products with strong commitment to providing patients with safe and effective treatments, while creating affordable analgesic options for medical institutions, and contributing to the development of the global analgesic field!” – said Dr. Hsu.

About XG005
XG005, independently developed by Xgene, is a new chemical entity (NCE) and a novel non-opioid dual-action conjugate of an NSAID and a calcium channel inhibitor. It simultaneously targets the anti-inflammatory and neuropathic pathways of pain and, through its unique multi-modal analgesic mechanism, can inhibit pain signals more effectively to achieve better clinical efficacy in a wide range of painful conditions. Xgene is pursuing development of XG005 in several indications including acute pain (Phase IIb/III in post-surgical pain the US), chronic pain (Phase II in OA pain in China), and chronic cancer pain (Phase II in China).

About Xgene
Xgene Pharmaceutical Inc. is a clinical stage, venture capital-backed, international company utilizing linker technology to create novel, multimodal, conjugated molecules for the treatment of pain and other neurological conditions. Xgene’s linker technology overcomes the challenges of the multimodal therapy approach, and offers potentially better, safer, and more efficient treatments. Current programs are focused on dual-action NCEs with improved analgesic efficacy and tolerability and the pipeline comprising late-stage clinical programs as well as assets in discovery and preclinical development. Xgene has gained recognition and support from leading investment institutions such as Morningside Capital, TF Capital, Ping’an Venture Capital, Hengxu Capital, CITIC Securities and other investment institutions.

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Xgene revised website Draft Version 04-08-2024

NDA Application of XG005 will follow a 505(B)(1) regulatory pathway

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)(1) regulatory pathway based on FDA’s feedback.” noted Dr. Gene Hsu.

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!”

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.

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-Deal street Asia

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’s Late-Stage Analgesic Unlocks the Potential of Non-Opioid Pain Management