Chongqing Medical University

TUESDAY, Sept. 3, 2024 -- Four weeks of low-frequency repeated transcranial magnetic stimulation (rTMS) positively impacts poststroke urinary incontinence, according to a study published online Aug. 8 in Scientific Reports . Jialu Chen, from the Second Affiliated Hospital of Chongqing Medical University in China, and colleagues investigated the therapeutic effect of low-frequency rTMS on the contralesional primary motor cortex (M1) in 100 patients with poststroke urinary incontinence. The analysis included patients randomly assigned to the rTMS group or a sham-rTMS group. The researchers found that after four weeks of intervention, the maximum cystometric capacity, maximum detrusor pressure, residual urine output, overactive bladder score (including frequency, urgency, and urgency urinary incontinence), and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form improved significantly in the rTMS group versus the sham-rTMS group. No changes in pelvic floor muscle electromyography were detected in patients in either group. "Future clinical experiments aimed at determining the effectiveness of rTMS for poststroke urinary incontinence patients should be based on the timing and degree of damage, which could result in more effective rTMS programs," the authors write. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., April 05, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that new and updated data from several studies of compounds discovered by HUTCHMED will be presented at the upcoming American Association of Cancer Research (“AACR”) Annual Meeting 2024, taking place on April 5-10, 2024 in San Diego, California. Initial preclinical data will be presented for HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of certain types of acute leukemia. Compared with five other menin inhibitors in clinical development, HMPL-506 showed the stronger inhibitory potency in MLL-rearranged and NPM1 mutant leukemia cell line models. Furthermore, HMPL-506 in combination with azacytidine, venetoclax or gilteritinib synergistically improved the anti-tumor effect against MLL-rearranged leukemias both in vitro and in vivo. The investigational drug candidate displayed favorable pharmacokinetic pro high selectivity and low risk of cardiac toxicity. A Phase I study of HMPL-506 is planned for the second half of 2024. Initial preclinical data will also be presented for HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC) in which daratumumab was conjugated with cytotoxic payload Monomethyl auristatin E (MMAE) via a novel linker. It demonstrated significant superior anti-tumor activity to daratumumab, including in several B-cell malignancies models with resistance to daratumumab treatment. Other presentations include preclinical data on the ERK 1/2 inhibitor, HMPL-295; early clinical data on the Syk inhibitor, sovleplenib, in lymphoma patients; additional clinical data from global studies of VEGFR inhibitor, fruquintinib, and MET inhibitor, savolitinib; and several investigator-initiated studies of fruquintinib and VEGFR/CSF-1R/FGFR inhibitor, surufatinib. Details of the presentations are as follows: Abstract title Presenter / Lead author Presentation details SPONSORED STUDIES HMPL-506, a novel, highly potent and differentiated menin-MLL inhibitor for the treatment of MLL-rearranged and NPM1mutant acute leukemia in preclinical models Min Cheng, HUTCHMED, Shanghai, China #2113 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 HMPL-A067 (HMA800067), a novel CD38-targeting antibody-drug conjugate (ADC), demonstrated superior anti-tumor activity to daratumumab in preclinical B-cell malignancies models Yan Xu, HUTCHMED, Shanghai, China #1890 Poster Session (PO.ET01.02 - Antibody-Drug Conjugates and Bispectific Antibodies) Monday, April 8, 2024 Preclinical characterization of HMPL-295, a potent and selective ERK1/2 inhibitor Jia Hu, HUTCHMED, Shanghai, China #1661 Poster Session (PO.MCB03.01 - Cell Signaling Components as Therapeutic Targets) Monday, April 8, 2024 Targeting YAP1/TEAD signaling re-sensitizes MAPK/ERK pathway inhibitors in KRAS-driven cancer cells Xianwen Yang, HUTCHMED, Shanghai, China #1931 Poster Session (PO.ET03.04 - Drug Resistance 2: Ras GTPase) Monday, April 8, 2024 Safety and Efficacy of Sovleplenib (HMPL-523), a Syk Inhibitor, in Patients with Relapsed or Refractory Lymphoma Paolo Strati, The University of Texas MD Anderson Cancer Center, USA #CT144 Poster Session (PO.CT01.03 - Phase 0 and Phase I Clinical Trials) Monday, April 8, 2024 Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 Stefano Lonardi, Veneto Institute of Oncology IOV-IRCCS Padua, Italy #6408 Poster Session (PO.CL01.10 - Predictive Biomarkers 5) Tuesday, April 9, 2024 Savolitinib (savo) + osimertinib (osi) vs savo + placebo (PBO) in patients (pts) with EGFR-mutated (EGFRm), MET-amplified advanced NSCLC with progression on osi James Chih-Hsin Yang, National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, Taiwan #CT251 Poster Session (PO.CL01.10 - Predictive Biomarkers 5) Tuesday, April 9, 2024 INVESTIGATOR-INITIATED STUDIES Enhanced anticancer efficacy via ROS-dependent ferroptosis: synergy between surufatinib and cisplatin in small cell lung cancer Xiaolin Li, First Affiliated Hospital of Nanjing Medical University, Nanjing, China #2122 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Efficacy and underlying mechanisms of surufatinib in non-small cell lung cancer treatment Yanfang Zheng, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China #2126 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Enhancing Radiosensitivity in Biliary Tract Cancer: The Dual Role of Surufatinib in Tumor Suppression and Macrophage Reprogramming Hong Ma, Wuhan Union Hospital, Wuhan, China #2127 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Surufatinib treatment in pancreatic cancer: unveiling the role of GPR34 in TAMs and enhancing immunotherapy efficacy Jihui Hao / Song Gao, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China #2128 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Efficacy and Underlying Mechanisms of Surufatinib Combined with PD-1 Monoclonal Antibody and Chemotherapy in Pancreatic Cancer Guanghai Dai / Ru Jia, Chinese PLA General Hospital (CPLAGH), Beijing, China #2129 Poster Session (PO.ET07.02 - Pharmacodynamic Biomarkers of Drug Response) Monday, April 8, 2024 Optimizing the treatment schedule of radiotherapy combined with VEGFR-TKIs and PD-(L) 1 inhibitors in metastatic colorectal cancer Tao Zhang / Zhenyu Lin, Cancer Center, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China #3827 Poster Session (PO.CL10.04 - Outcome Investigation with Real World Data) Monday, April 8, 2024 Clinical and epidemiological pro neuroendocrine differentiation- A hospital-based retrospective study Susheng Shi / Yaru Wen, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China #4630 Poster Session (PO.ET06.04 - Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes) Tuesday, April 9, 2024 Epidemiological characteristics and treatment strategies of gastric cancer with neuroendocrine differentiation (NED) Jun Zhang, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China #4864 Poster Session (PO.PS01.08 - Descriptive Epidemiology and Statistical and Epidemiological Methodology) Tuesday, April 9, 2024 Initial efficacy of surufatinib plus sintilimab and IBI310 for patients with high-grade advanced-neuroendocrine neoplasm: A multicenter, single arm phase 2 study Lin Shen / Ming Lu, Peking University Cancer Hospital and Institute, Beijing, China #CT266 Poster Session (PO.CT02.02 - Phase II Clinical Trials 2) Tuesday, April 9, 2024 About HUTCHMED HUTCHMED (Nasdaq/AIM:​HCM; HKEX:​13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. It has approximately 5,000 personnel across all its companies, at the center of which is a team of about 1,800 in oncology/immunology. Since inception, HUTCHMED has focused on bringing cancer drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also marketed in the U.S. For more information, please visit: or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED’s current expectations regarding future events, including but not limited to its expectations regarding the therapeutic potential of fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, the further clinical development for fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, its expectations as to whether any studies on fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067 would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study’s inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067, including as combination therapies, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in different jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential markets of fruquintinib, savolitinib, surufatinib, sovleplenib, HMPL-295, HMPL-506 and HMA800067 for a targeted indication, and the sufficiency of funding. In addition, as certain studies rely on the use of nab-paclitaxel, sintilimab, toripalimab, pemetrexed, platinum, etoposide or cisplatin as combination therapeutics, such risks and uncertainties include assumptions regarding their safety, efficacy, supply and continued regulatory approval. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED’s filings with the U.S. Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. CONTACTS Investor Enquiries +852 2121 8200 / ir@hutch-med.com Media Enquiries Ben Atwell / Alex Shaw, FTI Consulting +44 20 3727 1030 / +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) / HUTCHMED@fticonsulting.com Zhou Yi, Brunswick +852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Nominated Advisor Atholl Tweedie / Freddy Crossley / Daphne Zhang, Panmure Gordon +44 (20) 7886 2500

A compound -- one of 27 million screened in a library of potential new drugs -- reversed four types of chronic pain in animal studies, according to new research. The small molecule, which binds to an inner region of a calcium channel to indirectly regulate it, outperformed gabapentin without troublesome side effects, providing a promising candidate for treating pain. A compound -- one of 27 million screened in a library of potential new drugs -- reversed four types of chronic pain in animal studies, according to new research led by NYU College of Dentistry's Pain Research Center and published in the Proceedings of the National Academy of Sciences (PNAS). The small molecule, which binds to an inner region of a calcium channel to indirectly regulate it, outperformed gabapentin without troublesome side effects, providing a promising candidate for treating pain. Calcium channels play a central role in pain signaling, in part through the release of neurotransmitters such as glutamate and GABA -- "the currency of the pain signal," according to Rajesh Khanna, director of the NYU Pain Research Center and professor of molecular pathobiology at NYU Dentistry. The Cav2.2 (or N-type) calcium channel is the target for three clinically available drugs, including gabapentin (sold under brand names including Neurontin) and pregabalin (Lyrica), which are widely used to treat nerve pain and epilepsy. Gabapentin mitigates pain by binding to the outside of the Cav2.2 calcium channel, affecting the channel's activity. However, like many pain medications, gabapentin use often comes with side effects. "Developing effective pain management with minimal side effects is crucial, but creating new therapies has been challenging," said Khanna, the senior author of the PNAS study. "Rather than directly going after known targets for pain relief, our lab is focused on indirectly targeting proteins that are involved in pain." Inside the channel Khanna has long been interested in a protein called CRMP2, a key regulator of the Cav2.2 calcium channel that binds to the channel from the inside. He and his colleagues previously discovered a peptide (a small region of amino acids) derived from CRMP2 that could uncouple CRMP2 from the calcium channel. When this peptide -- dubbed the calcium channel-binding domain 3, or CBD3 -- was delivered to cells, it acted as a decoy, blocking CRMP2 from binding to the inside of the calcium channel. This resulted in less calcium entering the calcium channel and less neurotransmitter release, which translated to less pain in animal studies. Peptides are difficult to synthesize as drugs because they are short-acting and easily degrade in the stomach, so the researchers sought to create a small molecule drug based on CBD3. Starting with the 15 amino acids that make up the CBD3 peptide, they honed in on two amino acids that studies showed were responsible for inhibiting calcium influx and mitigating pain. "At that point, we realized that these two amino acids could be the building blocks for designing a small molecule," said Khanna. From 27 million to one In collaboration with colleagues at the University of Pittsburgh, the researchers ran a computer simulation that screened a library of 27 million compounds to look for a small molecule that would "match" the CBD3 amino acids. The simulation narrowed the library down to 77 compounds, which the researchers experimentally tested to see if they lessened the amount of calcium influx. This further pared the pool down to nine compounds, which were assessed using electrophysiology to measure decreases in electrical currents through the calcium channels. One compound, which the researchers named CBD3063, emerged as the most promising candidate for treating pain. Biochemical tests revealed that CBD3063 disrupted the interaction between the CaV2.2 calcium channel and CRMP2 protein, reduced calcium entering the channel, and lessened the release of neurotransmitters. "Many scientists have screened the same library of compounds, but have been trying to block the calcium channel from the outside. Our target, these two amino acids from CRMP2, is on the inside of the cell, and this indirect approach may be the key to our success," said Khanna. Four labs, four types of pain Khanna's lab then tested CBD3063 with mouse models for pain related to injury. The compound was effective in alleviating pain in both male and female mice -- and notably, in a head-to-head test with the drug gabapentin, the researchers needed to use far less CBD3063 (1 to 10 mg) than gabapentin (30 mg) to reduce pain. To explore whether CBD3063 helped with different types of chronic pain, Khanna partnered with researchers at Virginia Commonwealth University, Michigan State University, and Rutgers University. Collaborators ran similar studies administering CBD3063 to treat animal models of chemotherapy-induced neuropathy, inflammatory pain, and trigeminal nerve pain -- all successfully reversing pain, similar to gabapentin. But unlike gabapentin, the use of CBD3063 did not come with side effects, including sedation, changes to cognition such as memory and learning, or changes to heart rate and breathing. What's next The researchers are continuing to study CBD3063, refining its chemical composition and running additional tests to study the compound's safety and assess if tolerance develops. Long-term, they hope to bring a CBD3063-derived drug to clinical trials in an effort to offer new options for safe and effective pain relief. "Identifying this first-in-class small molecule has been the culmination of more than 15 years of research. Though our research journey continues, we aspire to present a superior successor to gabapentin for the effective management of chronic pain," said Khanna. Additional authors include Kimberly Gomez, Tyler Nelson, Heather Allen, Aida Calderon-Rivera, Sara Hestehave, Erick Rodríguez Palma, Paz Duran, Santiago Loya-Lopez, Samantha Perez-Miller, and May Khanna of NYU Dentistry's Pain Research Center; Elaine Zhu and Jing Wang of NYU Grossman School of Medicine; Handoko and Paramjit Arora of NYU's Department of Chemistry; Ulises Santiago and Carlos Camacho of the University of Pittsburgh; Yuan Zhou, Angie Dorame, and Aude Chefdeville of the University of Arizona; Upasana Kumar, Rory Shields, Wanhong Zuo, Huijuan Hu, and Olga Korczeniewska of Rutgers University; Eda Koseli, Bryan McKiver, and M. Imad Damaj of Virginia Commonwealth University; Denise Giuvelis and Tamara King of the University of New England; Kufreobong Inyang and Geoffroy Laumet of Michigan State University; Dongzhi Ran, Yi Lu, and Xia Liu of Chongqing Medical University; Marcel Patek of Bright Rock Path LLC; and Aubin Moutal of St. Louis University. The research labs are supported in part by the National Institutes of Health (NS098772, NS120663, DA042852, NS119263, GM115384, NS121776, NS121259, P30GM145497, and R01CA219637).