Randomized Double-Blind Placebo Controlled Phase II Study of a Galectin-3 Inhibitor (GB1211) and Pembrolizumab Versus Pembrolizumab and Placebo in Patients With Metastatic Melanoma and Head and Neck Squamous Cell Carcinoma

The purpose of this study is to determine the objective response of GB1211 and pembrolizumab versus pembrolizumab and placebo in patients with advance metastatic melanoma or head and neck squamous cell carcinoma.

开始日期2024-02-29

申办/合作机构

Providence Health & Services

[+2]

NCT05747573

/ Completed临床1期

An Open-label, Randomized, Three-period, Crossover Study to Compare the Pharmacokinetics of GB1211 Upon Dosing a Capsule Under Fasting Condition and a Tablet Under Fasting and Fed Conditions in Healthy Volunteers

This study is an open label, Randomized, Three-period, Crossover Study to Compare the Pharmacokinetics of GB1211 upon Dosing a Capsule under Fasting Condition and a Tablet under Fasting and Fed Conditions in Healthy Volunteers

开始日期2023-01-03

申办/合作机构

Galecto Biotech ApS

[+1]

CTIS2022-502200-67-00

/ Not yet recruiting临床1期

- GB1211-CPH-005

开始日期2023-01-03

申办/合作机构

Galecto Biotech ApS

100 项与 Selvigaltin 相关的临床结果

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100 项与 Selvigaltin 相关的转化医学

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100 项与 Selvigaltin 相关的专利（医药）

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项与 Selvigaltin 相关的文献（医药）

2024-12-26·JOURNAL OF MEDICINAL CHEMISTRY

Development and Characterization of a High-Affinity Selective Galectin-3 Mouse Tool Compound in Mouse Models of Cancer

Article

作者: MacKinnon, Alison C. ; Jansson, Karl ; Leffler, Hakon ; Peterson, Kristoffer ; Nilsson, Ulf J. ; Gravelle, Lise ; Roper, James A. ; Zetterberg, Fredrik R. ; Wachenfeldt, Henrik von ; Pedersen, Anders ; Kahl-Knutson, Barbro ; Slack, Robert J. ; Holyer, Ian

The interest in galectin-3 as a drug target in the cancer and fibrosis space has grown during the past few years with several new classes of compounds being developed. The first orally available galectin-3 inhibitor, GB1211 (h-galectin-3 K_d = 0.025 μM), is currently in phase 2 clinical trials. Due to structural differences between human and mouse galectin-3 a significant reduction in mouse galectin-3 affinity is observed for most highly potent human galectin-3 inhibitors including GB1211 (m-galectin-3 K_d = 0.77 μM). Pharmacokinetic experiments in mouse dosing GB1211 up to 100 mg/kg results in free plasma levels below m-galectin-3 K_d, which is not comparable to the data observed in humans. To better support translation into clinical studies, a new improved mouse galectin-3 tool compound, GB2095, was developed. Dosing this new compound in in vivo syngeneic mouse models of cancer resulted in reduction of the growth of breast and melanoma cancers.

2024-11-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Relative bioavailability and food effect of the galectin-3 inhibitor selvigaltin (GB1211) administered as a tablet in healthy participants (GALBA-1)

Article

作者: Poulsen, Karen Killerup ; Aslanis, Vassilios ; Abd-Elaziz, Khalid ; Brinch, Anne ; Zetterberg, Fredrik R ; Slack, Robert J. ; Tantawi, Susan ; Schambye, Hans ; Gravelle, Lise ; Herman, Kimberly ; Slack, Robert J ; Lindmark, Bertil ; Zetterberg, Fredrik R. ; Holyer, Ian ; Jacoby, Brian ; Morley, Wayne ; Phung, De ; Dogterom, Peter

PURPOSE:

Overexpression of galectin-3, a β-galactoside-binding lectin, is associated with fibrotic diseases and cancer. Selvigaltin is an oral galectin-3 inhibitor, previously administered as a 50 mg capsule. This study aimed to evaluate the relative bioavailability and food effect of selvigaltin as a 100 mg tablet in healthy volunteers.

METHODS:

In this single-dose, randomized, three-period, crossover study (GALBA-1; NCT05747573), participants received selvigaltin as a 100 mg tablet (under fasted and fed conditions) or as two 50 mg capsules (under fasted conditions). Primary endpoints included plasma and urine pharmacokinetic (PK) parameters. Secondary endpoints were safety and tolerability.

RESULTS:

Of the 13 enrolled participants, 12 completed the study. Under fasted conditions, geometric mean maximum observed plasma concentration (C_max) and systemic exposure (AUC_0─inf) of selvigaltin were 161.0% and 84.0% higher, respectively, after administration of a tablet vs. capsules. Under fed vs. fasted conditions, geometric mean C_max of the selvigaltin tablet was 20.0% lower, whereas AUC_0─inf was unaffected. Geometric mean percentage of total dose of selvigaltin excreted in urine over 0─96 h was 30.3% and 35.9% for the tablet under fasted and fed conditions, respectively, and 14.5% for the capsules. No treatment-emergent severe or serious adverse events or study discontinuations due to a treatment-emergent adverse event were reported.

CONCLUSION:

The tablet formulation of selvigaltin displayed higher bioavailability vs. the capsule formulation, with minimal effect of food on PK. Selvigaltin was well-tolerated during all treatments. These findings warrant further clinical development of the tablet formulation of selvigaltin without specific food restrictions.

CLINICAL TRIAL REGISTRATION:

NCT05747573; February 28, 2023.

2024-10-01·Clinical Drug Investigation

Single‑Dose Pharmacokinetics and Safety of the Oral Galectin‑3 Inhibitor, Selvigaltin (GB1211), in Participants with Hepatic Impairment

Article

作者: Zetterberg, Fredrik R. ; Krastev, Zahari ; Aslanis, Vassilios ; Jacoby, Brian ; Ungell, Anna-Lena ; Slack, Robert J. ; Tonev, Dimitar ; Lindmark, Bertil ; Schambye, Hans ; Zetterberg, Fredrik R ; Slack, Robert J ; Gray, Michael ; Smith, Becky ; Phung, De

BACKGROUND AND OBJECTIVES:

Selvigaltin (GB1211), an orally available small molecule galectin-3 inhibitor developed as a treatment for liver fibrosis and cirrhosis, was evaluated to assess the effect of hepatic impairment on its pharmacokinetics and safety to address regulatory requirements.

METHODS:

GULLIVER-2 was a Phase Ib/IIa three-part study. Parts 1 and 3 had single-dose, open-label designs assessing pharmacokinetics (plasma [total and unbound] and urine), safety, and tolerability of 100 mg oral selvigaltin in participants with moderate (Child-Pugh B, Part 1) or severe (Child-Pugh C, Part 3) hepatic impairment, compared with healthy-matched participants (n = 6 each).

RESULTS:

All participants received selvigaltin and completed the study. No adverse events were reported. The median time to reach maximum total plasma concentration following drug administration was of 3.49 and 4.00 h post-dose for Child-Pugh B and C participants, respectively; comparable with controls. Total plasma exposure was higher for participants with hepatic impairment compared with controls. Whilst maximum plasma concentration (C_max) was unaffected in Child-Pugh B participants, area under the plasma concentration-time curve from time zero to infinity (AUC_∞) increased by ~ 1.7-fold compared with controls, and half-life was prolonged (geometric mean 28.15 vs 16.38 h). In Child-Pugh C participants, C_max increased by ~ 1.3-fold, AUC_∞ increased by ~ 1.5-fold, and half-life was prolonged (21.05 vs 16.14 h). No trend was observed in plasma unbound fractions or urinary excretion of unchanged selvigaltin in either group.

CONCLUSION:

Hepatic impairment increased selvigaltin exposure without safety concerns. These data can inform dose recommendations for future clinical programmes.

TRIAL REGISTRATION:

Clinicaltrials.gov NCT05009680.

项与 Selvigaltin 相关的新闻（医药）

2025-03-19

·ir.galecto.com

Galecto Reports Full-Year 2024 Financial Results

Completed strategic review to focus on oncology and liver diseases with the acquisition of global rights to GB3226 (formerly BRM-1420), a dual ENL-YEATS and FLT3 inhibitor for multiple genetic subsets of AML from Bridge Medicines GB3226 on track for IND submission in Q1 2026 Phase 2 investigator-initiated trial (IIT) of GB1211 in combination with pembrolizumab (Keytruda®) in metastatic melanoma and head and neck squamous cell carcinoma continues to enroll patients BOSTON, March 19, 2025 (GLOBE NEWSWIRE) -- Galecto, Inc. (NASDAQ: GLTO), a clinical-stage biotechnology company focused on the development of novel treatments for cancer and fibrosis, today announced its operating and financial results for the quarter and year ended December 31, 2024. “A significant moment for Galecto in 2024 was the completion of our strategic review, which solidified our commitment to advancing innovative oncology therapies,” said Dr. Hans Schambye, CEO of Galecto. “The acquisition of global rights to GB3226 provides us with an opportunity to develop a unique approach to AML that has the potential to significantly improve outcomes for the AML patient population. GB3226 has shown strong potential in preclinical studies, showing activity against a range of AML-driving mutations, including those commonly associated with resistance and relapse. With its dual mechanism of action, GB3226 has the potential to provide rapid therapeutic effect via inhibition of FLT3 and promote sustained response through inhibition of ENL-YEATS.” Dr. Schambye continued, “We are focused on moving GB3226 into clinical development as quickly as possible while maintaining our commitment to advancing transformative treatments for cancer and liver diseases. With a strengthened pipeline and a clear strategic focus, we look forward to advancing these promising therapies for patients in need.” 2024 Corporate Highlights Acquired global rights to Bridge Medicines’ BRM-1420 program, now GB3226, a novel dual ENL-YEATS and FLT3 inhibitor for multiple genetic subsets of acute myeloid leukemia (AML). GB3226 is a potent and selective inhibitor designed to disrupt key oncogenic pathway signaling. Preclinical data showed GB3226’s superior efficacy to both FLT3 and menin inhibitors in animal models, as well as additive or synergistic activity in combination with standard-of-care treatments. Providence Portland Medical Center’s Earle A. Chiles Research Institute initiated a Phase 2 trial of GB1211 in combination with pembrolizumab (Keytruda®) in metastatic melanoma and head and neck squamous cell carcinoma. Appointed Dr. Amy Wechsler to the Board of Directors. Dr. Wechsler brings strong biotech leadership experience to the Galecto board. Matthew Kronmiller, Bridge Medicine’s Chief Executive Officer, joined Galecto’s management team as the Executive Vice President of Strategy and Chief Business Officer. Full-Year 2024 Financial Results Cash and cash equivalents as of December 31, 2024 were approximately $14.2 million. The Company anticipates that its cash and cash equivalents will be sufficient to fund operating expenses and capital requirements into 2026, including the submission of an investigational new drug application for GB3226 to the FDA. However, the Company will require substantial additional capital to finance its operations, including future clinical development of its GB3226 and GB1211 programs. Research and development expenses were $6.4 million for the year ended December 31, 2024, compared to $23.8 million for the year ended December 31, 2023. The decrease was primarily related to decreased clinical trial-related expenses due to discontinued clinical trial activities, decreased chemistry, manufacturing, and control ("CMC") activities, decreased personnel costs, and decreased consulting related costs and other research and development costs. Acquired in-process research and development costs were $4.4 million for the year ended December 31, 2024. These costs related to an asset purchase with Bridge Medicines pursuant to which we acquired global rights to Bridge Medicines’ BRM-1420 program. There were no acquired in-process research and development costs for the year ended December 31, 2023. General and administrative expenses were $10.5 million for the year ended December 31, 2024, compared to $12.7 million for the year ended December 31, 2023. The decrease was primarily related to decreased personnel costs and decreased other general and administrative costs. Net loss attributable to common stockholders for the year ended December 31, 2024, was $21.4 million or $(18.53) per basic and diluted share, compared with $38.3 million, or $(36.08) per basic and diluted share, for the prior year period. About Galecto Galecto is a clinical-stage biopharmaceutical company committed to realizing the promise of novel treatments for cancer and liver diseases. The Company’s pipeline consists of first-in-class small molecule drug candidates that target cancer and fibrosis signaling pathways, including (i) a preclinical dual inhibitor of ENL-YEATS and FLT3 (BRM-1420) for multiple genetic subsets of AML; (ii) an orally active galectin-3 inhibitor (GB1211) in combination with a checkpoint inhibitor for various oncology indications; and (iii) an orally active galectin-3 inhibitor (GB1211) for the treatment of liver cirrhosis. Galecto intends to use its website as a means of disclosing material non-public information. For regular updates about Galecto, visit www.galecto.com. Forward-Looking Statements Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include statements about Galecto’s preclinical and clinical development plans for GB3226 (formerly BRM-1420) and GB1211; that GB3226 could be additive or synergistic when used in combination with current standard of care therapies; the potential of Galecto’s product candidates to address or transform significant areas of unmet need and improve outcomes for patients; and Galecto’s expectation that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital requirements into 2026. Such forward-looking statements include statements about Galecto’s focus and plans for preclinical and clinical development of its product candidates and pipeline. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. For such statements, Galecto claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Galecto's expectations. Factors that could cause actual results to differ materially from the forward-looking statements include risks and uncertainties related to the development of Galecto’s product candidates and their therapeutic potential, having adequate funds and their use, and those disclosed in Galecto’s filings with the Securities and Exchange Commission (SEC), including, but not limited to, Galecto’s Annual Report on Form 10-K, as filed with the SEC on March [19], 2025. These forward-looking statements represent Galecto's judgment as of the time of this release. Galecto disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. For more information, contact: Investors/US Sandya von der Weid svonderweid@lifesciadvisors.com +41 78 680 0538 Source: Galecto, Inc.

临床2期高管变更财报

2025-03-06

·PRNewswire

TEPMETKO Continues to Strengthens its Position as a Leading METex14 Skipping NSCLC Therapy | DelveInsight

With increasing biomarker-driven cancer treatments, TEPMETKO benefits from growing adoption in precision oncology. Competition from other MET inhibitors like TABRECTA (capmatinib) exists, but TEPMETKO's once-daily dosing and efficacy profile offer differentiation. LAS VEGAS, March 6, 2025 /PRNewswire/ -- DelveInsight's " TEPMETKO Market Size, Forecast, and Market Insight Report" highlights the details around TEPMETKO, a kinase inhibitor indicated for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TEPMETKO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. EMD Serono's TEPMETKO (tepotinib) Overview TEPMETKO is a kinase inhibitor prescribed for adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping alterations. The active component is Tepotinib (as hydrochloride monohydrate), administered orally. Patients should be cautioned about the heightened risk of severe or fatal interstitial lung disease/pneumonitis, liver toxicity, and potential embryo-fetal toxicity, necessitating effective contraception during and shortly after treatment. Tepotinib specifically targets MET, including variants with exon 14 skipping mutations. It blocks HGF-dependent and independent MET phosphorylation, disrupting MET-driven signaling pathways. Additionally, at clinically relevant concentrations, Tepotinib inhibits melatonin 2 and imidazoline 1 receptors. In vitro studies show that it suppresses tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent cancer cells. In mouse models with MET-driven tumors, including those with MET exon 14 skipping alterations, Tepotinib reduced tumor growth, sustained MET phosphorylation inhibition, and, in one case, decreased metastasis formation. The recommended dose of TEPMETKO is 450 mg taken orally once daily until disease progression or intolerable toxicity occurs. Patients should take it at the same time each day, swallowing tablets whole without chewing, crushing, or splitting them. If a dose is missed and less than eight hours remain until the next scheduled dose, patients should skip it. In cases of vomiting after taking TEPMETKO, the next dose should be taken at the usual time. Learn more about TEPMETKO projected market size for NSCLC @ TEPMETKO Market Potential Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 81% of all diagnosed cases. Early detection greatly improves outcomes, but diagnosing NSCLC and other lung cancers is challenging because their symptoms are often mistaken for common illnesses or the long-term effects of smoking. Consequently, 80% of NSCLC cases are already at advanced stages by the time they are identified, making treatment more difficult. Around 80% of EGFR mutations in NSCLC involve either exon 19 deletions or the exon 21 L858R substitution, both of which are classified as sensitizing mutations. Until the last decade, chemotherapy was the primary treatment for advanced and metastatic lung cancer. However, this changed in 2015 with the approval of the first immune checkpoint inhibitor (ICI), KEYTRUDA (pembrolizumab), as a second-line therapy for advanced cases. This was followed by TECENTRIQ (atezolizumab) in 2016. Both therapies were later approved for first-line treatment, broadening their use to a larger patient population. In 2020, the combination of OPDIVO (nivolumab) and ipilimumab also received approval as a first-line treatment for metastatic NSCLC. According to DelveInsight, the NSCLC market size across the 7MM is projected to grow from USD 30 billion in 2024, with a substantial CAGR through 2034. This growth is largely driven by the introduction of emerging therapies during the forecast period (2025–2034). Discover more about the NSCLC market in detail @ Non-small Cell Lung Cancer Market Report Emerging Competitors of TEPMETKO The NSCLC pipeline is very robust with the promising therapies such as Telisotuzumab vedotin (AbbVie), Patritumab deruxtecan (Daiichi Sankyo/AstraZeneca), Datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), Eftilagimod alpha (Immutep), BNT311/GEN1046 (acasunlimab) (Genmab), V940 (mRNA-4157) + Pembrolizumab (Moderna Therapeutics/Merck), Plinabulin + Docetaxel (BeyondSpring), Olomorasib (LY3537982) (Eli Lilly and Company), Zipalertinib (Cullinan Oncology/Taiho Pharma), Ceralasertib (AZD6738) (AstraZeneca), TEDOPI (EP-2101; IDM 2101; OSE-2101) (OSE Immuno-therapeutics), Sigvotatug vedotin (PF08046047) (Pfizer), ANKTIVA (N-803) (ImmunityBio), Aumolertinib/Almonertinib/HS-10206 (Jiangsu Hansoh Pharmaceutical), Niraparib (GSK), Savolitinib (AstraZeneca/Hutchison MediPharma), TRODELVY (Gilead Sciences), Pyrotinib (Jiangsu HengRui Medicine), Ociperlimab (BGB-A1217) (BieGene), Volrustomig (AstraZeneca), Gotistobart (BNT316/ONC-392) (OncoC4/BioNTech), Ivonescimab (AK112/SMT112) (Akeso Biopharma/Summit Therapeutics), ZYNYZ (retifanlimab/INCMGA00012) (Incyte/Macrogenics), Divarasib (GDC-6036) (Roche/Genentech), Tiragolumab (RG6058) (Roche), Sacituzumab Tirumotecan (Merck and Kelun-Biotech), JEMPERLI (dostarlimab/TSR-042) (GSK and AnaptysBio), Zongertinib (BI-1810631) (Boehringer Ingelheim), BAY 2927088 (Bayer), Serplulimab (HLX10) (Shanghai Henlius Biotech), Rilvegostomig (AZD2936) (AstraZeneca), MK-1084 (Merck, Taiho Pharmaceutical, and Astex), Domvanalimab (Arcus Biosciences and Gilead Sciences), OPDUALAG (nivolumab and relatlimab) (Bristol-Myers Squibb), Belrestotug + JEMPERLI (iTeos Therapeutics and GSK), Firmonertinib (ArriVent BioPharma), Sunvozertinib (DZD9008) (Dizal Pharmaceutical), Cobolimab (GSK), Livmoniplimab (AbbVie), Fianlimab (REGN3767) (Regeneron Pharmaceuticals), BNT327/PM8002 (Biotheus/BioNTech), HS-20117 (Hansoh BioMedical), IO102-IO103 + Pembrolizumab (IO Biotech), Naptumomab estafenatox (NeoTX Therapeutics/Active Biotech), FF-10832 (FUJIFILM Corporation), BNT116 (BioNTechSE/Regeneron Pharmaceuticals), CAN-2409 (Candel Therapeutics), Mecbotamab Vedotin (BA3011/CAB-AXL-ADC) (BioAtla), Bemcentinib (BGB 324/BGB-3234/R-428) (BerGenBio/Rigel Pharmaceuticals), DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Lifileucel (Iovance Biotherapeutics), IBI363 (Innovent Biologics), Sotevtamab (AB-16B5) (Alethia Biotherapeutics), Avutometinib (VS6766) (Verastem Oncology), Vebreltinib (APL-101) (Apollomics), LP-300 (Lantern Pharma), JNJ-90301900 (Johnson & Johnson Innovative Medicine), AMG 193 (Amgen), Luveltamab tazevibulin (Sutro Biopharma), PRT3789 (Prelude Therapeutics), Disitamab vedotin (Seagen), PADCEV (enfortumab vedotin) (Astellas Pharma), RP1 (Replimune), TIVDAK (tisotumab vedotin) (Seagen), Zanidatamab (Jazz Pharmaceuticals), Utidelone injectable (UTD1) (Beijing Biostar Pharmaceuticals), REGN5093-M114 (Regeneron Pharmaceuticals), SLC-391 (SignalChem Lifesciences), fulzerasib (GenFleet), Davutamig (REGN5093) (Regeneron Pharmaceuticals), TAS3351 (Taiho Oncology), H002 (RedCloud Bio), JIN-A02 (J INTS BIO), FWD1509 (Forward Pharma), Sabestomig (AZD7789) (AstraZeneca), Sasanlimab (Pfizer), Selvigaltin (GB1211) (Galecto Biotech), Vepafestinib Helsinn (Healthcare/Taiho Pharmaceutical), EP0031 (A400/ KL590586) (Ellipses Pharma/Kelun-Biotech), Pamvatamig (MCLA-129) (Merus), Zidesamtinib (NVL-520) (Nuvalent), NVL-655 (Nuvalent), RMC-4630 (Revolution Medicines), REQORSA (quaratusugene ozeplasmid) (Genprex), PDC*lung01 (PDC*line Pharma), Evalstotug (BA3071) (BioAtla and BeiGene), PT-112 (Promontory Therapeutics), MRT-2359 (Monte Rosa Therapeutics), GAIA-102 (GAIA BioMedicine), Rigosertib (Traws Pharma), HMBD-001 (Hummingbird Bioscience), PLB1004 (Avistone Biotechnology), ANS03 (Avistone Biotechnology), MYTX-011 (Mythic Therapeutics), A166 (Sichuan Kelun-Biotech Bio-pharmaceutical), Atamparib (BN-2397) (Ribon Therapeutics), DELTACEL (KB-GDT-01) (Kiromic BioPharma), Carotuximab (ENV-105) (Kairos Pharma), YL202 (MediLink Therapeutics), and others. To know more about the number of competing drugs in development, visit @ TEPMETKO Market Positioning Compared to Other Drugs Key Milestones of TEPMETKO In February 2024, the FDA granted traditional approval to TEPMETKO for adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. In February 2022, the EC approved TEPMETKO as monotherapy for the treatment of adult patients with advanced NSCLC harboring alterations leading to METex14 skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. In February 2021, Merck announced that the US FDA has approved TEPMETKO following priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. This indication was approved under accelerated approval based on ORR and DOR. In October 2020, TEPMETKO received ODD for treating NSCLC with MET genomic tumor aberrations In March 2020, EMD Serono (the biopharmaceutical business of Merck KGaA), announced that the MHLW approved TEPMETKO for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations. In September 2019, the US FDA granted BTD for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy Discover how TEPMETKO is shaping the NSCLC treatment landscape @ TEPMETKO NSCLC TEPMETKO Market Dynamics TEPMETKO competes in a growing but highly specialized market where MET-targeted therapies are gaining traction due to their efficacy in addressing MET-altered tumors. The market for MET inhibitors is expanding as precision oncology advances and molecular diagnostics become more widely available, enabling better identification of patients who would benefit from targeted treatments like TEPMETKO. A key factor shaping TEPMETKO's market dynamics is competition. It directly competes with Novartis' TABRECTA (capmatinib), another MET inhibitor approved for the same indication. While TEPMETKO offers the advantage of once-daily dosing compared to TABRECTA's twice-daily regimen, both drugs have similar efficacy profiles, making physician and patient preference an important differentiator. Additionally, broader competition from next-generation MET inhibitors and combination therapies in clinical trials could impact TEPMETKO's long-term market position. Regulatory approvals and market access play a crucial role in TEPMETKO's adoption. The drug has been approved in multiple regions, including the U.S., Europe, and Japan, but reimbursement and pricing strategies vary by market. Payer policies, along with the cost-benefit analysis of MET inhibitors compared to other targeted therapies, influence prescription trends. Furthermore, real-world evidence and post-marketing studies will be critical in demonstrating TEPMETKO's sustained effectiveness and safety, which could support expanded indications and increased market penetration. Looking ahead, the MET inhibitor market is expected to grow with advances in biomarker-driven therapy, further refining patient selection. TEPMETKO's success will depend on continued clinical development, potential label expansions, and strategic partnerships to strengthen its competitive edge. As new entrants emerge, Merck KGaA's ability to differentiate TEPMETKO through combination strategies or enhanced formulations may determine its long-term sustainability in this evolving landscape. Dive deeper to get more insight into TEPMETKO's strengths & weaknesses relative to competitors @ TEPMETKO Market Drug Report Table of Contents Related Reports Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. C-MET Metastatic Non-small Cell Lung Cancer Market C-MET Metastatic Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key C-MET mNSCLC companies, including Novartis, Merck, EMD Serono, AbbVie, Regeneron Pharmaceuticals, Mythic Therapeutics, Apollomics, Johnson & Johnson Innovation, Haihe Biopharma, among others. C-MET Non-small Cell Lung Cancer Pipeline C-MET Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key C-MET non-small cell lung cancer companies, including AbbVie, Janssen Research & Development, Beijing Pearl Biotechnology Limited Liability Company, Novartis, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

上市批准免疫疗法优先审批

2024-12-27

·生物制药小编

迈向失败的Galectin-3

近日，Galectin Therapeutics公司的Galectin-3抑制剂Belapectin的18周III期临床失败。 Belapectin是Galectin Therapeutics的核心管线，此次失败的适应症为MASH 引起的肝硬化门脉高压，目前该公司除了此次失败的MASH适应症，还有一项与K药联合使用治疗癌症的II期临床。目前公司唯一的希望寄托于36周的临床数据，不过目前看下来投资者显然并不买账，公司股价已经跌至1美元。与之处境相似的则是另外丹麦公司Galecto Biotech，同样是Galectin-3抑制剂，Galecto此前的核心管线GB0139也在特发性肺纤维化（IPF）这一适应症上失败。 Galectin-3抑制剂的前路看上去相当暗淡。广泛表达的靶点，不均一的靶向半乳糖凝集素-3（Galectin-3）是一种比较特殊的β-半乳糖苷结合凝集素，它与其他半乳糖凝集素的不同之处在于其单体结构，该结构包含一个C端CRD（碳水化合物识别域）、一个中间脯氨酸-甘氨酸-丙氨酸-酪氨酸重复域和一个短的N端域。由于半乳糖凝集素可以二价或多价方式结合，因此其可例如交联细胞表面糖结合物以触发细胞信号传导事件，这使得其作用机制相当复杂，它能够与细胞膜、细胞外基质、生物液体和细胞内的大量蛋白质相互作用，参与了大量的生物学和病理学事件。图：Galectin-3的结构和主要功能来源：DOI: 10.1016/j.tips.2023.06.001 Galectin-3广泛分布在心、肾、肝、肺及肠道等组织器官中。它直接参与多种炎症、纤维化和恶性疾病相关过程。（如下图所示）不过，这里同时也引来了一个问题：Galectin-3到底是疾病过程的次要参与者还是致病因素？换句话说，Galectin-3抑制剂能直接用于治疗这些疾病吗？虽然Galecto Biotech和Galectin Therapeutics的失败为这一领域笼罩了一层阴霾，但是他们的开发方向仍然值得借鉴。目前的主要开发方向是专门针对高度保守的CRD。 Galectin-3的CRD成为靶向策略核心 Gal-3的CRD在生理上适合与天然多糖配体结合。这个CRD位于蛋白质表面，暴露于溶剂中，并含有高度极性的氨基酸。天然配体如二糖乳糖和N-乙酰乳糖胺通过它们羟基基团、Gal-3的极性氨基酸和水分子之间广泛的氢键网络以及相对较弱的范德华相互作用进行结合，因此具有较低的结合亲和力。合成抑制剂最成功的尝试是基于用芳香取代基修饰半乳糖，以便与少数氨基酸形成新的强相互作用。对于这些天然配体而言，含有对这些位点具有广泛相互作用的取代基的化合物有望实现更高的选择性。在Gal-3核心结合位点中，几乎所有的强效糖基配体都靶向两个关键氨基酸残基——Arg144和Arg186。Arg144是Gal-3的独特特征，因为大多数其他凝集素在其位置有不同的残基，而Arg186在凝集素中是保守的。在Galecto此前的管线GB0139——一种二糖Gal-3抑制剂中，装饰两个半乳糖单元的芳香取代基与这些精氨酸形成强烈的π-堆积相互作用。后续开发的GB1211则与GB0139不同，这种合成单糖抑制剂只含有一个半乳糖单元，并且只涉及Arg144的π-堆积相互作用，虽然这种抑制剂只与Arg144形成π-堆积相互作用，但它通过另一种方式（糖苷异头体取代基与蛋白质骨架形成了额外的有效相互作用）增强了与Gal-3蛋白的结合力。（如下图所示）其实GB0139除了IPF以外，早先也开发过新冠适应症，但显然因为众所周知的原因放弃了。而这次失败的Belapectin（GR-MD-02）是一种来源于苹果果胶的复合药物糖聚合物，主要作用是抑制Galectin-3蛋白，不过也能显著结合结合Gal-1。实际上从早先的II期临床视角来看，用Belapectin治疗MASH本身肯定是失败的。早先的数据显示，Belapectin在一项针对NASH、肝硬化和门静脉高压患者的II期试验中，GR-MD-02在肝静脉压力或肝纤维化参数上并未显示出显著疗效。在这种绝境的情况下，Galectin专门找了无食管静脉曲张亚组进行事后分析，发现接受低剂量GR-MD-02治疗的患者门静脉压力降低，静脉曲张发展减少，才找到了MASH引起的肝硬化门脉高压这一适应症。现在18周数据未达终点，被寄予希望的36周数据能否挽救公司就尚未可知了。总结迄今为止发现的大多数Galectin-3抑制剂都存在缺乏效力或选择性的问题，同时有些Galectin-3还显著结合Gal-1。Galectin-3的广泛分布问题也是一个挑战。胞内Gal-3通常更多地与凋亡或存活途径相关。或许在癌症适应症上可能更加适合那些带有细胞穿透性的Galectin-3抑制剂，而胞外Galectin-3抑制剂更加适合炎症和纤维化疾病。然而，这种胞外和胞内的区别没有想象中那么分得开，比如说GR-MD-02既在癌症中展开适应症，又在MASH相关疾病中开展适应症。或许未来的靶向策略方向又会换到挑战N端尾巴，或者是采用抗体去靶向CRD。适应症战略或许如上海中医药大学专利申请专利CN114272382中，去治疗冠心病等心血管疾病。参考来源： Bouffette S, Botez I, De Ceuninck F. Targeting galectin-3 in inflammatory and fibrotic diseases. Trends Pharmacol Sci. 2023 Aug;44(8):519-531. doi: 10.1016/j.tips.2023.06.001. Epub 2023 Jun 28. https://patentscope2.wipo.int/search/zh/detail.jsf?docId=CN357980571&_cid=JP1-M50GNE-29245-1 https://galectintherapeutics.com/pipeline-overview/

临床2期临床失败

100 项与 Selvigaltin 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性黑色素瘤	临床2期	美国	Earle Chiles Research Institute	2022-10-19
转移性黑色素瘤	临床2期	美国	Galecto Biotech ApS	2022-10-19
头颈部鳞状细胞癌	临床2期	美国	Galecto Biotech ApS	2022-10-19
头颈部鳞状细胞癌	临床2期	美国	Earle Chiles Research Institute	2022-10-19
非小细胞肺癌	临床2期	丹麦	Galecto Biotech ApS	2021-10-30
非酒精性脂肪性肝炎	临床2期	-	Galecto Biotech ApS	2021-03-01
肝硬化	临床2期	保加利亚	Galecto Biotech ApS	-
肝纤维化	临床1期	英国	Galecto Biotech ApS	2019-01-14

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05009680 (GULLIVER-2, Pubmed \| Clin Drug Investig) 人工标引	临床1/2期	肝功能不全	6	Selvigaltin 100 mg	構繭鹹憲鹹鹹壓淵觸鑰(鑰襯艱憲艱衊繭繭壓積) = No adverse events were reported. 獵廠觸憲積衊顧淵醖醖 (壓範鹽簾願獵鏇觸遞選 ) 更多	积极	2024-10-02
				SelvigaltinSelvigaltin 100 mg (Child-Pugh C)
NCT05747573 (GALBA-1, Pubmed \| Cancer Chemother Pharmacol)	临床1期	galectin-3	13	Selvigaltin 100 mg tablet (fasted)	顧願築鬱鏇網觸鏇襯網(醖願廠遞憲淵鬱範鬱齋) = 廠選鑰齋鑰襯鹽廠窪獵顧選蓋製齋齋餘鹹窪繭 (壓窪襯鏇構艱醖鏇鬱繭 ) 更多	积极	2024-08-21
NCT05240131 (GALLANT-1, ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	非小细胞肺癌一线	9	GB1211 200 mg+atezolizumab 1200 mg	廠鹹糧糧鹹淵簾範壓醖(網願觸築齋願選選選憲) = 襯襯範餘繭築窪夢構淵衊願蓋窪壓鹽蓋艱淵襯 (選淵觸壓獵簾蓋獵築淵 )	积极	2023-10-23
				GB1211 100 mg+atezolizumab 1200 mg	-
NCT03809052 (Pubmed)	临床1期	-	78	GB1211	遞壓範網壓淵襯醖遞蓋(獵襯鏇鏇窪願淵顧膚鹽) = delayed by 2 h 衊衊繭窪窪壓鑰衊選窪 (餘觸鑰願醖廠艱積願憲 ) 更多	-	2023-03-13
NCT05009680 (GULLIVER-2, Corporate Publications) 人工标引	临床1/2期	肝硬化	30	GB1211	鹽製觸製艱顧醖繭餘齋(襯餘窪襯艱窪繭蓋顧鹹) = 壓齋製淵鑰夢獵壓選遞鑰鹹鏇構願窪窪蓋鏇鑰 (築窪網網膚夢觸積簾衊 ) 更多	积极	2022-11-01
				Placebo	鹽製觸製艱顧醖繭餘齋(艱壓獵鹽遞遞範鹽鹽憲) = 鬱膚獵淵願醖遞願繭襯夢鬱淵餘網顧顧艱鬱鏇 (鹽繭膚鬱膚齋構廠觸網 ) 更多
NCT05009680 (GULLIVER-2, Corporate Publications) 人工标引	临床1/2期	肝硬化	54	GB-1211	蓋願糧壓鬱遞願艱築製(壓鏇遞蓋願蓋憲範廠糧) = 選獵積鑰網築蓋壓顧獵製齋選鏇蓋積壓鏇窪簾 (醖獵鏇憲憲範範蓋選鹹 )	积极	2021-12-13
				Placebo	-