COVID-19 is a community acquired pneumonia caused by infection with a novel coronavirus, SARS CoV2 and is a serious condition with high mortality in hospitalised patients, for which there is no currently approved treatment other than supportive care. Urgent investigation of potential treatments for this condition is required.
This protocol describes an overarching and adaptive trial designed to provide safety, pharmacokinetic (PK)/ pharmacodynamic (PD) information and exploratory biological surrogates of efficacy which may support further development and deployment of candidate therapies in larger scale trials of COVID-19 positive patients receiving normal standard of care.
Given the spectrum of clinical disease, community based infected patients or hospitalised patients can be included. Products requiring parenteral administration will only be investigated in hospitalised patients. Patients will be divided into cohorts, a) community b) hospitalised patients with new changes on a chest x-ray (CXR) or a computed tomography (CT) scan or requiring supplemental oxygen and c) hospitalised requiring assisted ventilation. Participants may be recruited from all three of these cohorts, depending on the experimental therapy, its route of administration and mechanism of action. The relevant cohort(s) for any given therapy will be detailed in the therapy-specific appendix.
Candidate therapies can be added to the protocol and previous candidates removed from further investigation as evidence emerges. The trial will be monitored by an independent Data Monitoring Committee (DMC) to ensure patient safety.
Each candidate cohort will include a small cohort of patients randomised to candidate therapy or existing standard of care management dependent on disease stage at entry. Cohort numbers will be defined in the protocol appendices.
This is a Phase IIa experimental medicine trial and as such formal sample size calculations are not appropriate.

Start Date03 Jul 2020

Sponsor / Collaborator

The University of Edinburgh

[+3]

NCT03832946 / CompletedPhase 2

A Randomized, 52 Week, Double-blind, Multicentre, Parallel, Placebo-controlled Phase 2b Study in Subjects With Idiopathic Pulmonary Fibrosis (IPF) Investigating the Efficacy and Safety of GB0139, an Inhaled Galectin-3 Inhibitor.

This is a randomized, double-blind, placebo-controlled phase 2b trial in subjects with IPF (idiopathic pulmonary fibrosis) investigating the efficacy and safety of GB0139.

Start Date19 Feb 2019

Sponsor / Collaborator

Galecto Biotech ApS

[+2]

NCT02257177 / CompletedPhase 1/2

A Placebo-controlled RCT in HV's Investigating the Safety, Tolerability and PK (Pharmacokinetic) of TD139, a Galectin-3 Inhibitor, Followed by an Expansion Cohort Treating Subjects With Idiopathic Pulmonary Fibrosis (IPF)

This study will be divided into 2 parts. Part 1 is a randomized, double-blind, single centre, placebo-controlled, single ascending dose (SAD) phase I study designed to assess the safety, tolerability, PK and PD (Pharmacodynamic) of TD139 in up to 36 healthy male subjects. Part 2 will be a randomized, double-blind, multi-centre, placebo-controlled, multiple dose expansion cohort, designed to assess the safety, tolerability, PK and PD of TD139 in up to 24 male subjects and female subjects of non child-bearing potential with IPF.

Start Date01 Sep 2014

Sponsor / Collaborator

Galecto Biotech ApS

100 Clinical Results associated with Olitigaltin

100 Translational Medicine associated with Olitigaltin

100 Patents (Medical) associated with Olitigaltin

Literatures (Medical) associated with Olitigaltin

01 Mar 2024·Brain, behavior, and immunity

Injured sensory neurons-derived galectin-3 contributes to neuropathic pain via programming microglia in the spinal dorsal horn

Article

Author: Wu, Yifei ; Liu, Yaqi ; Chen, Yiming ; Luo, Yuhui ; Zeng, Qian ; Hu, Qiaodan ; Jiang, Changyu ; Ji, Luyao ; Wu, Chaoran ; Li, Changlin ; Xu, Yuanfan ; Wu, Jiawei ; Shan, Leyan ; Li, Yitong ; Wang, Zilong ; Xu, Kangtai

Emerging studies have demonstrated spinal microglia play a critical role in central sensitization and contribute to chronic pain. Although several mediators that contribute to microglia activation have been identified, the mechanism of microglia activation and its functionally diversified mechanisms in pathological pain are still unclear. Here we report that injured sensory neurons-derived Galectin-3 (Gal3) activates and reprograms microglia in the spinal dorsal horn (SDH) and contributes to neuropathic pain. Firstly, Gal3 is predominantly expressed in the isolectin B4 (IB4)-positive non-peptidergic sensory neurons and significantly up-regulated in dorsal root ganglion (DRG) neurons and primary afferent terminals in SDH in the partial sciatic nerve ligation (pSNL)-induced neuropathic pain model. Gal3 knockout (Gal3 KO) mice showed a significant decrease in mechanical allodynia and Gal3 inhibitor TD-139 produced a significant anti-allodynia effect in the pSNL model. Furthermore, pSNL-induced microgliosis was compromised in Gal3 KO mice. Additionally, intrathecal injection of Gal3 produces remarkable mechanical allodynia by direct activation of microglia, which have enhanced inflammatory responses with TNF-α and IL-1β up-regulation. Thirdly, using single-nuclear RNA sequencing (snRNA-seq), we identified that Gal3 targets microglia and induces reprogramming of microglia, which may contribute to neuropathic pain establishment. Finally, Gal3 enhances excitatory synaptic transmission in excitatory neurons in the SDH via microglia activation. Our findings reveal that injured sensory neurons-derived Gal3 programs microglia in the SDH and contribute to neuropathic pain.

14 Aug 2023·International journal of molecular sciences

Epithelial Galectin-3 Induced the Mitochondrial Complex Inhibition and Cell Cycle Arrest of CD8⁺ T Cells in Severe/Critical COVID-19.

Article

Author: Liu, Yanping ; Yan, Qing ; Yang, Cheng ; Wang, Zhongyi ; Huang, Juan ; Feng, Ying ; Zhou, Jingjiao ; Wang, Yudie ; Wang, Yi

Previous research suggested that the dramatical decrease in CD8⁺ T cells is a contributing factor in the poor prognosis and disease progression of COVID-19 patients. However, the underlying mechanisms are not fully understood. In this study, we conducted Single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) analysis, which revealed a proliferative-exhausted MCM⁺FASLG^low CD8⁺ T cell phenotype in severe/critical COVID-19 patients. These CD8⁺ T cells were characterized by G2/M cell cycle arrest, downregulation of respiratory chain complex genes, and inhibition of mitochondrial biogenesis. CellChat analysis of infected lung epithelial cells and CD8⁺ T cells found that the galectin signaling pathway played a crucial role in CD8⁺ T cell reduction and dysfunction. To further elucidate the mechanisms, we established SARS-CoV-2 ORF3a-transfected A549 cells, and co-cultured them with CD8⁺ T cells for ex vivo experiments. Our results showed that epithelial galectin-3 inhibited the transcription of the mitochondrial respiratory chain complex III/IV genes of CD8⁺ T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). Further findings showed that the suppression of NRF1 translocation was associated with ERK-related and Akt-related signaling pathways. Importantly, the galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, thus enhancing the expression of the mitochondrial respiratory chain complex III/IV genes and the mitochondrial biogenesis of CD8⁺ T cells. Our study provided new insights into the immunopathogenesis of COVID-19 and identified potential therapeutic targets for the prevention and treatment of severe/critical COVID-19 patients.

01 Jul 2023·Experimental neurology

Role of galectin-3 in cardiac dysfunction induced by subarachnoid hemorrhage

Article

Author: Huang, Xuan-Xuan ; Guo, Wen-Jing ; Yuan, Dan ; Lin, Hong-Bin ; Pang, Xiang-Xiong ; Li, Feng-Xian ; Zhang, Qian-Qian ; He, Wan-Ying ; Zhang, Hong-Fei

Subarachnoid hemorrhage (SAH) is a severe acute cerebrovascular event that not only impairs the central nervous system but also negatively affects various other organs, including the heart. The underlying mechanisms, however, remain unclear. In this study, we discovered that mice with SAH exhibited significant cardiac injuries, such as extended QT and QTc intervals, cardiac fibrosis, and reduced cardiac ejection fractions. This phenomenon was accompanied by increased galectin-3 expression in the cardiac ventricle and can be reversed by galectin-3 inhibitor TD139. Interestingly, we also observed increased co-expression of galectin-3 in macrophage within the heart tissue of SAH mice. Additionally, when macrophage activation was suppressed using the beta-blocker propranolol, cardiac function improved, and galectin-3 expression in the cardiac tissue decreased. Collectively, our findings offer new insights into the role of galectin-3 in SAH-related cardiac dysfunction and suggest a macrophage-galectin-3 axis as a potential therapeutic strategy.

News (Medical) associated with Olitigaltin

27 Sep 2023

·www.fiercebiotech.com

Galecto lays off 70%, hunts for 'strategic alternatives' in wake of fibrosis drug fail

Galecto made no mention of whether its remaining clinical programs would be affected by the workforce restructuring or search for strategic alternatives. A month after halting work on an inhaled treatment for idiopathic pulmonary fibrosis in the wake of a phase 2 trial fail, Galecto is laying off 70% of its workforce as the Boston-based biotech mulls its options. The company has just completed a review of its business and is now conducting a “comprehensive exploration of strategic alternatives focused on maximizing shareholder value.” As is usual for biotechs in dire straits, the potential options include an acquisition, merger or yard sale of the company’s assets. Galecto made the usual caveat that it couldn’t guarantee that any transaction “will be completed on attractive terms, if at all.” But one thing that is for certain is that 29 employees—equivalent to 70% of the company’s entire workforce—will be heading out the door. The writing may have been on the wall for the biotech back in August, when Galecto announced that its small-molecule inhibitor of galectin-3, dubbed GB0139, failed to hit the trial’s primary endpoint of a demonstrating a slowing in decline in the volume of air exhaled from the lungs of patients with idiopathic pulmonary fibrosis. In fact, the average reduction in forced vital capacity was 316.6 ml among patients treated with a 3-mg daily dose of GB0139 for a year, compared to a less pronounced drop of 127.5 ml for those given placebo, meaning treated patients fared much worse. The drug had a bumpy ride to even get to this stage, with a data safety and monitoring board recommending in March 2021 that the company ax the 10-mg treatment arm after an “imbalance” in serious side effects was cropping up. With the 3-mg dose also coming up short last month, the biotech turned its attention to another galectin-3 inhibitor called GB1211, which is in development for liver cirrhosis. Galecto revealed at the time that it had recently wrapped a type C meeting with the FDA and was preparing for a placebo-controlled phase 2 trial in patients with decompensated nonalcoholic steatohepatitis (NASH) cirrhosis that it planned to launch early next year. There’s also an OXL2 inhibitor called GB2064 in a phase 2 trial for myelofibrosis. In its postmarket release yesterday, the company made no mention of whether these plans would be affected by the workforce restructuring or search for strategic alternatives. With $52.1 million in the bank as of the end of June, Galecto CEO Hans Schambye, M.D., Ph.D., had previously said he was optimistic about securing fresh capital to progress the NASH prospect.

Phase 2Clinical Trial Failure

27 Sep 2023

·www.pharmaceutical-technology.com

Galecto downsizes by 70% following Phase II trial failure

Phalguni Deswal @Phalguni_GD The trial termination decimated the company’s stock, and it has not recovered since then. Image Credit: Buravleva stock / Shutterstock. Galecto has fired 70% of its workforce and is considering a whole list of strategic alternatives a month after announcing the failure of a trial with its lead drug. In August, the company’s lead candidate, GB0139, failed to meet its primary endpoint in the Phase II trial (NCT03832946) for the treatment of idiopathic pulmonary fibrosis (IPF). The trial termination decimated the company’s stock, and it has not recovered since then. Still, the 26 September restructuring news has revived the stock to a certain extent. Galecto’s stock was up by over 32% in pre-market trading today. Galecto’s market cap is $17.9m. The placebo-controlled Phase IIb had a lot of momentum, with the company having no issues with patient recruitment , even during the Covid-19 pandemic. However, all of this was for nought as the trial failed to show a change in the rate of decline of forced vital capacity, a measure of lung function, from baseline at 52 weeks. Galecto is now considering a merger, asset divestment or acquisition. The company was pragmatic regarding its options and noted that it does not expect any transaction to be “completed on attractive terms, if at all”. The US-based company is one in a growing list of companies that have downsized due to a multitude of reasons that range from low funding, US Food and Drug Administration (FDA) rejections or decreased sales forecasts for marketed products. Other drugs in Galecto’s pipeline include GB1211, which is being evaluated in an open-label Phase II trial (NCT05240131) as a combination therapy with Roche’s Tecentriq (atezolizumab) for non-small cell lung cancer (NSCLC). GB2064 is being evaluated in an open-label Phase IIa trial (NCT04679870) investigating myelofibrosis , a rare blood cancer. The topline results from the trial are expected by the end of 2023. Galecto also received FDA approval to start a Phase IIa trial for GB1211, an oral galectin-3 inhibitor for the treatment of patients with decompensated non-alcoholic steatohepatitis (NASH) cirrhosis, although the company pointed out that the trial initiation will be contingent on securing additional funding.

Phase 2AcquisitionClinical Trial FailureIPO

26 Sep 2023

·firstwordpharma.com

Galecto to eliminate 70% of workforce

Galecto disclosed Tuesday that it plans to explore strategic alternatives for the business, including an acquisition, merger or divestiture. It also intends to implement a restructuring plan that includes reducing its workforce by about 29 people, or approximately 70% of its existing headcount. Company shares gained as much as 40% in after-hours trade.The move follows its decision in August to end development of its GB0139 drug candidate in idiopathic pulmonary fibrosis (IPF) after it failed the Phase IIb GALACTIC-1 study. Following the readout, CEO Hans Schambye said the company would be evaluating resource allocation with the goal of extending its cash runway into 2025.Analysts at H. C. Wainwright & Co. suggested at the time that there "[remained] intrinsic value in the Galecto pipeline," and that the decision to scrap GB0139 "ought not to have read-through to Galecto's other clinical-stage programmes. These assets do not share a molecular structure with GB0139 and are aimed at indications unrelated to IPF; namely, decompensated liver cirrhosis and myelofibrosis."In its statement on Tuesday, Galecto said there was no guarantee that its exploration would lead to it pursuing a transaction; or if pursued, that any transaction would be completed on attractive terms. It has also not set a timetable for completion of its evaluation process, nor does it plan to disclose further developments or guidance on the status of its programmes until it deems necessary.As of June 30, Galecto said its cash, cash equivalents and investments balance stood at $52.1 million.

Phase 2IPOClinical Trial Failure

100 Deals associated with Olitigaltin

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 2	GB	The University of Edinburgh	13 Jun 2020
Idiopathic Pulmonary Fibrosis	Phase 2	US	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	AU	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	BE	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	CA	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	FR	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	GE	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	DE	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	IE	Galecto Biotech ApS	19 Feb 2019
Idiopathic Pulmonary Fibrosis	Phase 2	IL	Galecto Biotech ApS	19 Feb 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03832946 (CTgov)	Phase 2	Idiopathic Pulmonary Fibrosis	172	GB0139 (A. GB0139 3 mg Once a Day)	tjuogguykd(gizcfnuapd) = ntiumjeaaj lfiptqggqe (vymfzwmgon, atzamhgkzq - xiikpofafm) View more	-	22 May 2024
				Placebo (B. Placebo Once a Day)	tjuogguykd(gizcfnuapd) = ojurpagpdt lfiptqggqe (vymfzwmgon, bpdqzkxjwo - bmbsgwalug) View more
NCT04473053 (DEFINE, Corporate Publications) Manual	Phase 1/2	COVID-19	41	Standard of Care+GB0139	nfvtrrlsdx(fuhfhmmrft) = cvvbkjpvwu ammcuupypo (wxpzopomja ) View more	Positive	22 Jun 2021
				Standard of Care	-
NCT02257177 (Pubmed \| Eur Respir J)	Phase 1	Idiopathic Pulmonary Fibrosis	60	TD139	zzmvpfijci(fvgwcrnhxo) = cudzyainir idmynczakq (vugpzxbnig ) View more	-	19 Nov 2020

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