Pseudomyxoma peritonei (PMP) is a highly mucinous adenocarcinoma growing in the peritoneal cavity and most commonly originating from the appendix. Glycans play an important role in carcinogenesis, and glycosylation is altered in malignant diseases, including PMP. We have previously demonstrated that fucosylation of N-glycans is increased in PMP, but we did not observe modulation of overall sialylation. As sialic acids can be attached to the rest of the glycan via α2,3- or α2,6-linkage, we have now analyzed the linkage patterns of sialic acids in tissue specimens of normal appendices, low-grade appendiceal mucinous neoplasms (LAMN), low-grade (LG) PMP and high-grade (HG) PMP. For the linkage analysis, the enzymatically released acidic N-glycans were first treated with ethyl esterification or α2,3-sialidase digestion followed by MALDI-TOF mass spectrometry. Significant increase in the relative abundance of α2,6-sialylated and decrease in α2,3-sialylated N-glycans was observed in PMP tumors as compared to the normal appendices (P < 0.025). More specifically, increased α2,6-sialylation (P < 0.05) and decreased α2,3-sialylation (P < 0.01) were detected in afucosylated and monofucosylated N-glycans of PMPs, whereas the less abundant multifucosylated glycans, containing terminal fucose, demonstrated increased α2,3-sialylation (P < 0.01). Importantly, the increase in α2,6-sialylation was also detected between PMP and the appendiceal precursor lesion LAMN (P < 0.01). The identified glycosylation alterations produce ligands for sialic acid-binding immunoglobulin-like lectins (Siglecs) and sialofucosylated glycans binding selectins, which play a role in the peritoneal dissemination and progression of the disease.

01 Nov 2018·Molecular & cellular proteomics : MCPQ1 · BIOLOGY

Glycomic Profiling Highlights Increased Fucosylation in Pseudomyxoma Peritonei

Q1 · BIOLOGY

Article

Author: Hautaniemi, Sampsa ; Haglund, Caj ; Thiel, Alexandra ; Heiskanen, Annamari ; Lepistö, Anna ; Ristimäki, Ari ; Leinonen, Hannele ; Satomaa, Tero ; Nummela, Pirjo ; Saarinen, Lilli

Pseudomyxoma peritonei (PMP) is a subtype of mucinous adenocarcinoma that most often originates from the appendix, and grows in the peritoneal cavity filling it with mucinous ascites. KRAS and GNAS mutations are frequently found in PMP, but other common driver mutations are infrequent. As altered glycosylation can promote carcinogenesis, we compared N-linked glycan profiles of PMP tissues to those of normal appendix. Glycan profiles of eight normal appendix samples and eight low-grade and eight high-grade PMP specimens were analyzed by mass spectrometry. Our results show differences in glycan profiles between PMP and the controls, especially in those of neutral glycans, and the most prominent alteration was increased fucosylation. We further demonstrate up-regulated mRNA expression of four fucosylation-related enzymes, the core fucosylation performing fucosyltransferase 8 and three GDP-fucose biosynthetic enzymes in PMP tissues when compared with the controls. Up-regulated protein expression of the latter three enzymes was further observed in PMP cells by immunohistochemistry. We also demonstrate that restoration of fucosylation either by salvage pathway or by introduction of an expression of intact GDP-mannose 4,6-dehydratase enhance expression of MUC2, which is the predominant mucin molecule secreted by the PMP cells, in an intestinal-derived adenocarcinoma cell line with defective fucosylation because of deletion in the GDP-mannose 4,6-dehydratase gene. Thus, altered glycosylation especially in the form of fucosylation is linked to the characteristic mucin production of PMP. Glycomic data are available via ProteomeXchange with identifier PXD010086.

01 Nov 2017·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

N-Glycomic Profiling of Pheochromocytomas and Paragangliomas Separates Metastatic and Nonmetastatic Disease

Q2 · MEDICINE

Article

Author: Kaprio, Tuomas ; Heiskanen, Annamari ; Haglund, Caj ; Satomaa, Tero ; Arola, Johanna ; Leijon, Helena ; Miettinen, Markku M ; Hiltunen, Jukka O

Context:

No effective methods for separating primary pheochromocytomas and paragangliomas with metastatic potential are currently available. The identification of specific asparagine-linked glycan (N-glycan) structures, which are associated with metastasized pheochromocytomas and paragangliomas, may serve as a diagnostic tool.

Objective:

To identify differences in N-glycomic profiles of primary metastasized and nonmetastasized pheochromocytomas and paragangliomas.

Setting:

This study was conducted at Helsinki University Hospital, University of Helsinki, and Glykos Finland Ltd. and included 16 pheochromocytomas and paragangliomas: 8 primary metastasized pheochromocytomas or paragangliomas and 8 nonmetastasized tumors.

Methods:

N-glycan structures were analyzed with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) profiling of formalin-fixed, paraffin-embedded tissue samples.

Main Outcome Measure:

N-glycan profile of tumor tissue.

Results:

Four groups of neutral N-glycan signals were more abundant in metastasized tumors than in nonmetastasized tumors: complex-type N-glycan signals of cancer-associated terminal N-acetylglucosamine, multifucosylated glycans (complex fucosylation), hybrid-type N-glycans, and fucosylated pauci-mannose-type N-glycans. Three groups of acidic N-glycans were more abundant in metastasized tumors: multifucosylated glycans, acid ester-modified (sulfated or phosphorylated) glycans, and hybrid-type/monoantennary N-glycans. Fucosylation and complex fucosylation were significantly more abundant in metastasized paragangliomas and pheochromocytomas than in nonmetastasized tumors for individual tests but were over the false positivity critical rate, when adjusted for multiplicity testing.

Conclusions:

MALDI-TOF MS profiling of primary pheochromocytomas and paragangliomas can identify diseases with metastatic potential based on their different N-glycan profiles. Thus, malignancy-linked N-glycan structures may serve as potential diagnostic tools for pheochromocytomas and paragangliomas.

News (Medical) associated with Glykos Finland Oy

17 Jun 2025

·pipelinereview.com

Orion and Glykos announce the extension of their research collaboration and licensing agreement for the development of next-generation ADCs

June 17, 2025 I Orion Corporation and Glykos Finland Oy today announced that they have extended their research collaboration and licensing agreement for the development of next-generation antibody-drug conjugates (ADCs). Under the extended agreement, Orion gains access to Glykos’ proprietary ADC technologies with the potential to expand into three additional programs in the future, in addition to the three ADC programs outlined in the previous agreement. Orion will be responsible for the target selection, research, development, and commercialization of up to three next-generation ADCs, with a focus on solid tumors. The financial terms of the extended agreement for the three new ADC projects are the same as in the original agreement for the first three projects. Glykos is entitled to milestone payments related to the development of the ADCs and product sales. Glykos is also entitled to receive royalties from the commercial sales generated by the three ADC programs. “This successful collaboration with Glykos allows us to continue leveraging their advanced ADC technology and underscores our commitment to developing new treatment options for cancer patients,” said Professor Outi Vaarala , Executive Vice President, Innovative Medicines and Research & Development at Orion. “The extension of our agreement with Orion highlights the potential of our ADC technology. We are excited to expand our collaboration with Orion, whose expertise in cancer therapies and strong clinical development capabilities are crucial for bringing new, effective treatments to cancer patients,” said Juhani Saarinen , CEO of Glykos. About Orion Orion is a globally operating Nordic pharmaceutical company – a builder of well-being for over a hundred years. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and consumer health products. The core therapy areas of our pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. In 2024 Orion’s net sales amounted to EUR 1,542 million and the company employed about 3,700 professionals worldwide, dedicated to building well-being. Orion’s A and B shares are listed on Nasdaq Helsinki About Glykos Glykos, focusing on antibody-drug conjugates (ADCs), is dedicated to revolutionizing cancer treatment. Glykos’ proprietary hydrophilic payload and linker technology addresses ADC limitations, offering benefits of high efficacy, increased tolerability, excellent pharmacokinetics, and optimized conjugation with any monoclonal antibody. Focused on expanding the therapeutic index, we aim to extend survival and enhance the quality of life for cancer patients. For more information, please visit www.glykos.fi. SOURCE: Glykos

License out/inADC

16 Jan 2024

·www.biospace.com

Orion Invests $415M in Korean Biotech LegoChem, Secures Majority Stake

Pictured: Businessmen shaking hands after a deal/iStock, PeopleImages Finnish pharma Orion Corporation on Monday dropped approximately $415.6 million to buy a 25% stake in Korean biotech LegoChem Biosciences, according to local news outlet The Chosun Daily. The transaction, which LegoChem disclosed to investors through Monday’s regulatory filing, makes Orion the largest shareholder of the antibody-drug conjugate (ADC) developer. Orion carried the purchase out through a Hong Kong-based subsidiary and the companies expect to close the deal on March 29, according to The Chosun Daily. Once finalized, LegoChem will become part of Orion’s corporate family but will retain its current frameworks and management. LegoChem’s core technology—dubbed ConjuALL—gives its ADC therapies a “trinity of improved properties,” according to the biotech’s website. The platform allows for the stable conjugation of the payload at a specific site, overcoming the typically random attachment that is typical in other ADCs, the company contends. The platform also enables the cancer-selective activation of both the linker and the toxic payload. For Orion, the LegoChem transaction is part of its R&D refocusing efforts, first announced in March 2022, designed to steer the company toward cancer and pain—and away from neurodegenerative and rare diseases. At the time, Outi Vaarala, Orion’s senior vice president of R&D, said in a statement that “the idea is to focus investment in these areas and to develop treatments for patients as efficiently as possible, rather than making smaller investments in a larger number of research areas.” Since then, Orion has expanded its partnerships in the oncology space. Last week, it inked a research collaboration agreement with Glykos to develop next-generation ADCs targeting solid tumors. Orion is also partnered with MSD—the international name for Merck—for a candidate therapy for metastatic castration-resistant prostate cancer. Last week, the companies launched two pivotal Phase III studies under this agreement, evaluating the efficacy and safety of the investigational CYP11A1 inhibitor in combination with hormone replacement therapy. For LegoChem, Orion is the latest pharmaceutical company to take notice of its ADC. In December 2023, the Korean biotech announced that it signed a $1.7 billion license agreement with J&J’s subsidiary Janssen to develop an anti-Trop2 ADC. In December 2022, LegoChem also entered into a research and license pact with Amgen, which gave the pharma access to its proprietary platform to design, develop and potentially commercialize ADCs for up to five targets. Considering the upfront payment and all milestones under the deal, LegoChem is eligible to receive up to $1.25 billion plus royalties. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

License out/inPhase 3ADCAcquisition

08 Jan 2024

·pipelinereview.com

Orion and Glykos announce research collaboration and licensing agreement to develop next-generation ADCs

January 08, 2024 I Orion Corporation and Glykos Finland Oy announced today that they have entered into a research collaboration and licensing agreement to develop next-generation antibody-drug conjugates (ADCs). Under the agreement, Orion gains access to Glykos’ proprietary ADC technologies, initiating an ADC program with the potential for expansion into two additional programs in the future. Orion will be responsible for the target selection, research, development, and commercialization of up to three next-generation ADCs, with a focus on solid tumors. Glykos is eligible for milestone payments related to signing of the agreement, target selection and sales milestones. Glykos is also entitled to receive royalties on commercial sales generated from the three ADC programs. Outi Vaarala , Senior Vice President, Innovative Medicines and R&D, Orion, said: “Collaboration with Glykos and possibility to utilize their ADC technology complements nicely our research portfolio in oncology and is yet another demonstration of our will to develop new treatment options for cancer patients with unmet needs.” Juhani Saarinen, CEO of Glykos, said: "The acknowledgment of our ADC technology by an esteemed pharmaceutical company like Orion is a strong statement to the transformative potential of these technologies in enhancing the therapeutic index of ADCs. We look forward to partnering with Orion and believe that with their expertise on cancer therapies and robust clinical pipeline, this partnership can deliver innovative medicines for cancer patients.” About Orion Orion is a globally operating Finnish pharmaceutical company – a builder of well-being. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and self-care products. The core therapy areas of our pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. Orion's net sales in 2022 amounted to EUR 1,341 million and the company had about 3,500 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki. About Glykos Glykos, focusing on antibody-drug conjugates (ADCs), is dedicated to revolutionizing cancer treatment. Glykos' proprietary hydrophilic payload and linker technology addresses ADC limitations, offering benefits of high efficacy, increased tolerability, excellent pharmacokinetics, and optimized conjugation with any monoclonal antibody. Focused on expanding the therapeutic index, we aim to extend survival and enhance the quality of life for cancer patients. For more information, please visit www.glykos.fi. SOURCE: Glykos

License out/inADC

100 Deals associated with Glykos Finland Oy

100 Translational Medicine associated with Glykos Finland Oy

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The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Drug(Targets)	Indications	Global Highest Phase

GLK-33 ( CD33 x Cytokines x Tubulin )	CD33-positive Acute Myeloid Leukemia More	Preclinical
Trastuzumab-MMAU ( HER2 x Tubulin )	Neoplasms More	Preclinical
ADC drug(Orion/Glykos)	Solid tumor More	Discovery

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