MRC2

Data demonstrate that uPARAP is highly expressed in tumor samples obtained from glioblastoma multiforme patients uPARAP targeting ADC shows cytotoxicity in glioblastoma multiforme cancer cells in vitro and exhibits potent in vivo anti-tumor activity in a glioblastoma multiforme PDX model Data provides evidence that uPARAP targeting ADCs are a potential novel treatment option for glioblastoma multiforme patients COPENHAGEN, Denmark, April 4, 2024 /PRNewswire/ -- Adcendo ApS ("Adcendo"), a biotech company focused on the development of first-in-class antibody-drug conjugates (ADCs) for the treatment of cancers with a high unmet medical need, will be presenting novel data on the expression of its novel ADC target uPARAP and the in vitro and in vivo activity of a uPARAP targeting ADC in glioblastoma multiforme (GBM) at the American Association for Cancer Research (AACR) Annual Meeting, held in San Diego, California, from April 5th to April 10th, 2024. The data has been evaluated in collaboration with the Finsen Laboratory, Rigshospitalet/BRIC, University of Copenhagen, Copenhagen, Denmark. uPARAP is a novel ADC target overexpressed by mesenchymal cancer cells including soft tissue and bone sarcomas, GIST as well as mesothelioma and glioblastoma, and has the potential to play a key role in modulating the tumor microenvironment. The data demonstrate that uPARAP is strongly over-expressed in glioblastoma cells and that a uPARAP targeting ADC exhibits strong in vivo anti-tumor activity in a glioblastoma PDX model. Based on its differentiated expression profile and rapid internalization capabilities, uPARAP is an attractive novel target for the development of a uPARAP-targeting ADC in this hard-to-treat disease area with a high unmet medical need due to limited treatment options. Details of the poster presented presentation are as follow: Presentation title: 6355/16 - Urokinase plasminogen activator receptor-associated protein (uPARAP) is overexpressed in human glioblastomas and is a novel attractive target for antibody-drug conjugates (ADC) Track: Clinical Research/Immunology Session: Antibodies 2 Authors: I. Gregersen1, C. R. Løkke1, J. B. Lange1, P. Barkholt1, C. Côme1, T. Broberg1, O. D. Lærum2, M. M. Petersen1, M. Knuuttila3, S.-M. Käkönen3, C. M. Lynch1, D. Mumberg1, N. Behrendt2, L. H. Engelholm 1,2 Date & Time: April 9th, 1.30pm – 5.00pm PDT Abstracts are available in an online itinerary planner found here, and will be available in an online only supplement to the AACR journal Cancer Research one month after the conference. Dominik Mumberg, Chief Scientific Officer at Adcendo, said: "We are excited to share promising data on the expression of uPARAP in glioblastoma as well as encouraging in vivo activity of a uPARAP targeting ADC. In addition to its highly differentiated expression profile in multiple mesenchymal cancers, uPARAP is a constitutively recycling endocytic receptor with unique internalization properties, making it a very attractive ADC target for the benefit of patients." Lars Engelholm, Associate Professor, and group leader at the Cancer Invasion Section of the Finsen Laboratory, said: "Treatment progress and therapeutic options in glioblastoma have so far been very limited. We are extremely encouraged by the data highlighted in this study, which provides further evidence on the potential effectiveness of uPARAP as a novel target for ADCs in glioblastoma multiforme. We look forward to continuing our scientific collaboration with Adcendo to further deepen our insights into the biology of uPARAP and its utility as target for ADC development in multiple mesenchymal cancers." 1Adcendo ApS, Copenhagen, Denmark, 2The Finsen Laboratory, Rigshospitalet/BRIC, University of Copenhagen, Copenhagen, Denmark, 3Aurexel Life Sciences, Askainen, Finland About Adcendo ApS Adcendo ApS is developing first-in-class antibody-drug conjugates (ADCs) for the treatment of underserved cancers. In 2023, the company completed a Series A extension financing round, taking its funds to 82m EUR to advance their ADC pipeline into clinical development. Investors include Novo Holdings, Ysios Capital, Pontifax Venture Capital, RA Capital Management, HealthCap and Gilde Healthcare. For further information, please visit About antibody-drug conjugates (ADCs) ADCs are a class of highly potent biopharmaceutical drug composed of a targeting antibody linked to a biologically active drug or cytotoxic compound. ADCs combine the unique and very sensitive targeting capabilities of antibodies, with the potent effects of the conjugated cytotoxic drugs, allowing sensitive discrimination between healthy and cancer tissues. About the uPARAP receptor uPARAP is a recycling endocytic receptor involved in collagen homeostasis and turnover. uPARAP exhibits a limited expression profile in healthy tissues but is highly upregulated in multiple mesenchymal cancers, including soft-tissue sarcoma, bone sarcoma, GIST as well as mesothelioma and glioblastoma, making it a highly attractive target for ADC development. SOURCE Adcendo

Researchers have discovered a protein called SEL1L that plays a critical role in clearing collagen from tissue, and which may be a therapeutic target to help prevent fibrosis, scar tissue that interferes with organ function. The paper provides clues that could lead to drug development for diseases like lung fibrosis which have no therapeutic options currently. Researchers at Weill Cornell Medicine have discovered a protein called SEL1L that plays a critical role in clearing collagen from tissue, and which may be a therapeutic target to help prevent fibrosis, scar tissue that interferes with organ function. The paper, published on Feb. 20 in Nature Communications, provides clues that could lead to drug development for diseases like lung fibrosis which have no therapeutic options currently. Corresponding author, Dr. Michael J. Podolsky, assistant professor of medicine at Weill Cornell Medicine, has led a team that searched the human genome for genes involved in the process that triggers specialized cells to engulf and digest excess collagen from tissue. Cells called fibroblasts and macrophages pick up collagen fragments for degradation in lysosomes, the trash compactors of cells. Normal lungs continuously synthesize collagen and degrade excess collagen, keeping the two processes precisely balanced to maintain healthy tissue architecture. Even when lungs are injured and the body responds by increasing the rate of collagen production, simultaneously collagen degradation is increased to prevent the formation of permanent scar tissue. However, when the two processes are uncoupled, the result is disease. In pulmonary fibrosis, for instance, collagen degradation does not keep pace with collagen production, resulting in an excess accumulation. The researchers discovered a mechanism that cells use to detect collagen production internally and regulate clearance of excess collagen in tissues. The protein SEL1L acts as a sensor that responds to collagen production by triggering another protein called MRC2 which is involved in the uptake and disposal of collagen. This study suggests that a defective collagen clearing pathway based on MRC2 is a key part of the imbalance in fibrotic disease. The data show when SEL1L is overproduced in cells, it leads to increased MRC2 production and thereby prevents the accumulation of collagen. This pathway could eventually be therapeutically targeted to drive increased clearance of collagen to improve fibrosis when it is impaired. Next, Dr. Podolsky, who is also an attending physician at NewYork Presbyterian/Weill Cornell Medical Center, plans to investigate how SEL1L is impaired in fibrotic human lungs. The lab is also exploring the molecular consequences of when MRC2 is inadequately triggered in pulmonary fibrosis. This research was supported in part by the National Institutes of Health grant K08 HL145015 and a Grant-in-aid from The Stony Wold-Herbert Fund.

Dr. Ottesen brings in-depth global clinical development expertise in oncology, including biologics, small molecules, immunotherapies and ADCs Adcendo further builds its world class team to accelerate development of lead ADC asset uPARAP and to expand its first-in-class ADC pipeline COPENHAGEN, Denmark, June 20, 2023 /PRNewswire/ -- Adcendo ApS ("Adcendo"), a biotech company focused on the development of breakthrough antibody-drug conjugates (ADCs) for the treatment of cancers with a high unmet medical need, is pleased to announce the appointment of Dr. Lone H. Ottesen as Chief Medical Officer (CMO). Dr. Ottesen is a highly accomplished drug developer with extensive global clinical development experience across oncology and immune-oncology with a track record of more than 20 years in both early- and late-phase clinical development. Dr. Ottesen held roles of increasing seniority in Global Oncology Development at GSK, Eisai and most recently at AstraZeneca, where she was Global Clinical Head in Late-Stage Clinical Development. She joins Adcendo from Circio, formerly known as Targovax, where she was Chief Medical Officer and previously Chief Development Officer. She received her MD and PhD at Aarhus University in Denmark. Michael Pehl, Chief Executive Officer of Adcendo, said "We are delighted to welcome Lone with her extensive global oncology drug development experience to lead our ambitious, clinical development strategy and help maximize the full potential of our unique first-in-class ADC pipeline. Lone brings a distinctive blend of experience in solid tumor oncology, ADCs and biologics within early and late-stage clinical development both at biotech and large pharmaceutical companies. We are extremely fortunate that Lone has joined our outstanding leadership Team of ADC experts as we aim to become a global leader in the field of ADCs." Lone Ottesen, incoming Chief Medical Officer at Adcendo, said "ADCs are at the forefront of a paradigm shift in cancer chemotherapy, and I am excited to join Adcendo to shape its IND-enabling activities and clinical plans. Adcendo is highly committed to bringing new and tailored ADC treatment options to patients with a high unmet medical need, based on a deep biological understanding of innovative targets, its access to industry leading linker/payload platforms and the longstanding experience of their team in ADC research and development. I am delighted to become part of an innovative company with patient care at the forefront of clinical development." Dr. Ottesen will be responsible for clinical strategy, development and operations as well as medical affairs for all current and future pipeline assets. She will join Adcendo in early August 2023. Adcendo has made significant progress in 2023 so far, recently announcing an extension of its Series A financing to 82M EUR to ensure broad development of its first-in-class ADC programs. The Company has also expanded its linker/payload collaboration with Duality Biologics ("Duality") to cover additional novel ADC targets as it further builds out its first-in-class ADC pipeline. About Adcendo ApS Adcendo ApS is developing breakthrough antibody-drug conjugates (ADCs) for the treatment of underserved cancers. In 2023, the company completed a Series A extension financing round, taking its funds to 82M EUR to advance into clinical development. Investors include Novo Holdings, Ysios Capital, Pontifax Venture Capital, RA Capital Management, HealthCap and Gilde Healthcare. For further information, please visit About antibody-drug conjugates (ADCs) ADCs are a class of highly potent biopharmaceutical drug composed of a targeting antibody linked to a biologically active drug or cytotoxic compound. ADCs combine the unique and very sensitive targeting capabilities of antibodies, with the potent effects of the conjugated cytotoxic drugs, allowing sensitive discrimination between healthy and cancer tissues. About the uPARAP receptor uPARAP is a recycling endocytic receptor involved in collagen homeostasis and turnover. uPARAP exhibits a limited expression profile in healthy tissues but is highly upregulated in mesenchymal cancers, including soft-tissue sarcoma & bone sarcoma, making it a highly attractive target for ADC development. In late 2022, Adcendo nominated its ADC development candidate. SOURCE Adcendo