Ali Salanti

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Positions and Employment

• 2018 -              Professor in translational microbiology (UCPH)
• 2013 - 2017     Professor (MSO) at University of Copenhagen (ISIM)
• 2008 - 2011     Associate Professor at University of Copenhagen
• 2008 - 2010     Senior research fellow and Group leader “VAR2CSA-team” 
• 2004 - 2007     Post. Doc at CMP at University of Copenhagen
• 2003 - 2007     Consultant for Nordic Vaccine Technology
• 2001 - 2001     Principal Investigator Lica Pharmaceuticals

 

Other Experience

• CEO of UCPH Spinout company, VAR2Pharmaceuticals.
• CEO of UCPH Spinout company, VARCTDiagnostics
• Co-founder and Member of board in Spinout companies Adaptvac, NextGenVaccines and OncoMal
• Group leader team VAR2CSA at Centre for Medical Parasitology
• Ad hoc Peer-reviewer for scientific journals (Nature, PLoS pathogens, JID, Lancet among others)
• Coordinator of several large research consortiums including EU, Gates and Innovation Foundation programs
• Evaluator and referee of International Scientific grant programs including Wellcome Trust and the UK medical Councils.
• Invited speaker at numerous high profiled international meetings, here among: Gordon conferences, ASTMH Meeting and Nobel Seminars

  

My Contributions to Science

1. Malaria Biology:

My research career started with a PhD stipend from the Bill and Melinda Gates foundation where I became a part of a large international endeavor, led by Dr. Patrick Duffy from NIH, with the aim of identifying the molecular background for placental malaria infection. Independently, I identified and characterized the VAR2CSA protein as the principle malaria parasite adhesion ligand mediating parasite adhesion to CSA in the placenta. I described this in two seminal publications published in J.Exp.Med (2003) and Mol.Microbiology (2004). I decided that I would not stop in this area of research until VAR2CSA was moved forward to human testing as a vaccine for pregnant women.

 

a)     Salanti A, Dahlbäck M, Turner L, Nielsen MA, Barfod L, Magistrado P, Jensen AT, Lavstsen T, Ofori MF, Marsh K, Hviid L, Theander TG. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J Exp Med. 2004 Nov 1;200(9):1197-203. PMID: 15520249 PMCID: PMC2211857

b)     Salanti A, Staalsoe T, Lavstsen T, Jensen AT, Sowa MP, Arnot DE, Hviid L, Theander TG. Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria. Mol Microbiol. 2003 Jul;49(1):179-91. PMID: 12823820

 

2. Clinical development of a Malaria vaccine

VAR2CSA is a large highly complex multi domain protein and before entering clinical development, we needed to define the exact immunogen. Over a period of 8 years and more than 30 publications, I describe the role of each domain, the immunogenicity in man and mice and the molecular structures. Together with Oxford University we were the first to produce the full length protein and with this in hand we defined the minimal region that could bind CSA with the same affinity as the full length protein. This work was extensively supported through the Bill and Melinda Gates foundation and three EU FP6 programs with me as principle investigator. Having defined the minimal binding region of VAR2CSA we were ready to initiate a clinical development program. Our team was the first ever at University of Copenhagen to be responsible for a GMP manufacturing and sponsor of clinical testing. This endeavor was a close collaboration with CMOs, CROs and clinical sites, and in 2016, led by Associate Professor Morten Nielsen (team VAR2CSA) we finished a phase Ia trial in Germany and in 2017 we finished a phase Ib trial in women in Benin.

 

a)     Dahlback M, Rask TS, Andersen PH, Nielsen MA, Ndam NT, Resende M, Turner L, Deloron P, Hviid L, Lund O, Pedersen AG, Theander TG, Salanti A: Epitope mapping and topographic analysis of VAR2CSA DBL3X involved in P. falciparum placental sequestration. PLoS Pathog 2006;2:e124. PMID: 17112315 PMCID: PMC1636682

b)     Nielsen MA, Pinto VV, Resende M, Dahlback M, Ditlev SB, Theander TG, Salanti A: Induction of adhesion-inhibitory antibodies against placental Plasmodium falciparum parasites by using single domains of VAR2CSA. Infect Immun 2009;77:2482-2487. PMID: 19307213 PMCID: PMC2687338

c)     Khunrae P, Dahlback M, Nielsen MA, Andersen G, Ditlev SB, Resende M, Pinto VV, Theander TG, Higgins MK, Salanti A: Full-length recombinant Plasmodium falciparum VAR2CSA binds specifically to CSPG and induces potent parasite adhesion-blocking antibodies. J Mol Biol 2010;397:826-834. PMID: 20109466 PMCID: PMC3715698

d)    Clausen TM, Christoffersen S, Dahlback M, Langkilde AE, Jensen KE, Resende M, Agerbaek MO, Andersen D, Berisha B, Ditlev SB, Pinto VV, Nielsen MA, Theander TG, Larsen S, Salanti A: Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria. J Biol Chem 2012;287:23332-23345. PMID: 22570492 PMCID: PMC3390611

e) Mordmüller B, Sulyok M, Egger-Adam D, Resende M, de Jongh WA, Jensen MH, Smedegaard HH, Ditlev SB, Soegaard M, Poulsen L, Dyring C, Calle CL, Knoblich A, Ibáñez J, Esen M, Deloron P, Ndam N, Issifou S, Houard S, Howard RF, Reed SG, Leroy O, Luty AJF, Theander TG, Kremsner PG, Salanti A, Nielsen MA.
First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria. Clin Infect Dis. 2019 Oct 15;69(9):1509-1516. 

3. Second generation vaccine development.

During my work on a malaria vaccine it became evident that recombinant soluble antigens are not good as vaccines. We observed failure upon failure in clinical trials for soluble recombinant vaccines to induce high tittered and long lasting protective antibody responses. It was also evident that that the HPV vaccine is an extraordinary exception. So I had the idea to make a combinatorial vaccine against placental malaria and HPV induced Cervical Cancer by conjugating the HPV VLP with the malaria protein, aiming at inducing long lasting and high tittered antibodies against both antigens. In 2013 I received a major grant from the Bill and Melinda Gates Foundation (grand challenge program) based on this idea and that was the starting point for developing a range of virus like particle vaccine, not only the VAR2CSA malaria vaccine. We have developed a VLP platform that allows conjugation of any antigen on the surface, thereby presenting the antigen in a dense, rigid and uniform way to the immunesystem – exactly like the HPV epitopes. We have strong preclinical proof of concept that this indeed triggers a strong immune response, even against self antigens. We established AdaptVac as a spinout company, and this company in close collaboration with Expres2ion Biotechnologies and UCPH has developed several vaccines candiates. Ones is a HER2 breast cancer vaccine about to enter the first clinical studies, and another is the ABNCOV2 SARS-COV-2 vaccine which is being finalized in phase 3 studies in 2023 by Bavarian Nordic. Internally we are preparing for a new phase 1 clinical trial with VAR2CSA presented on the VLP. The VLP team is today led my Associate Professor Adam Sander and the Malaria vaccine team is being led by Associate Professor Morten A. Nielsen

 

a)    Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, Clemmensen S, Roeffen W, van d, V, van Gemert GJ, Sauerwein R, Schiller JT, Nielsen MA, Theander TG, Salanti A, Sander AF: Bacterial superglue enables easy development of efficient virus-like particle based vaccines. J Nanobiotechnology 2016;14:30. PMID: 27117585 PMCID: PMC4847360

b) Smit MJ, Sander AF, Ariaans MBPA, Fougeroux C, Heinzel C, Fendel R, Esen M, Kremsner PG, Ter Heine R, Wertheim HF, Idorn M, Paludan SR, Underwood AP, Binderup A, Ramirez S, Bukh J, Soegaard M, Erdogan SM, Gustavsson T, Clemmensen S, Theander TG, Salanti A, Hamborg M, de Jongh WA, McCall MBB, Nielsen MA, Mordmüller BG; COUGH-1 trial study group. First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2. Lancet Microbe. 2023 Mar;4(3):e140-e148. doi: 10.1016/S2666-5247(22)00337-8. Epub 2023 Jan 1

c) Fougeroux C, Goksøyr L, Idorn M, Soroka V, Myeni SK, Dagil R, Janitzek CM, Søgaard M, Aves KL, Horsted EW, Erdoğan SM, Gustavsson T, Dorosz J, Clemmensen S, Fredsgaard L, Thrane S, Vidal-Calvo EE, Khalifé P, Hulen TM, Choudhary S, Theisen M, Singh SK, Garcia-Senosiain A, Van Oosten L, Pijlman G, Hierzberger B, Domeyer T, Nalewajek BW, Strøbæk A, Skrzypczak M, Andersson LF, Buus S, Buus AS, Christensen JP, Dalebout TJ, Iversen K, Harritshøj LH, Mordmüller B, Ullum H, Reinert LS, de Jongh WA, Kikkert M, Paludan SR, Theander TG, Nielsen MA, Salanti A, Sander AF. Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity Nat Commun. 2021 Jan 12;12(1):324. doi: 10.1038/s41467-020-20251-8.

 

3. Cancer Glycobiology and translation of this research

My extensive work on the understanding of the pathology of placental malaria, led me to understand why VAR2CSA expressing malaria parasites exclusively sequestered in the placenta. This was due to the presence of a distinct carbohydrate modification (CSA), only present in the placenta. We found that this carbohydrate was overexpressed to attract growth factors to mediate rapid growth of the fetus and placenta and to provide the possibility to expand the placental within the uterine tissues. I thought that these are the same features as seen in cancer and a simple experiment by mixing malaria parasites from a pregnant women with cancer cells in vitro demonstrated that indeed VAR2CSA could bind to CSA also on cancer tissues. In a huge multicenter endeavor led by me we demonstrated that the recombinant VAR2CSA binds the vast majority of cancer cells and cancer tissue biopsies with high affinity and high specificity, and very limited binding to normal tissue. To enable clinical translation we following this discovery developed antibodies with similar specificity as VAR2CSA for cancer. I am now dedicated to take this into a phase I trial in cancer patients. Our pre-clinical data demonstrate that upon IV injection, VAR2CSA as well as the new antibodies rapidly locates to a xenografted tumor, and if conjugating the protein or antibodies with a toxin, we can significantly reduce the tumor burden. Besides primary tumors, we have strong data showing that also cancer stem cells, metastases and circulating tumor cells have high levels of this onco-fetal type CSA that can be targeted with VAR2CSA and derived antibodies, opening for a multitude of diagnostic and therapeutic possibilities. We have embarged on a clinical development program to test a antibody drug conjugate in cancer patients, and are in the process of developing processes and analytical tools for GMP production. In collaboration with three hospital sites we have demonstrated that VAR2CSA with high specificity and sensitivity can capture circulating tumor cells from a wide range of tested cancer patients, and we have embarged on a clinical development project to have the methods approved by the FDA for diagnostic and prognostic purposes. We remain to understand the molecular biology behind of-CSA, for example the structure of of-CSA is unknown and the understanding of this combined with understanding of how the modification is initiated could provide ground breaking understanding of Cancer. The Spinout Company VAR2Pharmaceuticals is driving the development of the therapeutic product pipeline and the spinout VARCT Diagnostics holds the rights to use VAR2CSA to capture circulating tumor cells

 

a)     Salanti A, Clausen TM, Agerbaek MO, Al NN, Dahlback M, Oo HZ, Lee S, Gustavsson T, Rich JR, Hedberg BJ, Mao Y, Barington L, Pereira MA, LoBello J, Endo M, Fazli L, Soden J, Wang CK, Sander AF, Dagil R, Thrane S, Holst PJ, Meng L, Favero F, Weiss GJ, Nielsen MA, Freeth J, Nielsen TO, Zaia J, Tran NL, Trent J, Babcook JS, Theander TG, Sorensen PH, Daugaard M: Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein. Cancer Cell 2015;28:500-514. PMID: 26461094 PMCID: PMC4790448

b)     Sugiura N, Clausen TM, Shioiri T, Gustavsson T, Watanabe H, Salanti A: Molecular dissection of placental malaria protein VAR2CSA interaction with a chemo-enzymatically synthesized chondroitin sulfate library. Glycoconj J 2016. PMID: 27287227

c)     Clausen TM, Marina Ayres Pereira, nakouzi N, Oo, Agerbaek MO, Lee S, Orum-Madsen M, Kristensen A, Naggar A, Grandgenett P, Grem L, Hollingsworth M, Holst PJ, Theander G, Sorensen PH, Daugaard M, Salanti A: Oncofetal Chondroitin Sulfate Glycosaminoglycans are Key Players in Integrin Signaling and Tumor Cell Motility; Molecular Cancer Research. 2016;14:1288-1299. PMID: 27655130

d)     Seiler R, Oo HZ, Tortora D, Clausen TM, Wang CK, Kumar G, Pereira MA, Ørum-Madsen MS, Agerbæk MØ, Gustavsson T, Nordmaj MA, Rich JR, Lallous N, Fazli L, Lee SS, Douglas J, Todenhöfer T, Esfandnia S, Battsogt D, Babcook JS, Al-Nakouzi N, Crabb SJ, Moskalev I, Kiss B, Davicioni E, Thalmann GN, Rennie PS, Black PC, Salanti A, Daugaard M. An Oncofetal Glycosaminoglycan Modification Provides Therapeutic Access to Cisplatin-resistant Bladder Cancer. Eur Urol. 2017 Apr 10. PMID: 28408175

 

A complete List of Published Work is available at www.ncbi.nlm.nih.gov/pubmed/?term=salanti+A

 

Recent funding awards

• Novo Nordisk Foundation Distinguished Innovator (1M Euro, 2023)
• Eurostars (rank 1 out of 750). Cancer diagnostics. (2022)
• Novo Nordisk Foundation. Tandem. Cancer therapy (1M Euro 2022)
• Horizon Europe. Malaria vaccine (10M Euro consortium grant, 2022)
• Carlsberg Foundation. Semper Ardens. Covid19 vaccine (3M Euro, 2021)
• Innovation Foundation. Cancer diagnostics. Grand solutions (3M Euro, 2020)
• Danish Cancer Society. Therepeutic development of a anti-cancer therapy. 0.5M Euro (2017)
• ERC PoC for using rVAR2 to capture circulating tumor cells 0.2M Euro (2017)
• Danish Research Councils. The role of onco-fetal carbohydrates in cancer. 0.4M Euro (2017)
• ERC consolidator grant to develop rVAR2 to a therapeutic compound. 2M Euro (2014)
• Department of Defense (DoD). Using VAR2CSA to target breast cancer. 250.000 USD
• EU FP7. Clinical development of a placental malaria vaccine. 7.000.000 Euro
• Eurostars. Adjvuant testing. Size/Duration: 130.000 Euro (2012-14)
• Gates Foundation. Combinatorial vaccine against malaria and HPV. 675.000 Euro (2012-14)
• European Vaccine Initiative (EVI). Process development of a placental malaria vaccine. Size/Duration: 1.000.000 Euro 2012-2015
• Danish National Advanced Technology Foundation (HFT). Development and preclinical safety Assessment of a placental malaria vaccine Size/Duration: 2.000.000 Euro 2011-2014
• UCPH  Programme of Excellence. Plasmodium falciparum malaria pathogenesis and immunity Size/Duration: 2.500.000 Euro, 5 years (2012)

Publications: 140 Peer reviewed published papers  + 7 patent applications (8 granted).   

Management experience

I am currently leading a team of 38 research scientists ranging from master students to associate professors. I have been the grant holder and coordinator of several major FP7 EU supported projects as well as major Gates Foundations grants, as well as coordinator of a large HTF (Højteknologifonds) consortium. I the recent years I was awarded an ERC consolidator grant and ERC PoC grant to further consolidate my research tem. Management experience thus entails both consortium coordination, coordination of large international research teams, reporting to funding agencies as well as public outreach disseminating key results.

Innovation

Through our research and development at University of Copenhagen I have made 5 spinout companies, founded a broad and strong patent portefolie within vaccine development, vaccine delivery, cancer therapy and cancer diagnostics. In 2012 VAR2Pharmaceuticals and OncoMal was established and is now based in Copenhagen (COBIS) and Vancouver supported by private investors. In 2016-17 we made the spinout companies NextGen vaccines and AdaptVac based in the bioscience park in Hørshol as a joint venture with Expres2ion Biotechnologies and in 2017 we established VARCT Diagnstostics which is now running a number of clinic feasibility studies in cancer diagnostics around the world. Based on translational research our Centre for Medical Parasitology at UCPH was awareded with a "Centre of Excellence" Price in 2016.