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Scancell

From EverybodyWiki Bios & Wiki



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Scancell
File:Scancell Holdings.png
Traded asLSE: SCLP
ISIN🆔GB00B63D3314
IndustryBiotechnology
Founded 📆January 1997 (1997-01)
Founder 👔
Headquarters 🏙️,
Oxford
,
England
Area served 🗺️
Key people
Prof. Lindy Durrant (CEO)
(CSO)
Dr Sally Adams (CDO)
Members
Number of employees
🌐 Websitewww.scancell.co.uk
📇 Address
📞 telephone

Scancell Holdings plc is a clinical stage biotechnology company founded in the UK in 1997. It is developing novel treatments for cancer and infectious disease harnessing the adaptive immune system which includes antibodies and T cells.

The company was founded as an academic spin out from Nottingham University.[1] and floated on the Alternative Investment Market (AIM) in 2010[2].

Scancell is now headquartered in Oxford within the Oxford Science Park.[3] however it still retains a presence at Nottingham University within the Biodiscovery Institute[4].

History[edit]

Scancell was founded in 1997 based on research spun out of work at Nottingham University led by the current Chief Executive Officer and Chief Scientific Officer, Professor Lindy Durrant, an internationally recognised immunologist in the field of tumour therapy whose research interests lie in understanding and harnessing the adaptive immune system.

In July 2010, the company floated on the London Stock Exchange AIM Market[5] after trading on PLUS since September 2008. At the time the Scancell had just begun clinical trials of the companies lead ImmunoBody product SCIB1 - a DNA based cancer vaccine in advanced melanoma patients Phase I trials of which had commenced the month before in June 2010[6].

The company raised £1.73 million via an equity fundraise in 2011 to fund the completion of the Phase I trial of SCIB1. Previous to admission to AIM the company had licensed a number of monoclonal antibodies to Arana Therapeutics, this resulted in further milestone payment of £2.85 million in November 2011, further strengthening the balance sheet at Scancell[7].

In July 2013 Scancell raised a further £6.5 million before expenses to provide working capital for the completion of the Phase 1/2 SCIB1 clinical trial, as well as provide funding for a further ten patients on the higher 8 mg dose. This fundraising also provided funding for the pre-clinical development of a recently discovered new cancer platform known as Moditope[8].

The company subsequently has raised funds through multiple further placings in 2016, 2017 and 2018. In 2020 the company received a large cash injection of approximately £30 million from Redmile Group - a US based specialist healthcare and life sciences investment fund[9].

Platforms and technologies[edit]

Scancell has a number of patented platforms harnessing the immune system. These including modular DNA vaccines, peptide cancer vaccines, monoclonal antibodies as well as antibody Fc engineering technologies.

ImmunoBody[edit]

Scancell's ImmunoBody platform is a patented 'plug and play' DNA based vaccine platform technology that encodes an engineered human monoclonal antibody[10]. The antibody complementarity-determining regions are replaced with cancer epitopes from a specific cancer antigen. Key design features of the ImmunoBody vaccine include epitopes that bind to MHC class I receptors and MHC class II receptors. This gives rise to both a CD8 cytotoxic t cell and CD4+ T helper cell response. Furthermore retention of the Fc region of the protein targets activated dendritic cells via the Fc receptor. The design of the ImmunoBody vaccine results in antigen cross-presentation to dendritic cells which results in high avidity T cell responses with higher potency as well as a longer duration of immune response.

The modular design of the ImmunoBody platform means multiple vaccines can be generated rapidly, targeting different cancer or infectious disease epitopes by swapping out the cancer epitopes within each ImmunoBody. Scancell secured a licensing agreements with Merck for two key patents required for the further development of the ImmunoBody platform which granted the company non exclusive worldwide rights to use the two patents to further develop and commercialise the technology in both humans and animals[5].

SCIB1[edit]

SCIB1 is an ImmunoBody cancer vaccine incorporating epitopes from Gp100 and TRP-2 which had been identified from cloning T cells from patients who achieved spontaneous remission from melanoma skin cancers. These epitopes were incorporated into the ImmunoBody scaffold forming the SCIB1 cancer vaccine.

Scancell successfully conducted a Phase 1/2 clinical trial in 35 patients with Stage-3 or Stage-4 melanoma in patients with either tumours present or who had fully-resected disease at study entry. Dose dependent T cell responses were demonstrated in nearly 90% of patients with no serious adverse events or dose-limiting toxicity. Clinical read out of this trial was positive and led on to Scancell initiating a Phase 2 clinical study of SCIB1 in late-stage melanoma patients receiving pembrolizumab as standard of care[11][12].

iSCIB1+[edit]

Scancell redeveloped the SCIB1 ImmunoBody to include the same eptiopes as SCIB1 however, included additional eptiopes to improve the number of patients who could participate in the trial. iSCIB1 also included a further modification (see Avidimab) within the Fc region of the SCIB1 product which enhanced the Fc targeting of the resulting ImmunoBody to dendritic cells resulting in the induction of higher frequency T cell responses.

SCIB2/iSCIB2+[edit]

SCIB2 is an ImmunoBody cancer vaccine incorporating epitodes from the cancer antigen NY-ESO-1[13], overexpressed in several tumour types including Synovial sarcoma, esophageal, liver, stomach, prostate and lung cancer.

Scancell announced in 2017 that it would enter into a Clinical Development Partnership with Cancer Research UK to develop SCIB2 for the treatment of patients with solid tumours, including non-small-cell lung cancer[14]. This was scheduled to be delivered using a liposomal nanoparticle drug delivery formulation in the planned phase 1/2 clinical trial[15]. However, in February 2021, Cancer Research UK undertook a re-evaluation of the charities clinical partnerships and collaborations model in light of the ongoing COVID-19 pandemic which had impacted the Charity's funding. Scancell and CRUK through mutual agreement ended their clinical development partnership for SCIB2 which reverted to Scancell with no further commercial obligation from Cancer Research UK[16].

Similar to SCIB1, Scancell took this opportunity to enhance and modify the SCIB2 vaccine through the addition of Avidimab technology, developing iSCIB2 for pre-clinical investigation prior to proceeding with clinical trials in combination with PD-1 inhibitors in non-small cell lung cancer[13][17].

Moditope[edit]

Scancell discovered and patented a platform based on exploiting the immune response that removes stressed cells. This unique class of cancer vaccines is characterised by the induction of cytotoxic T cells targeted at stress-induced post-translational modifications. Cancer cells are often hypoxic and undergo autophagy as a means to survive. During this process stress-induced post-translational modifications such as citrullination[18] and homocitrullination[19] are generated, as well as proteolytic cleavage of proteins. This results in peptides which can be presented on the cell surface complexed with MHC class II molecules for recognition by T cells.

Scancell developed two vaccines based on this discovery (and utilising their patented Moditope platform) as well as entered into a number of collaboration agreements with organisations such as the Karolinska Institute[20] and BioNTech[21].

Modi-1[edit]

Modi-1 is the first Moditope vaccine developed by Scancell. This is a vaccine based on citrullinated peptides for the treatment of solid tumors including triple-negative breast cancer, ovarian, renal and head and neck cancer. The vaccine is composed of a combination of three citrullinated peptides from two target antigens commonly found in cancer cells. The first two component peptides originate from vimentin, a cytoskeletal protein which is preferentially digested during autophagy and found in many mesenchymal tumours. The third peptide comes from alpha-enolase which is involved in the process of glycolysis.

The three peptides are conjugated to a toll-like receptor 1/2 agonist licensed from ISA Pharmaceuticals (Leiden, Netherlands)[22].

A multi-centre multi-arm Phase 1 trial of Modi-1 was approved by the Medicines and Healthcare products Regulatory Agency in 2021[23] and patient enrollment began in early 2022 after delays due to the COVID-19 pandemic[24].

Modi-2[edit]

Modi-2 exploits a second post-translational modification called carbamylation where tumour-associated peptide epitopes are modified by converting lysine residues to homocitrulline generating unique T cell epitopes.

Scancell identified homocitrullinated epitopes linked to a wide range of cancer types derived from several proteins including vimentin, fructose-bisphosphate aldolase, keratin 8, immunoglobulin-binding protein 1, nucleophosmin, Heat Shock Protein 60 and alpha-enolase.[19]

GlyMab[edit]

Scancell developed a technology which enabled the production of highly specific monoclonal antibodies that recognise glycan sugar motifs uniquely found on the surface of many cancer targets. The glycan targeting antibodies generated by this platform are able to deliver chemotherapy agents to cells through antibody-drug conjugate technology, tumour imaging[25] or for use in chimeric antigen receptor T cell therapy.

The company created a portfolio of anti-glycan antibodies that have exceptionally high specificity and affinity for their targets[26]. Five monoclonal antibodies are currently undergoing preclinical characterisation and target validation including through four separate collaboration agreements including with a major European pharmaceutical company[27].

  • SC129 - specific for the sialyl-di-Lewisa glycan, a target for pancreatic cancer
  • SC134 - specific for fucosyl GM1, a target for small cell lung cancer
  • SC88 - specific for the Lewisacx glycan, a target for colorectal cancer
  • SC27 - specific for the Lewisy glycan, a target for gastric cancer
  • SC2811 - specific for Stage Specific Embryonal Antigen-4 on human and mouse T cells with stem-like properties – a target for any solid tumour

AvidiMab[edit]

During the development of the GlyMab platform, Scancell identified unique amino acid residues within the murine Fc region of antibodies which enabled monoclonal antibodies to self-associate upon target recognition, resulting in a more potent, high avidity antibodies. Transfer of these residues to human antibodies resulted in the promotion of non-covalent Fc-Fc interactions that enhanced the direct tumour-cell killing ability of these antibodies[28].

Scancell patented this technology which can be applied to enhance the efficacy of any chimeric, humanized or fully human antibody. The Avidimab modifications were also incorporated into the ImmunoBody platform and demonstrated enhanced efficacy of the platform in pre-clinical studies.

Glymabs enhanced with the Avidimab platform have been licensed to a number of leading antibody technology companies and pharmaceutical companies both within Europe and China on non-exclusive licences for evaluation purposes[29][30]. Under the terms of the collaboration and research agreements, Scancell and partners will evaluate the potential of anti-glycan monoclonal antibodies, enhanced with AvidiMab, in various formats including, antibody drug conjugates, bispecific antibodies, as well as stand-alone antibody products.

Partnerships and collaborators[edit]

Scancell has a number of partners and collaborators both within industry and academia. These include but are not limited to:

COVID-19 vaccine[edit]

In April 2020 during the first wave of the COVID-19 pandemic Scancell announced the formation of a consortium led by Professor Lindy Durrant along with researchers from the Centre for Research on Global Virus Infections and the Biodiscovery Unit (both University of Nottingham) as well as with Nottingham Trent University.

The focus of this collaboration was to utilise the companies ImmunoBody cancer vaccine platform with the aim of producing a simple, safe, cost-effective and scalable vaccine which was able to induce both T cell and virus neutralizing antibody responses.

The vaccine is a DNA based vaccine designed to target the SARS-CoV-2 nucleocapsid protein as well as the receptor-binding domain (RBD) and is able to generate both T cell responses and virus neutralising antibodies against the virus[35]. Due to the conserved nature of the nucleocapsid protein amongst betacoronavirus family members this second-generation vaccine may be able to generate immunity against other variants of COVID-19.

The vaccine consists of two components:

SCOV1 - a DNA plasmid which incorporates SARS-CoV-2 antigens from the original virus strain first identified in Wuhan, China.

SCOV2 - a DNA plasmid which incorporates SARS-CoV-2 antigens from known variants of concern.

The SCOV1 component of this vaccine is anticipated to be active against the original SARS-CoV-2 strain as well as the Alpha variant and to a slightly lesser extent to the Beta variant and Gamma variant[35]. Whilst SCOV2 is anticipated to boost the effects of SCOV1 whilst providing further enhanced protection against the Beta and Gamma Variants. In preclinical models, antibodies induced by vaccination with both SCOV1 and SCOV2 showed strong binding to the Delta variant and the Omicron variant.

Both vaccines are administered via a needle-free injection device developed by PharmaJet and are designed to be delivered either intradermally or intramuscularly[34].

The consortium received funding from Innovate UK[36] through the UK Research and Innovation 'Ideas to Address COVID-19' funding stream. This funding was used to initiate a Phase 1 clinical trial of a DNA based vaccine against COVID-19 named 'Covidity' in South Africa in September 2021[37]

External links[edit]

References[edit]

  1. ↑ "Spin out". www.nottingham.ac.uk. Retrieved 2022-05-01.
  2. ↑ "Stock". www.londonstockexchange.com. Retrieved 2022-05-01.
  3. ↑ "Scancell change of registered office". scancell.co.uk. Retrieved 2022-05-01.
  4. ↑ "Facilities" (PDF). www.scancell.co.uk. Retrieved 2022-05-01.
  5. ↑ 5.0 5.1 "Withdrawal from PLUS and Admission to AIM" (PDF).
  6. ↑ "SCIB1 trial". 16 August 2017.
  7. ↑ "Confirmation of second tranche payment of £2.85 million from Arana Therapeutics". Scancell Wireframe. Retrieved 2022-05-02.
  8. ↑ "Proposed Placing and Open Offer". Scancell Wireframe. Retrieved 2022-05-02.
  9. ↑ "Scancell raises £30m from funds managed by Redmile | Monday 02 May 2022". AJ Bell Youinvest. Retrieved 2022-05-02.
  10. ↑ Pudney, Victoria A.; Metheringham, Rachael L.; Gunn, Barbara; Spendlove, Ian; Ramage, Judith M.; Durrant, Lindy G. (March 2010). "DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8 + T cells". European Journal of Immunology. 40 (3): 899–910. doi:10.1002/eji.200939857. PMID 20039301. Unknown parameter |s2cid= ignored (help)
  11. ↑ "A trial of SCIB1 and pembrolizumab for advanced melanoma". Cancer Research UK. 2020-03-24. Retrieved 2022-05-02.
  12. ↑ "SCIB1 Phase 2 trial". 12 August 2021.
  13. ↑ 13.0 13.1 Xue, Wei; Metheringham, Rachael L.; Brentville, Victoria A.; Gunn, Barbara; Symonds, Peter; Yagita, Hideo; Ramage, Judith M.; Durrant, Lindy G. (June 2016). "SCIB2, an antibody DNA vaccine encoding NY-ESO-1 epitopes, induces potent antitumor immunity which is further enhanced by checkpoint blockade". Oncoimmunology. 5 (6): e1169353. doi:10.1080/2162402X.2016.1169353. ISSN 2162-4011. PMC 4938367. PMID 27471648.
  14. ↑ "Scancell soars as it confirms Cancer Research UK to fund and sponsor SCIB2 clinical trial". Proactiveinvestors UK. 2017-12-14. Retrieved 2022-05-02.
  15. ↑ "Nanoparticle formulation SCIB2".
  16. ↑ News, Alliance (2021-02-03). "Scancell Assessing SCIB2 Options As Cancer Research UK Pact Ends". Morningstar UK. Retrieved 2022-05-02.
  17. ↑ "SCIB2 also shown to synergise with checkpoint inhibitor blockade". Scancell Wireframe. Retrieved 2022-05-02.
  18. ↑ Choudhury, Ruhul H.; Symonds, Peter; Paston, Samantha J.; Daniels, Ian; Cook, Katherine W.; Gijon, Mohamed; Metheringham, Rachael L.; Brentville, Victoria A.; Durrant, Lindy G. (February 2022). "PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy". Journal for Immunotherapy of Cancer. 10 (2): e003526. doi:10.1136/jitc-2021-003526. ISSN 2051-1426. PMC 8830261 Check |pmc= value (help). PMID 35140112 Check |pmid= value (help).
  19. ↑ 19.0 19.1 Cook, Katherine; Xue, Wei; Atabani, Suha; Symonds, Peter; Al Omari, Abdullah; Daniels, Ian; Shah, Sabaria; Choudhury, Ruhul Hasan; Weston, Daisy; Metheringham, Rachael; Brentville, Victoria; Durrant, Lindy (2022). "Vaccine Can Induce CD4-Mediated Responses to Homocitrullinated Peptides via Multiple HLA-Types and Confer Anti-Tumor Immunity". Frontiers in Immunology. 13: 873947. doi:10.3389/fimmu.2022.873947. ISSN 1664-3224. PMC 9028767 Check |pmc= value (help). PMID 35464453 Check |pmid= value (help).
  20. ↑ "Scancell expands Moditope collaboration with Karolinska Institute". www.pharmaceutical-business-review.com. 10 August 2018. Retrieved 2022-05-02.
  21. ↑ "Scancell buddies up with 'new immuno-oncology powerhouse'". www.thepharmaletter.com. Retrieved 2022-05-02.
  22. ↑ "ISA Pharmaceuticals and Scancell enter collaboration agreement for the manufacturing, development and commercialisation of Modi-1 / AMPLIVANT® combination". ISA Therapeutics BV. 2018-02-15. Retrieved 2022-05-02.
  23. ↑ "MHRA Approves Clinical Trial Application for Scancell's Modi-1". PharmTech. Retrieved 2022-05-02.
  24. ↑ "A Phase 1/2, Multicentre, Open-Label Study of Modi-1 in Patients With Breast, Head and Neck, Ovarian, or Renal Cancer". Scancell Ltd. 2022-04-07.
  25. ↑ Houvast, Ruben D.; Vankemmelbeke, Mireille; Durrant, Lindy G.; Wuhrer, Manfred; Baart, Victor M.; Kuppen, Peter J. K.; de Geus-Oei, Lioe-Fee; Vahrmeijer, Alexander L.; Sier, Cornelis F. M. (2020-12-21). "Targeting Glycans and Heavily Glycosylated Proteins for Tumor Imaging". Cancers. 12 (12): E3870. doi:10.3390/cancers12123870. ISSN 2072-6694. PMC 7767531 Check |pmc= value (help). PMID 33371487 Check |pmid= value (help).
  26. ↑ Tivadar, Silvana T.; McIntosh, Richard S.; Chua, Jia Xin; Moss, Robert; Parsons, Tina; Zaitoun, Abed M.; Madhusudan, Srinivasan; Durrant, Lindy G.; Vankemmelbeke, Mireille (March 2020). "Monoclonal Antibody Targeting Sialyl-di-Lewisa-Containing Internalizing and Noninternalizing Glycoproteins with Cancer Immunotherapy Development Potential". Molecular Cancer Therapeutics. 19 (3): 790–801. doi:10.1158/1535-7163.MCT-19-0221. ISSN 1538-8514. PMID 31871270. Unknown parameter |s2cid= ignored (help)
  27. ↑ "Scancell Holdings Secures Research Collaboration Agreement for GlyMab Platform". Wall Street Journal. 17 March 2022. Retrieved 2022-05-02.
  28. ↑ Vankemmelbeke, Mireille; McIntosh, Richard S.; Chua, Jia Xin; Kirk, Thomas; Daniels, Ian; Patsalidou, Marilena; Moss, Robert; Parsons, Tina; Scott, David; Harris, Gemma; Ramage, Judith M. (2020-08-15). "Engineering the Human Fc Region Enables Direct Cell Killing by Cancer Glycan-Targeting Antibodies without the Need for Immune Effector Cells or Complement". Cancer Research. 80 (16): 3399–3412. doi:10.1158/0008-5472.CAN-19-3599. ISSN 1538-7445. PMC 7611157 Check |pmc= value (help). PMID 32532823 Check |pmid= value (help).
  29. ↑ "Scancell signs collaboration agreement for AvidiMab". NS Medical Devices. 2019-09-04. Retrieved 2022-05-02.
  30. ↑ "Scancell signs second AvidiMab collaboration, this time in China". Proactiveinvestors UK. 2019-12-16. Retrieved 2022-05-02.
  31. ↑ Taylor, Nick Paul (2018-01-09). "After $270M round, BioNTech pens TCR pact with Scancell". Fierce Biotech. Retrieved 2022-05-02.
  32. ↑ "Scancell says Ichor deal extension "clears the runway"". Proactiveinvestors UK. 2016-07-20. Retrieved 2022-05-02.
  33. ↑ "ISA Pharmaceuticals and Scancell enter collaboration agreement for the manufacturing, development and commercialisation of Modi-1 / AMPLIVANT® combination". ISA Therapeutics BV. 2018-02-15. Retrieved 2022-05-02.
  34. ↑ 34.0 34.1 "PharmaJet selected to deliver Scancell COVID-19 DNA Vaccine". PharmaJet. 2021-09-09. Retrieved 2022-05-02.
  35. ↑ 35.0 35.1 Brentville, V. A.; Vankemmelbeke, M.; Metheringham, R. L.; Metheringham, R. L.; Symonds, P.; Cook, K. W.; Urbanowicz, R.; Tsoleridis, T.; Coleman, C. M.; Chang, K.-C.; Skinner, A.; Dubinina, E.; Daniels, I.; Shah, S.; Dixon, J. E.; Pockley, A. G.; Adams, S. E.; Paston, S. J.; Daly, J. M.; Ball, J.; Durrant, L. G. (2021-06-18). "A novel bivalent DNA vaccine encoding both spike protein receptor-binding domain and nucleocapsid protein of SARS-CoV-2 to elicit T cell and neutralising antibody responses that cross react with variants". bioRxiv 10.1101/2021.06.18.448932 Check |biorxiv= value (help).
  36. ↑ "InnovateUK funding".
  37. ↑ "Clinical Trial". 30 May 2022.


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