To benchmark the utility of E06: A half-life extension, single-domain, shark antibody bio-tool, and progress it to a Phase 1 ready candidate clone
Lead Research Organisation:
University of Aberdeen
Department Name: School of Medical Sciences
Abstract
Scientifically we are developing a "bio-tool" that could be fused to a range of different therapeutic proteins/peptides to extend their serum half-life from hours to weeks, with the potential of greatly increasing their therapeutic potency. It works by hitching a ride on other long-lived proteins in the blood. Commercially, our medium-term goal is to create a Drug Discovery company, based on our unique, single-domain shark antibody (VNAR) platform, which will develop therapeutic agents in-house or in partnership with larger companies. To achieve this, meeting of scientific milestones is key, and in particular confirming non-immunogenicity (not seen by the human immune system & safe for use), and validate the most advanced of our products (E06 VNAR half-life extension bio-tool). Progress towards this goal will also provide a platform for NewCo formation and equity raising, and will deliver an asset capable of securing multiple revenue streams of licensing and partnered income.
People |
ORCID iD |
| Andrew Porter (Principal Investigator) |
Publications
Ubah O
(2018)
Next-generation flexible formats of VNAR domains expand the drug platform's utility and developability
in Biochemical Society Transactions
Kovaleva M
(2014)
Shark variable new antigen receptor biologics - a novel technology platform for therapeutic drug development.
in Expert opinion on biological therapy
Kovaleva M
(2017)
Therapeutic Potential of Shark Anti-ICOSL VNAR Domains is Exemplified in a Murine Model of Autoimmune Non-Infectious Uveitis.
in Frontiers in immunology
Steven J
(2017)
In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties to Facilitate Clinical Development.
in Frontiers in immunology
Ubah OC
(2017)
Novel, Anti-hTNF-a Variable New Antigen Receptor Formats with Enhanced Neutralizing Potency and Multifunctionality, Generated for Therapeutic Development.
in Frontiers in immunology
Ubah OC
(2020)
In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Constructs in a Mouse Model of Human RA: An Encouraging Milestone to Further Clinical Drug Development.
in Journal of immunology research
O'Dwyer R
(2018)
Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis.
in Journal of immunology research
Zielonka S
(2015)
Structural insights and biomedical potential of IgNAR scaffolds from sharks.
in mAbs
| Description | We have generated a candidate protein (bio-tool) that is capable when joined to other therapeutic proteins of increasing the useful time these drugs are available in the body from a few hours to over two weeks. Importantly although this bio-tool was originally derived from a shark we have humanised it in such a way to make the human body think that it is human protein and therefore will not be rejected. We have compared the success of our humanisation outcomes with other highly efficacious and commercially valuable protein drugs and we have achieved a level the same or better than these comparator molecules. We have now successfully protected through grants this molecule and the general humanisation approach when applied to shark VNAR binding domains. This IP has now progress to grant in some countries including the US. http://www.bbsrc.ac.uk/news/impact/elasmogen-shark-proteins-for-drug-discovery/ |
| Exploitation Route | This bio-tool is already being used by collaborators interested in improving the outcomes of protein based drugs that treat cancer and diseases of the blood. We are now in discussions with possible commercial partners considering taking a license to the technology. The South Korean compamny ImmunoForge Ltd took a license to the bio-tool (now described as the product enabler NDure) in Jan 2019. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| URL | http://www.elasmogen.com |
| Description | March 2015 Update: The most important way that our findings have been used is to provide data for the filing of patents to protect the intellectual property generated by our research and provide a valuable portfolio (drug generation platform, bio-tools and lead therapeutic molecules) which we hope we will be able to use to raise investment cash and spin out a new company. March 2016 Update: Elasmogen Ltd a biologics drug discovery new spin-out from the UoA was successfully launched (Feb 2016) with approximately £850 k of equity and grant funding and a staff of 6. The focus of the company is the site-specific delivery of anti-autoimmune soloMERs (humanised candidate VNARs) specific for the treatment of inflammatory disease of the eye and gut. March 2017: Elasmogen has continued to go from strength to strength winning a number of high profile UK sector specific awards and securing an addition £1.2 M in equity and grant funding. Our patent portfolio has also strengthened with an important Divisional grant in Europe and second patent granting in the US. We are also working with a number of global pharma and biotech partners including Amgen Inc. Q1 2018 Elasmogen raised an additional 1.6 M in grant and equity funding. |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BioMedical Catalyst |
| Amount | £700,000 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2017 |
| End | 01/2019 |
| Description | Innovate UK |
| Amount | £100,000 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2016 |
| End | 03/2017 |
| Description | SULSA MSD PhD studentship |
| Amount | £100,000 (GBP) |
| Organisation | Scottish Universities Life Sciences Alliance |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 11/2012 |
| End | 10/2016 |
| Description | Support for a commercialisation champion to aid company formation and lead investor funding of Elasmogen (the shark VNAR asset porfolio) |
| Amount | £15,000 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 04/2015 |
| Description | The generation of a bio-processing VNAR that specifically recognizes the heterodimeric form of bispecific antibody formats |
| Amount | £107,000 (GBP) |
| Funding ID | SF10104 |
| Organisation | Government of Scotland |
| Department | Scottish Funding Council |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2014 |
| End | 09/2018 |
| Title | Candidate half-life extension bio-tool |
| Description | A humanised shark VNAR specific for human serum albumin that increases the half-life of partner (therapeutic) proteins (and peptides) in three in vivo PK models from a few hours to more than two weeks. |
| Type Of Material | Antibody |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | A licensable therapeutic asset. One collaboration in Oncology is using this asset to develop novel protein drug conjugate molecules. A second academic collaboration is looking to increase the half-life of therapeutic proteins in relevant animal models of disease. |
| Description | Co-expression of therapeutic proteins with a VNAR half-life extension bio-tool. |
| Organisation | University of Surrey |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Supply of relevant genetic and protein materials suitable for cloning and assay development. |
| Collaborator Contribution | Cloning of our half-life extension bio-tool as a fusion with a therapeutic protein, expression and characterisation of the fusion protein in a suitable animal model of disease. |
| Impact | Started formally November 2014 |
| Start Year | 2014 |
| Description | Intracellular targeting or drug targets using soloMER biologics - with Amgen Inc and Feldan Ltd |
| Organisation | Amgen Inc |
| Country | United States |
| Sector | Private |
| PI Contribution | Drug target antigens are provided by Amgen, biologic drug target binders by Elasmogen Ltd and drug delivery technology by Feldan Ltd. This is a full drug discovery program focussed on two targets. |
| Collaborator Contribution | As above |
| Impact | As above but no outputs yet |
| Start Year | 2017 |
| Description | Intracellular targeting or drug targets using soloMER biologics - with Amgen Inc and Feldan Ltd |
| Organisation | Feldan Travel ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Drug target antigens are provided by Amgen, biologic drug target binders by Elasmogen Ltd and drug delivery technology by Feldan Ltd. This is a full drug discovery program focussed on two targets. |
| Collaborator Contribution | As above |
| Impact | As above but no outputs yet |
| Start Year | 2017 |
| Description | Isolatiuon of VNAR from novel shark species |
| Organisation | Technical University of Darmstadt |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | We have provided expertise in the cloning of antigen specific VNAR libraries from an immunised source |
| Collaborator Contribution | Darmstadt have provided expertise using a novel display system for the selection of antigen specific VNAR bimders |
| Impact | VNAR specific binders to a therapeutically relevant target, successful immunisation of a new elasmobranch species, paper in preparation |
| Start Year | 2013 |
| Description | VNARs as Bio-Processing tools for the production of bi-specific antibodies for use in human therapies |
| Organisation | Merck |
| Country | Germany |
| Sector | Private |
| PI Contribution | We have been isolating VNAR binders from our synthetic drug libraries that will recognise different formulations of Mercks therapeutic drugs. These VNARs have the potential to be used in bio-processing to aid the manufacture, purification and QC of these drugs at scale. |
| Collaborator Contribution | They have provided financial support for staff and consumables, materials for the selection process and BIAcore analysis of outputs using their facility in the US. |
| Impact | No definitive outcomes yet but all the early data looks very promising and we are in the late stage characterisation of our panel of specific binders. |
| Start Year | 2014 |
| Title | ANTIGEN BINDING DOMAINS FROM FISH |
| Description | A process for the production of an antigen specific antigen binding domain using a transformed host containing an expressible DNA sequence encoding the antigen specific antigen binding domain, wherein the antigen specific antigen binding domain is derived from a variable region of the immunoglobulin isotype NAR found in fish. |
| IP Reference | EP2281837 |
| Protection | Patent granted |
| Year Protection Granted | 2011 |
| Licensed | Yes |
| Impact | Spin-out company called Elasmogen Ltd |
| Title | Antigen Binding Domains |
| Description | This patent protects the immunisation of sharks to generate VNAR specific binders. Grants had already been achieved in Europe, Canada, Japan, Australia. |
| IP Reference | US patent application 13/280 837 |
| Protection | Patent granted |
| Year Protection Granted | 2014 |
| Licensed | No |
| Impact | Whilst no licensing income has been secured to date discussions are now on-going with potential licensees and infringers. This grant increases the likelihood of investor cash being secured into a new spin-out. It also underpins the collaborative research we carry out with other commercial partners. |
| Title | SINGLE DOMAIN BINDING MOLECULE |
| Description | The present invention provides a single domain specific binding molecule having the structure5 FW1-CDR1-FW2-HV2-FW3a-HV4-FW3b-CDR3-FW4 in which the Framework Regions FW1, FW2, FW3a, FW3b, and FW4, the Complementarity Determining Regions CDR1 and CDR3, and the Hypervariable Regions HV2, and HV4 have amino10 acid sequences as defined which provide a high affinity anti-human serum albumin (HSA) binding domain. |
| IP Reference | WO2013167883 |
| Protection | Patent granted |
| Year Protection Granted | 2013 |
| Licensed | Yes |
| Impact | Elasmogen Ltd |
| Title | Single Binding Domain Molecule |
| Description | This patent describes VNAR domains that bind to human serum albumin and extend the half-life, in three in vivo models, of fusion proteins (therapeutic proteins) from a few hours to over two weeks. |
| IP Reference | US20130302250 |
| Protection | Patent granted |
| Year Protection Granted | 2015 |
| Licensed | Yes |
| Impact | This patent and the domains that is describes are being used as part of commercial and academic collaborative projects. One is in oncology and the second hopes to increase half-life of an important therapeutic proteins. Both are covered by relevant agreements to protect foreground and background IP. |
| Company Name | Elasmogen Ltd |
| Description | Biologics drug discovery company focussed on the site-specific delivery of soloMER domains (humanised VNARs) for the treatment of auto-inflammatory and oncology conditions. |
| Year Established | 2016 |
| Impact | Raised around £850 k to spin out in grant and equity finance in February 2016. Was second in the 2015 Converge Business Plan Challenge out of 200 technology companies that applied. First in the Life Sciences sector. Has established a number of collaborations with pharma partners. Was recognised as "Perfect Pitch" winners at BioTrinity 2016 and was shortlisted as new start spin-out of 2016 in the UK OBN awards. Was a finalist in the 2016 Innovate Showcase competition. CEO Dr Caroline Barelle was named one of the top 14 female CEO's in Europe and in 2018 and won the Risings Stars: Extraordinary Talent SE Life Sciences Scotland. Elasmogen has also won the Start-up Slam - "Most Innovative Company at BioFit 2018 and in the same year at the Entrepreneurial Scotland Summit Awards was made "Academic Entrepreneurial company of the Year" Raised additional equity and grants totally £1.2 M in February 2017. Raised an additional £1.6 M in grants, upfront and equity in 2018. Currently has term sheet for an additional £2 M expects to close March 2019. Has been used as a CASE study by BBSRC: http://www.bbsrc.ac.uk/news/impact/elasmogen-shark-proteins-for-drug-discovery/ |
| Website | http://www.elasmogen.com |
| Description | 3rd UK - China Healthtech Open Innovation Workshop, platform presentation, Guangzhou, China, 17th June, Shark VNAR Biologics |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Two science focussed grant applications were submitted with Chinese and Chinese/US collaborators for funding by the Chinese Government. Unfortunately the grants were not awarded. They were considered to early stage in terms of there drug development potential. |
| Year(s) Of Engagement Activity | 2013 |
| Description | BIO Bio-Parnering San Diego June 23-26 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Excellent networking Later stage discussions with two companies concerning investment and scientific collaborations. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Biotrinity, European Biopartnering and Investment Conference, Newbury, UK, platform presentation, 16th May, Shark VNAR Biologics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The presentation stimulated interest from both companies and potential investors One face to face meeting eventually resulted in an oncology collaboration with a mid-sized UK pharma company |
| Year(s) Of Engagement Activity | 2013 |
| Description | CIC biomaGUNE, San Sebastian, invited seminar speaker, 22nd Sept 2014, Biologics with Bite |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Stimulated a good level of questions and one to one meetings with senior academics in the Institute The successful establishment of a collaboration and funding from the Spanish Government to allow Dr Mareque to visit Aberdeen for a six month sabbatical to carry our research combining shark VNAR and nanotechnologies. |
| Year(s) Of Engagement Activity | 2014 |
| Description | EPIC, Biopartnering Conference, London, UK, platform presentation, 6th June, Shark VNAR Biologics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Some limited interest at this meeting. Audience size and quality was small. Made useful contacts for future networking when identifying KOLs to help with VC DD process |
| Year(s) Of Engagement Activity | 2013 |
| Description | Macduff Marine Aquarium public lecture "Shark blood and how it can help humans" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Talk generated a great series of interactions with primary school children, parents and teachers. After the talk Dr Barelle was asked if she would be prepared to return the following year. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Shark Antibodies: Bigger Than Jaws - Genetic Engineering and Biotechnology News - 22 August 2013 |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Article sparked interest from other media outlets Helped increase the profile of the project. We were asked to write a Expert Opinion Review Article because of the profile of this media article |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.genengnews.com/insight-and-intelligenceand153/shark-antibodies-bigger-than-jaws/77899882/ |
| Description | UKTI Life Sciences Mission, Tokyo, 26th Feb, Osaka, 28th Feb, Platform presentations and poster, Shark VNAR Biologics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was predominantly about meeting Japanese companies that may wish to collaborate with the Aberdeen team to gain access to the VNAR platform technology or make therapeutic use of the bio-tool. We met around 6 pharma companies during this visit and have had follow up meetings back in the UK with two of these companies. No deals in place yet. |
| Year(s) Of Engagement Activity | 2013 |
| Description | University of Bradford, Institute of Cancer Therapeutics, invited seminar speaker, 1st Nov 2013 "Biologics with Bite |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Lots of questions and a chance to meet several academic specialists in oncology for brief face to face meetings Bradford Univesity were one of the co-ordinators of the China Mission. We were selected to be considered for the this Mission (see related engagement submission). |
| Year(s) Of Engagement Activity | 2013 |
| Description | University of Darmstadt, invited seminar speaker, 9th Dec 2013 "Biologics with Bite |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Stimulated good discussion from the audience of academics and company professionals We now have an academic research collaboration with the University. We also have an active collaboration with Merck Serono which eventually allowed us to secure funding (partly from Merck) for a CASE PhD student. |
| Year(s) Of Engagement Activity | 2013 |