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.

Publications

10 25 50

 
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 
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 Antigen binding domains from fish 
Description This was a Divisional grant in Europe of an earlier granted patent and covers the use of shark immunisation and the selection monoclonal binders from a library of binders derived from the immunised animal using any appropriate technology. The original patent only protected the use of phage display technology. This Divisional broadens that protection considerably. 
IP Reference EP2281837 
Protection Patent granted
Year Protection Granted 2016
Licensed Yes
Impact Spin-out company called 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.
 
Title Single domain binding molecule 
Description This is an important US grant of a humanised domain derived from EO6 and described in this grant. This asset now known as NDure TM and is available for licensing. A Divisional of this patent is key to the protection of humanisation of shark VNAR domains. 
IP Reference WO2013167883 
Protection Patent granted
Year Protection Granted 2017
Licensed Yes
Impact Elasmogen Ltd
 
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