technology
soloMERs® are Elasmogen’s proprietary drugs derived from small (approximately 11 kDa) antibody-like proteins found in sharks known as Variable New Antigen Receptors (VNARs). VNARs exist naturally as high affinity, target-specific binding domains that play a crucial role in the adaptive immune system of these animals. With a distinct ancestral origin from antibodies, this example of 400-million-year-old convergent evolution places VNARs outside of the complex patent landscape that describes and protects antibody drug discovery and has produced the smallest and most robust naturally occurring binding domains in the vertebrate kingdom. The conversion of VNARs into soloMERs®, a format that retains the unique characteristics of VNARs but is now suitable for human use (through humanisation or de-immunisation), has been granted as inventive and is captured by a patent family across multiple territories.
Elasmogen is uniquely positioned to build upon a growing portfolio of novel single chain clinical candidates to a range of drug targets, efficiently isolated from several diverse drug libraries of more than 100 billion unique VNARs and soloMERs® (Elasmogen’s “drug-engine”). These libraries combine the qualities of all known VNAR isotypes in a test-tube and their innovative design has been protected with a multi-layered IP position covering the platforms, formats, products and process.
The combination of small, stable, single-chain and structurally unique soloMERs® coupled with robust platforms for isolation against multiple disease targets has enabled Elasmogen to build a pipeline of differentiated therapeutic biologics designed to tackle complex diseases.
soloMER® platforms
Our soloMER® platforms can deliver binding domains of high specificity and affinity to novel epitopes in various target classes including but not limited to cell surface receptors, soluble cytokines and growth factors. We isolate antigen specific VNARs from our immunised (ELSI) or synthetic (ELSS) libraries and humanise or de-immunise them delivering clinical candidates (soloMERs®).
Elasmogen has a portfolio of drug libraries based on different isotype combinations and loop diversity creating a breadth of unique binding paratope topologies.
synthetic libraries:
Our in depth knowledge of VNARs has enabled the rational design of multiple synthetic libraries that retain the desirable attributes of these domains whilst expanding on the diversity of the natural repertoire through clever isotype fusions.
Our synthetic libraries deliver from single digit nM up to pM affinity domains.
Our patent protected humanisation and de-immunisation methods have been incorporated into the library designs to create soloMER® synthetic libraries. These soloMER® libraries will reduce development time and fast-track our products into the clinic.
immunised libraries:
Due to the evolutionary distance from mammals, there is no need to break tolerance and strong immune responses are achieved against multiple disease targets.
VNAR responses are subject to in vivo maturation and as a result target-specific domains of high affinity (pM) are isolated even in the absence of iterative selections.
lead domains are isolated using the robust technology of phage display enabling:
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cross-species selectivity to be dialled in to selections
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deselection with homologous antigens
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temperature and pH tolerant domains to be isolated
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solution phase antigen presentation via streptavidin-biotin link to increase the number of diverse leads delivered
reformatting of soloMERs®
The simple, single-chain nature of soloMERs® enables rapid reformatting into different drug products, tailored for optimal therapeutic efficacy. The advantages of small size, such as greater tumour and tissue penetration, can be retained whilst increasing the functionality of the product by creating dimeric and trimeric soloMER® fusions. Furthermore, the PK of these constructs can be tailored through the inclusion of our proprietary albumin binding soloMER® , NDure®. The amenability to both N– and C– terminal molecular fusions without loss of function or favourable biophysical properties has led to the creation of a portfolio of empirically designed multivalent soloMER® modalities.
By applying our robust but rationally informed reformatting techniques, a range of multi-valent, biparatopic, multispecific soloMERs® with enhanced in vitro potency and in vivo efficacy have been created. The soloMER® Quad® is a family of multispecific or multi-paratopic human IgG1 Fc fused soloMERs® , exhibiting super-potent activity in disease models.
modalities
soloMER® Drug Conjugates (SDC)
An advanced drug class that combines small molecules and biologics has been successfully developed based on soloMERs®. Site specific conjugation of linker-payloads to soloMERs® in various product formats has not affected their potency and have demonstrated selective cell killing translating into excellent efficacy in models of human disease.
oral delivery
Formulation of biologics for oral delivery is one of the most ambitious and disruptive development activities in the antibody therapeutics space. This approach will revolutionise patient care; most importantly improve drug safety and efficacy especially for site-specific disease targeting, e. g. IBD.
We are developing a pipeline of anti-inflammatory soloMER® products for oral delivery to treat a wide range of diseases.
