Shark molecules provide the basis of unique new therapeutics which could transform the treatment of inflammatory diseases and cancer. Karen Southern talks to Dr Caroline Barelle, CEO and founder of Elasmogen, the small biopharmaceutical company behind this potentially huge breakthrough.
Aberdeen-based Elasmogen recently secured £8 million investment for its soloMERTM platform, led by BGF and Scottish National Investment Bank with additional support from existing investor Scottish Enterprise. This will enable the company to continue developing its pipeline of next-generation drugs through pre-clinical trials.
soloMERTM is based on molecules naturally found in sharks’ immune systems, which are the equivalent of human antibodies but smaller and more stable. Elasmogen’s pipeline focuses on applying technology to treatments of solid-tumour cancers, systemic inflammatory diseases and inflammatory conditions of the gut.
Their lead programme, partnered with Almac Discovery, is a soloMER-Drug-Conjugate targeting ROR1 in solid tumour cancers This plays into the high growth class of antibody drug conjugates (ADCs), which are gaining interest as a means of developing more targeted cancer therapies.
The technology has roots in the University of Aberdeen where it was established in 2006, before being acquired by US pharma company Wyeth and later by Pfizer. Dr Barelle led the spin-out of Elasmogen and has guided the business since its inception.
Tell us about your work?
Elasmogen is a drug discovery and development biotechnology company. We have developed a technology based on antibody-like molecules (we call soloMERs) that form part of the adaptive immune system in sharks and leveraged this platform to bring new therapeutic drugs to the clinic.
What makes your soloMERTM platform unique?
There are multiple different factors which together really do enable this technology to overcome some of the limitations of current biologic drugs in the clinic.
One is size – our soloMERs are approximately 10x smaller than classical antibodies, facilitating great tissue penetration, particularly important when you are treating solid tumour cancers. Another key differentiator is how they bind to disease targets – they have a unique shape that enables them to bind into more ‘hidden’, deeper parts of these targets.
In essence, this opens up a greater opportunity to tackle the targets differently. In many cases it delivers a different mechanism of action, which opens up new ways of treating disease. In addition, our soloMERs are single-chain compared to the multiple chained, complex antibodies in the clinic.
Antibodies are designed naturally to bind one target with high affinity and selectivity. Our soloMERs can also achieve this, but critically we can take different soloMERs against different disease targets and link them together to make a single drug. Given the complexity of disease, this ability to re-format rapidly and hit more than one target really makes our technology broad-reaching. So, in a nutshell, this combination of properties make our technology truly unique.
How did it originate? What is the significance of the ‘shark’ molecule?
It all came about through academic research into the original of adaptive immunity – sharks are the oldest vertebrates on the planet with the basic toolbox for an antibody-based immune system.
As with many animals (particularly ones that have been evolving for over 400 million years!) there are similarities … and there are differences: one of these was the discovery of an antibody-like molecule called New Variable Antigen Receptor or VNAR. These simpler, single chain antibody-like molecules are the foundation for our soloMER technology. We start by isolating VNARs against disease targets and then ‘humanise’ them, i.e. alter their sequences to make them closer to our naturally occurring antibody molecules and prevent any unwanted immune responses. These humanised clinical candidates are called soloMERs.
What’s the position regarding pre-clinical trials? (e.g. successes / challenges)
We are currently at late stage pre-clinical with our lead product, which is a soloMER drug conjugate primarily developed for triple negative breast cancer. This has been a great success and enabled us to develop a follow-on pipeline of first-in-class bi-functional drug conjugate drugs. In addition, we have an incredible anti-inflammatory program which is exploiting the advantages of our technology to target a well-known disease molecule differently, creating a new mechanism of action and hopefully overcoming known issues with the existing portfolio of approved drugs. The main scientific challenges come with having a platform technology with broad reaching-opportunities against many targets for many diseases. Making those choices and balancing the risk within the pipeline (particularly when you are a small biotech company with limited resources) always makes that decision-making process challenging.
What has been your most surprising finding?
For me, it’s the constant ability of these domains to bind into different parts (epitopes) of disease targets. Engineering affinity and improved biophysical properties is a pretty standard process for molecular engineers; however, having a technology that inherently interacts and binds in a different way to different target classes create a real advantage. Coupled with the ease of re-formatting, it offers the ability to make incredibly effective drug candidates.
Is your work a game-changer for cancer and other therapies?
We certainly hope so, but the proof will only be delivered in the clinic. There are many innovative drugs out there and combining different modalities is a critical approach to treating difficult, complex diseases. Patients are individuals – as are their diseases – so it’s critical that we understand the positive outcomes from our drugs, but are always mindful of limitations and how we can learn, refine and improve our offering to deliver better outcomes.
How do you foresee Elasmogen’s short and long-term outlook, and positioning in the global market?
We are striving to get our first product into the clinic which is a key inflection point for the technology and the company. We envisage this being a mid-term milestone. In the shorter term we are building our internal pipeline and actively seeking value-adding partnerships where we can combine our technology with others out there to create new drug modalities. There is no question that we are in an incredibly crowded and highly competitive space, so gaining clinical validation is crucial for the technology and for us as a company to gain visibility on a global stage.
What has been the main inspiration for your work?
My grandfather suffered with Parkinson’s disease and as a child, I could not understand why my family couldn’t just take him to hospital where a doctor would give him medicine to cure him. Since then, it’s never been the endpoint of medical intervention that has excited me (i.e being the healthcare professional who delivers those medicines) but it’s been the deeper desire to understand the biology of disease and how to design drugs that better serve patients. If I can be a small part of contributing to a drug that makes a difference, then it’s job done for me.
In your opinion, what has been the single most important advance in biopharmacy in recent years?
Goodness, narrowing it down is one is a tough ask. However, for me it’s the switch to understanding the individual disease, the individual patient and designing combinatorial diagnostic and therapeutic approaches that deliver the best opportunity for treatment. I’m afraid that’s a bit of broad stroke but drug design should always have the patient at the centre regardless, right from the beginning.
What is the biggest challenge?
Out with all the existing known and unknown challenges and associated risks that come hand-in hand from being a science-based company, for us as a small biotech company in the northeast of Scotland … it’s funding.
Are there any other key messages you would like to share?
I consider it a privilege to work in the life sciences sector, particularly in the world of innovative drug design. I get to work with a great team of scientists and meet the most incredible people from all over the world, who ultimately all want to improve the lives of patients. Without question it’s challenging and at times stressful, but the positives far outweigh the negatives, and I wouldn’t change it for the world.
Dr Caroline Barelle, CEO of Elasmogen
Caroline is CEO and founder of Elasmogen, a company that discovers and develops soloMER biologics for the treatment of inflammatory diseases and cancer. Before establishing Elasmogen, she successfully led teams at Wyeth and subsequently Pfizer in Global Bio-therapeutic Technologies progressing early platform technologies to late-stage clinical development. Prior to this she was Alliance and Programs Manager at Haptogen Ltd and a key part of the acquisition team that successfully exited the business to Wyeth Inc. She has been awarded a prestigious Royal Society of Edinburgh Enterprise Fellowship, is a doctoral graduate from the University of Aberdeen in Biochemistry, and an MBA (distinction) from Robert Gordon’s University, Business School. Caroline is a member of the Enterprise Skills and Strategy Board, a member of the Opportunity North East Life Sciences Board, a Senior Associate for the Entrepreneurial Business School, Edinburgh and Entrepreneur in Residence for Queen’s University Belfast. She also sits on the BBSRC FoF and UKRI FLF review panels.