From humble beginnings in the founder’s basement, UK-based Aptamer Group is now supplying its Optimer binders to clients across big pharma. DDW’s Diana Spencer caught up with co-founder and CEO Dr Arron Tolley.
DS: What motivated you and Dr David Bunka, CTO, to create Aptamer and did you imagine you would one day be operating on such a global scale?
AT: We initially met at the University of Leeds, where David was a post-doctoral researcher studying aptamers, and I was completing my PhD. I quickly recognised the commercial value of aptamers as being able to address the gap in the market where antibodies fail to perform, and together we established the business to begin aptamer development. Based initially in my own home, with a lab in the basement and an office in the attic, we worked to establish proprietary aptamer selection processes that could be scalable and develop partnerships where we could demonstrate the power of aptamers as antibody alternatives.
As life science operates globally, the vision for the business was always to bring aptamers as an antibody alternative to researchers worldwide. The aim was to bring this technology to help researchers pursue new targets and enable new and improved applications where antibodies don’t offer the necessary performance. As the industry moves to reduce the use of animals in research and testing, aptamers also support here, as they are discovered, developed, and manufactured entirely in vitro, removing the need for animals in antibody discovery processes. As the industry’s awareness of alternatives to traditional antibodies continues to grow, there is increasing demand for these alternatives, which we are seeing particularly within the therapeutic sector, to enable targeted therapeutics and enable the emerging gene therapy market.
DS: The company now has clients across big pharma. To what do you attribute your success? What advice would you offer to similar start-ups?
AT: Integral to Aptamer Group’s offering is an in-depth understanding of molecular science. As a business of scientists, we remain passionate about the exciting developments in the industry, from research to precision therapies, and insatiably curious about the new possibilities that can be achieved by overcoming the limits of standard research tools and methods.
Our partnerships with big pharma have grown based on our detailed understanding of the science that underpins their specific challenges. This awareness allows us to innovate using our Optimer technology to support our partners to deliver faster and better solutions to improve healthcare. Within the affinity ligand space, common challenges include poorly performing antibodies that exhibit inadequate target selectivity and sensitivity. Additionally, the intractability of some targets with alternative ligand technologies means ligands simply cannot be developed to some targets, such as toxic or non-immunogenic targets. Also, the large, immunogenic nature of antibodies and protein ligands as therapeutic molecules means our partners are looking for alternative solutions that offer reduced immunogenicity and improved tissue penetration properties. Optimer binders are engineered to overcome these problems.
Addressing this need in the market has allowed us penetration to work with 75% of the top twenty pharma companies. This has driven further demand as the industry’s awareness of the technology and capabilities increases.
DS: How are aptamers currently used in the development of precision treatments? What advantages do they offer over antibodies?
AT: The major interest we see is in the targeted delivery of therapeutic molecules. We are working with partners to develop delivery vehicles for small molecule payloads as next-generation precision chemotherapy and supporting partners with targeted delivery and cell penetration for gene therapies. Optimer binders are highly selective for specific cell or tissue biomarkers, allowing delivery to the site of action.
When used as precision chemotherapies, the small size of these delivery vehicles compared to standard antibody technologies offers the potential for increased tissue penetration for hard-to-reach sites such as the centre of solid tumours. Equally, the controlled chemistry of Optimer offers the ability for precise aptamer-drug ratios, with conjugation at specific sites on the molecule to simplify therapeutic manufacture.
For gene therapies, the current challenge faced by developers is targeted delivery. GalNAc has provided great results for targeting hepatocytes, but similar molecules for targeting alternative cell types and diseases have yet to be discovered. Within our discovery processes, we can incorporate both the requirements for high selectivity to specific tissue or disease biomarkers and requirements for cell penetration. This ensures that gene therapy payloads can be targeted to the desired tissue and internalised into the target cell to deliver functional payloads. Gene therapies have been seen to be largely non-immunogenic and non-toxic. As such, working with large protein delivery vehicles like antibodies can remove these therapeutic benefits. Our aptamers, being oligonucleotide-based, use the same oligonucleotide chemistry as gene therapies, so retain the likelihood of low immunogenicity and toxicity when transferred to the clinic.
Beyond direct conjugation of therapeutic molecules for delivery, our aptamers can also be conjugated to larger vectors for use in precision medicines. We are interested in exploring the potential for targeting nanoparticles and viral vector retargeting with Optimer. These vectors could carry larger payloads to increase the precision of therapeutic mRNA or gene editing machinery for CRISPR.
Other precision medicine approaches can be taken with Optimer binders acting as the direct therapeutic moiety. We are currently exploring the use of aptamers in targeting a mutant splicing enzyme to reduce aberrant splicing in leukaemia. In this case, the aptamer acts as a direct therapeutic antagonist. Similar approaches can be used in targeting aptamers as antibody alternatives for the creation of agonists or blocking protein-protein interactions at immune checkpoints. Our aptamers offer the ability to pursue new targets that have proven inaccessible with antibodies and to tune therapeutic selectivity, affinity, and in vivo half-life during the discovery process to speed timelines and ensure the required therapeutic functionality.
DS: What do you feel are the most exciting projects you are currently involved in?
AT: We are really excited about the potential of Optimer binders as targeted delivery vehicles for therapeutics. Delivering such diverse payloads using these binders to new tissues and cell types could reduce off-target effects and improve patient dosing and tolerability. This would bring much-needed advancements to a broad spectrum of patients, including cancer, autoimmune conditions, and rare diseases. For example, a major challenge is in the treatment of central nervous system (CNS) diseases. Accessing the CNS to treat these diseases requires transport of therapies across the blood-brain barrier (BBB). Current approaches are largely focused on intrathecal delivery, but intravenous delivery with molecules that can cross the BBB would offer improved tolerability and compliance. Biomarkers like transferrin receptor 1 have shown the potential to carry therapies across the BBB for CNS access and treatment, and targeting such molecules or new more specific biomarkers could offer value in this field. The unmet need in the field of targeted delivery across many diseases is significant.
DS: You ended a partnership with Mologic after realising the market was saturated – what effect did this have on the business? Is the company still able to be agile in response to market trends like this?
AT: In response to the Covid-19 pandemic, we discovered and developed Optimer binders to the SARS-CoV-2 virus in just 17 days. This speed of discovery makes the platform ideal for responding rapidly to emerging diseases for potential future outbreaks anywhere in the world. The SARS-CoV-2 binders were further validated in lateral flow tests with nasal and saliva matrices and within multiple biosensors for clinical diagnostics and infection monitoring in wastewater. Following head-to-head evaluation against an alternative protein-based affinity ligand, our SARS-CoV-2 Optimer binders were selected for use in a commercial biosensor for wastewater monitoring, providing confidence in the performance.
Terminating the Covid-19 LFD development did not significantly impact the business, as our primary focus is on delivering binders to enable our partners in their projects.
While we chose to end the partnership to develop lateral flow tests for Covid-19 with Mologic due to market saturation, this work demonstrated the ability of the Optimer platform to rapidly develop high affinity, high specificity binders suitable for application across multiple platforms. This project still acts as a robust proof-of-concept for the potential of our technology in diagnostics and as assay reagents.
DS: You operate a pretty high-tech laboratory, giving you a quick turnaround time. Does the use of automation allow the company to maintain lower staff levels?
AT: A key feature of our Optimer platform is the significant automation we use in discovery and development. This integrated automation platform is proprietary to Aptamer Group and has been established in-house to support platform processing.
Our use of automation removes potential human error in our processes. It allows high throughput development for large-scale projects and the development of multiple projects at once to help our partners meet their project timelines. The platform is capable of processing hundreds of targets in parallel and is easily scalable to meet future demand.
Many of our automated processes run overnight, allowing scientists to come in and meet the next phase of work in the morning, making projects faster. In terms of staffing, the higher levels of automation we employ our staff to stick to standard working hours for a good work-life balance.
DS: What’s next for the company? Do you feel the use of aptamers could be expanded in the future? Is there untapped potential there?
AT: We continuously monitor and refine our processes to ensure that our platform works as efficiently as possible and returns the highest possible quality for our partners. To support this, we have recently introduced an assay development team that can validate the binders in the specific end-application required by the customer, whether this is IHC, ELISA assays or demonstration of gene therapy delivery and function in vitro. These methods and validation data can then be transferred to our partners, providing a turnkey solution and faster integration into their own systems.
Additionally, we have several developments that we are progressing in-house, including our new proprietary Optimer+ platform. This is a novel nucleotide chemistry platform based on an aptamer backbone with protein-like side chains. Bringing the advantages of aptamers together with the increased selectivity possible with a more diverse library from the additional side chains will broaden the applications and addressable targets of our existing technology. Evaluation of this technology is underway, and we anticipate launching this platform this year.
Biography:
Dr Arron Tolley is the Chief Executive Officer of Aptamer Group. He co-founded the company in 2008 and has been responsible for the management and strategic development of the company, leading private fund raising and the Group’s IPO in 2021. Aptamer Group discover and develop next-generation aptamers, Optimer, using their proprietary, automated, high-throughput platform to enable new therapeutic, bioprocessing and diagnostic approaches. Arron holds a PhD in Molecular Biology and Biophysics from the University of Leeds.
