Today, therapeutic antibodies are reaching the clinic in unprecedented numbers. However the path from laboratory to the clinic is far from smooth. Antibodies face a range of obstacles during development, from insufficient efficacy, to manufacturing difficulties to immunogenicity – any of which can spell the costly end of an antibody development program.

Since 2012, Fusion Antibodies has delivered over 160 successful antibody humanization projects to customers worldwide. For many of these projects, we and our customers observed that our humanized antibodies retained and even improved antigen affinity, compared to the parent antibody.

Antibody candidates originate from many sources, using ever-improving discovery technologies. However, achieving a balanced antibody profile can be challenging. Our customers need to identify and eliminate those initially promising antibodies that bind tightly, but later turn out to have problems with manufacturing, stability or immunogenicity. They need to be sure they have the right antibody before establishing a stable cell line, and be confident that their lead candidate can get through CMC testing and make it to clinic.

RAMP™ – a 2 step affinity maturation platform

To help customers face these challenges, we have poured our expertise into creating RAMP™ – our rational affinity maturation platform designed to accelerate and optimize selection of your lead antibody candidate.

RAMP™ combines innovative library design with stringent in silico screening of variants. This sieves out the strongest candidates into a micro-library that can be expressed in mammalian cells for further characterization.

Rational library design

Taking the parent antibody, we create a massive library of around 10^20 variants. Our proprietary rational design approach takes a leaf from nature, inspired by how B cells use somatic hypermutation to generate antibody diversity.

RAMP™ introduces mutations in both the CDR and framework regions to create diversity, allowing only amino acids that can naturally occur at each position in the human antibody sequence. This “natural” approach reduces the likelihood of hydrophobic patches of amino acids and the downstream risks of aggregation and immunogenicity.

At the same time, strict sequence checks are applied to screen out primary sequence liabilities such as deamidation sites, cleavage sites and free cysteines. These checks and balances help create a library of variants that are “pre-screened” for manufacturing and clinical use.

In silico refinement

The library is then refined using in silico software that rapidly models variant-antigen binding and predicts affinity and stability. Over the 3-week in silico phase, the initial library is funneled down into a micro-library of the 100 strongest variants. At this stage we either express the micro-library as full length IgGs in CHO mammalian cells or hand the micro-library back to the client for further in-house testing.

RAMP™ up your chances of getting to the clinic

RAMP™ for affinity maturation is a fast, reliable method for improving affinity and selecting your lead antibody candidate. In a promising performance test, RAMP™ improved the affinity of the best-selling breast cancer drug trastuzumab in silico and we’re currently validating the best variants experimentally.

RAMP™ can also be applied to “rescue” molecules, with promising functional activity but poor developability profiles, where finessing of the sequence is required. Our novel library design approach can also open up new sequence space to potentially build on your patent family and increase the value of your program.

Want to select the best possible antibody for the clinic?

Design, development and clinical testing of therapeutic antibodies is a race against the clock, and against competitors. Companies are increasingly turning to in silico approaches to turbo boost the process. At Fusion Antibodies, we were early adopters of in silico techniques. We’ve seen first hand how embracing this technology accelerates antibody design and development, which reduces costs.

AI and machine learning

Despite the buzz, the holy grail of true artificial intelligence (AI) – machines that can “think” and reason like humans do – remains elusive. In the meantime, deep machine learning is the established star of the in silico show. Machines are “trained” by feeding them large sets of experimental data and teaching them (via algorithms) how to perform a task. With each repetition of the task, the machine adds the experience to their knowledge bank, improves performance and comes up with results that humans didn’t necessarily expect. So how do in silico techniques, including machine learning, fit in to antibody development?

In silico antibody development

Antibody engineers have a plethora of options in their in silico toolkit for optimising antibodies. These bioinformatics tools include homology modelling to predict antibody structure, molecular docking to identify antibody-antigen interactions and algorithms to calculate energy changes in mutated versions of the antibody. Each of these processes can benefit from machine learning to speed up predictions and improve decision making. Stitching these processes together into an automating streamlined workflow saves even more valuable time.

Focus on libraries and screening

In silico techniques in antibody development have been described as third generation, following second generation in vitro and first generation in vivo methods1. Affinity maturation is a good example of how throughput has soared with in silico methodology. In silico libraries of around 10^25 variants have smashed through the experimental library size ceilings of mammalian display (10^10 variants) and phage display (10^12 variants).

Similarly, the time needed to screen through these libraries for the best sequence has decreased drastically from 3 months with mammalian cells or phage display, down to just 3-4 weeks in silico.

An added bonus is that in silico libraries and screening avoid the potential expression and biophysical issues related with phage display systems, while leaving the door open to promising variants that may not have expressed well in phage.

Challenges remain

The in silico approaches currently used in antibody design remain overwhelmingly knowledge-based. However, machine learning is only as good as the data you train it with. A current challenge is the scarcity of robust experimental open-access datasets, and a lack of widely accepted standards for validating data quality.

Another challenge is the changing skillsets needed by today’s biologists. Data scientists, programmers and technologists are now staple members of biology teams, and everyone needs to learn to speak a common language. Training university students in such interdisciplinary working will ensure the teams of tomorrow are well placed to harness the power of machine learning and in silico techniques.

Future applications

An exciting application of in silico technologies would be to open avenues of investigation previously hampered by experimental roadblocks. For example, G-protein coupled receptors (GPCRs) are a rational antibody target for many disease processes, but are notoriously difficult proteins to isolate out of the cell membrane where they are firmly embedded. In silico modelling could sidestep the difficulty posed by purification and antibody development. This means that proteins that were previously very difficult to raise antibodies against can now be targeted.

RAMP™Rational Affinity Maturation Platform

At Fusion Antibodies, we are firm believers in integrating bioinformatics and in silico techniques to accelerate our workflows and therefore your journey to the clinic. That’s why we developed RAMP™ – our rational affinity maturation platform. It takes RAMP™ just 3 weeks to create a massive library of around 10^25 variants of the parent antibody and to select out the best candidates using rapid in silico screening. The result is a micro-library of the 100 best candidates, selected for binding potential and stability.

Harness the power of our in silico RAMP™ technology to optimise your lead antibody faster.


Fusion Antibodies, a leading antibody discovery and development company, and E2DG, a drug development group, today announced a strategic collaboration to provide asset-centric drug discovery companies access to an end-to-end service in oncology drug discovery. The two companies will work together to deliver a seamless service offering for clients from discovery to manufacturing and PoC preclinical and phase I & II design and execution.

Under the agreement asset-centric oncology drug discovery companies will benefit from Fusion Antibodies’ expertise in the discovery and early development of novel and highly developable therapeutic antibodies and from the experience of E2DG in preclinical efficacy and phase I/II oncology clinical trials.

Christophe Mazars, CEO of E2DG, stated, “We have worked with Fusion Antibodies for more than eight years and we continue to deepen our relationship to provide the expertise, tools and services in oncology drug development to our clients. Collaborating with Fusion Antibodies provides our clients with access to platforms and tools to create exceptional antibodies against challenging targets, with the knowledge these antibodies will have been engineered, selected and optimised for performance and manufacturability.”

Paul Kerr, CEO of Fusion Antibodies, adds “E2DG’s track record of facilitating the delivery of ground-breaking oncology drugs to market is testament to their expertise in this space. We are delighted to be able to offer this next step for our clients who are committed to the provision of treatments that improve the lives of patients throughout the world.”

The strengths and synergies of these two companies will help drug discovery companies around the world to expedite the development of their therapeutic assets in a streamlined and efficient manner ensuring maximum value is added, in a capital efficient manner.  

About Fusion Antibodies

Fusion Antibodies delivers new technology and innovation throughout early-stage antibody discovery. As a drug discovery and research partner, our scientists increase the pace to the clinic by guiding clients to develop the best antibodies possible. From ideation through the early stages of drug discovery, we enable biotechnology and pharmaceutical organisations towards their end-goal – the provision of treatments that improve the lives of patients throughout the world.

About Early Drug Development Group (E2DG)

E2DG supports biotech start-ups, investment fund groups and academic organizations in oncology to foster their R&D programs in a time- and cost-effective manner. With strong preclinical and pharmacological capabilities and experienced medical oncologist input, we offer professional assistance on preclinical drug development approaches and Phase I Clinical Trials to maximize the chance of your project success in oncology.

E2DG is focused on preclinical and clinical research specialized in the development of innovative first-in-class therapeutic agents in oncology. We have performed several drug development programs with more than 20 companies –ranging from small biotech to the largest pharma companies– for the evaluation of over 20 different leads (at least 8 first-in-man) in oncology, covering both small molecules and monoclonal antibodies.

Fusion Antibodies are working with a number of clients on pilot projects for their latest technology – RAMP™ – Rational Affinity Maturation Platform.

RAMP™ was launched at the end of 2018 and clients have been coming on board to benefit from the innovative in silico approach to Affinity Maturation, particularly for time sensitive projects.

The range of clients includes one of the world’s top ten pharmaceutical companies, multiple biotech companies in Asia and Europe, and a UK based academic research institution.

Dr. Paul Kerr, CEO, Fusion Antibodies, said, “Having presented the technology platform at Antibody Engineering and Therapeutics, San Diego at the end of 2018, we are delighted that a number of projects have now commenced with us. We welcome the opportunity to help these clients address difficult roadblocks in their antibody development projects.”

Chief Technology Officer, Dr. Richard Buick commented, “We have already tested the power of our platform on one of the world’s bestselling drugs, Trastuzumab, and significantly improved its affinity. We are excited for the opportunity to demonstrate the power that lies in our approach.”

RAMP™, a Rational Affinity Maturation Platform, is designed to improve the ability of an antibody to bind without damaging the overall profile, has delivered results beyond affinity maturation. Factors that can be improved using the platform include stability, aggregation, yield, specificity and cross-reactivity, which are key considerations for clients who want to get their antibody to the clinic and market approval.

Paul Kerr, CEO, Fusion Antibodies
by Paul Kerr, CEO, Fusion Antibodies

Why investing in pre-clinical activity is crucial to maximise the chance of success in clinical trials

Most investigators and all investors in pharmaceutical development dream of creating a blockbuster—a drug so effective, useful and high-profile that it generates sales of at least $1 billion per year. However, even getting a new drug to market is a gruelling long-distance race, with many hurdles to surmount. At each of the three phases of clinical trials, the scale and cost of development increases—and a failure during the later phases can write off hundreds of millions of dollars in investment.

With the advent of drugs based on monoclonal antibodies, the game is changing. Advances in this field have opened the door to new therapeutic possibilities, such as the safe engagement of the immune system in cancer treatment; research in this area led to James P Allison and Tasuku Honjo winning the Nobel Prize in 2018.

Now well beyond the early days of ‘vanilla IgG’ antibody approvals, the development of antibody-based drugs has become highly sophisticated, and competition is fierce. As ever-larger numbers of pharmaceuticals companies invest in antibody development, the number of approvals is increasing year-on-year—in fact, just as I’m writing this, the Antibody Society has announced that four new drugs have entered regulatory review.

Antibody-based drugs tend to be much more successful in the clinic than traditional small-molecule drugs, due to higher specificity and fewer side effects. However, these more sophisticated technologies also create greater manufacturing challenges, and drug developers must prove a clear differentiation of their molecule to achieve success and approval in the long run. Many big challenges remain, which is why it’s important to work with the experts in antibody development.

De-risking projects to boost success rates

At Fusion Antibodies, we have worked in antibody development for almost 20 years. We have completed more than 150 antibody humanization campaigns, and of our first 15 projects, more than half have now entered clinical trials. This impressive success rate, in particular compared to our competitors in the antibody engineering field, indicates that Fusion’s unique approaches and expertise can make a significant difference.

Our clients are successful because they see the value of de-risking their projects at the earliest possible stage. When they have a promising candidate, we help them evaluate its biophysical characteristics, detect and address problems quickly, and ultimately increase their chance of success in the clinic.

Combining hard science with commercial sense

When developing a therapeutic antibody, it’s important to think about the big picture and consider commercial success. By considering manufacturability at the early stage of drug development you’ll be more likely to produce an antibody that not only does what you want it to do, but that will also be commercially viable.

For example, your complex bi- or tri-specific antibody may be wonderful at binding to its target, but if it’s impossible to manufacture cost-effectively or at scale, that’s a red flag for investors.

We can help you make the right decisions to find an optimal balance between specificity and yield, improving efficiencies in the drug development journey, and potentially saving millions of dollars in manufacturing costs during the clinical trials stage and beyond.

Avoiding expensive failures with preclinical preparation

As a quick example: I recently spoke to a venture capital investor who specialises in re-engineering antibodies. In the past, he had several times made the mistake of entrusting preclinical development activities to low-cost outsourcing companies. As a result, he had ended up with products whose expressibility, stability and yield were well below par.

Since first engaging with Fusion, he has recognised the value of working with a team that can help him make the right decisions throughout the discovery, development and manufacturing process.

Building a partnership for end-to-end development

At Fusion Antibodies, we pride ourselves on being a true business partner to our clients. We’re an antibody discovery and development partner dedicated to delivering the best results for our clients. Frequently, we’ve helped clients improve the performance of their antibodies so much that they have gained new intellectual property, adding five or more years to the life of their patents.

Above all, our services give our clients the best possible shot at preparing their antibodies for successful clinical trials, eliminating avoidable risks on the road to FDA approval, and making their IP more attractive to big pharma partnering.

If you’d like to learn more about how Fusion Antibodies can help you increase your chances of success at clinical trial, reach out to us today.

CIR Approved

Fusion Antibodies has been granted approval to participate in the Crédit Impôt Recherche (CIR) scheme, meaning our French clients can enjoy a significant tax break by partnering with us for pre-clinical antibody research.

Based on Article 244 quarter B of the French Fiscal code, French Partners can benefit from a tax credit of 30% of the cost for R&D services. The tax credit covers costs including salaries, social security contributions, amortization and depreciation allowances, operating costs, subcontracting, patents and monitoring. For further details on the CIR tax credit, click here.

Julie Gormley, Sales Director for Fusion Antibodies, commented: “We are delighted to secure CIR approval to be able to offer our French customers access to this substantial tax break. Successful antibody development depends on getting things right from the outset and at Fusion Antibodies we have vast experience in the pre-clinical stages which will ultimately contribute towards a more successful outcome at clinical trial”.

To learn more about partnering with Fusion Antibodies for pre-clinical research, click below.