Discovery & Development: Collaboration

IPT talks to Dr Fiona McLaughlin and Neil Bell of Avacta Therapeutics about the need for cohesion when researching and developing a new drug between life science companies, academia, and medical practitioners

IPT: When it comes to building a successful environment for R&D, what is important?

Fiona McLaughlin: In terms of R&D, the ability to collaborate and accelerate innovation is key. Being in a life science cluster should be one of the main factors. Being in a cluster makes a huge difference – it allows you to naturally meet people and have access to ideas that you might not otherwise encounter. It’s that serendipity which is the lifeblood of some of the most ground-breaking innovation that we see. Building that sense of community is integral.

Another aspect which is really important is inspiring people so that they feel like coming to work is an exciting prospect.

Neil Bell: On a practical level, laboratory experiments can involve long hours, and researchers may have to come back into the lab at unsociable hours, so it’s important to have working and collaborative spaces that are very accessible but highly secure. Finding state-of-the-art facilities which can offer both of those things – for labs and for offices – is key when considering collaboration between different teams.

Such spaces can be fantastic enablers of collaboration, facilitating communication across organisations and offering access to the best talent. Collaborative working spaces are about empowering the entire team, and site and support staff also play a key role in creating the right environment. Quite simply, we want our team to enjoy coming to work. They can then focus on their work and deliverables, which is about providing transformative solutions and improving outcomes for all patients.

As Fiona said, engaging with life science clusters is incredibly important. I’m a big believer in the strength and equality of

UK science, and in the ability of the UK to be world-leading across the major innovation sectors, which is absolutely vital for our growth and competitiveness. Harnessing UK talent and capabilities to deliver better solutions to the global market benefits everyone, and it’s a model that we can drive very effectively for novel drug development.

How can having a ‘bench to bedside’ approach improve the patient experience?

Fiona: Having a governance structure that allows you to think about the scientific rationale, the commercial rationale, the unmet needs, the competition, and the potential commercial validation from the very beginning can be incredibly beneficial. It creates a really clear strategy, without which drug development can be highly iterative and extremely expensive.

The ‘bench to bedside’ concept starts right from the initial trial phase, for example taking blood from the patients, then analysing it back in the lab to make it as data-rich as possible. This lets us explore optimal answers surrounding efficiency, safety, and dosage, with the patient always at the heart of the process.

Neil: It’s crucial to have a full understanding of the patient journey and their clinical unmet needs, also the physician’s unmet needs with regard to tools to treat patients, because they’re the experts in diagnosing and treating the disease in the patient.

The benefit of this integrated approach is being able to get the right treatments to market faster, but also configuring them optimally for specific patients and for individual healthcare systems. This can deliver immediate benefits to patients, returning them to health more quickly, and back to their normal working and family lives. That’s what it’s all about. There’s currently a debate across the pharma industry: should we actually have commercial people involved in early research? The answer is, absolutely, yes. You have to figure out how to move research along into the commercial environment. This gives you the facility to more closely understand the issues and challenges faced by patients, where the boundaries are, and how we can actually make medicines and therapies fit into their real-world environment.

What advancements offer the most potential for future development?

Fiona: Historically, we’ve worked with affimer-based platforms. These are really interesting platforms because the full potential hasn’t even been unlocked yet. One of the most promising areas is what we call bi-specific formats. With these we can target, for example, the T cells, and from the T cells to the tumour. Affimers differ from antibodies: different size, different distribution in the body, and different affinity binding to the target. It’s incredibly important that you understand your molecule, you understand the structures, and you know what you can mutate to improve, for example, stability.

Precision medicine is also really interesting, and several lines of research have used a type of masking technology, where you mask your drug and then at a specific point in the body, release that masking agent and obtain those targeted drug attributes. While the concept is not new, the challenge is adapting it to be selective for your particular protease. Previous efforts by researchers found that, once in the body, the delivery has been off-target, or involved unacceptably high toxicities, and that’s the core focus – delivering highly precise and effective targeting, while minimising toxicity. Using an old, but well-understood, drug as a pathfinder can be useful in this regard. You know the toxicities, and you know how it works, so it is the perfect drug to begin the process with. Your pathfinder needs to demonstrate that the concepts are right and prove that the scientific hypothesis translates into real-world usage with patients.

The Phase I stage for affimers is where you want to prove that the molecule has the expected pharmacokinetic characteristics, is stable, and is excreted as expected. The biologics are not usually as toxic as the types of small molecules we’re working on. It’s a different profile that you’re looking for, but usually with a biologic, you will be comparing it to the standard of care to look for an improvement. You don’t tend to compare biologics with small molecules, you compare them with the antibody that might target that same receptor if it exists. It’s the Phase I point at which you get really excited that the translational aspects have been met. Of course, how long that takes is dependent on many factors, including development budget. Often, you have to parallel track and go as fast as you can.

What benefits to new therapeutics development can be seen by bringing R&D into a centralised location?

Neil: By bringing R&D teams together into one location, it can afford enormous benefits for people and business. The ability to collaborate, to share information and ideas, and work as integrated teams, are all key to a successful organisation focused on delivering new, innovative therapies to complex markets. We work in a highly competitive industry and our competitors are just as focused as us and want to win. Therefore, it’s important to push ahead beyond your comfort zone to create an environment for people to succeed.

Companies have to have strong confidence and rationale that the mechanism of action – the targets – are actually where they need to go to. So, having that strong interaction with R&D brings that, and actually it works all the way through. Is the drug formulated in the right way? What specific formulation do we need to have? Where is the critical path for us to take it from research into development? What is nice to have, and what is essential to have in terms of data, and what kind of data do we need to take this through? So, the data journey is really important because that helps us configure the eventual NDA.

We always begin with the end in mind, and then work backwards. Collaboration is important because there are always good ideas coming from research people as well as development people. The goal is to dispense with functions entirely, if necessary. The future could, one day, involve a single development team, so even the terms ‘research’ and ‘development’ eventually might disappear as the industry moves forward.

Centralising your core team also involves thinking about the opportunity as a whole. Obviously, researchers need time to do their experiments, but they also need to be tuned into business parameters and drivers, understanding the urgency, and that time to market is crucial. As an industry, we need to explore ways of reducing time wastage and expediting the commercial journey. It’s a question of: how do we break down these barriers which are stifling progress? How can we deliver drugs to patients faster? Identifying and overcoming bureaucracy and other factors which are holding you back is one of the keys to accelerating development.

So that’s what we’re trying to do with R&D by bringing our teams together into a single location, where we can focus on the patient in need, and work together to develop the solution. Because every problem can be solved with enough resolve, as we’ve seen with the global effort to fast-track development of the COVID-19 vaccines. Ultimately, it comes down to a healthy appetite for risk.

People can be very averse to taking risks within a company, often with an eye to their career, rather than the greater mission, which you can understand. But I think we have got to give people a safe space to fail as well. It’s not a problem to fail – at least you tried.

Another big area where we’ve introduced more cohesion is process decision-making. We want to make decision-making crisper and faster. Empowerment is built on the ability to trust in your teams’ capabilities, so ensuring people are skill-matched, well-managed, and supported is absolutely vital to giving them real empowerment and working within agreed boundaries.

How important do you think collaboration is between private organisations such as yourselves, and academic bodies?

Fiona: Collaboration with academic institutions is critical. It provides access to the very latest knowledge from across the relevant disciplines, from experts who are totally focused on this field. We’ve always worked very closely with institutions, and one of the most effective ways we’ve found of engaging with academia is to fund a student for a year-long piece of research, for example. This not only gives you access to world-renowned oncologists, and all the associated research and clinical benefits, but also the public profile and kudos of partnering with world-leading institutions, working together to find solutions to some of our biggest health challenges. It’s a win-win for us and our academic partners.

Neil: Collaboration will always be important. We have to help people collaborate well and encourage them to have open conversations so that ideas can emerge, but also support them in innovative thinking about all the ways in which we can work effectively to deliver a result you can’t achieve on your own. Creating dialogue and partnerships between academia and the commercial sector is vital. In my mind, no industry is off-limits. To really innovate, we need to believe that we can go anywhere, and we can do anything, but it all starts with the ability to freely have those conversations. It’s always been my belief that you’ve got to have an entrepreneurial mindset to succeed in this business, and that a part of that includes you being process-driven, because we work in a highly regulated area of industry. Compliance requirements must be met. But that doesn’t mean sidelining creativity – encouraging people from across the organisation to contribute their ideas and perspectives drives progress. That’s where R&D is headed – encouraging everyone to contribute. Encouraging people to look at their own areas and think of innovative ways of moving faster.