To help us battle the ever-evolving challenges in drug discovery, it’s vital to learn what we can from the greatest success stories. One of the biggest blockbuster drugs in immunotherapy is Keytruda® (pembrolizumab), an antibody-based therapy now marketed by MSD, which was humanised in collaboration with the medical research charity LifeArc. We talked to LifeArc’s CEO, Melanie Lee, about what she thinks underpins the success of future drug discovery programmes. Drawing on her vast experience in diverse roles spanning the biopharmaceutical industry, medical charities, and academia, Melanie shares her insights with us below. What’s more, we’ll learn more from LifeArc at our upcoming Drug Discovery 2019 conference.

Register for Drug Discovery 2019: ‘Looking Back to the Future’, 5-6 November 2019

Q: What motivated you to become the CEO of LifeArc?

A: I could see that the job would give me the opportunity to really make a difference in translational science. As a charitable organisation, LifeArc can take a more long-term approach in this field than many commercial companies, and that ethos was very attractive to me. Ultimately, LifeArc’s aim is to turn academic research insights into innovative medicines and new diagnostics, and it’s this potential to benefit patients that really motivates me.

Supporting translational research has always been vital, but given the challenge of Brexit, it’s more important than ever for us to bolster opportunities for academics in the UK to move their ideas forward. Of course, the scope for LifeArc to advance research has really been expanded by the recent success of Keytruda.

Q: Could you give us a little background on Keytruda® and what its success means for LifeArc?

A: Keytruda® is a monoclonal antibody targeting the immune checkpoint PD-1. Normally, the PD-1 pathway functions to prevent autoimmunity, but cancer cells can take advantage of this to prevent T cell activation. So, by blocking PD-1, we can help the patient’s own T cells identify and kill cancer cells. Scientists at LifeArc humanised this antibody-based therapy, which is now marketed by MSD. As a result, we secured rights to a small portion of royalties from sales of Keytruda®.

Keytruda® is now used for many indications and in fact, in 2017 it became the first cancer treatment to be approved based on a specific genetic biomarker rather than tumour type or location, which was a real step forward in immuno-oncology.

Given the success of Keytruda®, we recommended we monetise a significant portion of our royalty interest, to give us the opportunity to sustain the charity for the long term. By doing so, we can support life sciences research and accelerate the development of new therapies, diagnostics and devices for those people in greatest need. This is our goal. To make sure we achieve it, we’ve worked hard to put the right systems and process in place to ensure the investments we make are responsible and will make a real, valuable contribution.

Q: Are there any lessons that can be carried forward from Keytruda® to other drug discovery programmes?

A: For Keytruda®, the key was our application of humanisation technology. Keytruda® is based on a mouse antibody, which would naturally be recognised as foreign and removed by the immune system before it could do its job. Therefore, it was critical to alter the antibody protein sequence to stop it being targeted by the human immune response.

Fortunately, we had access to excellent humanisation technology thanks to working with the MRC through MRC Technology, which became LifeArc. That technology had really been perfected to the point where we could take any antibody from another species and make it suitable for use in patients. Therefore, I’d say the success of this programme really depended on the application of an effective technology to a specific type of modality.

From working on Keytruda®, the true importance of having industrial skills in our team also became evident. This is a learning I can see benefitting all drug discovery and development projects. Having the right industrial expertise gives the ability to see the complete pathway from early discovery to development and then onto the clinic. In doing so, you will better understand what information you need when. Although this might sound simple, identifying what data you need is one of the biggest hurdles many developers face.

Q: What challenges need to be overcome in the drug discovery industry so that more drugs can be developed to patients’ lives?

A: That’s a very interesting question, particularly as the requirements for drug discovery are changing. Essentially, we used to treat broad categories of patients under a single banner such as ‘diabetes’, ‘cardiovascular disease’ or ‘hypertension’ – really massive classes of disease. And indeed, many of the very successful drugs of the past have been effective across these large categories.

Now, thanks to the genomics revolution, we’re learning that the patients we’ve classified under these very broad umbrellas actually fall into many different sub-categories. As we’ve looked into the genetics of this, we’ve discovered that many of the new therapeutic pathways are only important in a subset of people. This means that with novel treatment modalities we often need to stratify patients to treat them effectively.

In fact, Keytruda® is one of these drugs which requires screening for the relevant biomarker to determine the patient population in which the treatment will be most effective. As such, to me, the key challenge in drug discovery is how do we update our processes in R&D such that we are economically able to put these life-changing medicines on the market for a smaller section of the population?

Q: What long-term vision do you have for LifeArc?

A: The success of Keytruda® has had a huge impact on LifeArc, because it’s has significantly transformed our ability to support medical translation, through new approaches and collaborations and bolstering access to our expertise and resources.

But it’s important to note that we’ve had a number of other fruitful partnerships over the years. We are reviewing our strategy and we will not limit our ambitions. We will be considering a range of options that can provide sustainability and potential impact for patients, which is very exciting.

Q: Do you have any particular areas of focus for the future?

We’re starting to shift our focus to cover what we call the ‘four Ds’: Drugs, Devices, Digital and Diagnostics. In this way, we can bring together a more complete package of information to meet the future requirements of medicine.

In terms of therapeutic areas, we’re very interested in immunology and immuno-oncology, neurology and anti-infectives and we remain active in rare disease. Of course, these are all very popular fields, so we’ll have to decide what to do in-house and where we should work with others to ensure we get new treatments to patients. It’s important to us to get this balance right, as we pride ourselves on being a very collaborative organisation.

Q: Do you have any advice for early career researchers? 

A: The advice I always give to young people is to do what is most motivating for you. So, if you enjoy academia, stay in it and put your heart and soul into that. However, if you want to turn your hand to the application of science, then industrial careers are very interesting. Or, if you don’t see yourself at the bench long-term, you could also focus on developing a broader range of skills, such as leadership training, teamwork and presentation skills. By doing so, you can unlock a variety of career opportunities.

Q: Do you think attending multidisciplinary events such as the ELRIG Drug Discovery 2019 conference can benefit drug discovery scientists?

A: I think all young scientists should be given the opportunity to learn about the different disciplines that get pulled together in the context of drug discovery. Events such as the ELRIG Drug Discovery conference give people the opportunity to learn about range of scientific fields, keep up with the latest advances and gain value from networking. I’m fully in support of that.

ELRIG’s Drug Discovery 2019 conference is free to attend – register now to secure your place.