Insmed recently opened a new R&D facility in Cambridge, UK. The 17,000 square foot facility will focus on synthetic rescue for serious diseases. Overseeing the facility is Tom Heightman, Senior Vice President of Research at Insmed. We sat down with him to discuss trends in drug discovery and the power of genetics.
Why drug discovery over other areas of science?
From my teenage years, I had a strong desire to be involved in medicine, but I was far too squeamish to be a doctor!
I happened to meet a medicinal chemist at a family party. They explained what they did and how it sat at the interface between medicine and molecular science. I thought, “That’s it. That’s what I want to do.” I feel incredibly fortunate to have had that kind of epiphany so early on, and I’ve never looked back.
What are the most exciting trends that you're seeing in drug discovery?
There’s so much going on that it’s hard to know where to start. At the highest level, I think the sheer amount of data scientists have access to is transforming everything. We now have access to millions of human genome sequences to help us understand health and disease. Our ability to image processes in human cells and model disease is remarkable. Tools like AlphaFold allow us to predict protein structures with incredible accuracy, opening the door to in silico drug design.
When you bring all these developments together into the interdisciplinary toolkit we use to understand biology and translate that understanding into drug design, it really feels like we’re in a golden age of science. I’ve been in the industry for 27 years, and one of the great things about this field is that it keeps you forever young. Technology is always moving forward, and we’re constantly integrating new techniques and fresh thinking into what we do. It’s an exciting journey, and I wouldn’t change a moment of it.
And what about exciting new technology launches?
Gene sequencing is one that stands out immediately. The first human genome was sequenced just over 20 years ago at enormous expense, and now, even here in the UK with the UK Biobank, we have access to more than half a million human genomes. This is an incredibly powerful dataset. CRISPR gene editing is another key area. It’s a hugely powerful technology that is game changing.
In chemistry, we face the challenge of making the molecules we design and then testing them. Here, too, there have been incredible advances, particularly in organic synthesis using visible light photo-redox techniques. We can now create complex molecules that might have once required a 12-step synthesis and more than a month to make in a fraction of the time. In some cases, they enable us to make molecules that we simply couldn’t produce before.
It’s no good having AlphaFold and AI design the perfect molecule if you can’t then make and test it. The ability to actually synthesize those designs is an essential link in the chain – and it’s advancing very rapidly.
Is solubility still a big problem in the industry?
The onus is on drug designers to create brilliant molecules that not only engage their target in human cells, but have developable properties. We can now apply design approaches to a range of parameters, including solubility.
One cutting-edge area of science I haven’t mentioned yet is the analysis of small-molecule crystal structures and the use of AI to predict crystal lattices – and therefore solubility. This means we can design for solubility during the optimization process. This ties back to what I said earlier about it being a golden age of science. I have seen projects in the past that struggled with solubility, but formulation technology is advancing rapidly too, offering clever ways to overcome those challenges.
What is Insmed working on at the moment?
We already have a strong clinical pipeline in respiratory disease. Now, across our four research sites in the US and the UK – New Jersey, New Hampshire, San Diego, and Cambridge – we’re expanding into a range of other therapeutic areas.
In Cambridge, we have a particular focus on CNS diseases, especially neurodegenerative disorders. What’s powerful about our global research organization is that the company has brought together teams with expertise in different areas and modalities. This means we can draw on strengths across small molecules, oligonucleotides, biologics, and even gene therapy to select the most appropriate modality – or combination of modalities – for each specific case.
Our approach is to focus on target discovery. We start by unravelling the biology of a disease that has been poorly studied. As we build a better understanding of that biology and identify how we might manipulate it for therapeutic benefit, we consider the entire cellular chain: from the gene in the DNA, through expression into RNA, translation of that RNA into protein, and the protein’s life cycle in the cell.
Having access to multiple modalities means we can intervene at any point along that chain. It allows us to determine which approach produces the strongest effect on the biology, and which is best tolerated.
What influenced the recent decision to invest in Cambridge?
With three sites already in the US, looking beyond the country was a great way to access diverse thinking and alternative approaches. Cambridge is a truly powerful biomedical ecosystem. It brings together a world-leading ancient university, multiple academic institutes, a major hospital that continues to expand, and a thriving biotech and pharma hub. Together, these elements create an intellectual powerhouse that fosters diverse perspectives.
Specifically, Insmed was interested in synthetic rescue with a genetics-focused target discovery platform. That platform was the brainchild of Cambridge professor Sir Steve Jackson, who founded Adrestia, which Insmed acquired in 2023. Adrestia had developed the platform, begun assembling a world-class team of drug hunters, and the science underway there was highly complementary to Insmed’s own research.
There was also an exceptional cultural fit. The Cambridge team shares the same core values as the wider Insmed organisation: a commitment to patients, a spirit of collaboration, and a “How can I help?” mindset.
What aspects of the new facility are you most excited by?
We’ve brought together, under one roof, expertise in three key areas: cutting-edge cell biology and imaging, chemistry and drug design, and computational biology and data science. These are all stitched together with powerful integrative informatics. That level of integration is something I’m genuinely thrilled about.
Each of these core areas is also underpinned by some remarkable new technology and equipment. I have to mention our investment in the cell imaging and microscopy suite! There’s a real beauty to certain aspects of medical science and biology, and cell imaging is one of them. To be able to take a neuron from a patient-derived cell in the brain, image it, and watch – in almost real time – what’s going right and what’s going wrong, is extraordinary. To be able to then apply a drug molecule we hope will improve those processes, and actually see the changes happening inside the cell on a screen, is hugely compelling.
What can you tell us about Insmed’s current focus areas and plans for the future?
We have a focus on serious and rare diseases with unmet needs. We have a strong respiratory franchise and clinical pipeline. We’re also expanding our focus into CNS, neurodegeneration, and neuromuscular diseases.
The unmet need is enormous. There are more than 7,000 known rare diseases, and it’s estimated that one in 17 people will have a rare disease of some kind. More than 95 percent of those conditions currently have no treatment.
Although the numbers are sobering, there’s a hope. Advances in human genetics are revealing the underlying causes of many of these diseases. We’re seeing more initiatives to carry out genetic testing, which helps us understand what’s gone wrong in each case. This, in turn, allows the scientific community to apply new techniques and approaches to tackle them.
What other big industry trends are you keeping an eye on?
I may sound like a broken record, but the impact of human genetics and genomics on understanding health and disease is only going to get bigger. This isn’t just about drug design; it’s about how healthcare providers start integrating genetic data into diagnostic processes. This creates an ecosystem that’s highly favourable for companies like ours when we want to bring forward new medicines.
The other big area is the modality space. As we discussed earlier, we can intervene along the chain from DNA to RNA to proteins. Almost every year, a new modality emerges. The past decade has been the decade of targeted protein degradation, which has real potential to change how we address the protein life cycle. But new modalities will keep appearing, and we make a point of staying closely attuned to them. Sometimes, the existing repertoire simply doesn’t offer the right fit for the biological question we’re trying to answer, so having new options is hugely important.