GSK plc American Depositary Shares (Each representing two Ordinary Shares) Bernstein Insights: Healthcare Leaders and Disruptors – 3rd Annual Healthcare Forum

Yeah. Great. First of all, Courtney, thanks for having me. The role, I guess has two aspects. One is the end-to-end accountability for R&D for respiratory, immunology, and inflammation. So that's a fully integrated unit from discovery, target choice, through to translation, clinical development, asset leadership, through to product approval. So the full life cycle of assets. As you described, it currently represents a lot of activity through to the late stage in respiratory medicine and hepatology.

But also, I think some very promising programs in what we're increasingly thinking of just as comorbid disease that's the consequence of chronic inflammatory pathology. The other hat is the Translational Development Sciences, which is a relatively recent organization, which integrated three key components of the organization cross-category, so oncology, specialty, and vaccines ID. That was Asia R&D for reasons that probably are obvious, and the opportunity that we see represented by China, in particular, perhaps the unrealized opportunity to partner with China for translational medicine.

The second is genetics, genomics, and single-cell technologies, which we see as one of the most high-confidence areas to be able to build an understanding of target trait pairings.

The third being real-world evidence or development sciences, which integrates epidemiology and causal inference from large-scale routine healthcare data.

Yeah. So you're right to point out that GSK's got what I would really say is a unique heritage in respiratory medicine. But I think to pioneer is to be forward-looking and to continue to think about what's coming next rather than reflecting backwards. So, whilst that heritage and in health therapeutics and I guess the first wave of targeted biologics with the IL-5 franchise continues to be really important to the portfolio. NUCALA are incredibly important products. I think what we're seeing is the maturity of how we think about asthma is not necessarily true of a disease like COPD. So in asthma, we know that there are very effective therapeutics, and part of the reason is that we understand that the majority of that disease process is driven by Th2-driven inflammation. So a number of now monoclonal antibodies have been developed that are effective.

One of the key challenges is biopenetration and persistence. So there's an unusual level of poor persistence to biologics in asthma.

And in fact, the majority of patients come off short-acting biologics within a year, despite the fact that they are safe, well-tolerated, and the efficacy is unequivocal. That's led us, of course, to think about what could enable penetration and persistence.

The two things that we've identified is, one, a deliberate approach to the comorbid profile and the indication mix for any mechanism, and we're seeing that different biologics have a slightly different flavor of where they're effective across different disease processes, a number of which overlap in patients with asthma. The second is how do you reduce the burden of the management and administration? Obviously, that's led us to have confidence that an ultra-long-acting biologic, which almost completely relieves the patients of any burden of engaging in their management with just two injections a year, is going to be one of the key enablers. In contrast, in COPD, it's more a case of understanding the underlying drivers of risk.

It's a much more scientific mechanistic proposition that we see. The scale of the problem is vast in COPD, so it's 300 million patients affected globally, a life-threatening disease. As of today, only two approved advanced therapies with DUPIXENT and NUCALA.

Both of those are reserved for one segment of the disease. We really have invested time to understand what's driving different segments of COPD.

and then what's the rational approach to try and interrupt those disease processes with the right mechanism. That led us to diversify alongside IL-5, which remains a very important mechanism in obstructive lung disease, to acquiring an ultra long-acting TSLP- and also progressing our program for a long-acting IL-33, as well as a number of other approaches, including a PDE4 inhaled approach- and also what could end up being the first oligonucleotide in respiratory medicine.

We have a program that's currently in phase I-B, which is an siRNA.