Mereo BioPharma Group plc American Depositary Shares 12th Annual Cantor Fitzgerald Global Healthcare Conference

Thank you, Kristen. Thank you.

Thanks for hosting us today.

Sure. Mereo is a rare disease company. We have two late-stage programs and one program that is being readied for phase II. Our first program, setrusumab for osteogenesis imperfecta, with our partner, Ultragenyx, we recently reported the phase III data, and we have ongoing regulatory interactions. Our second program, alvelestat for alpha-1 antitrypsin deficiency, which is being phase III readied. We are, again, about to have some more regulatory interactions with the FDA, and that is partnered, a recent partnership that we announced with Sentynl. Then finally, we have vantictumab for another bone disease, rare bone disease, osteopetrosis, and that is being readied for phase II with our partner, āshibio. So we own European rights to all three of these programs. They are being funded through partnerships.

We have milestones of potentially up to $1 billion across the portfolio and very significant potential royalty income stream as well. Finally, we have a runway into late 2027.

We are very excited about our partnership with Sentynl. alvelestat, just to remind everybody, alvelestat demonstrated both biomarker and clinical efficacy in a number of neutrophilic-driven diseases. So actually bronchiectasis, cystic fibrosis, bronchitic COPD, and of course, alpha-1 antitrypsin deficiency. We have clinical efficacy. In ASTRAEUS, which was the phase II study in alpha-1 antitrypsin deficiency, we showed a 90% inhibition of neutrophil elastase activity, and that was a constant inhibition of neutrophil elastase. We also showed some efficacy on biomarkers, desmosine and Aα-val360. When we combine actually ASTRAEUS with the other phase II which was run for alpha-1 antitrypsin deficiency, ATALANTa, which included patients on augmentation, we also saw a reduction in exacerbations.

In terms of the endpoints that are important to physicians, we have discussed this at length with Sentynl, and FEV1 is an obvious one, pulmonary diseases, but this is a disease of the small airways, and FEV1 could take up to 5 years to demonstrate an effect, and it would be a large study. The other obvious one is lung density by CT, and it is one that really resonates with the physicians. It is something that they measure regularly. The challenge with CT is the demonstration of the CT effect absolutely substantively correlating with clinical outcomes, that there is insufficient evidence at the moment of that correlation. Then finally, we have exacerbations. We know that the more exacerbations these patients have, the further deterioration in their lung function they get.

There was one study, the AlphaNet study, and that showed that almost 70% of alpha-1 antitrypsin deficiency patients experience an exacerbation every year. So that is another potential endpoint.

Yeah. This is the key point. We had previously agreed with the FDA, SGRQ, so the PRO. It is a standard PRO used in COPD studies, typically as a secondary endpoint. For the EMA, we had lung density by CT, and they had told us that a p-value of 0.1 may be acceptable to run a short enough study. We had these two endpoints, and the challenge that we have had, these are independent primary endpoints. The challenge that we have had with potential partnering feedback is that, what happens if the results from the two different endpoints are discordant? What about if they are different? What happens then? That has been a real challenge.

Because with SGRQ, although it is a standard PRO that is used, as I mentioned in COPD studies, it has not been used as a primary endpoint before, and we were planning to validate this in the phase III study. That is why we are looking, based on all the feedback now, we are going along to the FDA with Sentynl at the table with us, which I think is a very positive move.