External Initiatives

Several of our team members attended the recent “Endpoint Considerations to Facilitate Drug Development for Niemann-Pick Type C” public workshop held by Duke’s Margolis Center for Health Policy. We were heartened to see so many members of the scientific and patient community with whom we’ve spoken participating in the various panels throughout the two-day event.

The meeting provided us with several key takeaways:

• The NPC-CSS has significant value (albeit with recognition of opportunities to improve in the future) because it helps measure a broad set of areas that are important to patients, families, and clinicians.

• The importance of recognizing that heterogeneity of disease progression means individual patients may vary a great deal in how they show benefit in some domains and not others, making intra-patient assessments and changes in individual disease trajectory important considerations for benefit.

• Biomarker analyses are an important way we can help further understanding of treatment response and disease progression.

• It’s important to take steps to improve the robustness of the natural history datasets inform future regulatory or clinical analyses.

We were pleased to hear that the discussion around biomarkers align with many of the areas we are investigating and plan to investigate further. We want to highlight the comments from Dr. Steve Romano, Mallinckrodt’s Chief Scientific Officer, during the closing panel entitled “Forward Looking” which included a robust cross-stakeholder discussion between patient advocates, leaders from the U.S. Food and Drug Administration (FDA), the National Institutes of Health (NIH) and the European Medicines Agency (EMA). Dr. Romano emphasized the need for a “more focused exercise” to look hard at the data already collected in the VTS-270 studies to see what might have been missed, acknowledging that “maybe we didn’t see everything that there was to see.”

Update on Mandos Publications

Our poster entitled, “Clinical benefit of treatment with adrabetadex in subgroups of patients with Niemann-Pick disease type C1” represents our first findings from new analyses of adrabetadex data and was presented virtually on Wednesday, February 9th at the WORLD Symposium in San Diego. We’re happy to have had the opportunity to publicly share our results with the community. As we plan additional publications and presentations, we will continue to seek input from key opinion leaders, advocates, and regulators to best advance understanding of the risk benefit of adrabetadex in NPC.

As always, we look forward to staying in touch, moving the adrabetadex program forward, and working with many of you through the year. Thank you all.