Celyad’s Phase III CHART-1 study in cardiac regeneration missed its primary endpoint, but a clinically defined subgroup with 60% of patients saw a positive outcome, p=0.015. Celyad management believes data are robust enough to discuss submitting a conditional marketing authorization to the EMA for European approval. Data on the CHART-1 composite endpoint will be presented on 28 August 2016. The US Chart-2 trial with a new endpoint and EDV focus will run if partnered. On the basis of limited data, the indicative value has been revised from $96.8 to $35.2 per share.
The Phase III C-Cure CHART-1 cardiac regeneration trial did not show statistical significance on its primary endpoint. However, 60% of patients did respond well in a retrospectively defined subgroup characterized by a “mid-range” end diastolic volume (EDV): the volume of blood in the left ventricle just before the heart contracts. All CHART-1 patients had a 35% or less ejection fraction (this is normally around 66%); the EDV is likely to be high due to heart distention. The primary endpoint was a composite (Bartunek et al, 2015), but no details on the responses to the six different factors used will be released until 28 August.
Celyad management hopes to file a marketing authorization with the EMA. The EMA is often pragmatic if there is an unmet medical need (as in this case) and a safe therapy (proven) with adequate supportive data (claimed). Celyad aims to do an EU marketing deal based on EMA approval. The part-US 240-patient Phase III CHART-2 study, once adjusted to only recruit responsive EDV patients, will go ahead, using a new, although only once partnered. Edison has revised the potential US launch date to 2022 from H2 2020. Resources and cash will now be focused on NKR-T
The probability for CHART-2 has been adjusted to 35%, previously 40%. No sales are forecast in the EU until the CHART-2 readout in 2021, then the European probability matches the US at 35%. Market sizes have been adjusted to include only the 60% of patients with appropriate EDV values. Possible EU upfront fees and milestones payments have been reduced. This takes the indicative value to $35 per share. We forecast cash to be about $17-22m by late 2017, depending on NKR-T investment and progress. This suggests further funding depending on deal payments received. Our 2016-17 financial forecasts do not assume any C-Cure deals. CAR cancer will be reassessed when Phase I/II completes.