Fibrocell Science has found out the hard way about the dangers of raising investors’ expectations. The company saw its stock climb since last week, when it promised an update on its epidermolysis bullosa gene therapy candidate FCX-007, but that seemingly benign update sent shares crashing today.
More data from a phase I/II trial of FCX-007 looked promising, so there was probably some element of selling the news. But reality could also be sinking in for Fibrocell’s backers: the group is about to start a phase III trial, but had only $14m of pro forma cash at the end of 2018, which at best will last only until the end of this year.
This might not be enough to finish the pivotal trial, now known as DEFI-RDEB. The study, which is slated to begin in the second quarter, will recruit 15-20 patients with recessive dystrophic epidermolysis bullosa (EB).
On a conference call today Fibrocell’s chief executive, John Maslowski, would not be drawn on how quickly the trial might enrol and when data might be available.
What is certain is that Fibrocell needs more money, but for now a fund raising looks out of the question: Fibrocell’s shares opened down 20% today, giving it a market cap of just $18.7m.
EB is an inherited disorder characterised by extremely fragile skin, and patients suffer from extensive wounds. Notably, the phase I/II update found that 63% of wounds treated with FCX-007 had completely closed at 12 weeks, versus none in the untreated cohort. This could bode well for the phase III trial, which has complete wound closure as its primary endpoint.
In phase I/II patients acted as their own controls, with some wounds receiving an intradermal injection of FCX-007, and some remaining untreated. The phase III study will take a similar approach.
The trials do differ in terms of dosing: in phase I/II patients received one injection of FCX-007; in phase III they will receive two injections, four weeks apart. This might lead to better wound closure in phase III, although of course this remains to be proven.
FCX-007, which Fibrocell is developing in collaboration with Intrexon, is produced by modifying a patient’s own fibroblasts. This process takes around four months, but once a bank has been created this can be used repeatedly for a given patient, meaning that a second injection would be relatively straightforward.
Gene therapy rivals
Fibrocell looks to be ahead of its bigger EB gene therapy rivals, Abeona Therapeutics and Krystal Biotech. All three initially aim to treat the dystrophic variety of the disease, which is caused by mutations in the COL7A1 gene (Gene therapies go skin deep to tackle epidermolysis bullosa, March 11, 2019).
Abeona has said it hopes to start a pivotal trial of its candidate, EB-101, in mid-2019, while Krystal is due to report phase II data with KB103 soon. Abeona has a market cap of around $350m, while Krystal's is around $380m.
Another player, Proqr, had been taking a different approach with an exon-skipping candidate, QR-313, targeting a subset of EB patients with a particular mutation. Yesterday, the company spun off QR-313 and its other EB candidates into a new entity, Wings Therapeutics, which will be financed by the non-profit group the EB Research Partnership. Proqr will hold a minority stake.
Presumably Proqr wants to focus on the rest of its pipeline, which is dominated by candidates designed to treat eye disorders, although the timing raised eyebrows: data are due any day from the phase I/II Wings trial of QR-313.
Fibrocell has also received money from the EB Research Partnership, bagging a $900,000 investment in December from the group and the Epidermolysis Bullosa Medical Research Foundation. But it will need more than this to get FCX-007 through phase III.