NASDAQ: PRQR / OUTPERFORM
($6.45, Mkt. Cap. $155M)
Nothing to be MAD about, PRQR Ph1b Multiple Ascending Dose Trial a Success
Bottom Line: PRQR announced successful completion of their safety and tolerability placebo-controlled Ph.1b multiple ascending dose (MAD) study evaluating QR-010 in homozygous F508del CFTR mutated cystic fibrosis (CF) patients.
In addition to favorable tolerability across all doses with no drug related adverse events, PRQR reported improvements in exploratory endpoints, most notably, improvements in patient symptoms according to the CFQ-R (12.5mg dose, p=0.0072) and a 10.9% (p=0.0461) improvement in percent predicted forced expiratory volume in 1 second (pp-FEV1) over placebo in a pre-defined subgroup with lower initial lung function at the 12.5mg dose. These data, in combination with previous positive proof-of-concept (PoC) results (LINK) in CF patients provides enthusiasm for development of PRQR’s novel RNA platform. We remain cautiously optimistic, as these are Ph.1b data and the drug development landscape in CF is fiercely competitive. Reiterate OP, PT increased to $12, up from $10.
No adverse events were observed in F508del CFTR gene mutated CF patients exposed to multiple ascending doses of QR-010 via inhalation.
We view these data as positive validation for PRQR’s RNA repair platform as it 1) further validates clinical safety/tolerability and 2) affords PRQR the opportunity to evaluate their RNA platform in a larger and more severe CF population. The current study evaluated four dose levels of QR-010 (6.25, 12, 25, 50mg) in mild CF patients exposed to 12 doses over a 4 week period. Exact plans for future development have not been laid out yet, but the company is notably evaluating collaborations, perhaps as a combo therapy, or as a monotherapy.
Changes in exploratory endpoints encouraging, as study had relative low power and mild CF patients.
QR-010's positive data on measures like nasal potential depolarization (NPD) and CFQ-R respiratory symptom scores are on par with Kalydeco’s (VRTX [OP]) results and suggests PRQR's agent could have clinical merit. Despite a relatively mild CF population, the sub-group of patients with 70-90% ppFEV1 were prespecified wherein QR010 showed a significant increase in ppFEV1 at 4 weeks. Functional read-outs for CFQ-R and pp-FEV1 showed a bell shaped dose response with a suboptimal dose (6.25mg), effective dose (12.5mg), and ineffective high dose (25, 50mg). Other exploratory endpoints were unaffected (i.e., body mass index and sweat chloride), as anticipated since the drug does is not delivered so broadly.
Changes to model, investment thesis, and valuation.
In light of today’s positive results regarding safety and preliminary efficacy, we have updated our model to reflect a 30% probability of success, up from 20%. In addition, we have adjusted peak penetration down to 33% from 45% given the increasingly competitive CF landscape.