Point’s big Splash falls short

Point Biopharma’s shareholders had been stalling the group’s takeout by Lilly as they awaited data from the pivotal Splash trial of PNT2002, likely in the hope that they might get something better than the $1.4bn offer price. Today, topline results from Splash suggested that any Point investors holding out might not have much room for negotiation.

Technically Splash is a success: it met its primary endpoint, showing a statistically significant improvement in radiographic progression-free survival with PNT2002 versus standard of care in pre-chemo metastatic castration-resistant prostate cancer. However, the overall survival data are unimpressive, having been confounded by a high degree of crossover from the control to the PNT2002 arm.

In this respect, Splash looks similar to the PSMAfore trial of Novartis’s rival PSMA-targeting radiopharmaceutical Pluvicto, results of which were presented at ESMO this year. That study also hit on rPFS, but the OS result was scuppered by crossover; today it was revealed that a similar percentage of patients in Splash crossed over from control to the active arm to the "record" 84% that did so in PSMAfore. 

Both trials tested the radiopharmaceutical after androgen receptor-directed therapy, such as Zytiga or Xtandi, versus a different type of androgen receptor-targeted therapy. 

Doubts have already been raised about the design of such trials, with hormone-switch therapy being described as a “weak control” at ESMO. 

In even worse news for Point and its partner Lantheus, rPFS looks numerically inferior for PNT2002 than it did for Pluvicto in PSMAfore, although such cross-trial comparisons should be undertaken with caution.

Cross-trial comparison of PNT2002 and Pluvicto in pre-chemo castration-resistant prostate cancer

Source: company release & ESMO.

Meanwhile, PNT2002’s adverse-event profile looks about in line Pluvicto’s. B Riley analysts deemed PNT2002 approvable, but said it was unlikely to take meaningful market share from Pluvicto.

Pluvicto is already approved in post-chemo use, but not in the pre-chemo PSMAfore indication. Notably Novartis has delayed filing in the latter setting while it awaits further OS data.

What next?

Point had recently been trading above Lilly's $12.50 per share offer price, presumably in the hope of a better deal. Today the stock opened down 11%, back to around $12.50, while Lantheus fell 18%.

The big question now is what the results mean for Lilly’s takeover of Point, agreed in October for $1.4bn. At the time, the relatively undemanding price tag raised questions about Point’s confidence in its big readout – especially when it emerged that Point had turned down a bigger offer, from an unnamed pharma company; that offer was specifically contingent on the Splash results.

Since then, Point shareholders have failed to vote in favour of the deal four times, resulting in Lilly extending the expiry of its offer, now pushed back to 22 December 2023. At the last count only 23% of Point shareholders were in favour.

But that last count predated today's Splash readout, and the toplined data pour cold water on hopes that Point might be able to spur a bidding war; they also raise questions about whether Lilly will still be interested, though trying to back out of the deal might be more trouble than it’s worth for Lilly.

The price tag is small change for the big pharma, which might be just as interested in PNT2002 as it is in Point’s radiopharmaceutical manufacturing capabilities and next-generation PSMA-targeted project, PNT2001. In light of the Splash results Point shareholders would be advised just to take Lilly’s offer.