Medivation eyes PARP-PD-1 cocktail; still no word on pidilizumab future

David Hung, Medivation CEO

With Bristol-Myers Squibb ($BMY) suffering a shock setback last week when its blockbuster PD-1 drug failed in a key lung cancer trial, this could crack open the door to Medivation ($MDVN) extending its PARP hope into this lucrative space.

During its quarterly results call yesterday, the Californian biotech--which is being sought by a number of Big Pharmas, including Sanofi ($SNY)--saw a new opening for its experimental PARP inhibitor talazoparib to be used with checkpoint inhibitors, notably in non-small lung cancer (NSCLC).

This comes a week after Bristol-Myers saw its seemingly all-conquering PD-1 checkpoint inhibitor Opdivo (nivolumab) fail a late-stage, first-line NSCLC cancer study--halting its chances of moving up the treatment pathway and allowing rival Merck ($MRK) to gallop on ahead with its data for a first-line setting with Keytruda (pembrolizumab).

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Credit Suisse Securities Kennen MacKay asked David Hung, founder, president and CEO of Medivation whether this failure could boost his own research hopes for talazoparib in NSCLC, and whether they will be seeking out combo trials with PD-1 meds.

Hung said: “I think that clearly the ability to up regulate PD-L1 is an important feature about this drug and it can make it really synergistic with PD-1 agents […] we think it would be very interesting to study this in other tumors where PD-1 might have less than stellar results.

“So I think that certainly does open a door. And also, we've indicated that among the six tumor types that we're interested in pursuing, that one of them is actually non-small cell lung in addition to our small cell programs. So we do think that PARP inhibition would be very exciting in non-small cell lung, and it is one of the indications that we are targeting. So we do think that that space is a little bit less crowded--we do intend to pursue that opportunity.”

PARP has in recent months become hot property in the pipelines of biotech companies after Tesaro ($TSRO) saw its experimental PARP inhibitor niraparib aced a Phase III study for certain ovarian cancer patients.

This saw the company’s shares soar and had a knock-on effect for Medivation as it boosted confidence in this oncology treatment class--a class that has not received as much as attention as other cancer meds, such as checkpoint inhibitors. It also saw Medivation become a more attractive target for its suitors, making Sanofi’s recent $9.3 billion bid for the biotech seem even more low-ball.

Tesaro has already announced plans to team up with Merck and Keytruda for its PARP drug. Hung believes however that talazoparib is more potent than niraparib and works in a different, and more efficacious, way.

Mohammad Hirmand, the biotech’s interim chief medical officer, said the niraparib data were “very positive on a number of fronts.”

He said Medivation was “Very intrigued by the potential for a PARP trapper to actually work in homologous recombination deficient (HRD) negative patients as well. And again, talazoparib--this is where it really shines. We already have a robust development plan in terms of pursuing a number of tumor types around all-comers.

“So we really think that with talazoparib being a very potent PARP trapper, like being the most potent PARP trapper, that we can really leverage that differentiated pharmacology and hopefully translate that into the clinic in a number of tumor types, both as monotherapy as well as with a combination of low-dose chemotherapy where we see good synergies to see whether we can actually see good benefit in an all-comer patient population, which would be again the next chapter in the use of PARP inhibitors.”

Talazoparib, licensed from BioMarin ($BMRN) last year, is currently in Phase III for patients with deleterious germline BRCA1 or BRCA2 mutations and locally advanced and/or metastatic breast cancer.

Meanwhile, a question over its troubled prospect pidilizumab also came up during the call, with MacKay asking whether an updated mechanism of action for pidilizumab would be presented this year.

The drug--which Medivation bought for $335 million deal in 2014 from CureTech--was designed as a PD-1 treatment, but recent studies showed that it could not actually work in this way, which saw the FDA halt the trial through a partial clinical hold while Medivation takes another stab at explaining the mechanism of action.

Clearly, this is still a head-scratcher for Hung, who said: “You know, we're still looking into that [defining a new mechanism of action], and certainly we have confidence in pidilizumab that when we can report it, we certainly will.

“But I think right now, the most important thing that we'll say about the molecule now is that it's pretty clear from the published studies and its most recent data set that this molecule has clinical activity. And that's still the absolutely most important thing. So we think this is a pretty interesting antibody.

“Of course, we're interested in finding out the mechanism of action, but we are very excited about the fact that we have seen activity especially in an indication like DIPG [diffuse intrinsic pontine glioma, an aggressive form of brain tumor] where nothing works. And to have a kid out two years on this drug is pretty startling in some ways. So we're very optimistic about it and do intend to try to pursue that indication on top of the other hematologic indications that we have already spoken about previously.”

Related Articles:
Anti-PD-1? Well, no, says Medivation as a partial hold forces a halt to 'pivotal' cancer study
Merck soars, Bristol-Myers tumbles on Opdivo fail in first-line NSCLC
Tesaro’s PARP ovarian cancer drug hits PhIII goal; prepares to file
BioMarin sells its PhIII cancer drug to Medivation for $570M
As Tesaro jumps 108%, Medivation can raise its price, and even Clovis climbs

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