Blueprint exec spots key Ayvakit readout, dealmaking plan as 'independent precision therapy company'

Blueprint Medicines has been a possible buyout target for large pharma companies thanks to its attractive precision cancer therapy focus. But some of the Massachusetts biotech’s recent moves suggest it has bigger plans.

Blueprint last year made its first acquisition, buying Lengo Therapeutics for a next-generation EGFR cancer candidate. And a few weeks ago, Blueprint struck financing deals worth up to $1.25 billion with Sixth Street and Royalty Pharma, with a $260 million credit facility set aside specifically for purchasing external assets.

“We have always been very clear that our goal is to build a world-leading independent precision therapy company—that’s our aspiration,” Blueprint’s chief operating officer Christy Rossi said in a recent interview with Fierce Pharma.

Christy Rossi, Blueprint COO (Blueprint Medicines)

The fundraising gives Blueprint additional resources to move toward that goal by investing in its internal portfolio and potential future targets in hematology and oncology, Rossi said, not because “there’s a particular kind of hole we’re trying to plug.” 

Blueprint is in a position of strength, Rossi added, but the company’s ambition will be tested soon. The company expects to read out key phase 3 data for Ayvakit in non-advanced systemic mastocytosis (SM) this month.

Ayvakit is already approved for advanced SM, a type of aggressive blood cancer. Non-advanced SM is more of a chronic disease, Rossi explained.

The population of patients with the indolent form is also much larger. Among an estimated 32,000 U.S. SM patient population, advanced disease only accounts for about 5% to 10%. But only half of the actual number of patients are being diagnosed, Blueprint noted based on U.S. medical claims data.

If approved, Ayvakit would be the first disease-modifying therapy for non-advanced SM. The drug would initially target about 7,500 non-advanced moderate to severe patients who are currently seeking treatment, while Blueprint aims to expand the market by increasing diagnosis, Rossi said.

Based on the treatment landscape, SVB Securities analysts last week put the peak sales for Blueprint’s KIT inhibitor franchise in the U.S. and EU non-advanced SM markets at $1.34 billion, compared with $486 million for the advanced disease. Besides Ayvakit, Blueprint is also in late-stage development of a second KIT inhibitor, BLU-263, in non-advanced SM.

But the SVB team also sees one challenge for Ayvakit’s big expansion plan.

According to SVB, Blueprint intends to price Ayvakit at the same level between advanced and non-advanced SM despite the two forms’ different severity and urgency. As such, SVB expects a “higher degree of scrutiny” on the drug’s data from part two of the PIONEER trial in non-advanced SM.

“[T]here was also a consensus that a $300k+ annual drug for a chronic disease that is predominantly life-altering versus life-threatening (as in aSM), would likely face increased commercial scrutiny by payers and providers,” the SVB team wrote in a note last week after hearing from investors.

For Ayvakit’s clinical trial, Blueprint worked with stakeholders to devise a patient-reported outcome measure called “total symptom score.” A 30% improvement on the score is considered a response.

“The percent of patients who met a 30% improvement … is something that clinicians believe is highly clinically meaningful,” Rossi said. Having at least a third of patients responding, as Ayvakit has shown in its phase 1 non-advanced SM study, is a “very meaningful impact” in doctors’ eyes, she added.

The phase 2 portion of the PIONEER trial is powered to detect an average 7 to 10 points of symptom reduction on the score, and that would correlate with about a third of patients meeting that 30% response criteria, Rossi said.

The SVB team figured the PIONEER trial has a 90% probability to hit its statistically significance goal but suggested the bar for commercial success may be higher now, given Blueprint’s “aggressive pricing strategy.”