Could a fourth lead drug finally bring Infinity an approval?
Maybe fourth time’s the charm?
Infinity Pharmaceuticals, the thrice-failed oncology biotech, announced updated data Tuesday from its new lead drug in a pair of cancers, showing that bladder cancer patients who took its molecule in combination with Bristol Myers Squibb’s Opdivo lived nearly twice as long as patients who took Opdivo alone. And the biotech showed the molecule appeared to offer a modest benefit for patients with triple-negative breast cancer.
“In our view, these data are overall positive and continue to support eganelisib potential,” Truist’s Robyn Karnauskas wrote in a note to investors, using the chemical name of the drug.
And yet Infinity’s stock $INFI slid on the news, dropping 31% Tuesday from $2.22 to $1.53, although it has since bounced back up.
The problem is one Infinity has faced before: Whether or not the drug is effective, it may not have a market. The biotech’s previous lead P13K drug, duvelisib, was abandoned after showing a 46% response rate in non-Hodgkin lymphoma — good, but not good enough to compete in a field where other options are available. (They dumped the drug to Verastem, who got it approved but generated little sales). It was the third Infinity drug to go down, after clinical failures for other molecules in 2009 and 2012 shook what had once been one of the biggest biotechs in targeted oncology.
Similarly, investors had been hoping to see a greater benefit in triple-negative breast cancer, an indication that’s notoriously tough to treat. Infinity showed its drug, when combined with Roche’s PD-1 blocker Tecentriq and chemotherapy, halted disease for 7.5 months, or just 0.2 months — six days — more than Roche showed Tecentriq and chemotherapy can alone.
Those data also came out the same day Merck announced Keytruda improved progression-free survival in triple-negative breast cancer, adding another option Infinity would have to compete against.
The data for bladder cancer were far stronger, but investors had been hoping the company would lay out a clearer path to approval. Instead, Infinity CEO Adelene Perkins promised an update toward the end of the year and analysts now expect the trial could take longer than anticipated. With the FDA taking a tougher stance on PD-1 approvals, the company will likely have to prove its combination can improve survival in a large study, pushing approval back toward 2025.
In the meantime, competitors are entering the market. Infinity has studied its drug in patients who have already gone through one line of treatment but have yet to receive a checkpoint inhibitor. But B. Riley Securities’ Kalpit Patel noted that PD-1s are increasingly being used in newly diagnosed bladder cancer patients, including in combination with Seagen’s new antibody-drug conjugate Padcev.
“We acknowledge a limited opportunity,” Patel said, estimating 4,200 patients per year would be eligible for Infinity’s drug if it succeeds.
Nevertheless, few analysts soured on Infinity altogether, particularly with shares selling at soda bottle prices. Eganelisib, a P13K-gamma inhibitor, is intended to reprogram the immune cells that cluster around the tumor, short-circuiting one of solid tumors’ key methods for avoiding T cells and other tumor-killing arms of the immune system.
Accordingly, the company hoped it would both improve responses in patients who already express PD-L1 and are likely to benefit from checkpoint therapy, and those who don’t express PD-L1 and are less likely to benefit. In theory, the molecule could convert some of these tumors to PD-L1 positive.
Analysts expect Infinity to push for an approval in PD-L1-negative patients for bladder cancer. And some argued that the triple-negative breast cancer data were skewed because Infinity had a greater number of negative patients than those in Roche’s original trial. Broken down by PD-L1 positive and negative, they noted, Infinity’s drug actually improved PFS by 2 months for negative patients and nearly 4 months for positive patients.
That kind of speculative analysis, though, is far from the kind of evidence it will take to get approval.
“While encouraging,” Patel wrote, “we currently exclude TNBC as a potential indication as we wait for data from additional number of patients as well as longer-term response durability/PFS results.”