Still reeling from PhII failure, Calithera beefs up its oncology portfolio with a little help from Takeda

2021-10-19

Calithera started the year by axing a third of its staff after a monumental Phase II flop in renal cell carcinoma. And while CEO Susan Molineaux has refused to give up on the program, she’s going to need an assist if she wants to close the year on a higher note. That’s where Takeda comes in. For two upfront payments of $10 million and $35 million, tiered royalties and an undisclosed amount in biobucks, Takeda is forking over two Phase II-ready cancer programs to Calithera — one of which targets KEAP1/NRF2 mutations, the same ones Calithera is now pursuing with its once-failed glutaminase inhibitor telaglenastat. “We have learned a great deal about the unmet medical need of patients with KEAP1/NRF2 mutations, as well as how to identify and recruit these patients, during the conduct of our KEAPSAKE trial evaluating telaglenastat,” Molineaux said in a statement. “This complementary approach in KEAP1/NRF2-mutant squamous NSCLC KEAP1/NRF2-mutant squamous NSCLC demonstrates our commitment to these patients and the pathway.” The first new candidate in Calithera’s basket is Takeda’s dual TORC 1/2 inhibitor sapanisertib TORC 1/2 inhibitor sapanisertib. It’s designed to target a key survival mechanism in KEAP1/NRF2-mutated tumor KEAP1/NRF2-mutated tumor cells, which are found in a considerable amount of patients with solid tumors, according to the companies. If all goes according to plan, the program is heading into a Phase II trial early next year as a monotherapy in patients with squamous NSCLC harboring a NRF2 mutation, with a readout coming in the next 12 to 18 months. The South San Francisco-based biotech is also getting mivavotinib, an SYK inhibitor SYK inhibitor that’s also expected to enter Phase II next year for patients with diffuse large B-cell lymphoma with and without MyD88 and CD79 mutations. Calithera also sees potential for studies in non-Hodgkin’s lymphoma and blood cancer. That makes five clinical programs now in Calithera’s pipeline, according to the company’s website. Calithera is still reeling from its Phase II failure in renal cell carcinoma, the results of which were read out back in January. Adding telaglenastat to Exelixis’ Cabometyx failed to improve progression-free survival, investigators concluded. In fact, patients on Cabometyx and placebo lived slightly longer — a PFS of 9.3 months compared to 9.2 months for those treated with telaglenastat and Cabometyx, which doesn’t mean much considering the hazard ratio of 0.94 was far off statistical significance (p=0.65). The company’s stock $CALA is still trading at less than half of what it was last December. Shares were up 1% in premarket trading on Tuesday, going for $2.03 apiece. While that was the end of the road for telaglenastat’s Phase II study in renal cell carcinoma, Molineaux is pushing forward with another Phase II study in KEAP1/NRF2 mutant NSCLC KEAP1/NRF2 mutant NSCLC patients, dubbed KEAPSAKE, which dosed the first patients last summer.

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