Collaborations

Following ASCO preview flop, Syndax bets on new combo deal with Nektar

San Fran’s I/O darling Nektar Therapeutics $NKTR is handing off access to its popular cancer candidate NKTR-214 to see how the therapy fairs when paired with Syndax’s struggling drug entinostat.

Briggs Morrison

The duo inked a collaboration and licensing deal that gives Syndax $SNDX the right to run a combo study testing the drugs against metastatic melanoma in patients who have previously progressed when on an anti-PD-1.

The hope is that entinostat, Syndax’s oral, small molecule Class 1 specific HDAC inhibitor, could be put to good use alongside NKTR-214, the CD122-biased agonist that was the impetus behind Bristol-Myers’ $3.6 billion deal with Nektar back in February.

“Previous Phase II data with entinostat and high dose IL-2 in renal cell cancer and our promising preclinical data generated with NKTR-214, laid the scientific and clinical foundation for this collaboration,” said Briggs Morrison, CEO at Syndax, in a statement. “Working with Nektar allows us to increase the potential impact entinostat may have in the treatment of PD-1 refractory metastatic melanoma patients, and complements the exciting data we have seen when combining entinostat with Keytruda in a similar population.”

Syndax needs this combo to work. That’s because earlier this month, the company shared an ASCO abstract that sent Syndax’s stock plummeting 23%. The company’s lead drug, entinostat, largely flopped a mid-stage combo trial testing the drug with Keytruda against NSCLC. The combo produced an objective response rate of only 11% in pre-treated cancer patients — with a progression-free survival rate of only 2.5 months.

But Morrison and team found a silver lining: a post hoc analysis identified a subgroup of patients who did better. Whittling the 57 patients reviewed for this readout down to 14 with high monocyte levels, Syndax got a PFS rate of 5.4 months and an ORR of 29%.

Syndax will launch the Phase Ib trial in melanoma, with plans keep an eye on biomarkers that might ID patients with enhanced responses, including “analyses exploring the potential of elevated levels of classical peripheral blood monocytes,” the company said.

“The combination of NKTR-214 and entinostat demonstrated a unique synergy in our preclinical models which warrants further study in the clinic,” said Jonathan Zalevsky, SVP and CSO of Nektar. “Importantly, we observed elevated levels of cytokine-positive tumor-infiltrating cytotoxic T cells following treatment with the combination. We believe this important preclinical finding could translate to improved tumor responses in patients who have become refractory to checkpoint inhibitors. We look forward to working with Syndax as this combination advances into the clinic.”

Financial details of the deal weren’t disclosed.


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