The future of biased IL-2 is uncertain, and Nektar seeks to merge

After failing three consecutive IL-2 clinical trials, Nektar began seeking concorposion
.
PureTech Health said in a statement that it had exchanged non-binding indicative proposals with Nektar Therapeutics for a possible merger, including an offer to acquire PureTech's share capital
.
Founded in 1990, Nektar Therapeutics is the leading player
in the IL-2 space.
The debut of the IL-2-biased activator developed by Nektar at the 2017 SITC conference has attracted widespread attention from the
industry.
In melanoma, NKTR-214 and PD1 achieved 64% (7/11) ORR, a stunning figure that not only led to a $3.
6 billion partnership with BMS, but also drove Nektar's stock price up
multiple times.
NKTR-214 is an IL-2-biased activator that passes through the PEG-based form of 6 mers, and after injection into the body, 6 PEG modifications gradually fall off, forming the forms of active 2-PEG and 1-PEG
.
PEGization on the one hand hinders binding to IL-2Rα, biased activation of Teff cells; On the other hand, PGE also effectively improves the half-life of NKTR-214
.
The FDA awarded it the title
of breakthrough therapy in July 2019.
At that time, whether it was the amazing clinical data or the huge bet of BMS, everyone was full of expectations
for NKTR-214.
But the prospects for NKTR-214 development soon began to dim
in the declining clinical efficacy.
In the expanded PIVOT-02 clinical study disclosed at the 2018 ASCO conference, ORR in melanoma patients has been reduced to 52.
6%.

After advancing to phase III clinical, NKTR-214 is still difficult to reflect clinical advantages
.
On March 14, 2022, NKTR-214+Opdivo Phase III clinical PIVOT IO-001 suddenly failed
.
After analysis, NKTR-214+ Opdivo combination therapy did not provide additional clinical benefit over Opdivo monotherapy, the primary clinical endpoints such as PFS and ORR were not met, and there was no statistical difference
in overall survival time OS.
On April 14, based on the clinical advance analysis of kidney cancer stage III and bladder cancer stage II, the results were not as expected, and finally BMS announced the termination of cooperation, and all clinical studies of IL-2 combined + Opdivo treatment were also terminated
.
The rupture of the partnership with BMS also triggered a major layoff in Nektar
.
A month after the announcement, Nektar Therapeutics announced a 70 percent layoff, and the company's chief medical officer, Dimitry Nuyten, MD, and chief commercial officer, John Northcott
, stepped down.
In addition, the company slashed its product pipeline to shift its focus to two other clinical-stage assets
.
The market reacted very differently to the news about the merger of the two companies, with PureTech's shares on both the NASDAQ and London Stock Exchange falling, while Nektar's shares rose
slightly.

References:

https://endpts.
com/rising-from-the-il-2-ashes-and-drastic-reorg-nektar-in-merger-talks-with-puretech/