Nantkwest tries to catch the NK cell wave

Nantkwest claims efficacy with its most advanced NK cell therapy but, as ever with Patrick Soon-Shiong companies, it’s complicated.

Nantkwest was one of the first companies to investigate NK cells, so it could hardly have escaped the mania sweeping the sector over this class of therapeutics. Its shares surged 25% this morning on a case report that the group claims validates its recently begun Car-NK cell study in pancreatic cancer.

This follows the stock’s climb in December, in tandem with Fate Therapeutics, which reported NK cell data at Ash, a meeting at which Nantkwest did not present. However, the relevance of yesterday’s convoluted press release, as well as the precise effect of Nantkwest’s NK cells, are hard to tease out, and remarkably Nantkwest had briefly mentioned the case report last month.

The findings relate to Quilt-3.080, a second-line pancreatic cancer study Nantkwest had started back in 2018 under the US Cancer Moonshot programme. This tested allogeneic NK cells expressing high-affinity CD16, combined with a wide range of therapeutics and/or chemotherapies.

Median overall survival of 8.2 months had been reported in May 2019, amounting to an improvement over the three months of historic controls, Nantkwest claimed. Not only is such a comparison highly unreliable, there is no way of telling which of the many components of the cocktail tested might have yielded a benefit.

More advanced

Yesterday Nantkwest said an expanded protocol in Quilt-3.080 had allowed five subjects to receive a more advanced NK cell therapy, which it calls PD-L1 t-haNK. And one of these patients had gone into complete remission.

In fact, the group had already mentioned this remission in a December 21 presentation, saying the CR was at seven months’ duration. The finding could be relevant since PD-L1 t-haNK is now in a pivotal study, Quilt-88, in first and second-line pancreatic cancer. In addition to high-affinity CD16, this NK cell therapy expresses IL-2 and a PD-L1-specific Car.

However, the relevance of such a case report is muddied by yesterday’s further revelation that this subject had previously received the original NK cell therapy as well as Pfizer/Merck KGaA’s Bavencio, so any effect could be due to these earlier treatments. Nantkwest says four of the five subjects are alive “8-16 months since beginning treatment on these expanded protocols”.

Déjà vu?

Success here could be déjà vu for Nantkwest’s chairman, Patrick Soon-Shiong, who in 2010 sold the pancreatic cancer company Abraxis to Celgene for $2.9bn.

Quilt-88 also includes N-803, an IL-15 superagonist in development by Immunitybio, a private biotech formerly called Nantcell that is run and controlled by Mr Soon-Shiong. Nantkwest has several existing deals with Immunitybio, and last month said the two groups would merge to give a combined business with an “expansive clinical-stage pipeline and intellectual property portfolio”.

However, the merger appears to be a means of tidying up Mr Soon-Shiong’s empire, since he also controls 67.6% of Nantkwest, according to the latest annual SEC filing. The move is a reverse takeover, and when it closes, due around mid-2021, Immunitybio holders will own 72% of the combined, listed entity.

Meanwhile, Mr Soon-Shiong’s resulting ownership will be 79.2%, according to an SEC filing. Until November Mr Soon-Shiong had additionally been chief executive of Nantkwest, but handed over this role to Richard Adcock, who will remain at the helm of the merged company.

Nantkwest’s first tie-up with Immunitybio is with this original entity, but a later deal struck under Mr Soon-Shiong’s direction was routed through Vivabiocell, a company Immunitybio (as Nantcell) had acquired in 2015. Nantkwest also has a 2016 deal with Altor Bioscience, which Nantcell bought out the following year.

As ever with Mr Soon-Shiong’s sprawling web of corporate entities, little is straightforward.

How Nantkwest is to become Immunitybio
Vivabiocell* Altor Bioscience* Liquid Genomics   Nantomics Nanocav Nantbio
    Renamed Nanthealth Labs*   (All controlled by P Soon-Shiong)
Acquired by Nantcell   Existing deals with Nantkwest (NK)
(>80%-owned by P Soon-Shiong)   (67.6%-owned by P Soon-Shiong)
Renamed Immunitybio        
Immunitybio to acquire Nantkwest, and to be the surviving traded entity (IBRX)
(79.2%-owned by P Soon-Shiong)
*Have separate existing agreements with Nantkwest. Source: US SEC filings.

This story has been updated to state Mr Soon-Shiong's resulting ownership of the combined entity.

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