As turnarounds go, the one Kiadis is experiencing is extraordinary. Last November the company was on its knees, having scrapped its lead project, but a pivot to a natural killer cell technology it had acquired a little earlier was just what the doctor ordered: today Sanofi stepped in with a deal to endorse that approach.
True, Sanofi is an unusual cell therapy partner, and the deal is initially worth only €17.5m ($19.7m), but a big pharma endorsement is not to be sniffed at. Remarkably, Kiadis had not paid any cash to acquire the tech, and the project the French group has licensed had not even appeared in analysts’ valuations.
Still, the deal does not look like an attempt to turn Sanofi into a cell therapy player. Rather, it focuses on the use of Kiadis’s NK cells bearing a particular antigen knock-out as an adjunct with one of its own drugs, the anti-CD38 MAb Sarclisa, recently launched for multiple myeloma.
The problem Sanofi has identified is that CD38, as well as being expressed on target multiple myeloma cells, is also present on some NK cells. Treating a multiple myeloma patient with an anti-CD38 MAb thus risks inadvertently also wiping out their NK cells, which make up part of an immune response.
Through Kiadis Sanofi has now gained K-NK004, an allogeneic NK cell product in which CD38 has been knocked out to make such cells resistant to CD38 blockade and prevent “fratricide”. In addition to the €17.5m signing fee, the deal includes up to €857.5m in milestones, royalties and two undisclosed preclinical NK cell therapies.
Kiadis had acquired K-NK004 along with Cytosen, a private NK cell company it got in an all-share transaction in April 2019. The Sanofi deal does not trigger any further payments to Cytosen’s vendors, Kiadis’s chief executive, Arthur Lahr, told Evaluate Vantage.
Until today it was only Cytosen’s unmodified NK therapies K-NK002 and K-NK003 that were highlighted, though preclinical data on the CD38 knock-out combined with the market-leading anti-CD38 MAb, Genmab/Johnson & Johnson’s Darzalex, were presented at Asco.
However, the idea of avoiding CD38-based fratricide is not new. Kiadis’s rival Fate Therapeutics is developing two CD38 knock-out NK cell projects, one of which, FT538, should begin clinical trials imminently.
|NK cell therapeutics with CD38 knock-out|
|Project||Company||Cell source||Gene editing method||Note|
|FT538||Fate||iPSC (stem cell line), activated by feeder cells with mbIL21/mbIL15||Mad7 Crispr nuclease||IND cleared in May to begin clinical trials; unpartnered|
|FT576||Fate||iPSC (stem cell line), activated by feeder cells with mbIL21/mbIL15||Mad7 Crispr nuclease||Also has anti-BCMA Car transgene; clinical trial due 2020; unpartnered|
|K-NK004||Kiadis||Universal adult donor, activated by PM21 (mbIL21 & 41bbL particles)||Crispr Cas9 nuclease||Licensed to Sanofi; Jefferies says no clinical trials likely until at least 2022|
|Source: company presentations.|
The two companies’ approaches differ in how the cells are sourced and their editing technology; while Fate has cited a 60% knock-out efficiency Kiadis’s Asco poster claimed 82%. Mr Lahr also cited Kiadis’s “better NK profile, and an approach to activate and expand the NK cells that really creates a unique phenotype that is extremely potent and persistent”.
Interestingly, Fate has not pursued a licensing plan with either of its CD38 knock-outs. Why did Kiadis not similarly keep its options open with K-NK004? It is Darzalex that has to defend its position, Mr Lahr argued, adding: “Sanofi had most to gain from a combination, so they’re going to be most motivated to push the product forward.”
While Sarclisa is dosed by repeat infusions, an K-NK004 adjunct could be given as a single course, or possibly at three-month intervals, Mr Lahr speculated. The bull case is that a Sarclisa combo could result in more remissions and fewer relapses than using Darzalex alone.
“It might completely change the landscape,” said Mr Lahr. Kiadis traded up 58% today, though at a time when a preclinical NK cell player, Nkarta, is looking to float at a $400m valuation Kiadis’s $70m market cap shows that investors have yet to buy into such optimism.