fyi; happy Thanksgiving !!!
Ash 2020 cell therapy preview – the battle for recognition:
With many of the usual targets on display Fate, Celyad, Allovir and others look to maintain momentum.
Ash conference is usually a mecca for cell therapy followers. Its 2020
instalment features plenty of Car-T and Car-NK presentations, though
investors might rue the fact that these risk being overshadowed by antibody modalities.
Clinical data to watch on adoptive cell therapies include those on
Fate’s allogeneic Car-NK project FT596 and Celyad’s Cyad-02, a Car using
short hairpin RNA technology. Meanwhile, Allovir will want to justify
enthusiasm for its recent flotation, while BCMA-targeted multiple
myeloma assets fight to stand out from the crowd.
The most advanced anti-BCMA Car-T therapy is Bristol Myers Squibb/Bluebird’s ide-cel, which faces a March 27, 2021 US FDA action date despite an earlier refuse-to-file letter.
The asset to watch, however, is Johnson & Johnson/Legend Biotech’s
cilta-cel, whose Cartitude-1 study is showing a remarkable 95% remission
rate, according to the Ash abstract.
Not only that, but Bristol/Bluebird’s follow-up, bb21217, looks
disappointing, Ash data suggest. A US NCI group including Dr James
Kochenderfer, who has also worked on ide-cel, is separately presenting
clinical results on a new approach, FHVH-BCMA-T, which uses a heavy
chain antibody fragment rather than the normal scFv.
With most abstracts citing relatively early data cut-offs, updates at
Ash itself will be keenly awaited. Among these Poseida will no doubt
field questions if responses to P-BCMA-101 continue to look better at
low than at high doses.
Long time coming
First clinical data on FT596, Fate’s first Car-modified NK cell
approach, have been a long time coming: the FDA signed off the IND in
September 2019, but the trial did not start until April this year.
Even so there might be disappointment as the Ash abstract details
only a single case study, in a lymphoma subject who went into partial
response after a single dose. Expectations for FT596 are high given the 73% response rate cited for an unrelated anti-CD19 Car-NK project run by MD Anderson’s Dr Katy Rezvani.
There might be more on FT596 at Ash, but some analysts are reining in
expectations of meaningful data before next year. In the unmodified NK
cell sphere, meanwhile, FC21-NK data could support Sanofi’s decision to buy Kiadis for $358m this month.
Celyad has been working on Car-T cells targeting NKG2D ligands for
some time, but Ash will feature the first clinical data on Cyad-02, a
construct that aims to improve on an earlier iteration, Cyad-01.
One problem with Cyad-01 is Car-T fratricide, caused by T cells' own
transient expression of NKG2D ligands; Cyad-02 aims to silence these
ligands using shRNA technology. The Ash abstract says Cyad-02 showed
threefold better expansion than Cyad-01, and promises to deliver
“preliminary clinical activity data”.
While Cyad-02 is an autologous therapy, Celyad is separately
developing allogeneic Cars. One of its allogeneic approaches also
uses shRNA for gene silencing, so the Cyad-02 data could provide proof
of concept beyond the use in the abstract.
Allogeneic therapies will of course be aired extensively at Ash, and a presidential symposium on 8 December will see UCLA’s Dr Gay Crooks discussing universal cell sources. Dr Crooks’s pluripotent stem cell generation technology was licensed to Kite before that company was bought by Gilead.
Other presentations of general interest include a paper suggesting that CD5 knock-out enhances Car-T cell activity, and another claiming that aberrations in CD58 curtail the efficacy of Yescarta.
The latter is also being highlighted at a December 5 press briefing,
along with preclinical data on Allovir’s anti-Covid-19 T-cell therapy
Investors in Allovir, whose stock has doubled since the group raised $318m in a July IPO, will pay close attention.
Ash 2020 will take place in virtual format on December 5-8.
Vantage analysis previously summarised upcoming Ash presentations that resulted in early share price moves, cancer-focused abstracts outside cell therapy, and those in non-oncology indications.