The Ash convention is often a mecca for cell remedy followers. Its 2020 instalment options loads of Automobile-T and Automobile-NK shows, although buyers may rue the truth that these danger being overshadowed by antibody modalities.
Scientific knowledge to observe on adoptive cell therapies embrace these on Destiny’s allogeneic Automobile-NK venture FT596 and Celyad’s Cyad-02, a Automobile utilizing brief hairpin RNA know-how. In the meantime, Allovir will need to justify enthusiasm for its current flotation, whereas BCMA-targeted a number of myeloma property battle to face out from the group.
Essentially the most superior anti-BCMA Automobile-T remedy is Bristol Myers Squibb/Bluebird’s ide-cel, which faces a March 27, 2021 US FDA motion date regardless of an earlier refuse-to-file letter. The asset to observe, nevertheless, is Johnson & Johnson/Legend Biotech’s cilta-cel, whose Cartitude-1 examine is exhibiting a exceptional 95% remission fee, in keeping with the Ash summary.
Not solely that, however Bristol/Bluebird’s follow-up, bb21217, seems disappointing, Ash knowledge counsel. A US NCI group together with Dr James Kochenderfer, who has additionally labored on ide-cel, is individually presenting scientific outcomes on a brand new strategy, FHVH-BCMA-T, which makes use of a heavy chain antibody fragment fairly than the conventional scFv.
With most abstracts citing comparatively early knowledge cut-offs, updates at Ash itself might be keenly awaited. Amongst these Poseida will little doubt discipline questions if responses to P-BCMA-101 proceed to look higher at low than at excessive doses.
Very long time coming
First scientific knowledge on FT596, Destiny’s first Automobile-modified NK cell strategy, have been a very long time coming: the FDA signed off the IND in September 2019, however the trial didn’t begin till April this 12 months.
Even so there could be disappointment because the Ash summary particulars solely a single case examine, in a lymphoma topic who went into partial response after a single dose. Expectations for FT596 are excessive given the 73% response fee cited for an unrelated anti-CD19 Automobile-NK venture run by MD Anderson’s Dr Katy Rezvani.
There could be extra on FT596 at Ash, however some analysts are reining in expectations of significant knowledge earlier than subsequent 12 months. Within the unmodified NK cell sphere, in the meantime, FC21-NK knowledge may help Sanofi’s choice to purchase Kiadis for $358m this month.
|Chosen Ash 2020 cell remedy shows|
|Auto1||Anti-CD19 Automobile-T||Autolus||Grownup ALL, 13 May 2020 lower: 16/19 MRD-ve CR, four relapses||160|
|Auto3||Anti-CD19/CD22 Automobile-T||Autolus||Alexander examine, Keytruda combo in lymphoma, 13 Jul 2020 lower||600|
|GC022C||Anti-CD19/CD22 Automobile-T||Gracell||24-hr manufacturing course of||159|
|MB-CART2019.1||Anti-CD19/CD20 Automobile-T||Miltenyi Biotec||Lymphoma, ORR 75%, 5/12 CR||404|
|UCART22||Anti-CD22 Automobile-T*||Cellectis||Grownup ALL, 1 Jul 2020 lower: 2/5 CR||163|
|A number of myeloma|
|Ciltacabtagene autoleucel||Anti-BCMA Automobile-T||J&J (ex Legend)||Cartitude-1 examine, 20 May lower: 95% ORR, mDoR not reached||177|
|bb21217||Anti-BCMA Automobile-T||Bluebird/BMS||1 Mar 2020 lower: 55% ORR, 8/44 CR||130|
|CT053||Anti-BCMA Automobile-T||Carsgen||30 Jun 2020 lower: 88% ORR, 19/24 CR||132|
|P-BCMA-101||Anti-BCMA Automobile-T||Poseida||30 Jun 2020 lower: 57% ORR (n=34)||134|
|FHVH-BCMA-T||Anti-BCMA Automobile-T (heavy chain)||NCI||90% ORR (n=20)||498|
|ALLO-715||Anti-BCMA Automobile-T*||Allogene||Eight Jul 2020 lower: 33% ORR (n=15), one loss of life attributable to an infection||129|
|FC21-NK||NK cells*||Kiadis (Sanofi)||AML, 14 Apr 2020 lower: 8/12 CR, mOS 17.6mth||68|
|GDA-201||NK cells*||Gamida Cell||Lymphoma, 73% ORR, 10/15 CR||63|
|FT596||Anti-CD19 Automobile-NK*||Destiny||Case report solely||2356|
|NKX101||NKG2D Automobile-NK*||Nkarta||No scientific knowledge||1040|
|Cyad-02||NKG2D Automobile-T (shRNA)||Celyad||Aug 2020 lower: 6 AML/MDS pts, no efficacy knowledge||990|
|UCART123||Anti-CD123 Automobile-T*||Cellectis||Ameli-01 AML examine, no scientific knowledge||1039|
|ALVR109||Anti-Covid-19 T cells*||Allovir||No scientific knowledge||612|
|*Allogeneic venture; the rest autologous.|
Celyad has been engaged on Automobile-T cells focusing on NKG2D ligands for a while, however Ash will function the primary scientific knowledge on Cyad-02, a assemble that goals to enhance on an earlier iteration, Cyad-01.
One downside with Cyad-01 is Automobile-T fratricide, attributable to T cells’ personal transient expression of NKG2D ligands; Cyad-02 goals to silence these ligands utilizing shRNA know-how. The Ash summary says Cyad-02 confirmed threefold higher enlargement than Cyad-01, and guarantees to ship “preliminary clinical activity data”.
Whereas Cyad-02 is an autologous remedy, Celyad is individually creating allogeneic Automobiles. One in every of its allogeneic approaches additionally makes use of shRNA for gene silencing, so the Cyad-02 knowledge may present proof of idea past the use within the summary.
Allogeneic therapies will in fact be aired extensively at Ash, and a presidential symposium on Eight December will see UCLA’s Dr Homosexual Crooks discussing common cell sources. Dr Crooks’s pluripotent stem cell era know-how was licensed to Kite earlier than that firm was purchased by Gilead.
Different shows of common curiosity embrace a paper suggesting that CD5 knock-out enhances Automobile-T cell exercise, and one other claiming that aberrations in CD58 curtail the efficacy of Yescarta. The latter can be being highlighted at a December 5 press briefing, together with preclinical knowledge on Allovir’s anti-Covid-19 T-cell remedy ALVR109.
Traders in Allovir, whose stock has doubled because the group raised $318m in a July IPO, pays shut consideration.
Ash 2020 will happen in digital format on December 5-8.
Vantage evaluation beforehand summarised upcoming Ash shows that resulted in early share price strikes, cancer-focused abstracts outdoors cell remedy, and people in non-oncology indications.