Liquid Biopsy · @Liquid_Biopsy
2nd Nov 2015 from TwitLonger
$CLLS Oppenheimer: #ASH15 Abstract Preview: First UCART19 Allogeneic
CART Data Expected at ASH
SUMMARY
We anticipate landmark first-in-human data for CLLS's UCART19 allogeneic
CAR-T to be presented at ASH. Our checks suggest first-human data for UCART19
will be presented, well ahead of 1H16 expectations. We understand that UCART19
may have been administrated in an investigator-sponsored (hence data not CLLS's
to disclose) compassionate-use setting, potentially at UCL, an academic collaborator.
We believe data will disclose results of UCART19 treatment of a pediatric ALL patient
with few other treatment options. We expect this first-human data to be a substantial
catalyst for CLLS, providing proof-of-concept for their disruptive off-the-shelf CART
approach and to inform key characteristics of their allogeneic therapy. We also
believe this data will be highly disruptive to CAR-T space, relevant to KITE and JUNO.
Abstract release Nov. 5, Late-breaker release Nov.16.
KEY POINTS
■ Checks suggest UCART19 data will be positive. ASH abstracts with initial
data first avail. Nov. 5, 9am ET. Key metrics: (1) dose, (2) mild/minimal-GvHD,
(3) proliferation/persistence, (4) response (CR/MRD), (5) tolerability (low cytokine
release syndrome, neurotoxicities), (6) disease burden, prior treatments (time
since last treatment) including prior allogeneic transplant, and prior response, (7)
possible patient follow-up/subsequent cure with transplant. We note alemtuzumab
has limited activity in ALL.
■ Mild GvHD possible, but not treatment limiting. CLLS's analyst day highlighted
that mild GvHD would be acceptable to physicians, due to high unmet need, and
potentially desirable. We note GvHD may be indicative of not only persistence,
but UCART19 inducing broader T-cell proliferation. CLLS GMP-validated geneediting
manufacturing yields 99.5% TCR-free T-cells, limiting GvHD.
■ UCART19 is anticipated to persist while under alemtuzumab
lymphodepletion regimen. We estimate that the persistence window will be
~6-10 weeks. Recall, UCART19 utilizes gene editing to knock out the CD52-
receptor to resist alemtuzumab treatment, but will eventually be rejected with
immune reconstitution, a key safety feature for regulators. Recent evidence
suggests that multi-year persistence of CAR-T is not necessary for successful
therapy and may yield long-term toxicity.
■ UCART19: Off-the-shelf needed for 90% of pediatric ALL patients. 90% of
the 3,000-4000 pediatric ALL patients diagnosed annually in US are estimated to
have insufficient/low-quality T-cells to support KITE, JUNO, NVS autologous.
■ We look to SITC (Nov. 4-8) for further KOL/investigator thoughts on abstract
data. Comparative data from CAR-T trials pg 4.
■ Data to represent first-in-human application of TALEN gene-editing.