ASH preview – CART comes of age


If ASH 2013 was the conference at which CART truly emerged as a force to be reckoned with in the haematological oncology pipeline, this year’s edition of the meeting will see investors try to tease out minute differences between the leading competitors fighting it out in this space.

Indeed, it can be said that 2014 was the year in which CART (chimaeric antigen receptor therapy) came of age, though given the huge expectations important questions still remain. Novartis, Kite Pharma, Juno Therapeutics, Cellectis, Bluebird Bio and Bellicum Pharmaceuticals will all feature at the ASH meeting kicking off this week, providing stock triggers for all the publicly listed players in this space.

Moreover, the NCI’s Dr Steve Rosenberg, who heads a co-operative R&D agreement between the NIH unit and Kite, will lead a session on December 7 dedicated to the curative potential of cell-transfer therapy for cancer, at which various approaches to CART, as well as the related approach of engineered T-cell receptor therapy, will be discussed.

A look at the stock markets shows how since December 2013 CART has come on in leaps and bounds (ASH – Novartis pulls the CART in autologous T-cell therapy, December 9, 2013). In June Kite floated to raise $147m, and this week revealed plans for a $138m follow-on, while Cellectis did a deal with Pfizer worth $80m up front.

Just last week Juno and Bellicum filed for IPOs to raise $150m and $115m respectively. Bluebird’s early-stage CART deal with Celgene was struck in 2013.

B-cell malignancies have represented low-hanging fruit for all the CART players, driven by swift and profound disease remission in certain patients. Possible areas of differentiation now include the choice of CAR T-cells’ co-stimulatory domains – CD28 and/or 4-1BB are favoured at present – and whether the therapy is seen as a bridge to stem cell transplantation or a replacement for it.

Side effects are also being closely watched, with Juno working on a bispecific CART to minimise off-target activity. The common cytokine release syndrome, which is apparently at its worst when the most advanced cancers are targeted, seems now to be controllable with steroids or IL-6 inhibition.

Imbruvica competition

Whatever CART’s promise, for the time being of course the chronic lymphocytic leukaemia company to beat is Pharmacyclics, and as before ASH will be a vital meeting for this group. Imbruvica, its oral small molecule, is proving remarkably resilient to competitor challenges and will feature in numerous presentations.

While the label for Gilead’s Zydelig disappointed, further competition for Pharmacyclics lies in store. Most important of the small molecules is AbbVie’s Bcl-2 inhibitor venetoclax. A published ASH abstract reveals that a modified dosing regimen might at last be putting to bed concerns about serious toxicities like tumour lysis syndrome.

Also relevant for Pharmacyclics followers is TG Therapeutics, which will present data on both its anti-CD20 MAb ublituximab and PI3K-delta inhibitor TGR-1202. TG will present further data on ublituximab in combination with Imbruvica as well as with TGR-1202, and on TGR-1202 monotherapy; investors want TGR-1202 to show comparable efficacy to Zydelig, with better safety.

As far as CART goes, all eyes are also on Cellectis and its promise of an allogeneic, rather than autologous, treatment. At the recent Jefferies meeting in London, Kite’s chief executive Arie Belldegrun told EP Vantage that he “did not think Cellectis [was] a threat”, since the French group was “at least three years behind” Kite – a significant lag in an area where the science is evolving so fast.

Confident statements like this, and Kite’s own super-bullish timelines, show just how huge the expectations are here, and how much could go wrong should any of the players now stumble.

ASH: selected CART abstracts
Project developer(s) ASH topic Date 
Various Curative potential of cell transfer therapy for cancer Dec 7
Novartis/Univ of Penn Phase II CLL data Dec 6
Juno Therapeutics/MS Kettering Paediatric relapsed B-cell ALL data Dec 8
Adult relapsed B-cell ALL data Dec 8
B-cell NHL (phase I interim safety analysis) Dec 8
Kite Pharma/NCI Diffuse large B-cell lymphoma (further phase I data) Dec 8
Phase I ALL data Dec 8
Cellectis/Pfizer Anti-CD123 allogeneic T-cells Dec 6
Preclinical activity of allogeneic UCART19 Dec 8
Bluebird/Celgene Preclinical activity of CD123-engager T-cells in AML  Dec 8
Bellicum Co-stimulation of CAR T-cells Dec 6

To contact the writer of this story email Jacob Plieth in London at For live updates from the ASH meeting in San Francisco, on December 5-9, follow @JacobEPVantage on Twitter.

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