Winners and losers – ASH is the new Asco

Asco is still the world’s most important oncology meeting but, as far as the potential to move stocks on transformational clinical data goes, this year’s ASH meeting gave it a good run for its money.

For evidence of the enthusiasm generated look no further than the pricing of recent fund-raisings – with Kite Pharma, Juno Therapeutics and Bellicum all taking advantage of the craze for T-cell therapies. Agios Pharmaceuticals’ somewhat debatable ASH data still enabled it to raise $220m, while the biggest share price gain overall was Bluebird Bio’s 116% (see table below).

To illustrate the point, EP Vantage has compared the share prices of ASH-relevant stocks between market close on November 5, just after which the meeting’s abstracts went live, and December 9, the meeting’s official final day. The stocks are ordered by percentage share price change.

Bluebird’s surge was driven by beta-thalassaemia data in just four patients that supported the view that the company had overcome long-standing problems of gene therapy delivery and adverse events. The group is now worth $2.4bn, and it is surely just a matter of time before it seizes the chance to raise more cash.

Neither has Acceleron announced a post-ASH secondary; the group also rose on beta-thalassaemia data, specifically concerning anaemia associated with the condition. The project is partnered with Celgene, which was one of the big-cap winners of ASH with a near-ubiquitous presence at the meeting by way of its multiple alliances and data on Revlimid and Pomalyst.

Despite reporting a second AG-221-related death Agios celebrated phase I data in advanced IDH2 mutation-positive malignancies in spectacular fashion. Its stock rose 35%, $20m came in when Celgene extended a partnership, and a $175m secondary was announced; the fund-raising was expanded to $220m yesterday.

These successes aside, by far the biggest story of ASH concerned advances in treatments involving T-cell manipulation, in particular chimaeric antigen receptor T-cell (CART) therapy.

Kite had floated on Nasdaq in June, and took the opportunity of ASH to announce a $150m secondary offering. Things went even better than planned, with the fund-raising being upsized and premium-priced this week to raise $189m. Juno and Bellicum priced their own IPOs just as ASH finished, and now look set to raise $175m and $115m respectively.

The flotation of Juno will be one of this year’s biggest biotech events, and shows just how the enthusiasm for CART therapies has grown. At these levels of hype any hint of a setback could be felt acutely, irrespective of how spectacular the leading players’ data have been.

Indeed, short interest in Kite is creeping up. The IP behind CARTs is far from clear, and safety and cost of manufacturing are being closely watched. A Juno-specific issue is the group’s management team: three executives were formerly with the cell therapy play Dendreon, which recently collapsed under its debts.

Bellicum specialises in work on a so-called “suicide switch”, which some believe will be required to allay CART safety concerns; Juno has a similar approach in preclinical trials. The Juno IPO is also noteworthy for unusually large earnouts for its academic partners – $375m to Fred Hutchinson centre and $150m to Memorial Sloan Kettering – though these are triggered at relatively high share prices.

Three fallers

It says something about a meeting being positively share price moving when only three fallers are identified among ASH-relevant stocks.

MEI Pharma failed to excite the markets with a phase II pracinostat poster in AML, while Seattle Genetics did manage to report a positive update on the Aethera study of Adcetris in Hodgkin’s lymphoma. But, despite a PFS benefit, lack of an overall survival advantage – the numerical difference actually favoured control – spooked investors.

There might also have been some read-across from positive Hodgkin’s data for the anti-PD-1s Keytruda and Opdivo, with the 9p24.1 genetic mutation providing a rationale for checkpoint inhibition in this setting.

Meanwhile, Epizyme’s DOT1L inhibitor EPZ-5676 produced only one additional complete remission to add to the two reported in January, though the group’s chief executive, Robert Gould, stressed to EP Vantage that eight of 34 leukaemia patients showed other signs of activity. Dosing had been escalated up to 90mg/m2 without generating significant benefit, so 54mg/m2 will now be expanded.

In contrast to last year Pharmacyclics had a good ASH, reporting a multitude of results to back expanded uses of its “pipeline within a drug”, Imbruvica. In an interview with EP Vantage Darrin Beaupre, vice-president of clinical medicine, highlighted future combination use with checkpoint inhibitors, and a follow-on BTK inhibitor.

Venetoclax threat

However, AbbVie/Roche’s venetoclax is a threat. Dosing adjustments appear to have allayed fears over tumour lysis syndrome, while one of the most impressive things about a venetoclax/Rituxan combo CLL trial profiled at ASH was that none of five responding patients who discontinued treatment had progressed up to 14 months later.

TG Therapeutics was up on several presentations, including an update showing no liver toxicity in a triple combo of Imbruvica, ublituximab and TG-1202. Outside oncology, Roche also scored a success with ACE910, its bispecific factor VIIIa-mimicking antibody for haemophilia. The highest dose cohort in a first-in-human study was unveiled at ASH, showing no bleeding episodes.

Geron’s 38% rise was the result of a deal struck with Johnson & Johnson, while the imetelstat update it presented at ASH actually sent the stock down this week. Sunesis rose from a low base, driven by ASH’s peculiar move to highlight in a late-breaker a data-mined result for vosaroxin (Qinprezo) in the failed Valor study.

Meanwhile, Isis reported data showing that its antisense oligonucleotide anticoagulant FXI-ASO at the highest dose was superior to enoxaparin. This was relevant not only to Isis but to other RNA stocks including Dicerna and Alnylam, which rose in tandem in a similar way that gene therapy players like Uniqure and Avalanche Biotechnologies climbed on the Bluebird data.

It is also worth pointing out the remarkable gains made by the Nasdaq biotech index overall since a lull in October seemed to presage the end of the worst excesses of the biotech bull market. But as long as good data continue to emerge and big pharma keeps buying – neither looks likely to ease up – markets will reward the relevant stocks.

The Nasdaq biotech index now stands up 36% year to date. Not only did a post-Asco summer lull not materialise, but ASH provided investors with a second big opportunity to fill their boots.

To contact the writer of this story email Jacob Plieth in London at [email protected] or follow @JacobEPVantage on Twitter.