Ash 2017 preview – Blueprint and Stemline celebrate

Beyond the excitement over CAR-T yesterday’s abstract drop for the upcoming Ash conference prompted several stock moves, the most notable of which was Blueprint Medicines’ 8% climb on a surprise inclusion in one of the meeting’s press briefings.

Also celebrating was Stemline Therapeutics, whose investors will eagerly await data from its controversial CD123-targeting compound SL-401, which just met the primary endpoint in its pivotal trial. Less fortunate were followers of Incyte, TG Therapeutics and Agios, which fell despite revealing ostensibly positive Ash updates (see table below).

Incyte’s offering comprises over 30 presentations, most relating to its marketed Jak inhibitor, Jakafi. Earlier-stage assets, including a follow-on Jak, INCB052793, the bromodomain inhibitor INCB057643 and the PI3k delta blocker INCB050465, should also generate investor interest.

PI3k assets might be undergoing a resurgence: Infinity recently surged 122% on excitement over IPI-549, a follow-on to duvelisib. Infinity ditched duvelisib, but Verastem has just revealed that this project will be filed in the first quarter. Nevertheless, Incyte was off 4% yesterday, perhaps as investors took another opportunity to sell on the news.

TG Therapeutics and Agios both fell 4%. The former will present several abstracts on another PI3k delta inhibitor, umbralisib, while the latter should pique interest at Ash with data for ivosidenib, an asset Celgene handed back some time ago; this is Agios’s next most advanced project after Idhifa, and should be filed for AML in the current quarter.

Stemline’s SL-401 is also to be filed in a similar timeframe, for blastic plasmacytoid dendritic cell neoplasm. Despite a recent scare over capillary leak syndrome SL-401’s pivotal phase II study this week met its primary endpoint – Stemline’s stock surged 29% – and investors will keenly await Ash for presentation of the full dataset.

Other CD123-targeting assets, such as Macrogenics’ flotetuzumab, will be closely watched given the side effects that nearly derailed Stemline, and which have sidelined the likes of Cellectis’s UCART123 and J&J/Xencor’s talacotuzumab.

A Blueprint for victory

The victor’s trophy on the day of the Ash abstract drop went to Blueprint – unusual in an age where immuno-oncology is all the rage – which rose 8%. The group’s small-molecule Kit-PDGFRa inhibitor BLU-285 has been deemed sufficiently promising in systemic mastocytosis to be highlighted in a December 10 Ash press briefing.

That afternoon, a separate press briefing will see Gilead and Novartis square off with CD19-directed CAR-T therapies for lymphoma. Also being highlighted are Bluebird’s results with bb2121, an anti-BCMA CAR for multiple myeloma (Ash 2017 – Early surges for Bluebird and Juno, November 1, 2017).

Data with bb2121 have so far been breathtaking, but the BCMA-targeting space is becoming crowded. Competition at Ash will include Novartis’s CART-BCMA, Glaxosmithkline’s antibody-drug conjugate GSK2857916, and Juno’s JCARH125 – a novel CAR with a human binder preferential for membrane-bound versus soluble BCMA.

Selected presentations at Ash 2017
Project Company Study Trial ID Ash abstract
BMN 270 Biomarin AAV5-FVIII gene therapy NCT02576795 603
Beta-globin gene therapy San Raffaele Telethon Transfusion-dependent beta-thalassaemia NCT02453477 355
CL20-i4-EF1α-hGC-OPT St Jude Children's Research Hospital Gene therapy for X-linked SCID NCT01512888 523
GBT440 Global Blood Therapeutics Paediatric sickle cell patients NCT02850406 689
ALXN1210  Xencor/Alexion Phase I PNH data NCT02598583 3482
SL-401 Stemline Therapeutics Pivotal phase II PBDCN data NCT02113982 1298
Flotetuzumab Macrogenics CD123 bispecific in AML/MDS NCT02152956 1365
Selinexor  Karyopharm Phase 1b/2 Stomp study in multiple myeloma  NCT02343042 3135
Yescarta Gilead Zuma-1 study in DLBCL NCT02348216 578
Kymriah Novartis Juliet study in DLBCL NCT02445248 577
JCAR017 Juno Transcend study in DLBCL NCT02631044 581
UCART19 Pfizer/Servier Paediatric ALL study update NCT02808442 1271
CD33-CAR-T cells Ziopharm/Intrexon CD33-positive AML study NCT03126864 1376
bb2121 Bluebird Multiple myeloma update NCT02658929 740
CART-BCMA Novartis Multiple myeloma update NCT02546167 505
JCARH125 Juno Fully human BCMA CAR in multiple myeloma None 1813
GSK2857916 Glaxosmithkline/Seattle Genetics BCMA ADC in multiple myeloma NCT02064387 741
ACTR087 Unum Therapeutics Ab-coupled TCRs in CD20+ lymphoma NCT02776813 580
INCB050465 Incyte Citadel-101 study of PI3k delta inhibitor  NCT02018861 410
Ublituximab + umbralisib TG Therapeutics Combined with Keytruda in r/r CLL NCT02535286 3010
Ivosidenib Agios IDH1-mutant AML NCT02074839 725
CC-122 Celgene Next-gen IMID in DLBCL NCT02031419 1551
BLU-285  Blueprint Medicines Phase I in advanced systemic mastocytosis NCT02561988 2
Betalutin Nordic Nanovector Anti-CD37 ADC in NHL NCT01796171 2769
Polatuzumab vedotin Roche Anti-CD79b ADC + Rituxan in DLBCL NCT02257567 2821
ADCT-301 ADC Therapeutics Anti-CD25 ADC in lymphoma NCT02432235 1510
ADCT-402 ADC Therapeutics First-in-human lymphoma study NCT02669017 187
TTI-621  Trillium Early acitivty in DLBCL NCT02663518 4116
CAEL-101 Fortress Biotech Chimaeric fibril-reactive MAb in AL amyloidosis NCT02245867 509
Mogamulizumab Kyowa Hakko Kirin Phase III Mavoric study in CTCL NCT01728805 817
Cemiplimab Regeneron Anti-PD-1 MAb +/- REGN1979 NCT02651662 1495

Given the data being generated it is unsurprising that BCMA is a major focus of Ash. Other broad areas of interest include diffuse large B-cell lymphoma, antibody-drug conjugates (ADCs) and therapies for genetic disorders.

Among the last group, press briefings will highlight gene therapies for beta-thalassaemia and severe combined immunodeficiency developed by San Raffaele Telethon and St Jude Children's Research Hospital respectively – neither appears to have an industry partner – and for haemophilia A from Biomarin (BMN 270).

And of numerous presentations featuring ADCs some of the most keenly awaited might be those featuring early data on ADC Therapeutics’ ADCT-301 and ADCT-402. The group recently completed a monster $200m private financing round that it said would largely go towards advancing these two assets into registrational trials; those who see in ADC an imminent biotech flotation will be especially interested.

Being private at least ADC does not need to worry about falling victim to a typical Ash pattern, whereby biotech stocks tend to trade up in the run-up to the meeting, before falling precipitously in its aftermath as the holiday season sets in. Though only the six Ash late-breaking presentations have yet to be revealed, no doubt plenty more price moves lie ahead.

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com or follow @JacobPlieth on Twitter. Jacob will be reporting from the Ash conference, which will be taking place in Atlanta on December 9-12.

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