Since two big events a year ago, when Gilead bought Kite Pharma for $11.9bn and Novartis’s Kymriah became the world’s first CAR-T therapy, investors interested in cell therapy have had little to shout about. But now there are signs of a resurgence.
The latest came on Friday, as the team that sold Kite revealed that its new venture, Allogene, would seek a $100m flotation – barely five months after being founded. Allogene is now Cellectis’s key partner, and so investors in the French group should be poring over newly revealed information in the IPO document.
The most interesting details concern the pipeline assets on which Allogene will focus. Most of these date back to Cellectis’s initial alliance with Pfizer, focusing on the discovery of 15 antigens of which only BCMA and EGFRvIII had been disclosed.
Allogene, of course, took over Pfizer’s rights to this deal, as well as rights to Cellectis’s lead, UCART19, which Pfizer had licensed from Cellectis’s partner Servier (Pfizer washes its hands of Cellectis, April 3, 2018). Allogene’s IPO filing also reveals previously secret financial terms of this last tie-up.
|CD19||UCART19||Ongoing phase I trials in paediatric & adult ALL|
|CD19||ALLO-501||NHL; manufacturing differs from UCART19|
|BCMA*||ALLO-715||Multiple myeloma IND filing 2019|
|Flt3*||ALLO-819||AML, same target as Rydapt|
|CD70*||Unnamed||NHL & renal cell cancer, same target as cusatuzumab|
|DLL3*||Unnamed||SCLC, same target as Rova-T|
|CD52||ALLO-647||Lymphodepleting MAb, same target as Campath|
|Note: *Talen-edited, allogeneic CAR-Ts derived from 15-target alliance between Pfizer and Cellectis. Source: Allogene S-1 filing.|
As for targets, Allogene says it will continue to pursue BCMA, fast becoming a crowded space, and newly discloses a focus on Flt3, CD70 and DLL3, which are far less popular with CAR-T players. DLL3 is the target of Abbvie’s ill-fated Rova-T, so Allogene will hope that a CAR-T approach delivers better efficacy than an antibody-drug conjugate.
ALLO-501 is structurally identical to UCART19, but uses a different manufacturing process, while ALLO-647 seems to be an attempt to develop a better lymphodepleting chemo than Campath. It appears that the EGFRvIII asset is not being taken forward.
The IPO proceeds will primarily fund UCART19, an asset that has proceeded at a glacial pace since clinical trials began in 2016. If Pfizer had lost interest in UCART19 then Allogene’s involvement will be viewed positively, and investors will also note the light the IPO document sheds on the details of the 2015 deal under which Pfizer acquired rights to UCART19.
This asset had been optioned to Servier, and Pfizer outmanoeuvred Cellectis by licensing it directly from Servier once that company had exercised its option with Cellectis. Until now all that was known was that the exercise, announced on November 19, 2015, cost Servier $38.2m up front, plus $300m in milestones.
Allogene’s IPO document reveals that Pfizer’s end of the deal cost the US big pharma giant just $29m up front and $381.5m in milestones, making Servier’s acquiescence seem puzzling. Moreover, Allogene states that the Pfizer/Servier deal was done “in October 2015”, meaning that by the time Servier triggered the Cellectis option in November the asset was effectively already Pfizer’s.
Whatever the details, the fact that Allogene is already attempting to float is remarkable. The company was born with a huge, $300m series A financing round in April, and this month added $100m in private cash.
In June the UK CAR-T player Autolus floated in a $150m listing, and the relatively early development stage at which both companies are going public will raise eyebrows. That said, if this is the sign of a resurgence, then neither company should find it difficult to raise more cash on Nasdaq.
Much of the sentiment behind Allogene stems from Arie Belldegrun and David Chang, the management team that sold Kite to Gilead. Both now run Allogene, and have attracted numerous other key ex-Kite employees – though one, Margo Roberts, inventor of an important Kite patent and formerly chief scientific officer, passed up this opportunity and recently emerged as a director of Celyad.
The next move from another private cell therapy group, Tmunity, based on work at University of Pennsylvania and run by Oz Azam, former head of cell therapy at Novartis, is eagerly awaited.