The private UK biotech Cell Medica already had a longstanding deal with Baylor College, so the new collaboration the partners signed on Friday might seem like a mere deepening of this relationship.
In fact it is much more than that, taking Cell Medica into CAR-T – a fact that should put the group in a strong position when it goes out to raise more cash later this year. And this is CAR-T with a difference, investigating constructs expressed on a distinct subtype of T cells, which no other group beside Baylor seems to be doing.
The focus is on autologous natural killer (NK) T cells, a relatively rare T-cell subtype. What makes NK T cells particularly interesting is that they home in on tumours particularly strongly even without antigen recognition, says Baylor’s Dr Leonid Metelitsa, as well as producing large amounts of cytokines.
“When we analysed primary tumour samples from patients with stage IV neuroblastoma ... in the tumour microenvironment we found that the only marker that could predict long-term outcome was the presence of NK T cells,” Dr Metelitsa, whose lab has pioneered work on this cell type over the past 16 years, tells EP Vantage.
As to targets, however, both Dr Metelitsa and Cell Medica’s chief executive, Gregg Sando, become cagey, saying these have yet to be decided. They do say the focus will be on CARs as well engineered T-cell receptors, and strictly on solid tumour indications.
However, on Friday the pipeline on Cell Medica’s website displayed NK T cell-associated CAR projects against the antigens GD2, GPC3 and CSPG4, as well as an engineered T-cell receptor project against Survivin.
Mr Sando admitted that these were some of the targets that Friday’s collaboration would cover. “But that’s just reflecting the history of the Baylor research ... we have the ability to look at different targets,” he told EP Vantage. “We haven’t at this point committed to a target.”
Shortly afterwards these projects were removed from Cell Medica’s website. The antigens are particularly interesting because, while several other groups are working on GD2, there seems to be little competing interest in the other three antigens.
|Some applications of Baylor's NK T cell technology|
|CMD-005||GD2||Neuroblastoma & SCLC||CAR expressed on NK T cells|
|CMD-006||GPC3||Liver cancer||CAR expressed on NK T cells|
|CMD-007||CSPG4||Triple-neg breast cancer, head & neck cancer||CAR expressed on NK T cells|
|CMD-008||Survivin||Pancreas, ovarian & stomach cancers||TCR expressed on NK T cells|
|Source: Cell Medica website, 17 June 2016.|
Cell Medica’s one clinical project comprises genetically unmodified, EBV-specific T cells, and relates to the group’s earlier deal with Baylor (Interview – UK’s Cell Medica looks to confirm T-cell therapy hopes, November 28, 2014).
Being newly armed with a CAR-T pipeline puts Cell Medica in an excellent position to attract new cash – another UK group, Autolus, raised £40m ($27m) in March with just a preclinical CAR-T pipeline. Mr Sando says financing will be sought in the second half of this year.
Over the past six years Cell Medica has brought in around £70m from private investors, and current reserves will fund the cash element of the up-front fee to Baylor.
Development will mirror other tie-ups between academia and corporates: “Baylor will do the early-stage development, preclinical into phase I. In the meantime we look at the manufacturing process, and come [into development] after that,” said Mr Sando. The exclusive licence is for up to five candidates.
The good news is that there are no major problems with handling NK T cells, and just like ordinary T cells they can be transported frozen. They only constitute around 0.1% of peripheral blood T cells, but fortunately can be expanded in very large numbers to clinical scale within three weeks, said Dr Metelitsa.
He also said it was necessary to select type 1 NK T cells and exclude type 2s, which have immunosuppressive properties, but this sorting is straightforward. Intriguingly Dr Metelitsa played down the Clinicaltrials.gov listing for Baylor’s anti-GD2 CAR NK T cell study, saying it would only inform future trial design.
|Ginakit cells||3rd-gen (CD28 & Ox40 co-stim) anti-GD2 CAR-NKT cells with caspase suicide switch; 18 neuroblastoma pts||NCT02439788|
“We need a better CAR, basically,” he stated. With Cell Medica Baylor will focus on cytokine-expressing CARs, as well as suicide switches, or other ways to modulate activity as efficacy is dialled up, and humanised antigen binders.
It will escape nobody’s notice that Baylor already has CAR-T deals with Bellicum, Bluebird, Celgene and Cellectis, while Autolus’s scientific founder, Dr Martin Pule, spent time at the centre before moving back to the UK. However, Mr Sando is confident that there is no IP overlap.
A Baylor spokesman adds: “We carve out a lane for all of our partners so that they don’t step on each other’s toes.”
EP Vantage has published a broad overview of the current opportunities and risks in the CAR-T space. A free copy of the report is available by download.