Big Pharma and CAR-T: Testing the water or in at the deep end?

Following Novartis and Gilead’s success, others are “scrambling to build up their T-Cell capabilities,” say venture capitalists. We look at where Big Pharma stands in this blossoming sector.

Big Pharma firms will be looking at strategies to enter the chimeric antigen receptor (CAR) T-cell space, if they have not already, spurred on by the approvals in 2017 of Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) .

This was the view of commentators and analysts at Phacilitate in Miami, Florida last month.

Having its feet in the water but differing levels of commitment. Big Pharma and CAR-T. Image: iStock/freie-kreation

Anna French, an associate at healthcare venture capitalist firm Qiming Ventures Partners, said Big Pharma firms “have been scrambling to build up their T-Cell capabilities. In some cases, there is a real commitment to that, and in other cases it’s a bit more exploratory.”

Reni Benjamin, MD and senior biotechnology analyst at Raymond James Financial, told delegates “all the major pharma companies now are in cell therapies,” though their interest and investment greatly differ.

Meanwhile Alberto Santagustino, head of Cell and Gene Technologies (CGT) at CDMO Lonza, said four fifths of innovation comes out of small companies. Historically, these biotech-type firms are snapped up by Big Pharma firms looking to supplement or replace their pipelines. While this has happened in the CAR-T space with the likes of Juno, Kite and Avexis, firms like bluebird, Servier and Sangamo remain independent, though embroiled in Big Pharma partnerships.

Focusing on CAR-T, we take a look at how Big Pharma has taken to this space.

Deep end

Adding up regulatory successes with investments and pipelines, Novartis comes out tops in the CAR-T space. The firm teamed up with the University of Pennsylvania in 2011, invested in a manufacturing site the year after, and became the pioneers in CAR-T through Kymriah’s approval.

Perhaps buoyed by Kymriah’s success, the firm has since laid out plans to widen its production network, and has boosted its pipeline through M&A activity. Novartis acquired AveXis for $8.7 billion last May, adding gene therapy lead candidate Zolgensma (onasemnogene abeparvovec), previously known as AVXS-101 in development for the treatment of spinal muscular atrophy (SMA).

Gilead Sciences also sits in the deep end of CAR-T, though broke into the space through the acquisition of Yescarta developer Kite Pharma for US$11.9 billion in August 2017, weeks before the product achieved US approval.

Since then, the firm has invested in its global Yescarta network, and entered a potential $3 billion collaboration with Sangamo Therapeutics to develop allogeneic therapies in oncology.

Megamergers and mixed interest

Not so submerged but moving towards the deep end is Bristol-Myers Squibb, through its proposed $74 billion merger with Celgene. If the deal goes through, it will propel Bristol Meyers Squibb into the CAR-T space.

Celgene has a partnership in place with bluebird bio, and in March 2018 the firm completed the $9 billion acquisition of Juno Therapeutics, adding CAR-T technology and manufacturing capabilities along with a pipeline of hematology and oncology therapies.

Takeda undoubtedly staked a claim to compete among the biggest of Big Pharma through the $62 billion takeover of Shire. But while the merger added a gene therapy candidate for hemophilia, Shire’s pipeline was devoid of CAR-T therapies as the firm sold these as part of its oncology portfolio to Servier in August last year.

But earlier this year, Takeda inked separate CAR-T co-development deals with Memorial Sloan Kettering Cancer Center (MSK) and Noile-Immune Biotech. Furthermore, Takeda’s acquisition of TiGenix following the European approval of allogeneic cell therapy Alofisel (darvadstrocel) shows the firm is aiming to be a serious player in the cell and gene therapy field.

Pfizer has been in the CAR-T space for several years through long-standing partnerships with Cellectis and Servier. But in April 2018, the firm sold the rights to 16 preclinical CAR-T assets and one clinical asset, an allogeneic CAR-T therapy in development for treatment of CD19-expressing hematological malignancies, to Allogene Therapeutics, a newly-formed firm from the founders of Kite Pharma.

Pfizer has taken a 25% stake in Allogene but the move may indicate Pfizer is looking to lower the risk of developing allogeneic CAR-Ts.

J&J, meanwhile, finally took the plunge into CAR-T in December 2017, through a $350 million worldwide collaboration and license agreement with Legend Biotech.

Poolside

Other Big Pharma firms have been less dynamic in the CAR-T space.

GSK partnered with Adaptimmune in 2014, and last year took an option to develop the engineered T-cell therapy NY-ESO program targeting various cancers. Meanwhile, GSK transferred its rare disease gene therapy programs to Orchard Therapeutics, taking a 19.9% stake in the firm in a similar deal to that of Pfizer and Allogene’s.

AstraZeneca partnered with Juno in 2015 to conduct combination clinical trials in immuno-oncology with a CAR-T candidate, but according to clinicaltrials.gov the completion of the study is a long way off.

Meanwhile Roche/Genentech has been quieter in the CAR-T space, though has invested in next-generation T-cell engaging bispecific antibodies.

Eli Lilly has so far resisted the space. On CAR-T, CEO Dave Ricks told Reuters “the data is amazing, but practically, it’s not reaching many people,” earlier this year.