Bayer's Gene Therapy Juggling

February 05, 2021 Bayer’s gene therapy juggling act

Jacob Plieth

Two arm’s-length acquisitions and two licensing deals have given Bayer a cell and gene therapy unit; now to bring it all together.

Big pharma buyers of biotech companies have historically struggled to preserve targets' entrepreneurial culture, and so a trend has emerged of acquired entities being run at arm’s length. This is precisely Bayer’s plan for Askbio, the private group it bought for $2bn last year to cement its gene therapy ambitions.

However, the German group’s efforts here are not confined to Askbio, stresses Wolfram Carius, the recently appointed head of Bayer’s cell and gene therapy division. With an earlier arm’s-length acquisition and two assets that were licensed in, Bayer’s biggest headache might be how to manage such a disparate business.

In fact, Askbio itself has three separate businesses: a pipeline of therapeutics, a revenue-generating contract manufacturing unit, and a division licensing out technologies, not to mention the occasional spin-out and sale of subsidiary companies like Bamboo and Chatham Therapeutics.

But maybe this is precisely the point of letting biotechs get on with what they do best. Under Bayer’s ownership Askbio will continue to have its own chief executive, Sheila Mikhail, and the same is true for Bluerock Therapeutics, a cell therapy business Bayer bought in 2019 that is still run by Emile Nuwaysir.

Ability and accountability

“Advancing at arm’s length we count on the innovation power of biotechs like Askbio and Bluerock, and give them the ability and accountability to move things forward, while adding ... the regulatory part,” Mr Carius tells Evaluate Vantage. “We think it’ll be a successful model.”

For Bayer the model comprises Askbio’s capabilities, in addition to Bluerock’s labs in New York and Boston, he says. Then, the factor VIII gene therapy BAY 2599023, which came via an Ultragenyx legacy company, is being developed in Berkeley, California, and Bayer has built out its own production capabilities in Toronto and Germany.

For its part, Askbio reckons Bayer was the best partner to bring its AAV-based projects to market, and Ms Mikhail reveals that “we had other companies that were talking with us. We could [alternatively] have done a big IPO and basically continued on our own.”

Perhaps a little-known technical detail swung the deal. “We need small molecules to turn on and off transgene expression,” says the Askbio chief. “With Bayer we’ll now get access to one of largest small-molecule libraries in the world.” Mr Carius admits that when Bayer decided over a year ago to go “full in” on gene therapy it might have been a bit late to the game, in common with many non-US peers. However, business development means that it now has a four-pillar strategy to build on: gene augmentation, gene editing, via Askbio, induced pluripotent stem cells (Bluerock) and anticancer allogeneic cell therapy (Atara).

Specifically this has resulted in an initial pipeline of seven cell and gene therapy assets, five of which are in the clinic.

Bayer's advanced cell & gene therapy projects

Project Originator Description Status

Ph1/2, NCT03588299, BAY Dimension data at Ash 2020; data 2599023/ Therapeutics (acq by Factor VIII gene therapy for haemophilia A due at EAHAD, HTRS, DTX201 Ultragenyx) ISTH, Ash 2021.

Autologous anti-mesothelin Car-T, 1XX co- ATA2271 Atara (via MSKCC) Ph1, NCT02414269* stim + PD-1 dominant negative receptor

AAV2/8- Askbio GAA gene therapy for Pompe disease Ph1/2, NCT03533673 LSPhGAA

NAN-101 Askbio I-1 gene therapy for congestive heart failure Ph1, NCT04179643

AAV2- Askbio (via Brain GDNF gene therapy for Parkinson's Ph1, NCT04167540 GDNF Neurotherapy Bio)

Bluerock Pluripotent stem cell-derived dopaminergic DA01 Therapeutics (via Ph1 imminent neurons for Parkinson's MSKCC)

Allogeneic anti-mesothelin Car-T, 1XX co- ATA3271 Atara (via MSKCC) stim + PD-1 dominant negative receptor, IND stage partial-match EBV+ve cells

*Academic-led study.

The deal with Atara, signed in December, marked Bayer’s cautious entry into Car-T therapy, where the focus will be solid tumours and allogeneic treatment, says Mr Carius.

Atara has shown what he says are clear hints of clinical activity with ATA2271, an autologous anti-mesothelin project, but the icing on the cake is rights to its allogeneic equivalent, ATA3271, based on Atara’s bank of partial-matched EBV-positive T cells, an asset whose next milestone is the filing of a US IND.

Other small players active in cell and gene therapies will be keen to see if Bayer’s deal-making continues. Some might be disappointed, as the company stresses that – at least with Askbio and Bluerock – it has full pipelines to be getting on with.

Nevertheless, Car-T is a different story. “The area where we’ll probably be most active in partnering is the allogeneic cell therapy platform, and maybe to a certain extent gene editing,” Mr Carius says. “We’re obviously very open for any external collaborations.”