JP Morgan 2022 – Beam and Mammoth hook big pharma partners

Beam signs Pfizer up for $300m up front, while Mammoth’s deal with Bayer is worth a more modest $40m.

Some investors believe that 2022 will be the year in which in vivo gene editing eclipses in vitro technology. And some big pharma groups obviously see potential here, with Pfizer and Bayer both announcing deals in the space today.

Pfizer has bet $300m up front on Beam Therapeutics’ base-editing technology, which promises greater precision than the conventional Crispr/Cas9 approach. Meanwhile, Bayer is paying $40m to collaborate with Mammoth on its “ultra-small” Crispr systems – joining Vertex, which already has an agreement with the private biotech for a similar sum.

Beam me up

Details on both partnerships are sparse. Pfizer and Beam will only say that they are targeting three undisclosed rare genetic diseases of the liver, muscle and central nervous system, which are separate from Beam’s existing programmes. And the groups will be using mRNA and lipid nanoparticles to deliver base editors to the target organs.

Beam’s own in vivo projects primarily target liver diseases, the most advanced being for glycogen storage disorder type 1a. The company also has in vitro projects for sickle cell disease, like various other groups, as well as base-edited Car-T therapies for blood cancers.

Beam is already working with Apellis on in vivo editing for complement-driven diseases, but this agreement is dwarfed by today’s deal with Pfizer.

Pfizer has long been interested in gene therapies, but progress has been far from smooth: assets in development for haemophilia A and Duchenne muscular dystrophy are on clinical hold, the latter after the death of a patient in a phase 1b trial. The DMD project, fordadistrogene movaparvovec – which Pfizer gained through the $625m purchase of Bamboo Therapeutics – had already been linked with severe muscle weakness and myocarditis.

And pivotal results with the Roche-partnered haemophilia B asset, which had once been expected last year, are not due until 2023.

Getting into gene editing – and in vivo gene editing at that – is an obvious next step for Pfizer. The group will have to hope that it has chosen wisely in Beam, which has likened its base-editing approach to a pencil versus the scissors of other gene editing technologies (Interview – Beam heralds new Crispr edit, but patent issues remain, May 17, 2018).

Far from Mammoth

Meanwhile, Mammoth is facing criticism from some quarters for its deals being “underwhelming” in terms of the up-front sums involved – but the group’s chief business officer, Peter Nell, defended its agreements.

“You have to put it into perspective,” he told Evaluate Vantage. “We’re in the discovery phase, and for that stage I think the deal terms are pretty good.”

He is adamant that Mammoth is not giving away too much, too cheaply. “That was part of our consideration, that we avoid that. But we cannot do 20 indications [alone].”

Otherwise Mammoth and Bayer are not saying much, apart from that the collaboration will involve five indications with an initial focus on liver disease, and that these do not overlap with the two undisclosed rare diseases covered by the Vertex deal (Vertex goes small with Mammoth deal, October 26, 2021). As with the Vertex tie-up, Mammoth is not disclosing whether the gene editing will be delivered via lipid nanoparticles or more conventional AAV vectors.

The unique selling point with Mammoth’s systems is that they use enzymes such as Cas14 and CasΦ, which are much smaller than Cas9. This is particularly relevant for AAV vectors, which have a limit on the size of the cargo they can carry.

Bayer's pharma division first got involved in Crispr/Cas9 gene editing through Casebia, a joint venture with Crispr Therapeutics formed in 2016. However, the German group took a step back in late 2019, and things have been quiet since.

Bayer does have various gene therapy projects in development, via the arm's length acquisitions of Askbio and Bluerock, plus other collaborations (Bayer’s gene therapy juggling act, February 5, 2021).

Stefan Oelrich, head of Bayer’s pharmaceuticals division, told Vantage over email that Mammoth’s technology could be combined with its stem cell-based efforts, as well as being a “standalone IND-generating engine”.

Last year Intellia provided the first evidence that in vivo gene editing could work, and the approach is clearly flavour of the month. Next, the partnerships announced today must bear some fruit to help justify the hype.

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