Kelonia turns its ASH late-breaker into a buyout

A 100% response rate – partly unconfirmed and among just four multiple myeloma patients – has proved enough to trigger the latest buyout of an in vivo Car-T company. The lucky biotech is privately owned Kelonia, which Lilly bought on Monday for $3.25bn up front plus the promise of more in future.

This suggests that, despite the recent proliferation of clinical-stage in vivo Car-T assets, the value of the companies involved is going up: the last one to be acquired, Orbital, was picked up for $1.5bn, while the biggest deal until now involved Capstan for $2.1bn. This is Lilly’s second move into in vivo Car-T, after the acquisition of the autoimmune-focused Orna Therapeutics in February.

Late-breaker

For Kelonia the die was cast as soon as this company scored an unexpected ASH late-breaker in December.

That dataset involved four multiple myeloma patients given Kelonia’s lead project, the anti-BCMA KLN-1010. The headline number was four responses, all MRD-negative, comprising two confirmed partial responses, one unconfirmed complete remission (earlier scored as a confirmed very good PR), and one unconfirmed partial response.

Very high response rates in multiple myeloma are nothing new, so probably the more interesting aspects of this dataset were the lack of ICANS or delayed neurotoxicity, and the fact that all instances of cytokine release syndrome were grade 1-2. Moreover, the KLN-1010 procedure needs no lymphodepletion, with robust Car-T cell expansion and persistence observed.

In vivo Car-T involves the generation of Car-T cells inside a patient’s body, rather than by removing, transfecting and reinfusing cells, as is standard with current ex vivo approaches.

Those following the various ways different groups are using to deliver the genetic material needed to create Car-T cells in vivo will note that Kelonia uses a modified lentivector for this purpose. That’s broadly similar to the approach taken by Interius (bought by Gilead for $350m), Umoja (optioned to AbbVie) and Esobiotec (acquired by AstraZeneca for $425m).

In contrast Capstan, which AbbVie took over last year for $2.1bn, delivers genetic material via lipid nanoparticle mRNA. And Orbital Therapeutics, which Bristol Myers Squibb acquired for $1.5bn, uses LNP-delivered circular RNA. However, both Capstan and Orbital were primarily focused on autoimmune disease, a focus underlined by AbbVie’s involvement with Umoja in B-cell malignancies.

Like AbbVie, Lilly now appears to be taking a dichotomous approach in in vivo Car-T, focusing oncology use on Kelonia, and autoimmune indications on Orna Therapeutics, which it acquired just two months ago. That deal was worth $2.4bn in biodollars, but the up-front amount wasn’t disclosed.

Selected in vivo Car-T deals

Source: OncologyPipeline.

One surprising aspect of the Kelonia takeout is that it wasn’t Astellas that acquired this company. Astellas and Kelonia have collaborated since early 2024 on the development of cancer-focused therapeutics, and as such Astellas will be more familiar than most with Kelonia’s approach; perhaps it came down to valuation, and only Lilly, flush with cash from its obesity franchise, had deep enough pockets and a sufficiently big appetite.

And this is certainly a premium-priced deal, notwithstanding the promise of the early KLN-1010 data; in addition to the $3.25bn in up-front cash Lilly has agreed to pay the Kelonia sellers up to another $3.75bn in milestones, the triggers for which remain undisclosed. Kelonia appears to have raised just $50m in venture capital, through a 2022 series A round.

In the meantime, the field of in vivo Car-T has been growing apace. OncologyPipeline currently lists 100 separate projects, including 20 in biopharma company-sponsored clinical trials. But actual human data remain limited.

The Astra-owned EsoBiotec is developing an anti-BCMA construct ESO-T01, which last year yielded two stringent complete responses, plus two partial responses, among four multiple myeloma patients treated in a Chinese trial. More recently this was updated to objective responses in four of five patients, including three stringent complete remissions.

However, on the safety side there were three cases of grade 3 cytokine release, and one patient died of ICANS. Right now this looks like a key point of differentiation for Kelonia.