AACR 2021 – Affimed wins, Oncternal loses

Phase 1 results at this weekend’s virtual AACR show an unexpected win for Affimed’s AFM13 and a disappointing update from Oncternal.

Merck & Co’s $2.8bn takeover of Velosbio last year made this weekend’s AACR an unmissable conference for investors in Oncternal, a group with links to Velosbio. However, Oncternal’s presentation of a clinical update for cirmtuzumab in breast cancer disappointed, and the stock fell 12%.

Instead, the biggest immediate winner of AACR was Affimed, which delivered a stunning 100% remission rate with AFM13, an NK cell-engaging bispecific to which it had pivoted in 2019; remarkably, Affimed’s data are not even contained in a formal AACR abstract.

Both the AFM13 and cirmtuzumab results have been a long time coming.

The cirmtuzumab trial, in Her2-negative breast cancer, started three years ago, and an update at the 2019 San Antonio Breast Cancer Symposium reported four partial remissions in seven evaluable subjects. 17 months later only eight more patients are evaluable, and there have been four further remissions, the AACR presentation revealed today.

Cirmtuzumab is an antibody against Ror1, and the slow pace of this study is likely explained by the fact that until Velosbio’s takeover last November few had paid this mechanism much attention. Velosbio has rights to develop cirmtuzumab specifically as part of an antibody-drug conjugate, coded VLS-101, and its former chief executive, Dave Johnson, had earlier chaired Oncternal.

The fall in Oncternal’s stock came in response to the AACR abstract being released yesterday; this showed seven of 15 subjects responding, and today’s presentation added an eighth partial responder.

Cirmtuzumab in Her2-negative breast cancer. Source: Dr Rebecca Shatsky & AACR.

But there was little on durability, beyond one response said to be ongoing 52 weeks later. And little is known about the relationship between target expression and response: only eight of 15 subjects had available tissue for analysis, and all eight were Ror1 expressers, but it has not been disclosed how many of these were responders.

If Oncternal’s share price fall is down to the slight numerical decline in remission rate between SABCS 2019 and AACR 2021 the small numbers involved suggest this to be short-sighted. A much greater concern for investors should be that, in a Ror1-related takeover flurry, Oncternal remains solo.

Affimed's shocker

Affimed had much better luck, closing up 23% yesterday after its shock revelation that MD Anderson’s Dr Katy Rezvani would discuss data at AACR describing AFM13 yielding four remissions, including two complete, in the first four Hodgkin’s lymphoma subjects treated in an academic-sponsored phase 1 trial.

This came out of the blue, as the unveiling of AACR abstract titles in March showed nothing of importance from Affimed. But it yesterday emerged that the case reports are due to be discussed at AACR on Tuesday as part of a major symposium summarising developments in NK cell therapies, whose prerecorded content is now available.

The study involves giving AFM13 together with cord blood-derived allogeneic NK cells, intending these to be recruited to the tumour site by the Affimed molecule. Dr Rezvani, an NK cell specialist, said the first three subjects in cohort one, given the lowest NK cell dose, all went into remission, one complete.

In a statement Affimed added a fourth case report of the first subject on a slightly higher cell dose, who was another complete responder. The four patients had failed multiple lines of Hodgkin’s lymphoma therapy, including Seagen’s Adcetris and PD-1 blockade, and one had relapsed on anti-CD30 Car-T and stem cell transplant.

It was nearly two years ago that Affimed pivoted away from developing T cell-recruiting bispecifics, a highly competitive field, to ones engaging NK cells, of which AFM13 is now its most advanced. AFM13 hits the Hodgkin’s lymphoma target CD30 as well as CD16A, a protein expressed on NK cells.

However, in contrast to the academic study, Affimed’s own clinical focus is to deliver AFM13 without adoptive cell therapy, relying on the molecule engaging the body’s own NK cells. A phase 2 Affimed-sponsored trial seeking to enrol 145 CD30-positive lymphoma or mycosis fungoides patients is under way.

On Wednesday afternoon Affimed is to hold a call to discuss the data further. Investors should look for information on how the case reports affect the group’s development plans for AFM13, an asset Evaluate Pharma sellside consensus sees selling $170m in 2026.

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