In licensing Kyowa Kirin’s anti-Ox40 MAb KHK4083 Amgen is ploughing a similar furrow to Sanofi. The French group bought Kymab at the start of the year to obtain its Ox40L inhibitor KY1005, which, like ’4083, is at the phase 2 stage in atopic dermatitis.
Amgen's move continues the rehabilitation of Ox40 modulation in autoimmune or inflammatory disorders after the unremarkable performance of Ox40 agonism in oncology. The next question is where today’s deal leaves Ichnos Sciences, the only remaining independent clinical-stage developer of Ox40 inhibitors.
Amgen has paid $400m up front for the privilege of leading development, manufacturing and sale of KHK4083 in atopic dermatitis worldwide except Japan, where Kyowa Kirin will retain all rights. In the US, the two groups will co-promote the MAb, and Kyowa Kirin will be able to opt in to co-promote in other markets too.
Milestone payments could add up to a potential additional $850m, and Kyowa Kirin could scoop “significant” global royalties if the project makes it to market. Amgen also hopes to apply data from its Decode Genetics subsidiary to find new indications in which ’4083 might have a chance.
Full data from ’4083’s phase 2 trial are to be released at the EADV conference in late September. Until then all that is known is that the Mab beat placebo on percent change from baseline in eczema area and severity index (Easi) after a four-month course, and significant differences were also seen in Easi-75 and IGA of 0 or 1 at the same time point.
Asked on a conference call how the project’s efficacy might stack up against established eczema products such as Dupixent, Amgen management would only refer to its “unique mechanism of action”. The group believes that as well as blocking Ox40 signalling ’4083 also helps deplete activated effector T cells. Effector T cells expressing Ox40 are believed to be present in dermatitis patients’ lesions.
Cross-trial comparisons suggest that, on efficacy, the bar to beat is Abbvie’s Jak Rinvoq. That said, the full phase 2 data on Sanofi’s KY1005 have not yet emerged either.
Toxicity will also be an important point, particularly in a patient population where long-term dosing is required for disease control. Again Amgen did not go into detail, but executives said they were “impressed” with ’4083’s safety.
So, with Amgen taking ’4083 forward and Sanofi working on KY1005, the remaining clinical-stage autoimmune-focused Ox40 project is Ichnos’s telazorlimab, also called ISB 830 and GBR 830. This too has completed phase 2 studies in eczema, and the similarities do not end there: Ichnos has made it clear that the MAb is available for partnering.
Perhaps this is a sign that Ichnos, which was spun out of the generics-focused group Glenmark Pharmaceuticals in October 2019, does not believe that it can make a go of this opportunity on its own, or at least that it wants to focus on its core oncology pipeline. Possibly, however, Ichnos has realised that larger groups are taking a punt on this mechanism, and has seen its chance to hook either a partner or a buyer.