Affimed did the decent thing scientifically and commercially in scrapping development of AFM11 yesterday. One thing that an industry pipeline flooded with CARs, antibodies and drug conjugates does not need is yet another project targeting CD19, and the markets shrugged off the discontinuation, sending Affimed down just 7%.
The bigger question is whether the problems that led to the move – AFM11 had been put on clinical hold last October after neurological side effects caused one death and two cases of life-threatening toxicity – might relate to the technology as well as the target.
There is no suggestion that this is the case, of course, but then neither has a satisfactory explanation been provided as to why the toxicity with AFM11 was apparently so bad. The typical side effects of CD19-directed CAR-T therapy and bispecifics, cytokine storm and neurotoxicity, can be severe, but are now largely controllable.
Moreover, it is difficult to see the problem as an imbalance of risk/benefit, as toxicity arising from T-cell recruitment tends to correlate with efficacy.
Affimed is not the only company to see bispecific toxicity issues. In 2017 Johnson & Johnson discontinued the anti-CD19 bispecific duvortuxizumab at least partly because of its side effects, while another Macrogenics bispecific, the B7-H3-targeting MGD009, has spent time on clinical hold.
Be that as it may, Affimed has now turned its back not only on CD19 but on the entire concept of T-cell recruitment. AFM11 comprised domains targeting CD19 and CD3, the latter to bind T cells and bring them into close contact with the antigen-expressing cancer cells.
Instead the group will now focus on projects that aim to engage innate immunity, it told an analyst presentation yesterday. Its assets here comprise bispecifics that hit an antigen of choice as well as CD16A, a protein that appears to be expressed on NK cells and macrophages – components of the innate immune system.
In reality the markets could have seen this change of focus coming a mile off. Last August Roche paid Affimed $96m in a discovery alliance focusing precisely on development of novel NK cell engager immunotherapeutics.
Affimed vs Argenx
Affimed investors will have to hope that this change of focus can reinvigorate the company’s anaemic share price. They might also be casting an eye at the group’s antibody design peer, Belgium’s Argenx, which boasts a valuation over 20 times that of Affimed.
Coincidentally Argenx yesterday also presented an R&D update, at which it highlighted an anti-complement C2 MAb, ARGX-117, which it called a “pipeline in a product” for severe autoimmunity. Nevertheless, its stock fell 5% on rumbling concerns over the group’s bloated valuation and lack of imminent catalysts.
For its part, Affimed spent much of yesterday’s call playing up the prospects of its new lead project, AFM13, which targets CD30, though here there has been a delay. A registrational study in CD30-positive lymphoma was to have begun by mid-2019, but will now not start until the second half while the group answers FDA questions about the protocol it has submitted.
Affimed also highlighted AFM24, which targets wild-type EGFR and is expected to be studied in solid tumours that overexpress EGFR, including those with KRAS mutations. Targeting KRAS is a hot topic, especially for followers of Amgen and Mirati tracking the upcoming Asco conference; little wonder that this preclinical bispecific got so much attention on Affimed’s call.