New Genmab/Abbvie tie-up rings old bells
Followers of Nordic Nanovector and Oxford Biomedica, among others, will pay close attention to an early focus of yesterday’s deal.
For some seasoned biotech investors yesterday’s broad alliance between Genmab and Abbvie will have rung old bells. While its headline focus is on the anti-CD20 bispecific epcoritamab, behind the scenes lie two other projects against antigens with which some will be very familiar: CD37 and 5T4.
The former is perhaps most famous as being the target of Betalutin, an asset according to whose fortunes Nordic Nanovector’s stock has waxed and waned. 5T4, meanwhile, used to be a major focus of several Oxford Biomedica approaches, but was brought crashing to earth with the failure of Trovax’s pivotal Trist study in 2008.
The CD37 approach, too, has seen discontinuations. As is to be expected, Genmab and Abbvie insist that their bispecifics, DuoHexaBody-CD37 (GEN3009) and DuoBody-CD3x5T4, are “potentially best in class” (Genmab brings on Abbvie for bispecific boost, June 10, 2020).
GEN3009 is a bispecific MAb by virtue of engaging two different epitopes on CD37, and Genmab says this is a unique approach; after showing promise in vitro it is in a dose-escalation lymphoma study. DuoBody-CD3x5T4 is a T-cell-engaging bispecific, but an IND for it has only just been submitted.
There is more advanced industry work on the former antigen than the latter. In late 2016 Norway’s Nordic Nanovector touched a record valuation of $785m as Betalutin impressed in late-line lymphoma settings, but the realisation that work is still very early, coupled with delays, have caused the stock to drift since.
Betalutin comprises an unusual approach, combining CD37 targeting with the radionuclide lutetium-177; a follow-up uses lead-212 as the radionuclide.
Debiopharm’s naratuximab is a more typical antibody-drug conjugate, and was acquired from Immunogen three years ago; a phase II trial should end imminently. Among the disappointments are another ADC, from Seattle Genetics/Astellas, which was canned despite showing promise in heavily pretreated non-Hodgkin’s lymphoma in 2017.
|Selected projects targeting CD37|
|Naratuximab emtansine||Anti-CD37 ADC||Debiopharm (ex Immunogen)||Rituxan combo in r/r lymphoma|
|Betalutin||Anti-CD37 MAb-Lu-177 conjugate||Nordic Nanovector||Lymphoma trial with lilotomab (anti-CD37 MAb) pre-dosing|
|GEN3009||Anti-CD37 dual-epitope MAb||Genmab/Abbvie||First-in-human lymphoma|
|CAR37 T Cells||Anti-CD37 Car-T||Massachusetts General||Haem-onc trial yet to start enrolling|
|NNV013||Anti-CD37 MAb-Pb-212 conjugate||Nordic Nanovector||–|
|Otlertuzumab||Anti-CD37 MAb||Aptevo||Disc in Nov 2018 after lack of efficacy in T-cell lymphoma|
|AGS67E||Anti-CD37 ADC||Seattle Genetics/Astellas||30% ORR, 7/52CR|
|BI 836826||Anti-CD37 MAb||Boehringer Ingelheim/Xencor||4 studies completed, 1 terminated, 1 withdrawn|
|Source: clinicaltrials.gov & EvaluatePharma.|
Still, if some previous work on CD37 prompts doubts over the target, this is nothing compared with that on 5T4, a tumour antigen discovered by scientists at Cancer Research UK back in the 1990s.
5T4’s most notorious casualty was Oxford Biomedica’s Trovax, which crashed in phase III 12 years ago. To be fair this was a cancer vaccine, so its failure might have had more to do with the approach than the target, but Oxford has separately flirted with MAb, ADC and even Car-T formats against 5T4, none making significant progress.
A second big failure was Active Biotech’s anti-5T4 ADC Anyara, whose phase II/III renal cell carcinoma study blew up in 2013 (Anyara sounds the death knell for 5T4-targeted anticancers, January 29, 2013). Remarkably, Active managed to offload Anyara to Neotx, which is now running a phase I trial in combination with Imfinzi.
The precedent for targeting CD37 and 5T4 might not be great, but at least Genmab and Abbvie can boast novel approaches to hitting these old-school antigens. All that remains is for them to show their worth in the clinic.
|Selected projects targeting 5T4|
|VTP-800||Anti-5T4 cancer vaccine||Vaccitech||Opdivo combo in prostate cancer|
|Anyara||Anti-5T4 ADC||Neotx (ex Active Biotech)||Imfinzi combo; failed ph2/3 in renal cancer|
|DuoBody-CD3x5T4||Anti-5T4 bispecific MAb||Genmab/Abbvie||IND filed Q1 2020|
|ALG.APV-527||Anti-5T4/4-1BB bispecific MAb||Alligator/Aptevo||–|
|OXB-302||Anti-5T4 Car-T||Oxford Biomedica||–|
|Trovax-DC||Anti-5T4 cancer vaccine||Oxford Biomedica||Failed ph3 Trist study|
|PF-06263507||Anti-5T4 ADC||Oxford Biomedica/Pfizer||–|
|Source: clinicaltrials.gov & EvaluatePharma.|
This story has been updated to include Vaccitech's VTP-800.