Few TGF-β assets remain unencumbered after Bristol’s Forbius buy

Snippets

Targeting TGF-β in oncology is an early yet crowded field, with most big pharma companies already active. Bristol Myers Squibb joined the throng yesterday with a deal to buy Forbius, which had been developing one of the few independent clinical-stage assets. AVID200 is a fusion protein that blocks TGF-β isoforms 1 and 3, which are thought to be drivers of fibrosis and tumour immune resistance. Forbius claims that the project does not hit TGF-β 2, which is crucial to minimise toxicities; this isoform is thought to play a role in normal cardiac function and its inhibition could promote metastasis. How this plays out in the clinic remains to be seen: phase I data at Asco this year did not stand out, with only two patients of 19 achieving stable disease, and three grade 3 adverse events reported. A Eular presentation in sclerosis arguably showed promise greater in fibrosis, an area in which Bristol Myers said it is also interested in moving forward. Readouts from competing projects in the coming months will be of great interest as this approach becomes better understood, particularly from assets that remain unpartnered. 

Selected oncology assets targeting TGF-β
Project Company Mechanism Trial ID Note
Phase II/III
M7824 (bintrafusp alfa) Merck KGaA/ Glaxosmithkline Anti-PD-L1/TGF-β fusion protein NCT03631706 & NCT03833661 Head to head vs Keytruda; data and filing likely in biliary cancer first
Phase I
AVID200 Bristol Myers Squibb (via Forbius) TGF-β1&3 fusion protein  NCT03834662 Data reported at Asco 2020
SAR439459 Sanofi Anti-TGF-β MAb NCT03192345 Combo with anti-PD-1 (Libtayo)
NIS793 Novartis/Xoma Anti-TGF-β Mab NCT02947165 Combo with anti-PD-1 (PDR001); two further trials registered but yet to start
PF-06952229 Pfizer TGF-β1 inhibitor NCT03685591 Advanced solid tumours; in combination with Xtandi and Ibrance in second phase
Vactosertib Medpacto TGF-β inhibitor NCT03724851 & NCT03732274 Combos with anti-PD-1 (Keytruda & Imfinzi)
ABBV-151 Argenx/Abbvie TGF-β-inactivating MAb NCT03821935 Combo with anti-PD-1 (ABBV-181)
GS-1423 Gilead (via Agenus) Anti-CD73-TGFβ bifunctional MAb NCT03954704 Advanced solid tumours
SHR-1701 Jiangsu Hengrui Medicine Anti-PD-L1/TGF-β fusion protein NCT03774979 China trials only. Large phase I ongoing with expansion into selected indications planned
SRK-181 Scholar Rock TGF-β1 inhibitor NCT04291079 Advanced solid tumours, +/- anti-PD-(L)1 Mab
Galunisertib Lilly TGF-β R1 kinase inhibitor Only academic  sponsored trials ongoing  Probably abandoned 
LY3200882 Lilly  TGF-β R1 kinase inhibitor NCT02937272 Possibly abandoned. Described as "next generation" agent
Trabedersen (OT-101) Isarna Therapeutics TGF-β2 antisense   No active trials, although funding secured in June to test in Covid-19
Source: EvaluatePharma, clinicaltrials.gov and company statements.
Forbius and Asco.

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