Celgene Corporation / Forma Therapeutics Holdings Inc.

Oncology (protein homeostasis / proteostasis targets)

Disease Overview

Protein homeostasis (proteostasis) covers the cellular machinery — chaperones, the ubiquitin-proteasome system, autophagy, the unfolded protein response — that regulates protein synthesis, folding, and degradation. Cancer cells, with high proliferation rates and elevated mutational load, depend disproportionately on intact proteostasis, making the pathway a tractable target class.

Competitive Landscape

By 2013, proteostasis was an emerging oncology target class anchored by validated proteasome inhibitors — Takeda/Millennium's Velcade (bortezomib) and Amgen/Onyx's Kyprolis (carfilzomib, approved 2012) for multiple myeloma — plus HSP90 inhibitors in development at Synta, Infinity, and others. Forma's platform extended beyond proteasome/HSP90 into broader proteostasis pathways (chaperones, UPR, deubiquitinases, metabolic enzymes affecting protein stability) and provided Celgene a discovery-stage option to complement its Revlimid/Pomalyst myeloma franchise where proteostasis biology was clinically validated. The 2013 deal: undisclosed upfront, up to $200M in research and early development funding, with Forma running candidates through Phase 1 and Celgene taking over global development for licensed assets ex-US, plus $315M+ milestones per first license. The collaboration was expanded in 2014 to include a buyout option, signaling Celgene's escalating conviction. Forma later spun out non-Celgene programs and pursued sickle cell disease (etavopivat) — eventually acquired by Novo Nordisk in 2023 — though no Celgene-licensed asset reached approval prior to BMS's 2019 Celgene takeover.