Acceleron Pharma Inc. and Fulcrum Therapeutics Inc., two Cambridge, Mass.-based companies that have benefited from partnerships, agreed to an R&D collaboration and license agreement to identify small molecules for treating an undisclosed target in pulmonary disease.  

Fulcrum receives $10 million up front and will be reimbursed for its R&D. Fulcrum also could receive research, development and commercial milestone payments of up to $295 million for the first product commercialized and a maximum of $143.5 million in additional milestone payments for all subsequent products commercialized. There’s also the potential for tiered royalty payments in the mid-single-digit to low double-digit range on net sales.  

Acceleron develops treatments targeting multiple ligands in the TGF-beta superfamily. In the deal, the company gets access to Fulcrum’s product engine, which identifies targets that can modulate genes to find their misexpression’s root causes.  

Joseph P. Schwartz, an SVB Leerink analyst, wrote Monday that the agreement is a win-win as Acceleron expands into the pulmonary space while Cambridge, Mass.-based Fulcrum gets a cash infusion that allows it to concentrate on its work in muscle, CNS and blood diseases.  

“With six additional screens planned for 2020, we think [Fulcrum]'s platform may continue to crank out potential drug candidates across multiple indications – now including pulmonary – that aim to address the root cause of each disease,” Schwartz wrote. “We believe [Fulcrum]'s proprietary discovery platform is a distinguishing and valuable asset.” 

Bryan Stuart, Fulcrum’s chief operating officer, told BioWorld the firms would not disclose the target disease but confirmed it’s pulmonary related. He pointed to the company’s recent progress in facioscapulohumeral muscular dystrophy (FSHD), now actively recruiting for a phase II study, and two INDs expected to be submitted in the middle of 2020, one for sickle cell disease and the other for beta-thalassemia. 

Following clinical failures in multiple indications, a p38 kinase inhibitor developed by Glaxosmithkline plc found a new champion in Fulcrum, which in April licensed it for the potential treatment of FSHD, a genetic muscle disorder. After securing an exclusive license for the drug in exchange for granting GSK "a high single-digit" percentage ownership of its company, Fulcrum has an ongoing phase IIb study of the drug, called losmapimod, in patients with FSHD at multiple sites in the U.S. and Europe. 

An IND is expected in the middle of 2020 for Fulcrum’s FTX-6058, a small molecule that acts to induce human fetal hemoglobin (HbF) levels, a clinically validated approach to address the root cause of sickle cell disease. In preclinical in vitro and in vivo data, FTX-6058 showed it could dose-dependently increase HbF cells to about 20%. H.C. Wainwright analyst Andrew Fein liked the prospect, saying in an Oct. 3 report that FTX-6058 "compared to [Novartis' just-approved therapy], is relatively inexpensive to manufacture, and involves less complicated logistics." 

On Nov. 10, nearly a month ahead of the PDUFA date, red blood cell maturation drug luspatercept cleared the FDA for treating anemia in adults with beta-thalassemia who require regular red blood cell (RBC) transfusions. Branded Reblozyl, the drug was developed in a collaboration between Acceleron and Celgene Corp.  

Celgene, now part of Bristol-Myers Squibb Co., and Acceleron filed BLAs in April, seeking approval of luspatercept for use in adults with very low- to intermediate-risk myelodysplastic syndromes-associated anemia who have ring sideroblasts and required RBC transfusions and for use in beta-thalassemia-associated anemia. The FDA, accepting the applications in June, granted priority review to the beta-thalassemia indication. 

Fulcrum shares (NASDAQ:FULC) closed up 2.95%, at $17.45, on Monday, while Acceleron (NASDAQ:XLRN) was up 2.89% to close at $52.61 per share.