Acceleron Pharma and Fulcrum Therapeutics Partner to Find Small Molecule Treatments

Acceleron Pharma and Fulcrum Therapeutics are working together to discover small molecules that can be used to treat pulmonary diseases, including pulmonary hypertension (PH).

Under this collaboration, Acceleron will be able to access Fulcrum’s proprietary product engine and target identification platform, in order to identify small molecules with the ability to regulate the expression of genes known to influence specific cellular pathways associated with the development and progression of pulmonary diseases.

The two companies want to pinpoint treatment targets and small molecule candidates for those targets.

“This collaboration brings together Fulcrum’s skill in identifying drug targets based on modulation of genetic pathways associated with disease, and Acceleron’s deep expertise in TGF-beta superfamily signaling in an effort to generate potentially disease-modifying therapeutics,” Habib Dable, chief executive officer of Acceleron Pharma, said in a press release.

Acceleron is focused on the involvement of the TGF-beta superfamily in serious and rare diseases. This superfamily plays several roles in the body, from the earliest stages of development (including differentiation and organ morphogenesis) through adult tissue homeostasis. Defects in the TGF-beta superfamily signaling have been associated with a wide range of diseases, including autoimmune, cardiovascular, and fibrotic diseases, as well as cancer.

Based on the agreement, Acceleron will be responsible for the development and commercialization of any therapeutic candidates discovered using Fulcrum’s platform. Fulcrum will be given a one-time upfront payment of $10 million, in addition to any reimbursement for applicable research and development costs.

Fulcrum will also be entitled to research, development, and commercial milestone payments, totaling up to $295 million for the initial product that is brought to market, and up to $143.5 million in supplemental milestone payments for all further commercialized products. Fulcrum will also be given tiered royalty payments on net sales.

“We are very pleased to partner with Acceleron on this important research initiative,” said Robert J. Gould, PhD, chief executive officer of Fulcrum Therapeutics. “This new opportunity to screen and identify pulmonary disease-specific therapies is another reflection of the broad potential applications of the Fulcrum platform in gene modulation.”

Currently, Acceleron is developing sotatercept as a potential treatment of pulmonary arterial hypertension (PAH). The therapy is designed to bind and trap members of the TGF-beta family, which controls cell functions that include bone morphogenetic protein (BMP) signaling in the lungs — an important pathway for the maintenance of blood vessel structure in the lungs, and which is involved in PAH development and progression.

Preclinical studies showed that sotatercept has positive effects on several aspects of vascular remodeling and PAH.

Acceleron is investigating sotatercept in PAH patients in two ongoing Phase 2 clinical trials — PULSAR (NCT03496207) and SPECTRA (NCT03738150). Top-line results from the PULSAR trial are expected during the first quarter of 2020.

“With this agreement, along with the advancement of the Acceleron-discovered assets sotatercept — in Phase 2 trials in pulmonary arterial hypertension — and ACE-1334 [potential therapy for pulmonary diseases], we underscore our growing commitment to the development of novel therapies for patients with pulmonary diseases of high unmet medical need,” Dable said.

The U.S. Food and Drug Administration (FDA) granted orphan drug status to sotatercept as a possible PAH treatment in 2019.