Regeneron Pharmaceuticals has entered into a strategic research collaboration with Parabilis Medicines to discover and develop a new class of therapeutics designed to target historically difficult-to-treat biological pathways, including intracellular proteins long considered “undruggable.”
The agreement centers on Parabilis’ Helicon peptide platform and will focus particularly on the development of Antibody-Helicon Conjugates (AHCs), an emerging therapeutic approach intended to combine targeted antibody delivery with intracellular protein modulation.
The collaboration reflects growing pharmaceutical industry interest in expanding beyond conventional biologic and small-molecule approaches to reach disease targets that have traditionally remained inaccessible to existing medicines.
Helicons are stabilized, cell-penetrating alpha-helical peptides engineered to enter cells and bind intracellular proteins, including flat protein surfaces that are poorly suited for traditional small-molecule drug binding. Because many disease-driving proteins exist inside cells and lack accessible binding pockets, scientists have historically described them as difficult or impossible to drug using conventional methods.
Regeneron and Parabilis said the collaboration will investigate Helicons both as independent therapies and as payloads attached to antibodies through Antibody-Helicon Conjugates.
The envisioned AHC platform builds conceptually on antibody-drug conjugates (ADCs), a rapidly growing category of precision therapeutics that use antibodies to selectively deliver toxic drug payloads into diseased cells, particularly cancer cells. However, instead of delivering cell-killing compounds, AHCs would transport Helicon peptides engineered to selectively modulate intracellular proteins, potentially allowing intervention in disease mechanisms that existing therapies cannot effectively address.
George D. Yancopoulos, board co-chair, president and chief scientific officer at Regeneron, said the collaboration aligns with the company’s strategy of advancing diversified scientific approaches to develop innovative medicines.
Yancopoulos said Helicons may help address previously inaccessible therapeutic targets and noted that pairing them with antibodies derived from Regeneron’s VelocImmune platform could enable precise delivery into selected cells, potentially creating an entirely new therapeutic class with applications across multiple disease areas.
Financially, the collaboration provides Parabilis with substantial upfront and long-term economic potential. Under the terms of the agreement, Regeneron will provide $125 million to Parabilis, including a $50 million upfront payment and a commitment to invest an additional $75 million in Parabilis’ next equity financing, subject to specified conditions.
Parabilis will also be eligible for development, regulatory and commercial milestone payments tied to future programs, along with tiered royalties reaching low double-digit percentages on net sales of approved medicines resulting from the collaboration.
The agreement initially focuses on five therapeutic targets and carries the potential for approximately $2.2 billion in total milestone payments to Parabilis if development objectives are achieved. Regeneron also retains the option to pursue additional targets through separate option payments.
Under the collaboration, both companies will work together to discover new Helicons and AHC candidates, while Regeneron will assume responsibility for downstream development, manufacturing and global commercialization.
The partnership highlights growing industry efforts to unlock hard-to-target disease biology using next-generation drug delivery systems and engineered therapeutic platforms aimed at expanding the boundaries of precision medicine.