Recursion Pharmaceuticals has acquired full rights to REV102, a potential first-in-class oral ENPP1 inhibitor for the treatment of hypophosphatasia (HPP), from joint venture partner Rallybio Corporation. The acquisition, valued at up to $25 million, positions Recursion to advance what could become the first oral disease-modifying therapy for this rare genetic disorder.
Targeting ENPP1 for Hypophosphatasia Treatment
REV102 targets ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), an enzyme implicated in the pathogenesis of HPP. The mechanism involves potent, highly selective inhibition of ENPP1, aiming to restore the crucial balance of inorganic pyrophosphate (PPi) necessary for proper bone mineralization, thereby addressing the underlying cause of HPP.
"By combining Rallybio's expertise in HPP preclinical and translational research with Recursion's integrated AI/experimental platform, we transformed this concept into the first potential oral disease-modifying treatment for HPP," said Stephen Uden, M.D., Chief Executive Officer of Rallybio.
Addressing Significant Unmet Medical Need
HPP is a devastating genetic disorder affecting over 7,800 diagnosed patients across the US and EU5, many of whom have limited access to current Enzyme Replacement Therapies (ERTs). The condition presents significant challenges for patients who currently rely on injectable treatments.
David Hallett, Chief Scientific Officer of Recursion, emphasized the importance of the acquisition: "Having full ownership of this important program allows Recursion to accelerate the development of the first potential oral disease-modifying treatment to HPP patients, who currently face significant challenges with limited access to existing therapies."
AI-Enabled Drug Design and Development
The REV102 program originated from a joint venture between Rallybio and Recursion, with Recursion leading the precision design of the compound. The Recursion OS - an integrated AI/experimental platform - was used to optimize for potency, selectivity, and PK/PD properties suitable for chronic dosing, enabling a candidate with potential best-in-class characteristics.
Early preclinical data has demonstrated a favorable safety profile in animal models and validated ENPP1 as a druggable target in later-onset HPP. As a preliminarily non-immunogenic small molecule, REV102 could potentially offer a safer profile compared to biological ERTs, which can sometimes induce immune responses.
Development Timeline and Financial Terms
REV102 is currently in IND-enabling studies, with the initiation of Phase 1 clinical trials expected in the second half of 2026. The lead candidate from the joint venture entered into IND-enabling studies in early 2025.
Under the acquisition terms, Rallybio is eligible to receive $7.5 million in upfront equity, a contingent equity payment of $12.5 million upon the initiation of additional preclinical studies, and a $5 million milestone payment in connection with the initiation of dosing in a Phase 1 clinical study. Rallybio is also eligible to receive low single-digit royalties on all future net sales by Recursion.
Strategic Impact
For Rallybio, the divestment extends the company's cash runway to mid-2027 while allowing focus on other pipeline programs. "Divesting this preclinical asset enables us to extend our cash runway while sharpening our focus on strategically advancing our pipeline in ways that leverage our drug development expertise," said Dr. Uden.
The acquisition represents a significant opportunity to provide a more accessible treatment and potentially reduce the substantial costs associated with long-term HPP management. REV102 is designed to potentially offer advantages in convenience and patient quality of life over injectable treatments currently available.
