BioMarin to Acquire Alesta Therapeutics for $275 Million Upfront to Advance Oral HPP Therapy ALE1

BioMarin Pharmaceutical will acquire Alesta Therapeutics in a deal centered on ALE1, an orally active small molecule being evaluated for hypophosphatasia (HPP), a rare genetic disorder caused by mutations in the ALPL gene. Alesta’s board and BioMarin’s board have approved the transaction, which the companies expect to complete in the third quarter of 2026, subject to customary closing conditions.

BioMarin will pay Alesta shareholders $275 million upfront, with up to $215 million in additional development and regulatory milestone payments. The company plans to fund the transaction with cash on hand.

ALE1 Targets a Central Metabolite in HPP

HPP disrupts bone and tooth mineralization and can produce a broad range of manifestations, including recurrent fractures, premature tooth loss, muscle weakness, fatigue and pain. The disorder can be difficult to diagnose because symptoms vary widely and may resemble more common conditions.

Asfotase alfa (Strensiq), an enzyme replacement therapy, is an established treatment for patients with HPP and is administered by subcutaneous injection. An effective oral therapy such as ALE1 could offer a less burdensome administration option if clinical development confirms its safety and efficacy.

ALE1 targets the pathway regulating inorganic pyrophosphate (PPi), a metabolite that accumulates in HPP and interferes with normal mineralization. By lowering excess PPi, the therapy could restore mineral metabolism and potentially address both skeletal and systemic manifestations of the disease.

More than 9,000 people have been diagnosed with HPP in the U.S., although the actual disease burden may be higher because of underdiagnosis.

Phase 1/2a Trial Evaluates Safety and Pharmacology

ALE1 is currently being studied in an ongoing Phase 1/2a clinical trial (NCT07179640) involving healthy volunteers and adults with HPP. The study is assessing safety, tolerability and pharmacokinetic and pharmacodynamic measures.

The program remains at an early clinical stage, and the source announcement does not report efficacy results or comparative clinical data. Therefore, whether ALE1 can produce meaningful clinical improvements in patients with HPP remains to be established in further development.

If successful, ALE1 could become the first oral therapy for HPP and provide an alternative to currently available injectable treatment approaches.

BioMarin Adds ALE1 to Skeletal Conditions Portfolio

BioMarin CEO Alexander Hardy said ALE1 fits the company’s strategy of expanding clinical-stage innovation into larger rare disease markets while addressing substantial unmet patient needs. The company will place the program within its Skeletal Conditions Business Unit following completion of the acquisition.

The transaction also includes a structural separation of Alesta’s other programs. Immediately before closing, Alesta will spin out all non-ALE1 assets into a new entity, with Alesta employees transferring to that entity. No Alesta employees will join BioMarin as part of the transaction.

Acquisition Expected to Close in Q3 2026

BioMarin expects the acquisition to have a modest dilutive effect on its 2026 financial results, excluding the $275 million upfront consideration. The company plans to update its full-year 2026 financial guidance after closing.

The next major value driver for ALE1 will be clinical development, particularly the emerging safety, pharmacokinetic and pharmacodynamic data from the Phase 1/2a program. Further studies will need to establish whether sustained PPi reduction translates into clinically meaningful benefits for people living with HPP.

Reference

BioMarin to Acquire Alesta Therapeutics to Gain ALE1, a Potential First Oral Therapy for Hypophosphatasia, Adding an Important Clinical Program to BioMarin’s Pipeline | BioMarin