Werewolf Therapeutics and Ambros Therapeutics Merge to Advance Neridronate in CRPS-1

Werewolf Therapeutics and Ambros Therapeutics have entered into an all-stock merger agreement to create a Nasdaq-listed biotechnology company focused on advancing neridronate for Complex Regional Pain Syndrome Type 1 (CRPS-1). The transaction is accompanied by commitments for an oversubscribed $150 million private placement, expected to fund the program through pivotal Phase 3 results and a potential U.S. regulatory submission.

Merger Brings Ambros’ Neridronate Program into Public Company

Ambros Therapeutics is an existing biotechnology company developing neridronate for CRPS-1. Under the proposed transaction, Ambros Therapeutics will become a wholly owned subsidiary of Werewolf Therapeutics. Following the merger, the combined publicly traded company will operate under the Ambros Therapeutics name, be headquartered in San Diego, and is expected to trade on Nasdaq under the ticker AMBX. The boards of both companies have approved the transaction, which is expected to close by the first quarter of 2027, subject to shareholder approvals, Nasdaq listing approval, effectiveness of a Form S-4 registration statement, and other customary closing conditions.

The companies also secured commitments for an oversubscribed $150 million private placement. The financing is expected to close concurrently with the merger, with Werewolf issuing common stock and pre-funded warrants. Ambros expects the proceeds to fund operations through topline results from the CRPS-RISE Phase 3 trial, expected in 2028, and a planned New Drug Application (NDA) submission, providing cash runway into the first half of 2029.

Neridronate Advances with Extensive Prior Clinical Exposure

Neridronate is a bisphosphonate developed by Abiogen Pharma S.p.A. and approved in Italy for CRPS, osteogenesis imperfecta, and Paget’s disease. Approximately 600,000 patients have received the drug across its approved indications. The FDA has granted neridronate Breakthrough Therapy, Fast Track, and Orphan Drug designations for CRPS.

The U.S. development program is centered on CRPS-RISE, a pivotal Phase 3 study evaluating intravenous neridronate in patients with warm CRPS-1. The trial uses a targeted patient population with characteristics that Ambros believes may be more likely to respond to treatment, including a positive triple-phase bone scan.

CRPS-RISE Evaluates Neridronate in Approximately 270 Patients

CRPS-RISE (NCT07210515) is a multicenter, randomized, triple-blind, placebo-controlled Phase 3 trial expected to enroll approximately 270 participants. Patients are randomized 1:1 to intravenous neridronate or placebo.

Eligible participants must have CRPS-1 confirmed under the Budapest Clinical Criteria, a known precipitating event such as a fracture, sprain, or contusion, disease duration of six months or less, and moderate-to-severe pain. The study also requires a positive triple-phase bone scan and features of the warm CRPS-1 subtype.

Participants receive four intravenous infusions over 10 days, with each neridronate infusion delivering 100 mg for a total dose of 400 mg, or matching placebo. The primary endpoint is the change in pain intensity from baseline to week 12 on an 11-point Numerical Rating Scale. Key secondary endpoints assess additional measures of pain reduction and patient-reported outcomes.

The program also includes long-term follow-up and an opportunity for CRPS-RISE participants with active disease who complete the study to receive neridronate. Ambros expects topline results in 2028 and has said discussions with the FDA indicate that a single successful pivotal trial could potentially support U.S. approval.

CRPS-1 Has No FDA-Approved Drug Treatment

CRPS-1 is a debilitating pain disorder that typically develops after a limb injury. The disease affects an estimated 65,000 newly diagnosed people in the United States each year, with no FDA-approved medicine currently indicated for treatment.

The condition can cause continuous severe pain in an affected arm, leg, hand, or foot, alongside swelling, redness, warmth, and hypersensitivity. Many patients initially develop a warm phase dominated by inflammatory features before progressing to a chronic cold phase with persistent pain.

$150 Million Financing Supports Path to Potential NDA

Jay Hagan, CEO of Ambros Therapeutics, said the merger and financing provide the resources needed to advance CRPS-RISE through its planned 2028 topline readout and a potential NDA submission. The company’s strategy combines neridronate’s extensive prior clinical exposure with a focused Phase 3 population and an FDA-aligned development path.

Following the merger, Hagan is expected to lead the combined company as CEO, with Cris Calsada as CFO and Gail Cawkwell, M.D., Ph.D., as chief medical officer. If CRPS-RISE demonstrates sufficient efficacy and safety, the company plans to use the data to support a potential U.S. NDA submission. The company’s intellectual property portfolio, together with Orphan Drug designation, is expected to support potential U.S. market exclusivity through 2045.

Reference

Werewolf Therapeutics and Ambros Therapeutics Announce Merger Agreement and Concurrent Oversubscribed $150 Million Private Placement | Werewolf Therapeutics, Inc.

Werewolf Therapeutics and Ambros Therapeutics Announce Merger Agreement and Concurrent Oversubscribed $150 million Private Placement I Ambros Therapeutics