AM-Pharma’s purpose is to save and improve the lives of patients confronted with severe medical conditions. Our proprietary compound, ilofotase alfa, is being developed as a potential enzyme replacement therapy for adult hypophosphatasia (HPP) patients. In a Phase 1b clinical proof of concept study in adult HPP patients, ilofotase alfa showed a pronounced effect on all HPP disease-specific biomarkers and normalized alkaline phosphatase activity levels. There were no safety concerns with ilofotase alfa in this study, consistent with previous clinical studies with ilofotase alfa in other indications involving about 1000 patients. These data support its further development as a treatment option for adult HPP patients who are currently underserved. We are a dedicated team driven to bring treatment options to patients in need, their families and healthcare professionals.
AM-Pharma, founded in 2002 and based in Utrecht, the Netherlands, is developing its proprietary recombinant human alkaline phosphatase therapeutic, ilofotase alfa, as a potential enzyme replacement therapy for the rare genetic disease hypophosphatasia (HPP).
AM-Pharma strives to develop medicines for patients confronted with severe medical conditions. Our proprietary asset, ilofotase alfa, is being developed for the treatment of patients with hypophosphatasia, a rare, genetic metabolic disorder, for which we have received orphan drug designation by the US FDA and EMA.
HPP is an inherited disease associated with low serum alkaline phosphatase activity.
In adults, reduced serum alkaline phosphatase activity generally results in functional limitations with quality of life compromised by muscle weakness, mobility constraints, pain and fatigue. Disease often occurs in middle-aged adults and has a progressive but varied presentation.
Patients can develop a range of other complications including: chondrocalcinosis, joint inflammation, osteoarthropathy, vertebral fracture, musculoskeletal discomfort, muscle fatigue, hypercalcemia, nephrocalcinosis, kidney failure, chronic inflammation, and neurological symptoms such as severe pain. Data from patients in the Global Hypophosphatasia Registry show that considerable disability and compromised quality of life occur even in patients without overt skeletal manifestations.
For adults with pediatric-onset HPP there is currently one treatment option, an alkaline phosphatase enzyme replacement therapy (asfotase alfa) administered via subcutaneous injection, to treat bone manifestations. Asfotase alfa is not indicated for hypophosphatasia identified in adults.
However, moderately affected patients are less likely to be diagnosed when young and, as a result, are ineligible for asfotase alfa treatment, and they therefore do not receive disease-specific treatment as symptoms develop in later life. As a result, older patients with moderate to severe disease often remain untreated and can be left with reduced quality of life and severely debilitating pain, muscle weakness, and mobility issues. There is a clear unmet need for individuals whose hypophosphatasia is diagnosed in adulthood.
Ilofotase alfa is able to cleave pyrophosphate to release inorganic phosphate which can be incorporated into hydroxyapatite crystals that mineralize bones, with the potential to restore skeletal integrity in HPP patients. Ilofotase alfa does not contain a bone-targeting sequence, which raises the possibility that it could also manage non-bone consequences such as pain and muscle weakness associated with elevated levels of other substrates such as pyridoxal 5’-phosphate (PLP). Recent preclinical studies support ilofotase alfa’s potential to extend the effects beyond bone health, with potential benefits for other body systems, such as muscle, affected by HPP[1].
Further preclinical proof-of-concept was demonstrated in mice with a knockout mutation in the TNAP gene. Ilofotase alfa alleviated multiple HPP manifestations in these animals: improving bone and dental mineralization and cartilage development; reducing the development of craniosynostosis, kidney inflammation/calcification, and seizures; and normalizing body weight and lifespan[3].
The Phase 1b clinical proof of concept study with ilofotase alfa in adult HPP patients showed increased alkaline phosphatase activity levels, a dose-dependent, pharmacological relevant effect on all primary disease-specific biomarkers (PPi, PLP, PEA), and a positive safety profile[2].
The pre-clinical data indicate potential efficacy for ilofotase alfa in HPP and are supported by clinical data in healthy volunteers; additionally clinical safety data in healthy volunteers and patients with other disease indications[4], indicate a very favorable safety profile.
The Phase 1b study with ilofotase alfa in adult HPP patients showed a pharmacologically relevant effect on disease specific biomarkers, normalized alkaline phosphatase activity levels and a positive safety profile. Ilofotase alfa is now Phase 2-ready as convenient, subcutaneous administration.
For partnering opportunities, please email our CEO, Juliane Bernholz, PhD.
[1] DeMambro V, et al. Improved VO₂max, muscle function and endurance in adult HPP “PAKO” mice treated with ilofotase alfa. In: Proceedings of the American Society for Bone and Mineral Research (ASBMR) Annual Meeting; 2025. Abstract 1020. Accessed via: https://asbmr.confex.com/asbmr/2025/meetingapp.cgi/Paper/5008
[2] Seefried L, Bernholz J, Kraan M, Nitschke Y, Rutsch F, Mallek M, Kleinert S, Genest F. A randomized Phase 1b trial evaluating the pharmacodynamics of ilofotase alfa in adults with hypophosphatasia. J Bone Miner Res. 2025 Dec 11:zjaf185. doi: 10.1093/jbmr/zjaf185. Epub ahead of print.https://doi.org/10.1093/jbmr/zjaf023
[3] Gasque, Kellen CS, et al. Improvement of the skeletal and dental hypophosphatasia phenotype in Alpl−/− mice by administration of soluble (non-targeted) chimeric alkaline phosphatase, Bone 72 (2015): 137-147.
[4] Pickkers, Peter, et al., Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL), Intensive care medicine 50.1 (2024): 68-78.
AM-Pharma is backed by a strong syndicate of international investors, including venture capital funds and corporate venture funds. To date, the company has raised over €190 million in equity. The Company’s main investors include:
Mark Altmeyer, MBA – Chairman of the Board
Prior to joining AM-Pharma’s Supervisory Board, Mark Altmeyer was founder, President and Chief Executive Officer at Arvelle Therapeutics, in addition to serving as Executive Director of Arvelle’s Board of Directors. At Arvelle, he led the development of the company until its acquisition by Angelini for USD 1 billion. In advance of that transaction, he established Arvelle’s global headquarters in Switzerland, secured USD 200 million initial funding and built the European team to over 100 employees in under two years. Before Arvelle, Mark served as President and Chief Commercial Officer at Axovant Sciences, where he was responsible for establishing Axovant’s global commercial capabilities and launch preparations for various pipeline products. Earlier in his career, Mark served as President and CEO at Otsuka America Pharmaceutical, leading the transformation into a successful commercial organization, doubling total revenues from USD 2.5 billion to nearly 5 billion in five years. Mark held senior commercial and business development positions at Bristol-Myers Squibb, Cetus Corporation and Bristol Labs in the United States. He holds an MBA from Harvard Graduate School of Business and a BA in economics from Middlebury College.
Martijn Kleijwegt, MSc
Martijn Kleijwegt founded LSP, the predecessor of EQT Life Sciences in 1998, and is a Partner in the EQT Life Sciences team. He was instrumental in the successes of Prosensa (NL, IPO in 2013, sold to Biomarin for €548 million in 2015), Movetis (BEL, IPO in 2009, sold to Shire for €428 million in 2010), Crucell (NL, IPO in 2000, sold to Johnson & Johnson for €1.75 billion in 2011), Rhein Biotech (NL, IPO in 1999, sold to Berna Biotech for €279 million in 2002), and Qiagen (GER, IPO in 1996, valued 30 June 2017 at €6.6 billion).
After starting his career at Philips, he gained extensive experience in the life sciences sector as General Partner of Euroventures Benelux, one of the first venture funds in Europe with life sciences in its investment scope. Martijn led the life sciences investment strategy and built the Euroventures Life Sciences (ELS) fund. In 1998, Martijn founded LSP and together with the other general partners built it into what it is today. Martijn currently represents LSP on the supervisory boards of Kiadis Pharma (NL), OxThera (SE), Orphazyme (DK), Pharvaris (GER), Arvelle therapeutics (NL/CH) and Eloxx Pharmaceuticals (USA/IS).
He holds a master’s degree in economics from Amsterdam University.
Raphaël Wisniewski, MSc
Raphaël Wisniewski is a Managing Partner at Andera Partners (formerly Edmond de Rothschild Investment Partners).
Raphaël serves as a Director on the Board of ReViral, MedDay Pharmaceuticals, Artios Pharma, Dynacure, Grey Wolf, Axonics Modulation and as an observer on the Boards of Poxel and Enyo. Previously, he worked in Healthcare Corporate Finance at Goldman Sachs starting at Salomon Smith Barney. He was also in the Finance Departments of Health in London and in the Department of General Healthcare in London, the private hospital group.
Raphaël is a graduate of the Ecole des Hautes Etudes Commerciales, Paris, and holds a master’s degree in economics and finance from the Institut d’Etudes Politiques (IEP), Paris.
Geert-Jan Mulder, MD
Geert-Jan Mulder is a Managing Partner at Forbion.
He currently serves on the Board of several Forbion portfolio companies. In addition, Geert-Jan led the firm’s successful investment in bluebirdbio, which went public in 2013, where he supported the company in clinical development and served as the chairman for several years. Other investments include Acorda Therapeutics, which went public in 2006 and where he was part of the AMPYRA® (dalfampridine) board panel to evaluate a new regulatory endpoint in Multiple Sclerosis, PanGenetics B.V., Transave, and Exosome Diagnostics. In addition, he is a co-author of several Forbion and Forbion portfolio related scientific publications.
Geert-Jan received his MD from the University of Utrecht (NL) and spent two years as a clinician in Obstetrics and Gynecology at the University Medical Center of Utrecht (UMC).
Rémi Droller, MSc
Rémi Droller is a Managing Partner of Kurma Partners.
Prior to that, he held positions at CDC Innovation from 2000 to 2003 and at AGF Private Equity (now Idinvest Partners) from 2003 to 2010, where he was in charge of developing the life sciences investment activity. Rémi serves on the Board of Dynacure (France), ImCheck Therapeutics (France), Orphazyme (Denmark – listed on the Copenhagen Stock Exchange), Oxthera (France) and Pharvaris (the Netherlands).
Rémi has a master’s degree in molecular biology (Paris VI University) and a master’s degree in finance and innovation management (AgroPariTech).
Eric van den Berg, MSC, MBA
Erik served as CEO at AM-Pharma from 2011 through 2023 and has over 25 years’ experience.
Erik is Chairman of Step Pharma and TargED Biopharmaceuticals and co-founder and previous (executive) Chairman of Lava Therapeutics (NASDAQ: LVTX), co-founder and previous (executive) Chairman of Heatmatrix Group (sold to BosNieuwkerk) and was board member of Lead Pharma and the Dutch biotechnology organization.
As Senior Executive at Organon he was responsible for global biotechnology business development. Prior to joining Organon, Erik worked in business and corporate development at the biotechnology company IsoTis (SWX/Euronext: ISON – sold to Integra Lifesciences), and as a Management Consultant at Arthur D. Little. Erik has been involved in the execution of over 20 transactions and partnerships, including a $600M alliance with Pfizer, $290M partnership with Kyowa Kirin and raised ~€500M in equity and debt financing for biotechnology companies from seed through IPO.
Erik holds a master’s degree in chemistry from the University of Utrecht (NL) and an MBA from Manchester Business School (UK).
Joël Jean-Mairet, PhD
Joël is managing partner and co-founder of Ysios Capital.
Previously, he co-founded Glycart Biotechnology in 2001 and was its CEO until it was successfully sold to F. Hoffmann La-Roche four years later. Glycart Biotechnology was the originator of the anti-CD20 antibody – obinituzumab/Gazyva®, the first breakthrough designated drug approved by the FDA for B-CLL. He holds an MS in Biotechnology and a PhD from the Swiss Federal Institute of Technology (ETH) in Zurich.
Joël is currently on the boards of directors of Adcendo, SpliceBio, ONA, board observed at Mineralys and Executive Chairman of Inbiomotion. He has been Chairman of the board of Cellerix/Tigenix (now Takeda), board member of Aura Biosciences (Nasdaq: AURA), LAVA Therapeutics (Nasdaq: LVTX) and Sanifit Therapeutics (now Vifor Pharma), and board observer at Biovex (now Amgen). Joël has earned numerous awards, including the Wall Street Journal’s Europe Innovation Award in 2001.
