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Gildeuretinol
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Stargardt
Disease
Stargardt disease, which affects more than 30,000 people in the United States, is one of the most common genetic causes of blindness in children and young adults. No treatment exists.
WITH More than 30,000 pEOPLE in the U.S. Stargardt disease IS MORE COMMON THAN OTHER GENETIC DISEASES SUCH AS CF, PKU and SMA
Of the six most common genetic, autosomal recessive diseases, Stargardt disease is the only one without a treatment.
| Disease | US Patients | Incidence |
|---|---|---|
| Alpha-1 antitrypsin deficiency (A1AT) | ~100,000 | ~3:10,000 |
| Sickle cell disease (SCD) | ~90,000 | 1:500-1,200 births |
| Stargardt disease* (STGD1) | >30,000 | ~1:8,000 |
| Cystic fibrosis (CF) | 30,000 | ~1:3,500 births |
| Phenylketonuria (PKU) | 16,500 | ~1:16,000 |
| Spinal muscular atrophy (SMA) | 9,000 | ~1:8,000 births |
*Reference: Worldwide carrier frequency and genetic prevalence of autosomal recessive inherited retinal diseases, 2019. Approximately 5% of the population is a carrier for an ABCA4 variant
The Root Cause: Defects in the ABCA4 Gene
Sight is made possible by a biochemical chain reaction in the eye: Vitamin A enables photoreceptors in the eye to convert light into electrical signals that are sent to the brain. Vitamin A is essential to the eye’s ability to see but also has a propensity to form dimers – or clumps – that are toxic to retinal pigment epithelium (RPE) layer.
Mutations in the ABCA4 gene were identified as the cause of Stargardt disease in 1997. The normal role of the ABCA4 protein is to ensure the flow of n-retinylidene-PE, a vitamin A isomer, through the photoreceptor membrane.
In Stargardt patients the ABCA4 protein is defective or absent, which allows excess vitamin A concentration and dimerization, and results in toxic by-products that irreversibly damage the RPE layer, leading to progressive vision loss.
Gildeuretinol (ALK-001),
A Once-a-day oral, investigational therapy For the Treatment of Stargardt Disease
Gildeuretinol (ALK-001) is the first and only medicine in clinical development to selectively address the underlying mechanism of Stargardt disease, by reducing the rate of vitamin A dimerization in the eye.
Toxic vitamin A aggregates (“dimers”) have been implicated in the pathophysiology of Stargardt and dry-AMD. Gildeuretinol is a chemically-modified vitamin A and is taken once daily by mouth.
In in vitro studies, researchers have demonstrated that gildeuretinol slowed dimerization of vitamin A by 4-5 fold, and in in vivo models, gildeuretinol has reduced vitamin A dimer formation in the eye by 80%, leading to preservation of visual function in animal models of Stargardt disease.
Gildeuretinol was designed to perform all of the functions of vitamin A needed to support sight, but without the tendency to dimerize or clump, thus avoiding the toxic by-products that damage the retina. Researchers engineered gildeuretinol as a novel, selectively modified version of vitamin A, where three hydrogen atoms are replaced with deuterium atoms, a stable, non-radioactive isotope of hydrogen. This modification is what dramatically reduces the rate of dimerization.
Gildeuretinol CLINICAL RESULTS: A FIRST FOR Stargardt PATIENTS
In 2022, clinical investigators reported results from a double-masked, placebo-controlled, randomized study of gildeuretinol (ALK-001) in 50 patients with advanced Stargardt disease at the American Academy of Ophthalmology.
gildeuretinol SlowS the Growth Rate of Atrophic Lesions in Stargardt Patients
Gildeuretinol met the pre-specified primary efficacy endpoint with high statistical significance, with a consistent trend of clinical benefit seen in secondary efficacy analyses.
In the clinical trial known as TEASE-1, gildeuretinol dosed once a day resulted in decreased retinal damage as compared to placebo, based on observed growth rates in atrophic lesions as measured by fundus autofluorescence (FAF). Gildeuretinol was well-tolerated with a safety profile consistent with the well-characterized safety profile of vitamin A.
In addition, an innovative, open-label study in children, known as TEASE-3, has indicated an ability for gildeuretinol, when given early, to halt the disease progression before retinal damage and vision loss occurs. Results from this clinical trial are anticipated to be presented in an upcoming medical forum.
Alkeus’ Clinical Program with gildeuretinol is designed to support broad use in Stargardt Disease
References: Visual acuity loss and clinical observations in a large series of patients with Stargardt disease, 2003;
Visual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt disease (ProgStar) Study, 2016.
Four clinical trials of gildeuretinol in Stargardt Disease are ongoing or completed, with the first two data readouts demonstrating positive clinical efficacy data.
Pursuing a Rapid Path to Market
The U.S. FDA has granted Breakthrough Therapy Designation and Orphan Drug Designation to gildeuretinol (ALK-001) for the treatment of Stargardt disease. Alkeus is engaged in discussions with regulatory authorities to define the most appropriate path to bring gildeuretinol to Stargardt disease patients as rapidly as possible. Alkeus plans to submit an NDA for approval of gildeuretinol in Stargardt disease as soon as possible in 2025.
Broad Potential to Treat Eye Disease
The pathological features of Stargardt disease—lesions in the retinal pigmental epithelium (RPE) layer, visible using high-resolution optical imaging —are common across several degenerative eye diseases.
There is mounting scientific evidence that the same process—excessive vitamin A dimerization, leading to toxic by-products that irreversibly damage photoreceptors in the retina—drives the progressive lesion growth not just in Stargardt disease but in these other diseases as well.
In addition to Stargardt disease, gildeuretinol is being evaluated in Geographic Atrophy (GA), an advanced form of dry age-related macular degeneration (AMD). More than 1 million people in the United States and more than 5 million people worldwide have GA.
Dry AMD is common in people over the age of 50. In dry AMD, layers of the retina slowly deteriorate over time. GA may occur in later-stage dry AMD patients, and is characterized by discrete areas of damage to the RPE layer, which leads to a progressive decline in central vision.
Although multiple mechanisms are associated with dry AMD and GA, it is clear that the toxic by-products of vitamin A are significant drivers of damage to the RPE layer.
In 2019, Alkeus initiated a Phase 2/3 study of gildeuretinol in Geographic Atrophy (GA), with a primary goal of measuring the ability of ALK-001 to slow the growth rate of GA lesions. Topline results were presented at the American Academy of Ophthalmology 2024 annual meeting.
In addition to Stargardt disease, gildeuretinol is being evaluated Geographic Atrophy (GA), an advanced form of dry age-related macular degeneration (dry AMD). More than 1 million people in the United States and more than 5 million people worldwide have GA.
About ALKEUS
Alkeus was co-founded by Leonide Saad, Ph.D. and Ilyas Washington, Ph.D. with the goal of treating degenerative eye diseases in a completely new way: developing a molecule that could reduce the potential for toxicity when vitamin A dimerizes —clumps —in the eye. This dimerization is a key underlying contributor to the irreversible retinal damage that is common to a number of eye diseases.
Alkeus has steadily progressed its lead molecule gildeuretinol (ALK-001), demonstrating its tremendous promise and advancing a comprehensive clinical program.
Alkeus is co-founded by Ilyas Washington, Ph.D and Leonide Saad, Ph.D
Publication of preclinical studies demonstrating that gildeuretinol (ALK-001) significantly reduces formation of vitamin A dimers, and slows retinal damage in genetic models of Stargardt disease
Gildeuretinol enters Phase 1 clinical development
First Phase 2 clinical study of gildeuretinol begins, for patients with advanced Stargardt disease
Phase 2 studies of gildeuretinol begin in children and young adults with early-stage and moderate disease
Alkeus initiates a Phase 3 study of gildeuretinol in Geographic Atrophy (GA) secondary to dry AMD
FDA grants breakthrough therapy designation to gildeuretinol for Stargardt disease
Phase 2 results presented at American Academy of Ophthalmology Annual Meeting show that gildeuretinol slows the growth rate of atrophic lesions in patients with advanced Stargardt disease
Alkeus secures $150 million in Series B funding to support rapid registration path for gildeuretinol in Stargardt disease; Joshua Boger, Ph.D. named Executive Chairman
Alkeus team
David Arkowitz, M.B.A.
Chief Financial Officer
Michel Dahan
President and Chief Executive Officer
Tamara Dillon
Chief Human Resources Officer
Seemi Khan, M.D., M.P.H., M.B.A.
Chief Medical Officer
Leonide Saad, Ph.D.
Co-Founder and Chief Scientific Officer
David Setboun, Pharm.D., M.B.A.
Chief Operating Officer
Eric L. Trachtenberg, J.D., M.B.A.
Chief Legal Officer
Ilyas Washington, Ph.D.
Co-Founder
Chris M. Adams, Ph.D., M.B.A.
Director
JOSHUA BOGER, PH.D.
Chair of the Board of Directors
Michel Dahan
President and Chief Executive Officer
Andrew A.F. Hack, M.D., Ph.D
Director
Leonide Saad, Ph.D.
Co-Founder and Chief Scientific Officer
Ian Smith
Director
Chen Yu, M.D., M.B.A.
Director
Christoph M. Adams, Ph.D., M.B.A.
Director
Dr. Adams has served as a member of our Board of Directors since November 2022. He has more than 30 years of experience on the business side of pharmaceutical and orphan drug development, including business strategy, commercial planning, product management, licensing, mergers and acquisitions. In 2013, he co-founded Cydan, an orphan drug accelerator focused on improving the lives of patients with rare genetic diseases. Together with the Cydan team, Dr. Adams raised more than $200M and co-founded and three new companies: Vtesse, Imara and Tiburio Therapeutics. Prior to Cydan, he served as Chief Business Officer of FoldRx Pharmaceuticals, where he contributed to the development of VYNDAQEL® (tafamidis) for TTR amyloidosis. Previously, he served in various business development and marketing roles at ViaCell, Transkaryotic Therapies and Ciba-Geigy. Dr. Adams also serves on the Board of Directors of Aviceda Therapeutics and Reveal Pharmaceuticals. He was previously also on the boards of Cydan II, and Kinetix Pharmaceuticals. He holds a PhD in organic chemistry and a diploma in organic chemistry and biochemistry from the University of Zurich, and an MBA from INSEAD of Fontainebleau, France.
Joshua Boger, Ph.D.
Chair of the Board of Directors
Joshua Boger, Ph.D., Chair of the Alkeus Board of Directors, founded Vertex Pharmaceuticals in 1989. He retired as Vertex’s Chief Executive Officer in 2009 and continued to serve on the Vertex Board and Chair Vertex’s Science & Technology Committee until 2017. Dr. Boger served as Executive Chairman at Alkeus from June 2023 to June 2024. Prior to founding Vertex, Dr. Boger was Senior Director of Basic Chemistry at Merck Sharp & Dohme Research Laboratories in Rahway, N.J., where he headed both the Departments of Biophysical Chemistry and Medicinal Chemistry of Immunology & Inflammation. During his ten years at Merck, Dr. Boger developed an international reputation in the application of computer modeling to the chemistry of drug design and was a pioneer in the use of structure-based rational drug design as the basis for drug discovery programs. Dr. Boger holds a bachelor of arts degree in Chemistry and Philosophy from Wesleyan University (Connecticut) and a master's and doctorate degrees in Chemistry from Harvard University. His postdoctoral research in molecular recognition was performed in the laboratories of the Nobel-prize winning chemist, Jean-Marie Lehn in Strasbourg, France. He is the author of over 50 scientific publications and holds 32 issued U.S. patents in pharmaceutical discovery and development.
Michel Dahan
President and Chief Executive Officer
Andrew A. F. Hack, M.D., Ph.D
Director
Dr. Hack is a Partner of Bain Capital Life Sciences, LP, a private equity fund that invests in biotechnology, pharmaceutical, medical device, diagnostics, and enabling life science technology companies globally. From July 2015 to March 2019, he was Chief Financial Officer of Editas Medicine where he had responsibility for finance, investor relations, business development, information technology, and operations. Previously, Dr. Hack served as a portfolio manager at Millennium Management where he ran a healthcare hedge fund focused on investing in biotechnology, pharmaceutical, and life sciences companies from 2011 to 2015. Earlier in his investment career, he was a securities analyst at a number of healthcare-focused hedge funds and investment banks in New York. Dr. Hack currently serves on the boards of directors of Dynavax Technologies Corporation, Imperative Care, JenaValve Technology, Mersana Therapeutics, and Nuvalent. He previously served on the boards of directors of Affinivax, Atea Pharmaceuticals, Allena Pharmaceuticals, BCLS Acquisition Corporation, and Xilio Therapeutics. Dr. Hack received an A.B. in biology with special honors, an M.D., and a Ph.D. in molecular genetics and cell biology from the University of Chicago.
Leonide Saad, Ph.D.
Co-Founder and Chief Scientific Officer
Dr. Saad holds a Ph.D. with a focus on tissue engineering and regenerative medicine from MIT, a Financial Technology certificate from MIT Sloan School of Management, a MS in Mechanical Engineering from MIT, a BS and MS in Applied Mathematics from University of Paris VI, and is a graduate from Ecole Polytechnique, Paris, with a concentration in organic chemistry and physics.
Ian Smith
Director
Ian Smith is a biotechnology leader with more than 25 years of strategic leadership, corporate and business development, finance and operations experience. He currently serves as a Senior Advisor to Bain Capital Life Sciences, Executive Chair of Solid Biosciences and a member of the Board of Directors of Foghorn Therapeutics. He also provides executive advisory services to multiple biotech companies. Previously, he was Executive Chair of Viacyte, and a member of the Board of Directors of Acorda Therapeutics, Aavanti Bio and Infinity Pharmaceuticals. Ian was Executive Vice President and Chief Operating Officer of Vertex Pharmaceuticals, as well as Chief Financial Officer between 2001 and 2019, during which Vertex grew from a research-based organization to a global commercial company with multiple successfully launched medicines. Prior to joining Vertex, Ian was a Partner in the Ernst & Young Life Science Practice.
Chen Yu, M.D., M.B.A.
Director
Dr. Yu is the founder and Managing Partner at TCGX. Dr. Yu has extensive operating experience with leadership roles at both private and public companies, including as Chief Operating Officer at Sagent Pharmaceuticals and Chief Business Officer of ChinaKangHui. Dr. Yu has served on the board of over a dozen private/public companies, including Structure Therapeutics, Artios, Upstream Bio, Arbor Biotechnologies, Tarsus Pharmaceuticals, Sagent Pharmaceuticals, China Kanghui, Rempex, Nabriva, Surgical Specialties, Sentre Heart, and NKF Pharma. While at Vivo, his previous firm, he also led investments in Zai Labs, RiverVision, CRISPR Therapeutics, Intellia, Durata, Precision Biosciences, Trauson, and Revolution Medicines. Dr. Yu received his M.D. and M.B.A. from Stanford University and graduated magna cum laude with a B.A. in Biology from Harvard University.
David Setboun, Pharm.D., M.B.A.
Chief Operating Officer
David Setboun is an operations and commercial leader with foundational experience driving innovative therapies into and through clinical development at multiple biotechnology companies, and he has broad functional expertise across strategy, operations, commercialization, business development. Prior to Alkeus, David was EVP and Chief Operating Officer at Brainstorm Cell Therapeutics and Vice President, Corporate Development and Strategy at Life Biosciences. Prior to these roles, David was Vice President and Managing Director for France at Biogen and Country President, Portugal at AstraZeneca and Global Brand Director at Eli Lilly. David has a reputation for inventive, mission-focused leadership and for the last 10 years David has dedicated his career to promoting and developing targeted therapies for rare diseases. He is also an angel investor and the founder of a nonprofit in longevity science. David earned an MBA from HEC Paris and a PharmD from the University of Paris Saclay. He is also an alumnus of Harvard Business School (AMP 194).
Ilyas Washington, Ph.D.
Co-Founder
Dr. Ilyas Washington is a professor, inventor, scientist, and co-founder with backgrounds in university and industry research and development. In 2010, Dr. Washington co-founded of Alkeus Pharmaceuticals with Dr. Leonide Saad. In 2018, Dr. Washington started biOOrg3.14 to invent therapies differently using radically different approaches. Before starting biOOrg3.14, Dr. Washington was the Michael Jaharis Assistant Professor at Columbia University Medical Center in the Department of Ophthalmology. His research has focused on understanding how unavoidable environmental phenomena such as light, gravity, magnetic fields and diet influence and dictate human health on a molecular level. Dr. Washington holds a PhD in organic chemistry from UCLA and a BA in chemistry from Bard College. He completed postdoctoral work at Columbia University and trained under the mentorship of Koji Nakanishi, Nick Turro (Columbia University), Ken Houk (UCLA) and Hilton Weiss (Bard).
SEEMI KHAN, M.D., M.P.H., M.B.A.
Chief Medical Officer
Eric L. Trachtenberg, J.D., M.B.A.
Chief Legal Officer
Tamara Dillon
Chief Human Resources Officer
David Arkowitz, M.B.A.
Chief Financial Officer
David Arkowitz has more than 30 years of finance, operations, business development and commercial leadership experience in the life sciences and biotech industries. In addition to his track record leading finance functions and operations, Mr. Arkowitz has extensive business development and commercial product launch experience.
SEE LATEST NEWS
Alkeus Pharmaceuticals Announces Positive Gildeuretinol Data Will Be Presented During the 12th International FLORetina ICOOR Congress December 5–8 in Florence, Italy
CAMBRIDGE, Mass., December 5, 2024 – Alkeus Pharmaceuticals, Inc. today announced that results from its clinical studies of investigational oral gildeuretinol for the treatment of Stargardt disease (TEASE) will be presented at the 12th International FLORetina ICOOR...
Alkeus Pharmaceuticals Receives FDA Rare Pediatric Disease and Fast Track Designations for Gildeuretinol as a Treatment for Stargardt Disease
Designations underscore significant unmet need in Stargardt disease, a rare and serious pediatric disease for which no treatment exists. Data from Alkeus’ TEASE program were presented at the American Academy of Ophthalmology’s 2024 annual meeting. Alkeus plans to...
Alkeus Pharmaceuticals Appoints David Arkowitz as Chief Financial Officer
Accomplished Finance and Commercial Leader Brings Extensive Life Sciences Expertise CAMBRIDGE, Mass., October 31, 2024 – Alkeus Pharmaceuticals, Inc. today announced that David Arkowitz, M.B.A., has joined the company as Chief Financial Officer. “David is an...