Retinal degeneration, like many other complex diseases, involves progressive failures in multiple systems. Standard approaches targeting one single pathway has historically failed to work. A more sophisticated approach targeting multiple pathways is thus required.
The use of stem cells and their secretome for neuroprotection has emerged as novel therapeutic approach over the last decade. However, their success in the clinic has proved limited. In particular, stem cell therapies are confronted with two obstacles
Undetermined cell fate leading to cell differentiation towards a heterogeneous cell population and uncontrolled cell-cell interactions
- Ganglion cell
- Amacrine cell
- Bipolar cell
- Müller cell
- Horizontal cell
- Rod photoreceptor
- Cone photoreceptor
Unpredictable in-vivo microenviroment leading to unwanted cell-matrix interaction
Cellular Development Platform
At InGel our scientists have discovered a novel cell state, during the cell differentiation process, for the retinal neurons including rods, cones and the ganglion cells. In this state, the cells are fated to only differentiate towards one cell type, therefore achieving high purity, but and the same time are still proliferative and can be expanded to hundred of millions. We named them Precursor Cells.
Unlike multi-potent stem cells that may differentiate towards many cell types, these precursor cells make great therapeutic candidates because they do not encounter the unwanted behaviors from a heterogeneous cell population and messy cell-cell interactions. We can also conduct elegant target engagement studies by isolating the pure cells’ secretome and identify the mechanism of neuroprotection.
- Fetal derived
- Confirmed phenotype, morphology
- High purity (>95%)
- Highly neuroprotective
- Fetal derived
- Confirmed phenotype, morphology
- High purity (>98%)
- High engraftment
- ESc derived
- Confirmed phenotype, morphology
- High purity from human, mouse and pig sources
Hydrogel Delivery Platform
The other problem confronting regenerative cell therapy is its delivery in vivo. Many studies have shown that the cellular response varies greatly depending on its microenvironment. Mechanical cues such as the injection shear stress alone will trigger apoptosis. Other factors, such as spatial cues (cell anchorage), chemical cues (healthy vs diseased host tissue environment) also trigger different cell behavior in vivo.
That is why the other key innovation at InGel is the engineering of a biomimetic hydrogel matrix, enabling the in vivo delivery of the retinal neurons. Our material scientists took inspiration from the human eye and engineered a hydrogel that mimics the human vitreous, consisting of only Hyaluronic acid and Gelatin. This elegant and simple design allows for both intravitreal and subretinal injections and can be tuned to exhibit different stiffness and degradation timeline.
Last, because the matrix is engineered to mimic the human vitreous, the degradation of the hydrogel follows an enzymatic degradation, via collagenase and hyaluronidase already present in the eye. This offers a promising safety profile as the metabolites are constantly being cleared by the human eye.
We are focused on complex retinal degenerative diseases with high unmet need.
Retinitis pigmentosa (RP) comprises a large group of inherited vision disorders that cause progressive degeneration of the retina, the light sensitive membrane that coats the inside of the eyes. Peripheral (and night) vision gradually decreases and eventually is lost; then followed by the loss of central vision, color vision until patients become completely blind.
A common condition affecting more than ten million patients in the US alone, Dry age-related macular degeneration (AMD) is a slow deterioration of the cells of the macula, often over many years. The macula is the part of the retina that controls sharp, straight-ahead vision. While it doesn’t always cause complete blindness, losing the central vision can make it harder to see faces, read, drive, or do close-up work.
Glaucoma is a group of diseases that damage the nerve connecting the eye to the brain (the optic nerve). It results in progressive vision loss and eventually blindness. About 3 million Americans have glaucoma but only 50% know they have the condition. This is because glaucoma may not cause any symptoms initially.
RegenesisTM is a target discovery and validation platform for neuroprotective pathways in the eye. It leverages single cell proteomics profiling for rod photoreceptors and their secretome. By modifying specific gene or gene combo in the pure human rod photoreceptor, InGel is able to isolate protein of neuroprotective significance first in vitro and later in vivo. The in vitro testing stage is high-throughput, as testing can be performed in pure human cone photoreceptor population.
With a PhD from MIT in polymer sciences Pierre Dromel has been extensively focusing on engineering biomimetic systems that can enhance regenerative medicine. With expertise in neuroscience from Imperial College London and engineering he created 3D hydrogel delivery systems from natural sources to combat the biggest challenge faced by regenerative medicine with a primary focus on eye diseases. Dr. Dromel saw this challenge early on in his work and has dedicated his research to improving stem cells purity, viability, and structural support matrix. Replacing cells, restoring vision, and bringing back light to blind patients is the core mission of InGel Therapeutics, a company he co-founded. As CEO of InGel Tx, he is focused on innovating novel therapeutics and engineering approaches to bring them to patients suffering from retinal degenerative diseases.
Dr. Deepti Singh has a PhD. in biogenetics and has been conducting research in the cross-section of bioengineering and developmental biology over the past fifteen years. Specifically, she has developed various bioengineering techniques to alter cellular microenvironment and their metabolism, differentiation, phenotypical behaviors. In the earlier years, she has accumulated extensive experience in biomaterial design and stem cell culturing, across a variety of cell types including mesenchymal stem cells, cartilages, and skin tissues. She proceeded to research neurobiology at Yale University under the guidance of Dr. Lawrence Rizzolo, where her work was a DOD-funded project to restore vision for soldiers blinded by a blast injury; she developed various protocols to differentiate both embryonic and induced pluripotent stem cells into retinal progenitor cells. After joining Dr. Michael Young’s lab at Harvard, she continued her retinal stem cell research by focusing on novel cell enrichment and expansion techniques. This eventually resulted in her invention of a microfluidics-based approach to further differentiate and isolate retinal progenitor cells into lineage-specific retinal precursor cells, such as rods, cones, and retinal ganglion cells, while still keeping them in the mitotic state; This breakthrough discovery led her to co- found InGel Therapeutics as its Chief Scientific Officer.
Patrick Jiang spent the last ten years working in the biopharma industry, with roles in both the commercial and business development group. Specifically, he was an early employee at Horizon Therapeutics, and later was part of the launch team of Horizon’s blockbuster drug, Teprotumumab (TEPEZZA), in the treatment of Thyroid Eye Disease. It was during this time he developed a strong interest in diseases affecting the back of the eye and therapeutic strategies in the field of regenerative medicine. In 2021, he left Horizon to pursue his MBA at Harvard Business School, where he met Professor Michael Young, Pierre Dromel, and Deepti Singh. Impressed by the team and their scientific inventions, he decided to take a leave of absence upon finishing his first year and an internship at Genentech’s business development group. Patrick joined InGel Therapeutics as its co-founder and Chief Business Officer, where he is responsible for a range of business development, strategy and fundraising activities.
Scientific & Clinical Advisory Board
Scientific Advisory Board
Dr. Michael J. Young is recognized for his significant contributions to the field of regenerative ophthalmology. Affiliated with the Schepens Eye Research Institute, an integral part of Harvard Medical School, Dr. Young's groundbreaking research has primarily centered around retinal diseases and potential regenerative therapies. His endeavors have shed light on stem cell-based approaches to treat conditions like age-related macular degeneration (AMD) and retinitis pigmentosa. Over the years, he has pioneered techniques to transplant retinal cells into diseased eyes, seeking ways to restore or prevent vision loss. Beyond his research, Dr. Young's influence extends to his roles as an educator and mentor, fostering the next generation of ophthalmologists and vision researchers. His unwavering commitment to advancing our understanding of retinal diseases and exploring therapeutic avenues stands as an inspiration to the medical community. His work at the Schepens Eye Research Institute underscores the importance of translational research in bridging the gap between laboratory findings and real-world applications, bringing hope to countless individuals affected by vision-related conditions.
Myron Spector, Ph.D., is Professor, Emeritus Orthopaedic Surgery (Biomaterials), Brigham and Women’s Hospital, Harvard Medical School, and Affiliate, Massachusetts Institute of Technology, where he teaches 2 subjects: Tissue Engineering and Organ Regeneration; and Design of Medical Devices. He has 50+ years of experience in researching and developing biomaterials-based treatments for a wide array of medical problems, principally involving the principles and practice of tissue engineering and regenerative medicine. His studies in the past 15 years have been directed toward the development of injectable biopolymer gels incorporating cells and/or regulatory molecules (viz., growth factors) for the treatment of lesions in the central nervous system, and musculoskeletal and dental tissues. His anorganic bovine bone graft product has been used in 15 million patients worldwide. From 1993-97, Professor Spector served as the Chairman of the FDA Advisory Panel for General and Plastic Surgery Devices. He served as the President of the Society for Biomaterials (1990-91), and has received awards from: the Society for Biomaterials (2002 Clemson Award for Applied Biomaterials Research); the Orthopaedic Research Society/American Academy of Orthopaedic Surgeons (2001 Elizabeth Winston-Lanier Kappa Delta Award); and The Hip Society (2004 John Charnley Award). In 2005 he co-founded the journal, Biomedical Materials: Materials for Tissue Engineering & Regenerative Medicine and served as its Editor-in Chief through 2019. Professor Spector has published 350+ journal articles.
Dr. Stephen Redenti is a Professor in the Department of Biological Sciences at Lehman College and in the CUNY Graduate Center Doctoral programs in Biochemistry and Molecular, Cell and Developmental Biology. A central goal of the Redenti Lab is to advance understanding of cell and tissue communication to contribute to repair of damaged neural tissue. To identify molecular mechanisms contributing to intrinsic cellular intelligence and decision-making we draw on evolutionary and developmental biology, bioinformatics, computer modeling and collaborative bioengineering strategies. An additional line of research in the lab involves analysis of stem cell and progenitor cell extracellular vesicle release rate, morphology, and molecular content. Our initial studies have focused on induced pluripotent stem cell microvesicles characterization. We use Nanosight analysis, electron microscopy, proteomics, gene expression analysis and in silico modeling. The goals of this work include defining the significance of stem cell extracellular vesicles in maintaining pluripotency and toward application in nerve tissue regeneration.
Motoichi Kurisawa received his PhD degree from the School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), in 1998. He joined the Institute of Bioengineering and Nanotechnology (IBN), A*STAR, in 2003, and is currently a Team Leader and Principal Research Scientist. He is a recipient of the outstanding paper award from the Journal of Artificial Organs in 1997 and 2002, and won the Grand Prize at The Crown Prince Creative, Innovative Product and Technical Advancement (CIPTA) Awards in 2015. He has served on the editorial board of the journal Biomedical Materials since 2016.
Clinical Advisory Board
Dean Eliott M.D., is Stelios Evangelos Gragoudas Professor of phthalmology at Harvard Medical School. Dr. Eliott, Director of the Mass. Eye and Ear Retina Service, is a recognized leader in surgery for complexretinal conditions. As a clinical innovator and clinician scientist, Dr. Eliott wasamong the first surgeons to perform clinical trials in intravitreal sustaineddrug delivery device implantation, epiretinal vision-restoring electrical deviceimplantation, subretinal stem cell transplantation, and gene therapy for avariety of blinding retinal disorders. He discovered an innovative the rapeutic approach to prevent intraocular scarring and blindness after retinaldetachment surgery, and was co-founder of Helio Vision Inc., which was acquired by Aldeyra Therapeutics.
Dr. Pennesi's interest in degenerative retinal disorders began shortly after his first year in college, when he spent a summer working at the Retina Foundation of the Southwest. He worked under the supervision of Dr. David Birch and saw patients with retinal degenerations such as retinitis pigmentosa as well as studying animal models of this disease. After college, Dr. Pennesi completed a combined M.D./Ph.D. at Baylor College of Medicine in Houston, Texas. His thesis work focused on identifying new animal models of retinal degeneration. He received numerous awards while in graduate school, including the John J. Trentin Award for earning the highest GPA in his class and the BRASS scholarship for playing an active role in community service. For his residency training, Dr. Pennesi spent his internship year in San Diego at Scripps Mercy Hospital, followed by his ophthalmology residency at the University of California, San Francisco. Dr. Pennesi joined the faculty of Casey Eye Institute and is now a Professor in Ophthalmic Genetics and as the chief of the Ophthalmic Genetics Division. Both Research to Prevent Blindness and the Foundation Fighting Blindness have recognized Dr. Pennesi with career development awards to support his ambition to conduct transitional research that will bring treatments for diseases such as retinitis pigmentosa from the laboratory to the clinic. Additionally, he is the recipient of the 2011 ARVO/Alcon Early Clinician Scientist, the Alcon Young investigator Award in 2014, and the Casey Eye Institute Resident teach award. His research focuses on developing novel treatments for inherited retinal diseases. He is currently exploring the potential of a new class of drugs to up regulate protective growth factors in the retina.
Charles C. Wykoff, MD, PhD is Director of Research at Retina Consultants of Texas; Chairman of Research, Retina Consultants of America; and Deputy Chair of Ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital. He received his baccalaureate from MIT, PhD from Oxford University while on a Marshall Scholarship, and MD from Harvard Medical School. His basic science research related to cellular adaption to oxygen availability and VEGF biology contributed to the 2019 Nobel Prize in Medicine that was awarded to his PhD supervisor Peter Ratcliffe. Dr. Wykoff completed ophthalmology residency and vitreoretinal fellowship at Bascom Palmer Eye Institute where he served as Chief Resident/Co-Director of Ocular Trauma and received a Heed Fellowship and the Ronald G. Michels Award. He is passionate about translational research and novel ways to accelerate drug and device development. He has published over 300 peer-reviewed manuscripts and serves on multiple scientific and medical advisory boards, safety monitoring committees, and global steering committees for endeavors spanning the innovative process from early to late-stage developments. He serves on the ASRS Board of Directors, is a founding member of the Ophthalmology Retina Editorial Board, is the Chief Medical Editor for Retina Specialist, and a past President of the Vit-Buckle Society. He is a member of the NEI Audacious Goals Steering Committee and has been awarded multiple Achievement, Honor and Senior Honor Awards including the ASRS Young Investigator and the AAO Secretariat Awards. His guiding philosophy is to build and strengthen innovative, ethical teams focused on developing new approaches to improving outcomes for blinding diseases.
Eric D. Nudleman, M.D., Ph.D. is an Associate Professor of Clinical Ophthalmology at UC San Diego Shiley Eye Institute. He joined UC San Diego (UCSD) after completing his fellowship in vitreoretinal surgery at the renowned William Beaumont Hospital. Prior to his fellowship, Dr. Nudleman graduated from Stanford University with bachelors and doctoral degrees. He earned his medical degree at Albert Einstein College of Medicine of Yeshiva University in New York then went on to Washington University School of Medicine in St. Louis, Missouri for his residency. Dr. Nudleman is the recipient of many prestigious honors such as the Ronald G. Michels Fellowship, Heed Fellowship, the Doris P. and Harry I. Wexler Prize, Rosenbaum Research Award, and the Association of University Professors of Ophthalmology/Research to Prevent Blindness Resident and Fellow Research Forum Award. He has participated in multiple National Eye Institute and industry-sponsored clinical trials. At UCSD, Dr. Nudleman's clinical focus is on vitreoretinal diseases and surgery, with a special interest in pediatric vitreoretinopathies. His laboratory focuses on developmental angiogenesis and the role of the Wnt signaling pathway with a particular interest in identifying novel targets to treat vascular diseases.
Laurens Bouckaert is an established biotech executive with extensive experience in global commercialization across multiple therapeutic areas, most recently in ophthalmology for over 10 years. Mr. Bouckaert is recognized for his commercial expertise having been involved as an essential member of the product teams for a diverse range of therapeutics. Mr. Bouckaert’s current focus is on providing strategic support to emerging companies with innovative approaches to treating ophthalmic diseases, including guiding on optimizing the company’s portfolio for investors and strategic partners based on the commercial and development landscape. Mr. Bouckaert has a Masters Degree in Pharmaceutical Science and an MBA in Marketing Management from Vlerick Leuven Gent Management School (Belgium).
Eliot Lazar is an anterior segment surgeon who for a quarter century has been intimately involved in the evolution of the ophthalmology industry. He has played a central role in supporting the strategic landscape and has played an important part in assisting emerging companies in their growth and development. In this role Dr. Lazar has also been critical in the translation of technologies into relevant therapeutics, including both devices and therapeutics. He has also been intimately involved in the development and advancement of drug delivery technologies to the eye. Dr. Lazar has leaned into the financial side of the ophthalmology industry and in this role has also encouraged and informed the investment community as they move forward. He has worked endlessly to promote ophthalmology to the investment community and has collaborated in support of transactions of all sizes. Eliot continues to advocate for the industry across a broad spectrum and aspires to deploy his talents in the development of relevant clinical therapeutics to fulfill the unmet needs in ophthalmology.
A bioinspired gelatin-hyaluronic acid-based hybrid interpenetrating network for the...https://www.nature.com/articles/s41536-021-00195-3
Injectable gelatin hydroxyphenyl propionic acid hydrogel protects human retinal progenitor...https://www.sciencedirect.com/science/article/abs/pii/S2352940720300494
The effect of injectable gelatin-hydroxyphenylpropionic acid hydrogel...https://www.sciencedirect.com/science/article/abs/pii/S0142961212000695?
Controlling Growth Factor Diffusion by Modulating Water Content in Injectable...https://www.liebertpub.com/doi/full/10.1089/ten.tea.2020.0313
3D hydrogels protect human retinal progenitor cells from stress exerted during transplantationhttps://iovs.arvojournals.org/article.aspx?articleid=2746936
In Situ Cross-linking Hydrogel as a Vehicle for Retinal Progenitor Cell Transplantationhttps://journals.sagepub.com/doi/full/10.1177/0963689719825614
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