RhyGaze is a cutting-edge biotechnology company based in Basel, Switzerland, and Philadelphia, Pa., USA, focused on developing gene therapies for retinal diseases causing blindness. Founded on pioneering research from the Institute of Molecular and Clinical Ophthalmology Basel (IOB), RhyGaze aims to restore vision and transform the lives of patients worldwide. IOB scientists Drs. Botond Roska, Bence György and Charles Gubser are the scientific founders of RhyGaze.
Sector: Life Sciences
Tenvie Therapeutics
Tenvie is a biotechnology company committed to engineering small molecules that transform the treatment of neurological diseases. The company’s foundation is purpose-built with a diverse portfolio of small molecules and a proven team of CNS drug developers to rapidly deliver multiple clinical assets. Tenvie is advancing a pipeline of therapeutics focused on treating neurological, cardiometabolic, and ophthalmic diseases. Its portfolio of wholly owned, highly brain-penetrant, and precision-designed peripherally restricted small molecules address three key drivers of disease: resolving inflammation, rescuing metabolic dysfunction, and restoring lysosomal function. The company’s most advanced programs target NLRP3 and SARM1, with additional programs in preclinical development. You can follow Tenvie on LinkedIn.
Pioneering Progress: The Lenmeldy™ Story
Orchard Therapeutics’ Lenmeldy™ is a first of its kind treatment for an ultra-rare pediatric hereditary disorder.
F-Prime is dedicated to advancing pioneering science and technologies that redefine patient care. Since 2002, F-Prime has facilitated the regulatory approval and commercialization of 33 products and drugs. In our series, Pioneering Progress, we will be showcasing the success stories behind the approval of drugs and products from our portfolio companies.
A Devastating Childhood Disease
Metachromatic leukodystrophy (MLD) is an ultra-rare hereditary disorder caused by mutations in the ARSA gene which render the body unable to break down certain lipids inside cells. This results in progressive destruction of a fatty protective layer on the outside of nerve cells called myelin, leading to impairment of an individual’s movement, severe neurological decline, and ultimately death.
MLD is estimated to affect 1 in 40,000 to 1 in 160,000 live births worldwide1. The disease most commonly manifests in infants and young children, though it can present later in life. Symptoms vary depending on the age of onset but typically include muscle weakness, difficulty walking, loss of motor skills, cognitive decline, seizures, and loss of vision and hearing.
Historically, there has been no way of stopping the disease’s progression and treatment options have been limited to symptom management and supportive care.
New Hope for MLD Patients
Recognizing the potential for bone marrow gene therapy to transform how patients with ultra-rare diseases such as MLD are treated, F-Prime partnered with Bobby Gaspar, M.D., Ph.D., a world-renowned physician and Professor of Pediatrics and Immunology at University College London’s Great Ormond Street Institute of Child Health. Working with Bobby and his global network of academic collaborators, F-Prime formed a new company called Orchard Therapeutics.
Using the combined expertise and resources of F-Prime, Bobby and his collaborators Orchard assembled a portfolio of gene therapies that act on the bone marrow of patients. In 2018, Lenmeldy™ entered the spotlight when Orchard acquired the gene therapy programs of GSK, as the big pharma pivoted away from rare disease.
“As a leading expert in bone marrow gene therapy for severe inherited disease, Bobby brought deep technical and clinical know-how to fuel Orchard’s R&D. F-Prime supplemented his expertise with a company creation engine,” said Alex Pasteur, Ph.D., Partner at F-Prime. “We were a thought partner to Bobby throughout the founding of Orchard, and we helped him to acquire the Lenmeldy program from GSK.”
Throughout its development, Lenmeldy consistently generated promising clinical data, which earned the project lead program status within Orchard’s pipeline. Due to the rarity of MLD, it was essential to educate regulators and other stakeholders about the natural history of the disease, difference clinical methods for assessing symptoms, and Orchard’s new approach.
Upon reaching market approval in Europe in 2020 (as Libmeldy™) and in the U.S. in 2024 (as Lenmeldy™), the therapy became the first-in-class disease-modifying treatment for MLD patients. At the time of approval, the product had the most extensive follow-up data for any gene therapy in the U.S., demonstrating the treatment’s long-term safety and efficacy.
The approval of Lenmeldy was based on studies involving 37 children who received a single dose of the gene therapy2. Remarkably, 100% of children with pre-symptomatic late infantile (PSLI) MLD who were treated with Lenmeldy were alive at six years old, while only 58% of children in the natural history group survived to that age. At five years of age, 71% of children treated with Lenmeldy were able to walk independently, and 85% exhibited normal language and performance IQ scores – outcomes that had not previously been observed in MLD children. Additionally, a slowing of motor and cognitive decline was observed in children with pre-symptomatic early juvenile (PSEJ) and early-symptomatic early juvenile (ESEJ) MLD.
Stakeholder education remains a priority for Orchard post approval of Lenmeldy, with the focus shifting from regulators to physicians and payers. To ensure that the full patient population benefits from Lenmeldy’s curative potential, it has been important for Orchard to accelerate adoption by rolling out standardized diagnosis and newborn screening programs.
Empowering Change with Strategic Investment
We extend our appreciation to Bobby, his collaborators and the entire Orchard team for their efforts throughout the journey of Lenmeldy, which marks a groundbreaking advancement in the treatment of MLD. The success of Lenmeldy not only transforms the outlook for MLD families but also demonstrates the potential for bone-marrow gene therapy to address other severe inherited neurometabolic diseases.
“Our partnership with Bobby – who has spent 10 years at Orchard immersed in company creation, clinical development, regulatory engagement and business development – continues with Bobby joining F-Prime as Venture Partner, ready to help F-Prime build another company with an innovative approach and a mission to help patients in life-altering ways,” said Pasteur.
F-Prime is committed to building transformative companies by supporting the next generation of innovators as they tackle the toughest challenges in healthcare. The success of Lenmeldy serves as an inspirational example, offering hope to MLD families and fueling continued efforts toward future breakthrough treatments for rare diseases.
- Chang, SC., Bergamasco, A., Bonnin, M. et al. A systematic review on the birth prevalence of metachromatic leukodystrophy. Orphanet J Rare Dis 19, 80 (2024). https://doi.org/10.1186/s13023-024-03044-w
- https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-children-metachromatic-leukodystrophy
AvenCell
AvenCell derives its name from the French word “avenir” to reflect the aim to be the FUTURE of cell therapy. AvenCell is building a truly transformative cell therapy company that targets difficult-to-treat cancers, with its lead programs focusing on acute myeloid leukemia (AML) and additional programs targeting other hematological malignancies. AvenCell was formed with the goal to create truly allogeneic cells that persist as long or longer than autologous therapies and develop a universal and switchable construct that allows complete control and target redirection of T cells after they are infused into a patient. Integration of these two platforms allows for complete separation of the manufacturing of cells from ultimate patient and cancer target, thus providing significant scalability potential at orders of magnitude more efficient than current approaches.
Natasha Rodgers, MB BChir
Natasha Rodgers is an Associate in F-Prime’s London team, working across the life sciences sub-sectors including therapeutics and medical technology. Prior to joining F-Prime, Natasha was an associate consultant at Bain & Company. She also worked as a junior doctor in Edinburgh and Oxford with a particular focus area in Intensive Care. Natasha holds an MB BChir from Cambridge University and an A.B. in Molecular and Cellular Biology from Harvard University.
Clare Bernard
Clare Bernard is a Venture Partner at F-Prime. She is focused on new company creation at the intersection of tech and the life sciences. Prior to F-Prime she led data science and software efforts at the Broad Institute, managing the team that developed several widely used open-source bioinformatics tools and software platforms including the Terra platform and GATK. She also led product and engineering at Tamr, a Cambridge-based software company that uses machine learning to integrate large datasets.
She received her B. in math and physics from Johns Hopkins University and her PhD from Boston University for research in particle physics conducted at the Large Hadron Collider.
Pioneering Progress: The FARAPULSE™ Story
Atrial Fibrillation (AF) Challenges and Treatments
Currently, atrial fibrillation (AF) is the most common form of irregular heart rhythm (also known as an arrhythmia) – impacting 40 million people globally1. It is projected that by 2030, the United States alone will grow to have 12.1 million people suffering from AF1. In addition to being a lifelong challenge, AF is a progressive disease that can be fatal, as it is linked to a risk of blood clots, stroke, heart failure, and other serious complications2.
If not addressed, initial symptoms may become more frequent and then permanent, yet only a small fraction of the population (about 15% of cases in the U.S.3) are treated for the root cause of the disease. Most patients are on anti-coagulants or other drugs to prevent clots and strokes; however, those medications have potentially dangerous side effects including bleeding, gastrointestinal issues, hematomas, and more.
“Therapy for AF – a condition that is now recognized as a worldwide epidemic – did not even exist 25 years ago, and we are still in the early stages of treating or even preventing AF,” said Robert Weisskoff, PhD, Senior Partner at F-Prime. “There was a clear need to improve upon existing methods and train an entire workforce of medical professionals to conduct a new procedure that offers patients rapid, safe, and durable results before the disease manifests permanently.”
When F-Prime met the Farapulse team, there were two existing interventions to treat AF – burning or freezing, both with considerable drawbacks. The first option, radiofrequency (RF)-based ablation burns small regions to reverse AF. It was the first technology introduced commercially, but it is lengthy process and requires highly skilled medical professionals. The second option, cryotherapy ablation (cryo), freezes those same regions. Cryo can be completed more quickly but lacks the same precision and control. Both techniques pose risks such as permanent damage to nearby tissues, such as the diaphragm or esophagus, and narrowing of the pulmonary veins. While these risks are relatively small, their potential consequences can be devastating.
Harnessing Technology for Targeted Solutions
In search of a better method to address AF, Steven Mickelsen, MD at the University of Iowa leveraged a technology known as pulsed field ablation (PFA), initially meant to treat cancer. PFA utilizes a high-voltage, low-energy source in a minimally invasive manner to selectively ablate targeted cardiac tissue without heating or freezing. PFA can selectively kill specific cells within a very well-defined region and offers a reliable, one-time intervention that reduces the number of repeat procedures that could be required. The team at Farapulse, led by Allan Zingeler, Raju Viswanathan, PhD, and an experienced MedTech R&D group, adapted the technology into a catheter-based approach that leveraged many of the same advantages of RF and cryo. However, PFA offers a quicker and equally effective treatment, while avoiding the potentially negative repercussions. Additionally, it is simpler to learn than other treatment options, facilitating wider adoption.
The effectiveness of PFA was validated in clinical trials (including a large randomized pivotal trial for the FDA in the U.S.), demonstrating it to be as safe and reliable as conventional thermal ablation methods. Real-world data from the MANIFEST-17K registry, presented at the American Heart Association’s (AHA) Scientific Sessions, further underscored its safety profile across more than 17,000 patients. Building on this success, FARAPULSE™, has since revolutionized atrial fibrillation treatment as the world’s clinical leader in PFA, with over 70,000 patients treated to date. Boston Scientific continues to be enthusiastic about expanding FARAPULSE into new markets, including China and Japan, targeting the latter half of 2024.
Transforming Healthcare with FARAPULSE™
F-Prime was among the earliest institutional investors alongside Boston Scientific, to recognize the promise of this transformative approach to treat AF. Boston Scientific identified a significant market opportunity and provided funding for Mickelsen’s original concept, aimed at competing with devices used by cardiac surgeons to treat AF during valve replacement procedures. Throughout the development stages, F-Prime played an integral role, particularly during the transition from an extracardiac to an intravascular approach, ensuring the product’s progression.
Weisskoff attributes the success of the product to a “small but highly experienced team. Our contributions involved helping them navigate fundraising, IP, and personnel dynamics, as well as develop an exit strategy before the U.S.-based pivotal trial.” He also emphasizes that the strategic timing of involving Boston Scientific, which later acquired the company, and the careful structuring of their engagement, were crucial in successfully navigating FARAPULSE through to approval.
Looking beyond AF, PFA technology holds promise for treating other conditions such as type 2 diabetes, where it aims to enhance glycemic control and restore insulin sensitivity. It may also have implications for chronic obstructive pulmonary disease (COPD) – potentially improving respiratory function by widening bronchial tubes. Advancements in PFA-based technologies also have the potential to lead to more selective cancer treatments. Through ongoing support, F-Prime is committed to backing innovative companies like Farapulse that are reshaping the landscape of medicine and are working toward setting a new standard-of-care for diverse medical needs.
- Hearth Rhythm Society
- Johns Hopkins Medicine
- Boston Scientific Crosses the FDA Finish Line with Farapulse, Medical Device and Diagnostic Industry
Bobby Gaspar, MD, PhD
Bobby Gaspar is a Venture Partner with F-Prime based in London. Bobby is a world-renowned scientist and physician and accomplished strategic and organizational leader with more than 25 years of experience in medicine and biotechnology. He is one of the principal scientific founders and current chief executive officer of Orchard Therapeutics, a global gene therapy leader recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe. Bobby has been a pioneer in gene therapy and the evolution of hematopoietic stem cell (HSC) gene therapy technology—including some of the first studies in patients with severe primary immune deficiencies—bringing it from some of the first studies in patients into late-stage clinical trials. His unparalleled expertise and deep relationships with key physicians and treatment centers around the world are integral to Orchard’s efforts to identify patients with metachromatic leukodystrophy (MLD) and other severe genetic conditions through targeted disease education, early diagnosis and comprehensive newborn screening.
Bobby was named to the inaugural TIME100 Health list in 2024, recognizing him as one of the world’s most influential individuals impacting human health. In addition to his role at Orchard, Bobby also serves as the chair of the board of directors at Eligo Biosciences, a privately-held biotech company expanding the scope of genetic medicines through gene-editing of the microbiome. He is also a venture partner at F-Prime, a global venture creation and investment firm with $4.5 billion under management.
Bobby is an honorary professor of pediatrics and immunology at the University College London (UCL) Great Ormond Street Institute of Child Health and has led multiple clinical trials that have shown that gene therapy can successfully correct the genetic defect in immune deficiencies. He studied medicine and surgery at Kings College in London before completing his PhD at the UCL Great Ormond Street Institute of Child Health.
Nicholas Haining, BM, BCh
Nicholas Haining, BM, BCh is a Venture Partner at F-Prime based in the Cambridge office. Nicholas is also the Chief Scientific Officer and co-founder of Arsenal Biosciences, a cell therapy company based in South San Francisco.
During his time as an Associate Professor of Pediatrics at Harvard Medical School and an Associate Member of the Broad Institute of MIT and Harvard, his lab defined some of the key transcriptional and epigenetic regulators of T cell exhaustion and used in vivo genetic screens to identify immune vulnerabilities of cancer cells in mouse models. Nicholas’ clinical expertise is in hematopoietic stem cell transplantation, and he worked on the bone marrow transplant team at Boston Children’s Hospital for nearly twenty years.
More recently, he served as Vice-President, Discovery Oncology and Immunology at Merck Research Laboratories, where he led a multi-site, multidisciplinary team developing innovative approaches to identify therapies for cancer and immune diseases.
Nicholas was elected into the American Society for Clinical Investigation, and has received the Presidential Early Career Award for Science and Engineering.
As a physician-scientist, immunologist and drug developer, Nicholas received his undergraduate and medical degree from Oxford University, UK. He subsequently completed his medical training in Pediatrics at Boston Children’s Hospital and in Pediatric Hematology/Oncology at Dana-Farber Cancer Institute.
Amber Therapeutics
Amber Therapeutics is developing Amber-UI, a breakthrough adaptive neuromodulation therapy to treat women suffering with mixed urinary incontinence with the hope of transforming the clinical outcome and quality of life of a large untreated population. Amber-UI runs on the Company’s fully implantable Picostim system that targets the pudendal nerve to both stimulate and sense physiological responses. The therapy is configurable to the individual’s need and can respond dynamically to different events, adapting as needed between modes of operation. Amber’s technology platform is highly versatile and can be used to explore other novel therapy applications in both the pelvis and the broader nervous system, demonstrated by the work being carried out by the Company’s academic partnerships.