Rarecast

Multiple sulfatase deficiency is a rare and progressive neurodegenerative disease. The patient advocacy organization United MSD Foundation has been able to advance a gene therapy into preclinical development for the ultra-rare condition through modest investment by pursuing a focused research strategy and leveraging partnerships. In May 2023, The Bespoke Gene Therapy Consortium, the National Institutes of Health-led public-private partnership selected the program for its clinical trial portfolio and will fund a phase 1/2 clinical trial for the therapy. We spoke to United MSD Foundation Executive Director Sarah Cortell Vandryspen, and UT Southwestern Gene Therapy Core Director Steven Gray. about United MSD Foundation’s research strategy, what enabled it to advance a gene therapy as fast as it did, and what other patient organizations can learn from its success.

Despite the growing demand for genomic data and the falling price of genome sequencing, costs continue to restrain its use. Single Technologies, which is developing a three-dimensional approach to sequencing, believes it can cut the cost to just $10 per genome for consumables. That’s a drop from estimates of about $600 today. We spoke to Johan Strömqvist, CEO and founder of Single Technologies and Bob Kain, advisor to the company, about its 3-D Sequencing, how it works, and how this can open up expansive use of the technology.

Nonsense mutations prematurely end the translation of a gene into protein and can result in a serious deficiency. About 10 to 15 percent of inherited genetic diseases involve nonsense mutations. Alltrna is developing transfer RNA therapies designed to correct the problem in protein synthesis caused by these aberrations. What’s particularly exciting about the approach is that a single therapy has the potential to work across nonsense mutations regardless of the gene in which they occur. We spoke to Michelle Werner, CEO of Alltrna, about nonsense mutations, how the company’s transfer RNA therapies work, and why the approach has the potential to address so many diseases at once. 

Effie Parks is well known in the rare disease community as both a patient advocate and host of the Once Upon a Gene podcast. Like many advocates, she was thrust into the world of rare diseases following the diagnosis of her son Ford with an ultra-rare neurodevelopmental disorder known as CTNNB1 syndrome. Recently she published a map of the journey that a family undergoes when seeking a diagnosis a rare disease, a humorous answer to the orderly way organizations typically portray the experience. We spoke to Parks about her experience with the diagnostic odyssey for her son Ford, her version of the map to a genetic diagnosis, and what organizations usually get wrong. Click here to view the map.

Inherited retinal diseases are a group of genetic conditions that cause progressive and severe vision loss, such as retinitis pigmentosa, choroideremia, and Stargardt disease. Though they vary in terms of their genetic drivers, they are characterized by degeneration of photoreceptor cells in the retina. Collectively, inherited retinal diseases affect more than 2 million people around the world and are largely without reliable treatment options. Kiora Pharmaceuticals is developing a new class of therapies that can restore vision in these conditions by targeting retinal ganglion cells and enabling them to become light sensing to compensate for the degeneration of rods and cones in the eye. We spoke to Brian Strem, CEO of Kiora Pharmaceuticals, about inherited retinal diseases, how Kiora’s experimental therapy works to treat these conditions, and a recent collaboration that will help drive clinical development of its lead experimental therapy.

For people in rural communities, access to genomic testing can require getting on a waitlist, delays in clinical assessment, and multiple visits to urban medical centers. A pilot study from Children’s Mercy Research Institute in Kansas City, Missouri, found that by partnering with a rural clinic in a direct-to-provider model it was able to more than double the historic rate for rare disease diagnosis among the rural population and also cut the time-to-diagnosis by about five months. We spoke to Ana Cohen, assistant director of molecular genetics at CMRI, about its direct-to-provider model, how providing local support to patients at their regular clinics allowed them to bypass bottlenecks, and how the approach can shorten the time to a diagnosis for people with rare diseases in rural communities.

The cornea is a transparent and multi-layered dome that sits at the front of the eye. It not only provides protection, but bends light to focus it on the retina. Many corneal diseases cause scarring that reduces the transparency of the cornea and results in the loss of vision. In fact, corneal diseases are a leading cause of blindness. Claris Bio is seeking to address the need for therapies to treat corneal disease by developing recombinant human deleted hepatocyte growth factor to improve and accelerate corneal healing. We spoke to Clarke Atwell, CEO of Claris Bio, about the cornea, the role hepatocyte growth factor plays in its healing, and the rare and chronic condition neurotrophic keratitis that it is focusing on as its lead indication.

Lennox-Gastaut syndrome and Dravet syndrome are two rare, developmental and epileptic encephalopathies. Drug developers have sought to address epilepsies by altering the electrical activity in the brain. Ovid therapeutics, though, has taken a novel approach with its experimental therapy soticlestat by seeking to restore homeostasis to the brain. We spoke to Meg Alexander, chief strategy officer of Ovid, about rare epilepsies, how the company’s experimental therapy soticlestat works, and the potential to apply the approach to other CNS conditions. Since recording this episode, there have been new results on soticlestat released. Ovid’s partner Takeda this week reported that soticlestat narrowly missed its primary endpoint in its phase 3 Dravet syndrome study while showing clinically meaningful and nominally significant effects in multiple key secondary efficacy endpoints. It also missed its primary endpoint of reduction in major motor drop seizures as compared to placebo in a separate phase 3 study in Lennox-G

Zevra Therapeutics, formerly KemPharm, rebranded itself in early 2023 following the acquisition of the experimental therapy arimoclomol for the rare lysosomal storage disorder Niemann Pick disease type C. Zevra is Greek for “zebra,” a symbol of rare disease. The company subsequently built out its rare disease pipeline through the acquisition of Acer Therapeutics in November 2023. An FDA decision on arimoclomol is due by the end of September. We spoke to Neil McFarlane, president and CEO of Zevra Therapeutics, about Niemann Pick disease type C, the FDA’s upcoming decision on whether to approve the drug, and its broader efforts to build itself into a rare disease therapeutics company. 

For certain rare diseases, therapies derived from human plasma, the largest component of blood, represent critical lifesaving and life-sustaining medicines. In many cases, it may represent the only therapeutic option. Takeda pharmaceutical’s Plasma-Derived Therapies Business Unit works across immunodeficiencies, neuroimmunology, hematology, pulmonology and other conditions. We spoke to Giles Platford, president of the Plasma-Derived Therapies Business Unit at Takeda, about its work in plasma-derived therapies, its recently approved therapy for the rare neuromuscular condition CIDP, and what issues need to be addressed to ensure an adequate supply of human plasma for therapeutic applications. 

Encoded Therapeutics is developing gene therapies that can target any cell type that has a unique genetic profile. The company’s lead experimental therapy is in development for the epileptic encephalopathy Dravet syndrome, although the company expects to pursue metabolic, liver, and cardiovascular conditions in the future. We spoke to Salvador Rico, chief medical officer of Encoded Therapeutics, about its lead program in Dravet syndrome, its efforts to develop gene therapies with optimized regulatory elements to target specific organs, and why he believes its approach is a point of differentiation for the company. 

Tuberous sclerosis complex is a genetic disorder that is characterized by tumor growth in various organs in the body, as well as neurological effects. Most people with TSC experience epilepsy early in life and many develop autism or other neuropsychiatric issues. The TSC Alliance has invested more than $37 million in research since 1984. Its efforts and collaborations have resulted in six U.S. Food and Drug Administration approved treatments for some aspects of the disease or related conditions. We spoke to Steve Roberds, chief scientific officer of the TSC Alliance, about the organization's success with crafting a research agenda, how it’s been able to invest in ways that catalyze research, and what it’s done to facilitate drug development by industry. 

Sunitha Malepati entered the world of patient advocacy after her child was diagnosed with a rare, neurodevelopmental disorder. More recently she founded the Buffalo Initiative to change drug discovery and development by creating a fund to invest in scientific enterprises driven by patient organizations and their collaborative networks. We spoke to Malepati about how she grew frustrated with the drug development landscape, how the Buffalo Initiative plans to fund patient advocacy organizations drug development efforts, and what the initiative is doing to reduce the time and cost of developing a therapy.

The work of gene therapy pioneer Genethon, a non-profit organization created by the patient association AFM-Telethon, has already seen its research lead to Zolgensma, the gene therapy for spinal muscular atrophy, as well as a growing pipeline of candidates for other rare diseases. But it came to realize it needed to pursue more than just licensing agreements to ensure its work ultimately benefited people who needed its therapies. As a result, the organization has taken a range of different approaches to ensure the development of its gene therapies. We spoke to Frederic Revah, CEO of Genethon, about the limits of licensing out its discoveries to biopharma, the different development strategies it pursues, and how it determines the best path for a particular development program.

Much of the challenge of developing genetic medicines lies in having the right vector to deliver the therapy to the cells within the body where they need to go. 4D Molecular Therapeutics has developed platform technology that generates large numbers of genetically diverse, synthetic adeno-associated viral vectors that have desired characteristics using a process known as directed evolution. It is using these vectors to build a pipeline of genetic medicines across a broad set of conditions. We spoke to Alan Cohen, senior vice president of clinical development and therapeutic area head of pulmonology for 4DMT, about the limitations of existing vectors for genetic medicines, 4DMT’s directed evolution platform technology, and its programs in cystic fibrosis and Fabry disease. 

As genetic testing continues to expand, it is bringing into focus a shortage of genetic counselors who can work with patients to explain results and answer questions. Igentify is helping genetic counselors manage more patients by providing an AI-based platform that can take some of the load off of them by helping onboard patients, obtaining consents, and educating them. We spoke to Doron Behar, co-founder and CEO of Igentify, about the company’s Digital Genetic Assistant, how it works, and why it will allow genetic counselors to handle a much larger volume of patients.

Duchenne muscular dystrophy is an inherited disease caused by genetic mutations that no longer allow the dystrophin protein to function properly. It turns out that dystrophin not only plays a role in muscle fiber, but in muscle stem cells as well and is critical for regeneration of muscle tissue. Without dystrophin, people with Duchene suffer progressive muscle tissue damage, functional decline, and ultimately loss of life. Satellos is developing an experimental small molecule therapy that restores innate muscle repair and regeneration. We spoke to Frank Gleeson, co-founder and CEO of Satellos, about its regenerative therapy for Duchenne, how it works, and why it may provide benefits to patients with other conditions that result in muscle degeneration. 

The Bespoke Gene Therapy Consortium, a public-private partnership backed by the Foundation for the National Institutes of Health, in February published its first playbook. The playbook provides a roadmap for streamlining product development and navigation of the regulatory pathway for AAV gene therapies with the goal of getting new treatments to patients sooner. We spoke to Courtney Silverthorn, vice president of strategic alliances and innovation for the Foundation for the National Institutes of Health; and Sharon King, manager of advocacy and community engagement for Aldevron and founder and president of Taylor’s Tale; about the Bespoke Gene Therapy Consortium, its new playbook, and how it will help gene therapy developers get their medicines to patients faster. 

The small patient populations of rare diseases, the limited natural history of these conditions, and the lack of long-term experience with new treatments all contribute to the difficulty in determining the value of rare disease therapies. The issue can be further complicated by whether value is calculated in a single payer system, or a multi-payer system. Recently the Innovation and Value Initiative issued a report with the Everylife Foundation for Rare Diseases from a long-term project to bring together stakeholders to explore patient-centered outcomes across rare diseases to inform those discussions. We spoke to Rick Chapman, chief scientific officer of the Innovation and Value Initiative, about the challenges of assessing the value of rare disease therapies, the role qualitative data should play in value assessments, and the recommendations from the report. 

Astellas Pharma took a big step into gene therapies when it announced an agreement at the end of 2019 to acquire Audentes Therapeutics for $3 billion. The company continues to build on that acquisition and has just completed construction on a 154,000 square foot, state-of the art cell and gene therapy facility to bring together teams dispersed across 20 locations. We spoke Ha Tran, medical head of cell and gene therapy for Astellas Pharma, about the company’s vision for cell and gene therapies, its efforts to restart trials for its X-linked myotubular myopathy gene therapy, and how it is looking to other programs beyond that.