Rarecast

Many gene therapy companies seek to exploit a platform technology or leverage a specific vector. Rocket Pharmaceuticals is pursuing a multi-platform pipeline of treatments that directly target the genetic mutation underlying rare, childhood disorders. We spoke to Gaurav Shah, CEO of Rocket, about the companies approach to gene therapy, the conditions it’s targeting, and how it determines what gene therapies it will pursue.

When someone receives a diagnosis of a rare disease, they often find themselves in a strange land with no roadmap. The Tuberous Sclerosis Complex Alliance is helping patients with TSC better manage their condition with the TSC Navigator, an online tool intended to guide individuals and families through the complexities of TSC across their lifespans and live fuller lives. We spoke to TSC Alliance CEO Kari Rosbeck and TSC Alliance Director of Medical Affairs Ashley Pounders, about the TSC Navigator, the thinking behind it, and why it could serve as a model for other patient organizations to follow.

PI3K inhibitors have been an area of great interest for drug developers targeting cancers, but they’ve been difficult to turn into promising drugs due to safety concerns and a lack of efficacy in clinical trials. Pharming, though, believes PI3K can be a valuable target to treat APDS, a rare, immune condition. The company is working to develop Leniolisib, which it licensed from the drug giant Novartis in 2019. We spoke to Anurag Relan, chief medical officer of Pharming, about APDS, the role its PI3K inhibitors can play in treating the condition, and why these drugs may have broader use in autoimmune and inflammatory diseases.

While gene therapies hold great promise for patients with rare genetic diseases, one obstacle for ultra-rare conditions is that drug developer may view patient populations as being too small to make the development of a gene therapy economically viable. Taysha Gene Therapies, through its partnership with UT Southwestern, is rapidly developing a robust pipeline of gene therapies that leverage the same vector, manufacturing, and course of administration to enable the company to pursue indication that might not otherwise be feasible. The approach shows how rare disease patient advocates, academic researchers, and biotechnology companies can collaborate to enable treatments that would not otherwise be developed. We spoke to R.A. Session II, founder and CEO of Taysha Gene Therapies, about the origins of the company, its unique relationship with gene therapy innovator Steve Gray and UT Southwestern, and the critical role patient organization have played in the process.

Most people think of gene therapies as a way to replace a mutated gene with a copy that functions properly. But gene therapies are also being developed as a way to get the body to produce therapeutic proteins. AbbVie in September announced a strategic partnership with RegenxBio to develop and commercialize the company’s experimental gene therapy for wet age-related macular degeneration and other eye conditions. The one-time treatment, delivered to the eye, encodes for an antibody fragment designed to inhibit VEGF like the antibodies ophthalmologists regularly inject into the eyes of patients to treat the condition. We spoke to Ken Mills, CEO of RegenxBio, about wet-age macular degeneration, the company’s collaboration with AbbVie, and the potential to use gene therapy to alter the way patients with this and other eye conditions are treated.

While gene editing therapies promise to dramatically change the way that rare genetic diseases are treated, one challenge has been to find ways to deliver them directly into the body rather than first altering a patient’s cells in the lab and reinfusing them. iECURE is developing mutation agnostic in vivo gene editing therapies to address liver diseases. The company has exclusive licensing rights to three liver disorder programs from the University of Pennsylvania’s Gene Therapy Program and an option to license more than 10 additional candidates. We spoke to Joe Truitt, CEO of iECURE, about its in vivo gene editing therapies, its focus on liver diseases, and how it’s leveraging its partnership with Penn’s Gene Therapy Program.

Gene editing is an emerging therapeutic area that promises to correct the underlying genetic causes of diseases. Graphite Bio is readying to enroll its first patient in a phase 1/2 clinical study of its experimental gene editor GPH101 to correct the mutation in the beta-globin gene that drives sickle cell disease. Though the condition can manifest itself differently from patient to patient, it can cause painful episodes due to the clumping of sickle-shaped blood cells that obstruct blood flow in small blood vessels, as well as other acute complications including stroke and infections that can contribute to early mortality in these patients. We spoke to Josh Lehrer, CEO of Graphite Bio, about the company’s experimental sickle cell gene editing therapy, how it works, and what makes it a next-generation gene editor.

Homology Medicines is developing a range of genetic therapies based on a unique set of adeno-associated virus vectors derived from human hematopoietic stem cells that allow it to target a wide range of tissues. It is developing both gene therapies and gene editors simultaneously using these vectors. It’s lead program is an experimental gene therapy for phenylketonuria or PKU, a rare, genetic metabolic condition that causes an enzyme deficiency that results in an inability to breakdown the amino acid phenylalanine, which is common in protein containing foods. We spoke to Arthur Tzianabos, CEO of Homology Medicines, about the company’s genetic therapies, its program in PKU, and how it pairs its vectors and approach to meet the needs of a given condition.

Jon and Shirley Dicks’ daughter Elle first started developing problems swallowing when she turned 10 months old. As her difficulty eating progressed, she stopped growing. Her parents grew frustrated by doctors dismissing her symptoms until a passing comment that she seemed to have a sensitivity to light allowed a specialist to diagnose her with the rare, lysosomal storage disorder cystinosis. We spoke to the Dicks about Elle’s diagnostic odyssey, how having a diagnosis changed care for her, and the challenges they have faced caring for a child with a rare condition.

The ability to diagnose and treat rare diseases begins with data. The growing awareness about the need to collect data and do so in ways that are meaningful and usable to research and drug development communities, has mobilized a number of efforts to capture and make patient data available. AllStripes, formerly known as RDMD, completed a $50 million venture round in August to help it launch 100 new rare disease research programs. We spoke to Nancy Yu, co-founder and CEO of AllStripes, about the growing efforts around the collection of patient data, where AllStripes fits into this emerging landscape, and how data can transform the outlook for diagnosing and treating people with rare diseases.

While there is a steady stream of new gene therapies expected to be approved in the next decade, there are hundreds of diseases that could benefit from gene therapies but are not pursued by drug developers because they affect too small a population to be considered commercially viable. In an effort to change the economics of gene therapy for ultra-rare diseases, the Foundation for the National Institutes of Health is establishing the Bespoke Gene Therapy Consortium under its Accelerating Medicines Partnership program. The proposed five-year, $102.5 million program involves the National Institutes of Health’s National Center for Advancing Translational Sciences, the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research, and a group of commercial gene therapy developers. We spoke to P.J. Brooks, deputy director of the Office for Rare Diseases Research at NCATS and one of the architects of the program, about the need it is trying to address, why it is looking beyond translational scien

Despite the ability of whole genome sequencing to diagnose patients with rare genetic disease, the technology still leaves many patients without a clear diagnosis. Rady Children’s Institute for Genomic Medicine, which has innovated the use of rapid whole genome sequencing in the neonatal and pediatric ICU, is now working to diagnosed patients left undiagnosed by whole genome sequencing with long-read whole genome sequencing through a collaboration with Pacific Biosciences. We spoke to Matthew Bainbridge, principal investigator and associate director of clinical genomics at Rady Children’s Institute for Genomic Medicine, about the collaboration, how long-read sequencing differs from traditional whole genome sequencing, and why this is helping to find answers for undiagnosed patients with rare genetic diseases.

Many rare diseases cause unique changes to facial features that can provide insights for doctors seeking searching for a diagnosis. Researchers at Children’s National Hospital have developed software uses machine learning technology and images captured with a cellphone to quickly recognize disease patterns not immediately obvious to the human eye to help physicians accelerate the diagnosis of genetic syndromes by recommending further investigation or referral to a specialist in seconds. We spoke to Marius George Linguraru, who led the Children's National team that developed the digital biometric analysis software, about the diagnostic tool, how it works, and a deal with a newly formed company to commercialize the technology. 

Advances in communication, information, and monitoring technologies have enabled the advent of decentralized clinical trials, but the COVID-19 pandemic crystalized the interest of regulators and trial sponsors. In fact, most biopharmaceutical companies today now expect to use elements of decentralized clinical trials in studies going forward. Science 37 is providing a software platform to enable decentralized clinical trials and offering a range of services on top of that to meet the needs of trails sponsors. We spoke to Jonathan Cotliar, chief medical officer of Science 37, about the move toward decentralized clinical trials, how technology is changing the types of data that can be gathered, and how it is forever reshaping clinical trials.

Chronic kidney diseases represent a growing worldwide problem with a lack of effective treatments. An improved understanding of the biology of kidney disease is fueling growing drug development activity. Chinook Therapeutics is focused on rare, severe chronic kidney diseases with well-defined clinical pathways. Its lead clinical program, atrasentan, is in a late-stage study in IgA nephropathy, a leading cause of chronic kidney disease. We spoke to Tom Frohlich, chief operating officer of Chinook, about rare kidney diseases, the company’s lead therapeutic candidate, and its plans for commercialization.

While genetic medicines promise to transform the way rare diseases are treated, one of the greatest challenges to realizing the full potential of these new therapies is the delivery of them to the cells within the body where they must go to be effective. James Dahlman, associate professor in the Department of Biomedical Engineering at Georgia Tech and Emory University, has been working to address this issue through the development of nanoparticles that could serve as vectors. We spoke to Dahlman about the delivery challenges of genetic medicines, how nanoparticles compare to viral vectors, and what it takes to develop new vectors that can deliver genetic medicines to where they need to go. This episode is part of our ongoing Platforms of Hope series that explores advances in gene therapy and gene editing.

RNA therapies offer great promise for addressing rare genetic diseases by disrupting the translation of pathogenic genes into disease-causing proteins or getting the body to produce a needed protein it lacks. But the challenge of delivering these therapies to tissue where they need to go to be effective has limited the diseases that have been treated with these therapies to date. DTx Pharma has developed platform technology to address the challenges of delivering RNA therapeutics and is building a pipeline of RNA therapies. We spoke Arthur Suckow, co-founder and CEO of DTx, about the delivery challenge of RNA therapies, how DTx’s platform technology addresses these, and how a $100 million financing from earlier this year will be used to fuel its growth.

When Genzyme won approval for an enzyme replacement therapy for Gaucher disease in 1991, the company launched a humanitarian aid program for rare diseases. Now as part of Sanofi, the pharmaceutical company has continued and expanded the program, which now includes five different lysosomal storage disorders, as well as rare blood disorders. We spoke to Bill Sibold, executive vice president of Sanofi Genzyme and president of Sanofi North America, about the company’s Humanitarian Aid Program, how it works; and how it overcomes the regulatory, infrastructure, and medical challenges of delivering these treatments to patients around the globe.

Ashley Walker spent the first 20 years of her life misdiagnosed as having a form of muscular dystrophy. It was only after her twin sons Alexander and Jayden suffered severe respiratory complications following their birth that she and her boys were all diagnosed with X-linked myotubular myopathy, a rare neuromuscular disease. Though the condition predominantly affects males, female carriers like Walker can also experience symptoms that can range from mild to debilitating, and even life-threatening. Her sons died eight years ago, a little more than a year after being born. Today, Walker is unable to work and requires breathing assistance at night, but she has become a patient advocate, and works to raise awareness about the disease known as XLMTM and the need for treatments. We spoke to Walker her own rare disease journey ahead of an externally-led XLMTM Patient-Focused Drug Development meeting, what life with XLMTM is like, and her hopes that new treatments are not far away.

The use of model system, such as fruit flies and worms, to screen existing drugs for their potential to treat rare genetic diseases offers a relatively fast and economic method to find candidates for repurposing. The success at screening 4,000 compounds in a worm model of the neurodegenerative disease ALS to identify a candidate that is now in human clinical testing gave rise to Modelis, a Canadian company that is now repeating the exercise in other rare diseases. We spoke to James Doyle, CEO of Modelis, about model system, how the company creates genetic avatars of patients; and how it works with rare disease drug developers, patient organizations, and patients to identify candidates for repurposing.