RARECast

A Pipeline Win as BridgeBio Learns to Balance Theory with Practice

BridgeBio has been an innovator in applying portfolio theory to its business model as a way to broaden access to capital. The company recently had a big win with its approval for Attruby, its treatment for the rare condition transthyretin amyloidosis cardiomyopathy. The approval is a boost for the company, which, like many biotechs, had to scale back on programs in the face of the downturn in capital markets in recent years. We spoke to Neil Kumar, co-founder and CEO of BridgeBio, about the appr...

Considering What It Will Take for Payers to Embrace Advances in Sequencing

The Genomic Answers for Kids program at Children's Mercy Kansas City has increased access to cutting-edge genomic sequencing for children suspected of having rare genetic diseases and improved the diagnostic yield of these tests. The program has collected samples from 8,000 rare disease patients and their family members and diagnosed about 2,000 people to date. Nevertheless, payers have been reluctant to increase reimbursement rates for more comprehensive genomic testing, posing a challenge to i...

Finding Strength

Anthony Monaco takes part in weightlifting and crossfit competitions, but that came only after he was diagnosed at the age of 19 with the rare, neuromuscular condition Friedreich’s ataxia. As the condition progressed, he had to give up on his plans of becoming at tattoo artist. Once he became reliant on a wheelchair, he began to withdraw from the world, not wanting people to see his disability on full display. That changed when he went with a friend on an extended cross-country trip that provide...

A Non-Profit Works to Advance a DMD Gene Therapy

Genethon, the non-profit gene therapy developer created by the patient association AFM-Telethon, began working with Sarepta Therapeutics in 2017 to develop a gene therapy for the rare neuromuscular condition Duchenne muscular dystrophy. Now that Sarepta has won approval for a separate gene therapy to treat the condition, Genethon is advancing development of its experimental gene therapy on its own. We spoke to Frederic Revah, CEO of Genethon, about Duchenne, the organization’s efforts to complet...

Accepting What We Can’t Understand

In “More than We Expected: Five Years with a Remarkable Child,” James Robinson recounts the life and death of his son Nadav, who was born with a congenital heart condition. The book follows the family’s efforts to address and manage Nadav’s rare condition. As tragic as losing a child is, Robinson says his book is not a sad story. In fact, the book is filled with Robinson’s encounters with the wonders of parenthood, human kindness, and unexpected connections. We spoke to Robinson about his experi...

A Gene Therapy Company Born from a Father’s Efforts to Save his Daughter

Noam Baumatz entered the world of gene therapy as a father in pursuit of a life-savings treatment for his daughter Noga, who was born with an ultra-rare immunodeficiency. Though she died before a treatment could be developed, Baumatz launched Noga Therapeutics to try to help others in the rare disease community. The company’s platform technology uses lentiviral-based vectors to genetically reprogram blood stem cells. It is developing therapies for both rare and common diseases. We spoke to Bauma...

Lowering Barriers to Clinical Trial Participation with Do-It-Yourself Blood Sample Collection

Scaling N-of-1 Therapies to Viability

The work of Boston Children’s Hospital’s Timothy Yu to develop a customized antisense oligonucleotide to treat Mila, a child with an ultra-rare neurodegenerative disease, created much excitement for the potential of N-of-1 therapies. Julia Vitarello, Mila’s mother, has talked about going from Mila to millions and co-founded EveryONE Medicines to enable the development of individualized therapies on a large scale. Earlier this year the company named industry veteran Kent Rogers as its CEO. We spo...

Building Gene Therapies that Address Gain and Loss of Function Simultaneously

For some genetic diseases, there is not only the need to replace the function of a gene that is lost, but to also address toxicities that a mutated gene may cause. There is currently no available treatment targeting diseases that result from both loss and gain of function mutations. NGGT uses dual-functional vectors to simultaneously remove harmful, mutated genes and replace them with normal, healthy genes to restore cellular function. We spoke to Guang Qu, chief operating officer and co-founder...

How One Woman Climbed from Patient to Advocate

Allison Freedman was an avid hiker, mother of young twins, and had just completed an MBA when she began suffering from severe back and rib pain and overwhelming fatigue. Repeated visits to the doctor and medical testing left her without a diagnosis. As her pain worsened, imaging revealed she had multiple broken ribs and vertebrae. At 42, a bone marrow biopsy confirmed that she had the blood cancer multiple myeloma. Freedman underwent intensive treatment including chemotherapy and a stem cell tra...

Shortening the Diagnostic Odyssey

Despite advancements in genetic testing, people with rare diseases often face a prolonged diagnostic odyssey involving multiple physician visits and misdiagnoses. Genetic testing company GeneDX is working to shorten the path to a diagnosis by expanding access to sequencing, collaborating with researchers, and accumulating data to better understand gene-disease relationships. We spoke to Katherine Stueland, CEO of GeneDx, about the state of genetic testing, what its 2022 acquisition by the AI-dri...

Making Exomes More Revealing

Standard exome sequencing, which maps the protein coding regions of the genome, will deliver a diagnosis of someone with a rare disease in about 35 percent of cases. Ambry Genetics' ExomeReveal seeks to improve the diagnostic yield of these tests by adding RNA analysis to exome testing. That can help resolve variants of uncertain significance in about 2 to 3 percent of the cases. Ambry will also perform continuous reanalysis of the results over time to take into account new gene-disease relation...

How One Patient Organization Catalyzed Drug Development

Monica Coenraads, the mother of a daughter with Rett Syndrome, has played a critical role in catalyzing development of therapies to treat the rare, neurological disease. She co-founded and served as director of research for the Rett Syndrome Research Foundation. She later founded and today serves as CEO of the Rett Syndrome Research Trust. Her work shows how patient organizations can bridge the translational divide and de-risk rare disease drug development for biopharmaceutical companies. We spo...

Enabling On-Demand Therapies

Earlier this year, the company gained attention when it reported that developed a customized antisense oligonucleotide to treat a boy with an ultra-rare neurodevelopmental disorder in a year’s time. The company is leveraging AI to develop oligonucleotide medicines on demand. We spoke to Chris Hart, co-founder, president and CEO of Creyon Bio; about the proof-of-concept achieved with its recent N-of-1 therapy, the business model for Creyon, and the potential for its approach to reduce the time an...

After Driving an N-of-1 Therapy for Her Son, an Advocate Turns to Helping Others

When Yiwei She’s son Leo was diagnosed with a severe neurodevelopmental condition, he was one of only two people known to have the ultra-rare disease. In a year, though, working with Creyon Bio, the family was able to move from the start of research for an ASO to treating Leo with the experimental therapy. We spoke to She, founder of the TNPO2 Foundation, about how her family was able to treat her son Leo with an experimental ASO with relative speed, the work the TNPO2 Foundation is doing to acc...

Putting Rare Disease Organization in the Business of Drug Development

Rare disease patient organizations are increasingly driving the discovery and development of therapies to treat the conditions on which they are focused. Organizations are seeking ways to accelerate these programs and advance them to the point where a biopharmaceutical partner might be willing to take them over. DevineBio was created to partner with patient organizations and provide them with the capability to discover and develop therapies and advance them to the clinic. We spoke to Chris Hopki...

Understanding the Many Questions Gene Therapies Raise

Gene therapies have emerged as an important and growing area of medicine, but various players in the healthcare continuum are trying to understand the unique development, regulatory, and other issues surrounding this emerging modality. Avery McIntosh and Alex Sverdlov, both biostatisticians, have edited the new book “Development of Gene Therapies: Strategic, Scientific, Regulatory, and Access Considerations,” a reflection of their efforts to understand the complex of considerations the advent of...

A Test to Identify People Likely to Develop ALS

Siblings and children of people with the rare, neurodegenerative disease amyotrophic lateral sclerosis are being offered a test in the United Kingdom at no-cost to see if they carry mutations to one of more than 40 genes that would make it likely for them to develop the condition. Sano Genetics developed the test under a grant from Innovate UK. The hope is the effort will expand the understanding of the condition while allowing people who are likely to develop the disease to make informed decisi...

How an Ultra-Rare Disease Patient Foundation Advanced a Gene Therapy

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...

Making the $10 Genome a Reality

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 ...

A No-Nonsense Effort to Develop a Therapy that Works Across Genetic Diseases

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 ...

Mapping a Perilous Journey with Humor

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. ...

Restoring Vision in Inherited Retinal Disease

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 ...

Bringing Genome Sequencing to Rural Populations

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 ...

Addressing a Blind Spot in Treatments for the Cornea

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 a...

Taking a Different Approach to Rare Epilepsies

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 pote...

A Rare Disease Drug Developer Tries to Earn Its Stripes

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...

Using Plasma to Treat Rare Diseases

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-der...

Differentiating Gene Therapies through Regulatory Elements

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 regul...

How One Patient Organization Leverages Research Investments

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....