Rarecast

Michelle Teng, a techbio entrepreneur, co-founded the H-ABC Foundation after her daughter was diagnosed with the ultra-rare and fatal leukodystrophy. The foundation funded research that identified the causal mutation of the condition and pointed the way to a potential therapy. Teng later joined with Dan Williams to co-found SynapticsBio to advance that work and develop an experimental antisense oligonucleotide therapy to silence the mutated gene underlying a form of the progressive neurological condition. We spoke to Williams, co-founder and CEO of SynaptixBio, about H-ABC, how the company’s experimental therapy works, and the role patient advocates have played in the company’s efforts to advance its experimental therapy.

Gene therapies that use viral vectors generally are not redosable because once patients are exposed to the virus used to insert the gene, their immune system will become activated against them. Immusoft is using a patient’s own B cell and engineering them to produce needed proteins by transforming them into biofactories without the use of a viral vector. The company’s lead experimental therapy is an autologous B cell therapy engineered to produce the enzyme that people with the rare lysosomal storage disorder MPS I are deficient. We spoke to Sean Ainsworth, CEO of Immusoft, about MPS I, the limits of existing enzyme replacement therapies, and the potential benefits of using engineered B cells to treat people with the metabolic disorder and other conditions. 

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 approval of Attruby, the company’s late-stage pipeline, and what he’s learned about its business model in the process.

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 its sustained and expanded use for children who can benefit from it. We spoke to Tomi Pastinen, director of the Center for Pediatric Genomic Medicine at Children’s Mercy Kansas City, about the success of the program to date, the reimbursement challenges, and the future of the technology. 

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 provided him with a new outlook on life. We spoke to Monaco about coming to terms with his diagnosis, how he was forced to abandon some dreams, and how he was able to find new ones to pursue. 

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 complete clinical development of its gene therapy for the condition, and how it might commercialize the treatment. 

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 experience as the father of a child with a rare disease, life in hospital wards across two continents, and the feeling of pride in his son that remains.

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 Baumatz about his experience with his daughter, the vision for Noga Therapeutics, and the company’s business decision to pursue both rare and common diseases.

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 spoke to Rogers about the challenges of building a sustainable business model for the development of individualized therapies, the regulatory hurdles it may face, and what it will take to get payers to embrace such medicines.

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 of NGGT, about the company’s approach to gene therapies, how it is leveraging its platform technologies to cost-effectively accelerate development of these therapies, and the pipeline it is building.

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 transplant. At one point she became bedridden. Though she went into remission, she had been unable to live the active lifestyle she previously enjoyed and took to physical therapy to build back her strength and regain her abilities. At 50, she managed to climb Mount Kilimanjaro in Tanzania and now mentors others with multiple myeloma. We spoke to Freedman about her journey through diagnosis and treatment, her recovery, and why she went from not wanting to talk about her condition to being a patient advocate.

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-drive genomics company SEMA4 has meant to it, and what she thinks it will take to make meaningful change to the diagnostic odyssey. 

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 relationships as they are discovered. This provides a diagnosis to about 5 percent of those without an answer. We spoke to Brigette Tippin Davis, chief operating officer for Ambry Genetics, about the diagnostic odyssey for people with a rare disease, Ambry’s new ExomeReveal test, and what people can do to accelerate their path to a diagnosis.

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 spoke to Coenraads about her experience with Rett syndrome as a mother of a daughter with the condition, how she crafted a scientific agenda for the organizations she founded, and what other rare disease organizations can learn from her experience. 

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 and cost of drug development.

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 accelerate the diagnosis of other children with ultra-rare conditions, and its efforts to find accessible and affordable pathways to treatments for others. 

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 Hopkins, CEO of DevineBio, about how the company works with patient organizations, how far it will advance programs, and its exit strategy.

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 these therapies raise. We spoke to McIntosh, director at Pfizer, and Sverdlov, senior director of statistical analysis at Novartis, about their new book, how a pair of biostatisticians view the challenges of gene therapy development, and why these therapies don’t easily fit into existing models. 

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 decisions about their lives. We spoke to Paul Wicks, vice president of neuroscience for Sano, about its test for ALS-related gene mutations, how it works, and why some healthy people might want to take advantage of it.