Rarecast

AMO Pharma is developing drugs for a variety of rare neurologic conditions with a pipeline of experimental therapies seeking to treat Phelan-McDermid syndrome, congenital myotonic dystrophy, and Rett syndrome. The company believes it can advance therapies efficiently by acquiring molecules that have already been studied at either a preclinical or clinical stage and jump starting their development in new indications. We spoke to Michael Snape, chief scientific officer of AMO Pharma, about the company’s approach to drug development, how it selects drugs and diseases to pursue, and its lead therapeutic candidates.

Imago BioSciences is developing therapeutics that change the behavior of malignant blood cells by targeting an enzyme that regulates gene transcription. LSD1 is an epigenetic enzyme that controls how genes are turned on and off in specific cells and plays a key role in the rare bone marrow cancer myelofibrosis. We spoke to Hugh Reinhoff, Jr., CEO of Imago, about myelofibrosis, the company’s experimental therapy bomedemstat to treat the condition, and the case for targeting epigenetic processes to address proliferative diseases of the bone marrow.

Earlier this year Chiesi Farmaceutici established Chiesi Global Rare Diseases, a new business unit to advance research and product development for rare and ultra-rare diseases. The unit, headquartered in Boston, has an initial focus on lysosomal storage, hematologic, and ophthalmologic disorders. We spoke to Giacomo Chiesi, head of Chiesi Global Rare Diseases, about the company’s approach to building its rare disease pipeline, its experimental therapy for Fabry disease, and how it fits in with the company’s broader rare disease strategy.

Rafael Pharmaceuticals is focused on developing therapies that act on the metabolism of rare cancers. It designs drugs that attack regulatory processes that are unique to cancer cells and not found in healthy ones. Its lead drug candidate, devimistat, targets enzymes that are involved in cancer cell energy metabolism and found in the mitochondria of cancer cells. We spoke to Sanjeev Luther, president and CEO of Rafael, about the company’s lead indication of pancreatic cancer, its drug discovery platform, and why it is focused on rare cancers.

When Keith McArthur’s son Bryson was born, he was a happy and loving baby. Soon, though, Bryson began missing developmental milestones and doctors determined he had a neurological disorder. After nearly a decade, Bryson was diagnosed with a variant in his GRIN1 gene. Keith McArthur, who today is CEO and head of science for the CureGRIN Foundation, tells Bryson’s story in an eight-part podcast series produced with the CBC called Unlocking Bryson’s Brain (Hyperurl.co/Bryson). We spoke to McArthur about Bryson, the efforts of the CureGRIN Foundation to find a cure for the condition, and what he hope to accomplish with the podcast series.

There are a number of rare disease where a genetic mutation results in the deficiency of an enzyme or other critical protein that can lead to a progressive or life-threatening condition. Patients have been treated with the chronic administration of recombinant versions of the proteins they lack. While this provides benefit, it requires regular infusions or self-administered shots, is costly, and disruptive. Sigilon is developing what it calls “Shielded Living Therapeutics,” encased cells that can be implanted to provide steady levels of the protein a patient lacks and free them from the need for constant administration of these biologics. We spoke to Rogerio Vivaldi, president and CEO of Sigilon Therapeutics, about the company’s living therapeutics, how it’s able to protect these cells from attack from the immune system, and how they function once inside the body.

Gene therapies to treat retinal diseases promise to reverse blinding conditions, but the approach most gene developers take is to replace a mutated gene underlying a genetic disease with a functional version of that gene. The problem is that this approach can only address a narrow set of patients with each gene therapy. Ocugen, which Is developing gene therapies for eye diseases, believes it can treat a range of rare retinal conditions with a single therapy by introducing a functional gene that has the effect of modifying the expression of multiple genes at once. We spoke to Shankar Musunuri, CEO of Ocugen, about the company’s modifier gene therapy platform, how a single gene therapy can work on multiple eye diseases, and how it may alter the economics for gene therapy for rare eye conditions.

WHIM syndrome is a rare, inherited, primary immunodeficiency disease caused by mutations to the CXCR4 receptor gene. Because of the role CXCR4 plays in the immune system, it is implicated in a number of rare diseases. X4 Pharmaceuticals, a company founded by rare disease pioneer Henri Termeer and other Genzyme alums, is developing a pipeline of CXCR4-targeted therapies. We spoke to Paula Ragan, co-founder, president and CEO of X4, about WHIM syndrome, the role CXCR4 plays in the immune system, and how the company’s experimental therapy Mavorixafor may be able to treat a range of rare conditions.

Syros Pharmaceuticals is developing a platform for targeting the regulatory genome with therapies to address diseases at a fundamental level. At the end of last year, the company entered into a collaboration with Global Blood Therapeutics to develop new therapies for sickle cell disease and beta thalassemia. Under the collaboration, Syros is using its platform to discover drugs that turn on the production of fetal hemoglobin as a way to treat these rare, hereditary, blood disorders. The production of fetal hemoglobin is usually shut down soon after birth. We spoke to David Roth, chief medical officer of Syros Pharmaceuticals, about the collaboration, how Syros’ approach works, and why activating fetal hemoglobin is viewed as a promising approach to treating these genetic blood diseases.

Forma Therapeutics had long been a platform-based drug company that used high-throughput screening to discover new drugs that would be developed by partners. After many years, Forma began transitioning to become a fully integrated therapeutics company focused on rare blood disorders and cancer. It brought in Frank Lee, who had been a senior vice president of global product strategy at Genentech, as CEO to help execute the company’s new plan. We spoke to Lee about why he joined Forma, the company’s program in sickle cell disease, and his vision Forma as a company that develops and commercializes its own medicines.

FSHD is a rare, progressive, muscle wasting disease that affects the face, shoulders, and arms before advancing to the lower body. Like many rare conditions, it is caused by an underlying genetic mutation. Fulcrum Therapeutics is developing an experimental therapy for FSHD, the lead candidate in a pipeline of medicines that target the root causes of genetic diseases. We spoke to Robert Gould, president and CEO of Fulcrum, about FSHD, the company’s experimental therapy to treat the condition, and how he thinks about the company’s broader pipeline.

Prader-Willi syndrome is the most common genetic cause of life-threatening childhood obesity. It is a rare and complex condition that is characterized by unrelenting hunger, or hyperphagia, as well as intellectual disability, short stature, and incomplete sexual development. Millendo Therapeutics is developing livoletide, an experimental, first-in-class therapy that treats hyperphagia by targeting the underlying hormone dysregulation of Prader-Willi syndrome. We spoke to Julia Owens, CEO of Millendo, about Prader-Willi syndrome, the changing development path of livoletide, and what the company has learned as it shifted its focus to a different patient population.

As rare disease patients and advocates seek to raise awareness around the globe for World Rare Disease Day at the end of February, one notable place they will gather is on Capitol Hill in Washington, D.C. It’s become an annual tradition for rare disease advocates to talk face-to-face with lawmakers to bring the abstractions of rare disease down to a human level and speak about the needs patients and their caregivers face. We spoke to Steve Silvestri, director of public policy for the Everylife Foundation for Rare Diseases, about Rare Disease Week on Capitol Hill, the case for patients and caregivers to become advocates, and how they can go about doing so.

Fibroblast growth factors are a group cell signaling proteins that play a critical role in growth and development. They have been implicated in achondroplasia, the most common genetic form of dwarfism, but these growth factors are also involved in a number of rare cancers. QED Therapeutics, a BridgeBio company, is developing infigratinib, an experimental tyrosine kinase inhibitor that targets multiple fibroblast growth factors, for both achondroplasia and certain forms of bile duct and bladder cancers. We spoke to Susan Moran, CEO of QED Therapeutics, about the company’s experimental tyrosine kinase inhibitor, the role fibroblast growth factors play in seemingly disparate rare diseases, and the challenges of learning to work with very different types of patient communities.

Conducting rare disease clinical trials can be challenging because of small and geographically dispersed groups of patients who may face difficulties in travelling to trial sites. Regulatory requirements for cell and gene therapies, even if only administered once, require long-term follow ups that extend for many years and provide an ongoing burden for patients. Jeeva Informatics Solutions is seeking to address those challenges through it harnessing of digital health technologies to bring the trial to the patient. We spoke to Harsha Rajasimha, founder and CEO of Jeeva, about the challenges of conducting rare disease clinical trials, the potential of digital health technologies to address those issues, and how ready regulators and sponsors may be to embrace these technologies to transform the way they conduct clinical trials today.

Terry Pirovolakis became immersed in the world of rare disease after his son Michael was diagnosed with spastic paraplegia 50, an ultra-rare and progressive neurodegenerative disease. Later this month, interdisciplinary teams from around the world will gather as part of a 30-day hackathon to develop therapeutic strategies for Michael’s condition. We spoke to Pirovolakis about Michael’s disease, how the hackathon will work, and why he’s trying to turn this into a sustainable model for other people with ultra-rare diseases to develop treatments for conditions without any.

David Giljohann likens his company’s spherical nucleic acid (SNA) constructs to Koosh balls. But instead of having elastic strings extending from their core, this new class of immunomodulatory and gene regulating drugs are covered with nucleic acids that stick out in all directions. The arrangement allows these oligonucleotides to be taken up by all cell types and can be delivered throughout the body allowing them to overcome some of the limitations of existing nucleic acid therapies. We spoke to Giljohann, CEO of Exicure, about the company’s SNA therapies, how they work, and why they have the potential to treat a wide range of conditions including rare neurological diseases.

Protalix Biotherapeutics plant cell-based platform has been a point of differentiation for the company, a faster and more scalable way of producing protein therapeutics. The company first product, an enzyme replacement therapy for Gaucher disease, offered a proof of its approach. The company is pursuing therapies for Fabry disease and cystic fibrosis, as well as inflammatory diseases, but it is also in the process of rethinking its strategy of biobetters. We spoke to Dror Bashan, CEO of Protalix, about the company’s manufacturing platform, its therapeutic pipeline, and its desire to move toward addressing unmet medical needs.

Antisense pioneer and Ionis Pharmaceuticals Executive Chairman Stanley Crooke has launched a nonprofit to design and deliver custom RNA-targeted therapies free of charge for individual patients with ultra-rare diseases. The organization, n-Lorem Foundation, will leverage Ionis’ technology platform to speed the discovery and development of custom antisense oligonucleotide. We spoke to Crooke about the genesis of n-Lorem, how it will determine whether to work with an individual patient or researcher, and the challenges for regularizing the process of designing n-of-1 therapies for ultra-rare disease patients.

One of the reasons for the clinical failure of drugs is that animal models often fall short as predictors of how a drug will work in humans. StemoniX believes it can cut the time and cost of drug discovery with its microOrgans that are engineered from human induced pluripotent stem cells. These microOrgans can be used for high throughput human drug screening without the need for drugs to enter a human subject. We spoke to Ping Yeh, CEO of StemoniX, about the company’s technology platform, how it works, and its recent agreement with the AI company Atomwise to discover and develop small molecule candidates to treat the rare neurological condition Rett syndrome.