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.