Following on from our profile on five of the most promising clinical-stage biotech companies developing orphan therapies in Europe, here we move to the world’s biggest biopharmaceutical market and R&D hub, shining the spotlight on five of the most important and innovative rare-disease start-ups in the USA.
The US passed its first Orphan Drug Act (ODA) in 1983, defining rare disease as any disease or condition that affects fewer than 200,000 people in the US – one in 1,500 people. Today, the total number of Americans living with a rare disease is estimated to fall between 25 to 30 million, though exact numbers are not known. In recent years, a number of rare disease patient registries have been established to capture more information on the rare disease patient populations in the country, including the IAMRARE™ Registry Program set up by the National Organization for Rare Disorders (NORD) and the Rare Diseases Registry Program set up by the National Center for Advancing Translational Sciences (NCATS).
NORD is the rare disease patient advocacy organization in the country and has over 37 years of serving the interests of patients with rare diseases. President and CEO Dr Peter Saltonstall highlighted the fact that NORD is “the only major umbrella organization that has no industry presence on our board. We are governed, managed and owned by patient organizations. NORD has truly become a trusted voice of patients in the US. We go to Capitol Hill and we are listened to because we are seen as the genuine voice of patients.”
Approximately 7,000 rare disorders have been identified but the vast majority – 90 percent – do not have any US FDA-approved treatment, though the numbers have improved sharply since the passage of the 1983 ODA. Before the ODA, there were only 34 orphan drugs approved in the US, and today, there are over 700.
On a lighter note, the zebra is the official symbol of rare diseases in the US due to the uniqueness of its black and white stripes.
While there are thousands of rare disease biotechs to choose from in the US, we take a first look with the following five, all of which have distinguished themselves in various ways.
Location: Cambridge, Massachusetts, US
This US biotech focuses specifically on people living with sickle cell disease and other hemoglobinopathies, with their lead product, IMR-687, being a highly-selective, potent small molecule PDE9. IMR-687 received a number of orphan drug designations from the European Commission and the US FDA, for sickle cell disease and for beta-thalassaemia.
In March 2020, the company raised USD 75 million in an IPO that had to be downsized as a result of the global COVID-19 pandemic, which was just beginning to hit the Northern hemisphere.
While the company is starting with sickle cell disease, they eventually hope that IMR-687 could potentially serve patients suffering from other hemoglobinopathies globally.
CEO Dr Rahul Ballal joined Imara in 2018, bringing a long track record of business development, strategic partnership building and company financing through previous positions at Canadian biotech Northern Biologics and US-based Flexion Therapeutics, where he closed a USD 175 million strategic partnership with Patheon UK.
Location: Lexington, Massachusetts, US
Evocatively named biotech Keros Therapeutics borrowed its name from a remote Greek island that is difficult to reach, representing the company’s ambition to develop therapies for rare diseases that are hard to treat. Their focus is on rare hematologic and musculoskeletal disorders.
Their first lead candidate is KER-050, currently in Phase 2 for Myelodysplastic syndrome (MDS) and Phase 1 for myelofibrosis (MF). MDS are a group of disorders caused when something disrupts the production of blood cells, and if left untreated, may progress to leukemia. Myelofibrosis is a rare type of blood cancer where the bone marrow is replaced by fibrous scar tissue.
Their second lead candidate is KER-047, currently in the clinic for anemia and Fibrodysplasia ossificans progressiva (FOP), an extremely rare and debilitating condition where muscle and connective tissue are gradually replaced by bone.
CEO Dr Jasbir Seehra founded the company in 2015, after stints at the Genetics Institute, Wyeth, Acceleron Pharma and Ember Therapeutics. Keros Therapeutics also IPOed in the middle of the COVID-19 pandemic, closing an upsized USD 96 million round in April 2020.
Location: Waltham, Massachusetts, US
Dyne Therapeutics focuses on companies with serious muscle diseases, developing innovative oligonucleotide therapeutics through their proprietary FORCE™ platform.
All three of their lead candidates are still in the preclinical stage, targeting myotonic dystrophy (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy, but the company pulled off a USD 233 million IPO in September 2020, and raised another USD 168 million in January 2021.
President and CEO Joshua Brumm joined in 2019, bringing a wealth of biotech experience at companies including Kaleido Biosciences, Versartis, Pharmacyclics, ZELTIQ Aesthetics and Proteolix, as well as investment banking experience through previous roles at Citigroup Global Markets and Morgan Stanley.
Location: Watertown, Massachusetts, US
Founded in 2007 before RNA therapeutics became all the rage, Dicerna Therapeutics focuses on both rare and common diseases with a genetic component, using their proprietary GalXC technology to create both potent and targeted RNAi therapeutics that uses RNA interference (RNAi) to silence or turn off the genes responsible for causing disease.
Having been around for nearly 15 years, Dicerna Therapeutics has a number of clinical candidates and a host of partnerships with industry players, including Roche, Eli Lilly, Novo Nordisk, Alexion Pharmaceuticals (since acquired by AstraZeneca) and Alnylam Pharmaceuticals. Their three lead candidates target primary hyperoxaluria (PH) – rare genetic metabolic disorders characterized by the accumulation of a substance, oxalate, in the kidneys and other organs – chronic hepatitis B virus (HBV) and alpha-1 antitrypsin (A1AT) deficiency-associated liver disease.
Led by co-founder Dr Douglas Fambrough, who became president and CEO in 2010, the company IPOed in 2014, raising USD 90 million. After 10 years as a genomic scientist, Dr Fambrough spent a number of years at Oxford Bioscience Partners, a Boston-based VC firm, and also cofounded Sirna Therapeutics, a first-generation RNAi pioneer that was acquired by Merck and Co. (MSD outside the US and Canada) in 2006 and later sold to Alnylam in 2014.
Location: San Francisco, California, US
A little different from the rest of the companies on this list, AllStripes (previously known as RDMD) does not actually develop drugs on its own but is a research platform dedicated to empowering rare disease patients and communities to engage more closely with the development of rare disease therapies.
Founded by CEO Nancy Yu and Onno Faber – a rare disease patient himself inspired to start AllStripes because of his personal frustration with the drug development process – AllStripes gives patients a platform to contribute to new treatment studies from home. Yu previously worked in biotech investment banking and healthcare investment on Wall Street as well as a stint at 23andme, one of the leaders in consumer DNA test kits.
In April 2020, the company raised USD 14 million in a Series A round. In February 2021, they expanded their rare disease research programs to the UK.
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