Sickle cell disease research is seeing a flurry of activity with several companies currently testing therapies for the genetic blood disorder and one company recently receiving FDA approval. Imara aims to set itself apart from the pack and it is preparing to go public to support continued clinical development of its own sickle cell drug.
In documents filed with securities regulators late last week, Imara set a preliminary $86 million target for its IPO. The Cambridge, MA-based company has applied for a Nasdaq listing under the stock symbol “IMRA.”
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Imara develops drugs that treat rare genetic disorders of hemoglobin, the oxygen-carrying protein in the blood. Sickle cell disease is an inherited blood disorder in which hemoglobin form in the shape of a crescent or sickle. This shape restricts blood flow and limits the delivery of oxygen to tissues.
Sickle cell disease patients have low levels of an enzyme called cyclic GMP, which is associated with reduced blood flow, increased inflammation, a greater tendency for the blood cells to stick to things, and a reduced ability for the blood vessels to widen and improve blood flow, Imara says in its IPO prospectus. The company’s lead drug, IMR-687, is a small molecule that blocks a signaling protein called PDE9, an approach intended to lead to higher cyclic GMP levels. These higher cyclic GMP levels in turn reactivate fetal hemoglobin, a natural hemoglobin produced during fetal development. The Imara drug is currently in Phase 2 testing in sickle cell disease. The company also plans to test the drug in beta thalassemia, a rare inherited blood disorder that leads to low hemoglobin levels.
Other companies have reached clinical trials with different approaches to sickle cell disease. Bluebird Bio (NASDAQ: BLUE) is developing a gene therapy for the disease. In December, the Cambridge-based company reported encouraging data from an ongoing Phase 1/2 data testing its treatment, called LentiGlobin. Gene-editing therapies are in development from Vertex Pharmaceuticals (NASDAQ: VRTX), CRISPR Therapeutics (NASDAQ: CRSP), and from Sangamo Therapeutics (NASDAQ: SGMO) and its partner, BioVerativ (NASDAQ: BIVV).
If Imara successfully brings a sickle cell therapy to the market, its chief competition will likely be voxelotor (Oxbryta), a Global Blood Therapeutics (NASDAQ: GBT) drug that won accelerated FDA approval last fall. Like Imara’s drug, Global Blood’s therapy is a once-daily pill. Voxelotor treats sickle cell disease by blocking the process by which red blood cells take their characteristic sickle shape.
Imara says in its filing that it aims to differentiate its drug with a novel approach. Though PDE9 inhibitors have previously been studied for neurodegenerative diseases, there are no approved therapies that target the molecule. Furthermore, the company says its drug takes a “multimodal” approach to the disease. In addition to increasing fetal hemoglobin, the drug reduces the formation of red blood cells into sickle shapes and decreases the expression of adhesion molecules that cause red blood cells, white blood cells, and platelets to stick to each other and to the interior of blood vessels.
A Phase 2a study testing the Imara drug in sickle cell patients is expected to report preliminary data in the fourth quarter of this year, according to the Imara prospectus. The company plans to start a Phase 2b sickle cell study in the first half of this year; preliminary data are expected in the first half of next year. A separate Phase 2b study in beta thalassemia is planned for the first half of this year, with preliminary data expected in the first half of 2021. Imara says it plans to use the IPO cash to fund clinical testing in both sickle cell and beta thalassemia.
IMR-687 was initially developed by Danish firm H. Lundbeck. Imara acquired rights to that drug along with other technologies related to the treatment of hemoglobin disorders in a 2016 cash and stock deal. The company launched that year, formed by Cydan Development, the startup accelerator of venture capital firm New Enterprise Associates (NEA). Cydan aims to find compounds that hold promise addressing rare, genetic diseases. The accelerator forms startups around these technologies and advances them far enough to be acquired or taken public, which generates returns for investors.
That’s what happened to Vtesse, a startup that was developing a treatment for Niemann-Pick disease type C, a genetic condition that leads to cholesterol buildup in organs. Mallinckrodt Pharmaceuticals (NYSE: MNK) acquired Vtesse in a $200 million deal in 2017. Despite the payoff to investors, the science did not pan out. In 2018, Mallinkrodt announced that the drug failed to beat a placebo in a pivotal study.
Imara has raised more than $77 million, most recently a $45.8 million Series B round of financing last May. Imara’s largest shareholder is NEA, which holds a 31.8 percent stake in the company, according to the filing. Lundbeckfond Invest owns 16.3 percent, followed by Pfizer Ventures with 11.2 percent.