Imara – Advancing Sickle Cell Therapies

19th June 2019

Sickle cell disease is a serious and lifelong health condition. It is the name for a group of inherited health conditions that affect the red blood cells. The most serious type is called sickle cell anaemia. Sickle cell disease is particularly common in people with an African or Caribbean family background.

We recently were joined by Imara CEO Rahul Ballal and Chief Medical Officer Willem Scheele for an Investor and Analyst update hosted in London by Jefferies. Rahul and Willem provided an update on the exciting progress they are making with Imara’s lead drug, IMR-687, which is being developed for Sickle Cell Disease (SCD) and other inherited haemoglobin diseases (such as beta-thalassemia).

Sickle cell disease is a progressively debilitating health condition, which impacts the quality of patients’ lives as well as their life expectancy even when diagnosed early in life. People with sickle cell disease produce unusually shaped red blood cells that can cause problems because they stick inside blood vessels, causing pain and severe anaemia by depriving cells and organs of oxygenated blood.

There are few medical therapies available for these patients and the most widely used therapy, hydroxyurea (HU), is a chemotherapeutic originally developed as a cancer treatment and is associated with safety and tolerability issues that limit its use and effectiveness in the real world.

Rahul explained the scientific rationale and clinical data behind IMR-687 that first attracted Arix to the opportunity, and ultimately led to Arix’s investment in Imara in March 2019 (see press release):

  • A differentiated mode of action that addresses both the unhealthy red blood cells AND the white blood cell driven inflammation in blood vessels (other therapies typically address EITHER the red OR the white blood cell pathology)
  • Compelling preclinical in predictive animal models of SCD that suggest potential for IMR-687 to be superior to HU
  • A clean safety profile confirmed in healthy human volunteers
  • Early signs of clinical efficacy from the ongoing Phase 2a study in adult SCD patients

In addition, Arix was impressed by Imara’s team and that this opportunity was complementary to the existing portfolio: adding a new therapeutic area (benign haematology) and a near term catalyst (interim Phase 2a data is expected in the second half of 2019).

Rahul also discussed the recent changes in the regulatory landscape for SCD, specifically the precedent set by FDA agreeing an Accelerated Approval pathway for Global Blood Therapeutics Inc.’s ‘Voxelotor’ therapy based on improvements in Total Haemoglobin (a surrogate endpoint) rather than requiring a demonstration of clinical benefit for approval. The implication for Imara is that there may be an expedited route to approval by demonstrating increases in another surrogate endpoint, Foetal Haemoglobin (HbF), which is widely accepted by expert physicians as a strong indicator of clinical outcomes.

Rahul made a critical point about the importance of “Access” in SCD as this patient population has historically had poor experiences with healthcare institutions and patient engagement is an issue. IMR-687 has been designed with this in mind, and the drug is formulated to be a once daily oral pill requiring limited physician interaction / monitoring (unlike with HU which requires monitoring and dose adjustment) and is heat-stable, meaning that it will be suitable and practical to deliver therapy to patients outside of the developed world where refrigerated or injected drugs pose significant logistical challenges.

The commercial opportunity in the developed world is clear, there are >160,000 SCD patients in US / EU and they can cost healthcare systems $100,000+ per year in hospitalisations and managing complications of the disease. Many drug developers overlook developing nations due to the low pricing potential of novel therapies there, however Imara recognises that there is an obligation to bring innovative therapies such as IMR-687 to patients in need regardless of geography and will explore commercially viable models or sources of funding to support launches in addition to the typical developed countries targeted by drug developers.

19th June 2019 is World Sickle Cell Awareness Day.

Sickle cell can affect anyone, although it predominantly affects people from African and Caribbean backgrounds. Approximately 15,000 people in the UK have sickle cell disorder; and around 350 babies with SCD are born in the UK every year. SCD affects approximately 100,000 Americans.

  • 1 in 76 babies born in the UK carry sickle cell trait. [1]
  • SCD occurs among about 1 out of every 365 Black or African-American births.[2]
  • SCD occurs among about 1 out of every 16,300 Hispanic-American births.
  • 1 in 13 Black or African-American babies born in the US carry sickle cell trait (SCT).

Arix is proud to support World Sickle Cell Awareness Day through its work with portfolio company Imara, and hope that soon there will be a cure for this debilitating condition.