Patient population in
the developed world

50,000

X-linked disease with
incidence of 1 in 5,000 births

DMD is a fatal genetic disease that occurs in approximately 1 in 5,000 males with one third of cases arising in boys with no familial history of the disease.

Our utrophin modulation programme is a potential disease-modifying approach to treat all patients with DMD.

ABOUT DUCHENNE MUSCULAR DYSTROPHY

Duchenne Muscular Dystrophy, or DMD, is one of the most common, fatal genetic disorders diagnosed in children around the world.  DMD is an X-linked disease, meaning that it predominantly affects males, and it results in the progressive wasting of muscles throughout the body.  The disease has an estimated incidence of 1 in 5,000 and a patient population in the developed world of approximately 50,000.  Approximately two thirds of new DMD cases are due to inherited mutations with the remaining one third resulting from spontaneous mutations where there is no family history of the disease.

DMD is caused by different mutations in the dystrophin gene that result in DMD patients being unable to produce dystrophin, a protein essential for maintaining healthy muscle function.  The absence of dystrophin results over time in the deterioration of muscles and leads to the loss of ambulation, loss of respiratory and cardiac function and ultimately death, typically by the time DMD patients reach their late twenties.  There is currently no approved therapy for the treatment of DMD applicable to all DMD patients that seeks to alter the progression of the disease.

 

UTROPHIN MODULATION:
A POTENTIAL UNIVERSAL TREATMENT FOR ALL DMD PATIENTS

Our utrophin modulation programme is developing oral, small molecule drugs that increase the production of a protein call utrophin.  Utrophin is a naturally occurring protein that is functionally and structurally similar to dystrophin.  Utrophin is produced during the early stages of muscle fibre development but is switched-off in maturing muscle fibres, at which point dystrophin is produced to perform the same functional role.  When a muscle fibre is damaged, utrophin is also produced during the early stages of the repair mechanism.

Utrophin vs Dystrophin

Our utrophin modulation approach aims to use small molecule drugs to maintain the production of utrophin to compensate for the absence of dystrophin in DMD patients and so protect healthy muscle function.  A significant advantage of utrophin modulation is that it is independent of the underlying genetic fault and therefore has the potential to treat 100% of DMD patients.  We also believe it could be complementary to other DMD treatment approaches.

The concept of utilising utrophin as a treatment for DMD was developed by our co-founder and scientific advisor Professor Kay Davies at the University of Oxford.

 

OUR UTROPHIN MODULATION PROGRAMME

Summit is a leader in the field of utrophin modulation. Our most advanced utrophin modulator, ezutromid (SMT C1100), is in a Phase 2 clinical trial called PhaseOut DMD. PhaseOut DMD aims to provide proof of concept for ezutromid and utrophin modulation by measuring muscle fat infiltration, as well as by measuring utrophin protein and muscle fibre regeneration in muscle biopsies. Further information on this trial is available at: ClinicalTrials.gov. We also have an online resource for the Duchenne community, which includes answers to frequently asked questions on our utrophin programme and clinical trials: www.utrophintrials.com.

In parallel, we are also applying our know-how to develop a pipeline of future generation utrophin modulators as we seek to maintain and expand our leadership position in the field of utrophin modulation.  This research is being undertaken in collaboration with the University of Oxford.

DMD is an orphan disease, and the US Food and Drug Administration (‘FDA’) and the European Medicines Agency have granted Orphan Drug designation to ezutromid.  Orphan drugs receive a number of benefits including a period of market exclusivity following approval and additional regulatory support. The FDA has also granted Fast Track and Rare Pediatric Disease designations to ezutromid in the treatment of DMD.

On 4 October 2016, we announced an exclusive license and collaboration agreement, which granted Sarepta Therapeutics European rights to our utrophin modulator pipeline for the treatment of DMD. Read the press release for more information.