Indel Therapeutics - Technology

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The prevalence of MRSA (termed a "superbug") is spreading rapidly in hospitals and is routinely encountered in the emergency department. In U.S. hospitals the number of MRSA infections as a percentage of all S. aureus infections has reached 60% and rising; in 2005 there were more than 94,000 invasive MRSA infections and 19,000 deaths attributed to MRSA.

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Gram Negative Antibacterial Programs

Indel is also working on the discovery of a number of novel indel targets for difficult-to-treat Gram negative pathogens such as Pseudomonas, Enterobacter, Klebsiella, Acinetobacter and others. Currently, there are virtually no new antibiotics in the clinical pipeline for the treatment of resistant Gram-negative infections. Indel has a several discovery programs focused on addressing this critical unmet medical need.

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Neglected Diseases Program

Elongation Factor-1α (EF-1α) has been identified as an important indel-differentiated target that is conserved across the top seven parasitic disease that affect humans, including Leishmania, Malaria, Chagas Disease, African Sleeping Sickness and others. EF-1α is an essential protein that is highly conserved across all living cells and is crucial for constructing proteins from amino acids. When you interfere with protein synthesis, the cell will die. Indel has demonstrated that Leishmania EF-1α is a virulence factor that allows the pathogen, an intracellular infection, to persist in the human macrophage. This finding was a surprise since it has greater than 80% sequence identity with human EF-1α. From this research the Company identified a structural difference responsible for this virulence factor, an indel-differentiated region that has been demonstrated to be an attractive small molecule drug target allowing selective inhibition of Leishmania EF-1α. In addition to in vitro validation of this targeting approach in Leishmania, Indel also has preliminary data indicating activity and selectivity in Malaria.

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The global impact of the diseases that could be treated by a pan-parasitic drug that targets the highly conserved protozoan EF-1α indel target is significant. These diseases are predominately found in developing nations, and the economic burden of these diseases on those countries comprises a significant percentage of their gross domestic product.

• Leishmaniasis threatens 350 million men, women and children in 88 countries worldwide. It is estimated that 12 million people are currently infected, with as many as 2 million new cases occurring every year – and the incidence of the Leishmaniasis is on the rise.

• In 2008, there were 247 million cases of malaria and nearly one million deaths – mostly among children living in Africa. In Africa a child dies every 45 seconds of Malaria, the disease accounts for 20% of all childhood deaths.

• Chagas disease affects 8-10 million people living in endemic Latin American countries, with an additional 300,000-400,000 in non-endemic countries including Spain and the United States. An estimated 41,200 new cases occur annually in endemic countries and 14,400 infants are born with congenital Chagas disease annually. About 20,000 deaths are attributed to Chagas disease each year.

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Indel Target Database

The Company has developed an Indel Target Database that allows it to quickly identify, prioritize and select indel-differentiated bacterial targets for a range of clinically and commercial important pathogens.