Altus' in-depth knowledge of protein crystallization has resulted in a proprietary pipeline of orally-delivered and injectable protein replacement products.

Trizytek™ (porcine-free enzymes)

Trizytek (formerly known as ALTU-135) is a microbially produced, pancreatic enzyme replacement therapy (PERT) for malabsorption due to pancreatic insufficiency (PI). A deficiency of pancreatic enzymes causes poor absorption of nutrients, leading to malnutrition, impaired growth, and reduced survival typically in individuals with cystic fibrosis (CF), chronic pancreatitis (CP), and pancreatic cancer.

CF is a life-threatening, genetic disease affecting approximately30,000 patients in the United States. Approximately 90% of CF patients are afflicted with pancreatic insufficiency and, as a result, need to take PERT.

CP is a disease that is characterized by ongoing inflammation and scarring of tissue in the pancreas, which can cause PI. CP is a disease that is difficult to diagnose and patients with CP may initially experience unexplained abdominal pain. The true prevalence of CP is unknown, but it is estimated that 0.04% to 5% of the United States population may have this disorder.

Trizytek is an orally administered PERT consisting of three digestive enzymes: lipase, protease and amylase, specifically selected for their superior properties. Trizytek is designed to be a one-capsule-per-meal enzyme replacement that is intended to improve digestion and absorption of fats, proteins, and carbohydrates in patients living with PI. Unlike current products that are all derived from pig pancreas, Trizytek has the potential to be the first porcine-free, stable and pure, fixed-ratio enzyme replacement therapy for PI.

Altus' Phase III DIGEST Trials were initiated in May of 2007. Our efficacy trial measures the fat absorption in CF patients with exocrine pancreatic insufficiency through the measurement of the coefficient of fat absorption. Trizytek has been granted fast track designation by the FDA.

ALTU-238

ALTU-238 is a long-acting, crystalline formulation of somatropin (recombinant human growth hormone r[hGH]) in development for the treatment of growth hormone deficiency (GHD) in pediatric and adult populations. In pediatric populations, growth failure is diagnosed in children who are well below the normal growth curves for their age ranges. Pediatric GHD may result from various genetic disorders, including Prader-Willi Syndrome or Turner Syndrome, or it may be acquired through other unexpected channels or for other unknown reasons. Major pediatric growth hormone deficiencies are estimated to be present in 1 in 3,500 children in the United States.

GHD is also found in adults and manifests itself primarily through cardiovascular and body mass index (BMI) symptoms. Adult GHD can result from childhood onset GHD that persists into adulthood, or adult onset GHD, which is usually attributed to growths on the pituitary gland, surgery, trauma, or is of unknown origin. The prevalence among adults is 1 in 10,000 in the United States.

Unlike current r(hGH) therapies that are administered daily, ALTU-238 is being developed and tested to provide a once-per-week dosage formulation that can be administered through a fine gauge needle. It is designed to mimic natural hGH by binding to growth hormone receptors, triggering increased plasma levels of insulin-like growth factor-1 (IGF-1). IGF-1 is a naturally occurring hormone that stimulates the growth of bone, muscle and other body tissues in response to hGH and, in turn, regulates hGH release from the pituitary gland. ALTU-238 has completed a phase 2 clinical trial in adults with GHD.

ALTU-237

ALTU-237 is a recombinantly produced, orally delivered crystalline formulation of an oxalate-degrading enzyme in development for the treatment of hyperoxaluria. Hyperoxaluria describes any condition in which there is too much oxalate present in the body and is generally characterized as either primary hyperoxaluria (PH), enteric hyperoxaluria (EH), or recurrent kidney stones. These hyperoxaluric conditions are caused by an abnormality in the absorption, metabolism, and excretion of oxalate or through the intake of high oxalate diets. This may result in an increased risk of kidney stones and, in rare instances, crystal formation in other organs that may lead to organ failure. Kidney stone disease is a common disorder and can occur in 10% of adult men and 3% of adult women during their lifetimes.

There are a variety of kidney stones, but calcium oxalate stones are the most common in people with kidney stone disease. Although it is a natural bi-product of metabolism, oxalate is not known to be necessary for any human body process and normally more than 90% is excreted by the kidney. ALTU-237 is designed to maintain stability and activity in the gastrointestinal tract allowing it to degrade dietary oxalate directly in the small intestine and thus prevent its absorption. This reduction of intestinal concentrations of oxalate creates a concentration gradient that pulls excess oxalate out of systemic circulation and into the gut where it can then be degraded and excreted from the body.

For the majority of PH, EH, or recurrent kidney stone patients there are limited effective pharmacological treatments. In August 2007 Altus initiated a Phase I clinical trial of ALTU-237.

ALTU-236

ALTU-236 is an orally administered, cross-linked enzyme crystal formulation of a phenylalanine degrading enzyme for the treatment and prevention of hyperphenylalaninemia due to phenylketonuria (PKU). PKU is a genetic defect that leads to an enzyme deficiency that prevents liver cells from converting phenylalanine (Phe) to tyrosine . This leads to very high levels of circulating Phe, known as hyperphenylalanemia, which results in severely impaired cognitive function and mental retardation. Due to the lack of any pharmacological treatments, patients with PKU must manage symptoms by adhering to a strict diet which can significantly reduce their quality of life. Epidemiological studies based upon newborn screening data indicate that this disorder occurs in approximately 1 of every 11,000 to 15,000 births.

Due to its crystalline nature, ALTU-236 is designed to maintain stability and activity in the gastrointestinal tract allowing it to degrade dietary Phe directly in the small intestine and thus prevent its absorption. Our research will evaluate the potential of ALTU- 236 to reduce the intestinal concentrations of Phe, creating a concentration gradient that pulls Phe into the gut from systemic circulation, and thereby lowering systemic circulation of Phe. ALTU-236 is currently in preclinical development.

ALTU-242

ALTU-242 is an orally administered enzyme being developed to specifically reduce long-term effects resulting from excess levels of urate, which may precipitate into urate crystals, and accumulate in joints leading to painful erosive arthritis, also known as gout. Gout is the most common inflammatory joint disease in men older than 40 years of age and affects approximately 2.7 of every 1,000 adults in the United States, around 500,000 adults annually. This trend is believed to be similar globally, with gout affecting an approximated 1% of populations in Western countries.

ALTU-242 is designed to maintain stability and activity in the gastrointestinal tract allowing it to degrade urate directly in the small intestine. Our research will evaluate the potential of ALTU-242 to reduce the intestinal concentrations of urate, creating a concentration gradient that pulls excess urate from systemic circulation into the gut where it can then be degraded and excreted from the body. ALTU-242 is currently in preclinical development.