Alnara’s Pancreatic Enzyme Replacement Therapy, Liprotamase, currently Under FDA Review

Eli Lilly and Company and Alnara Pharmaceuticals, inc. recently announced they have signed a definitive merger agreement whereby Lilly will acquire Alnara, a privately held biotechnology company developing protein therapeutics for the treatment of metabolic diseases. Alnara’s lead product in development is liprotamase, a non-porcine pancreatic enzyme replacement therapy (PERT). Liprotamase is under review by the U.S. Food and Drug Administration for the treatment of exocrine pancreatic insufficiency (EPI). Causes of EPI include cystic fibrosis, chronic pancreatitis, pancreatectomy and other conditions.

Patients with pancreatic insufficiency cannot properly digest and absorb fat, protein, and carbohydrates — preventing adequate nutrient absorption. PERT is a treatment involving the administration of three pancreatic enzymes. EPI often is associated with cystic fibrosis, a life- threatening genetic disorder.

Cystic fibrosis affects approximately 30,000 children and adults in the United States and nearly 100,000 people worldwide. Approximately 90 percent of cystic fibrosis patients receive pancreatic enzyme replacement therapy to improve nutritional status and bowel-related symptoms related to pancreatic insufficiency.

Financial terms of the agreement are not being disclosed. The transaction is contingent upon clearance under the Hart-Scott-Rodino Antitrust Improvements Act and other customary closing conditions. J.P. Morgan Securities inc. acted as the exclusive financial advisor to Alnara Pharmaceuticals and WilmerHale is serving as legal advisor to Alnara Pharmaceuticals.

“The acquisition of Alnara provides Lilly with a promising entry into enzyme replacement therapy — an area with unmet medical needs as well as opportunities for novel compounds that give patients additional treatment options,” said Bryce Carmine, executive vice president of Lilly and president of Lilly BioMedicines. “Alnara has been very successful in the development of liprotamase — as indicated by its recent submission to the FDA — and we look forward to partnering with Alnara’s experts during the regulatory review process.”

Alexey Margolin, Ph.D., chief executive officer of Alnara, said: “Our agreement with Lilly is an important development as we move liprotamase through FDA regulatory review. Lilly’s deep expertise in the U.S. pharmaceutical business, including regulatory affairs and the development of innovative compounds that address unmet medical needs, created a natural fit and could allow for opportunities in markets beyond cystic fibrosis. We look forward to finalizing the transaction and working together on next steps to bring liprotamase to patients.”

If approved, liprotamase will allow many patients to use significantly fewer pills compared to current treatment options. Treatments in the PERT class reduce malabsorption and enhance nutrition in patients with EPI. because it is not derived from a porcine source, liprotamase could provide the added benefit for patients of reduction in the risk of viral exposure. A pediatric formulation of liprotamase also is in development.

About Liprotamase & Pancreatic Enzyme Replacement Therapy (PERT) Liprotamase is an oral, non-porcine pancreatic enzyme replacement therapy designed to treat maldigestion, malabsorption and malnutrition as a result of exocrine pancreatic insufficiency associated with cystic fibrosis, chronic pancreatitis, pancreatic cancer, pancreatectomy and other pancreatic diseases. Patients with pancreatic insufficiency cannot properly digest and absorb fat, protein, and carbohydrates preventing adequate nutrient absorption. PERT is a treatment involving the administration of pancreatic enzymes, which in the case of liprotamase includes protease, amylase and lipase. Results from an international, Phase 3 open-label, long-term safety study presented at the North American Cystic Fibrosis Conference in October, 2009 demonstrated the safety and nutritional benefits of liprotamase. The nutritional parameters measured during the study showed nutritional maintenance relative to the U.S. population, as well as a significantly reduced pill burden.

About Alnara Alnara Pharmaceuticals, inc. is dedicated to developing and commercializing novel protein therapeutics for the treatment of metabolic diseases. The company’s innovative approach focuses on designing effective protein therapies that can be orally delivered directly to the gastrointestinal tract without being absorbed into the bloodstream. Alnara’s lead product is liprotamase, a novel, non-porcine pancreatic enzyme replacement therapy, which has completed Phase 3 clinical development in collaboration with the Cystic Fibrosis Foundation Therapeutics, inc. (CFFT) and is currently under review by the FDA. The company is committed to bringing breakthrough new treatments to patients with unmet medical needs. Alnara was co-founded in 2008 by Alexey Margolin, Rich Aldrich and Christoph Westphal. Based in Cambridge, Massachusetts, Alnara is backed by an experienced management team and top-tier venture investors, including Third Rock Ventures, Frazier Healthcare, MPM Capital, Bessemer Venture Partners and Longwood Founders Fund. for more information, visit alnara.com.

About Eli Lilly and Company Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers – through medicines and information – for some of the world’s most urgent medical needs. for more information, visit lilly.com.

SOURCE: Eli Lilly and Company & Alnara Pharmaceuticals, inc.

It took nearly nine years for doctors to figure what was wrong with Tami Slawson’s son, who started having trouble moving his legs, shoulders and arms in preschool.

At 13, he was diagnosed with a rare genetic disorder called mucopolysaccharidosis type 1, or MPS1. His sister, suffering from similar symptoms, was diagnosed at the same time. she was 9.

By then, however, the damage had been done.

“If we would have known what was wrong, we could have started treatment at birth,” Slawson said. “They wouldn’t have these issues.”

The liposomal storage disorder is extremely rare, affecting only about 1,000 people in the United States. but Torrance-area researchers say genetic tests done at birth should include MPS1 because there is a cure that could spare children from the damage of this disease.

“There is a strong argument for testing any disorder that has a treatment,” said Patricia Dickson, a researcher at Los Angeles Biomedical Research Institute.

Dickson and others published findings this week in the journal Science Translational Medicine showing that enzyme replacement therapy, when started at birth, eliminates almost all of the symptoms associated with the disorder.

The study was funded by the National Institutes of Health and several nonprofit foundations.

MPS1 is in the same family of disorders as Tay-Sachs disease. due to a genetic defect, the body lacks an enzyme that breaks down byproducts of chemical reactions in the body’s cells. Gradually these byproducts build up, leading to cell, tissue and organ damage.

Those who suffer from the disorder receive weekly injections of the missing enzyme. in the study, damage to the liver, spleen, lungs, kidneys and heart was eliminated when this treatment started immediately.

Because of the delay in diagnosis, Slawson’s children have suffered permanent damage to their organs. Her kids have undergone surgeries to replace heart valves, and repair carpal tunnel syndrome in their hands and hearing loss.

“There is not a part of the body that MPS doesn’t affect,” Slawson said.

In California, babies at birth are tested for five types of genetic disorders: phenylketonuria (PKU), an autosomal recessive genetic disorder; hypothyroidism, when the thyroid gland doesn’t make enough of the hormone; hemoglobin disorders; galactosemia, a rare disorder in which the body is unable to metabolize galactose in sugar; and a range of disorders that lead to cystic fibrosis.

None of these is considered liposomal storage disorders, which affect about one in 1,000 newborns. They are contracted in the often rare case when both parents have a recessive or active gene for the disorder.

The enzyme replacement treatment for MPS1 was developed at LA BioMed, and approved by the Food and Drug Administration in 2003. It must be taken weekly for life.

“The important thing is that we have a treatment for this,” Dickson said. “There is now compelling evidence that conducting this $2 genetic test at birth can lead to much better outcomes for people.”