It was compassion that moved Yutaka Niihara to start Emmaus Medical Inc. more than 10 years ago. The hematologist and University of California Los Angeles (UCLA), professor would have been content to continue with his medical practice and teaching, had it not been his passion for research and his desire to find a treatment for the intense pain crises his sickle cell patients suffered.

In the course of their academic research at UCLA, Niihara and Charles Zerez found that glutamine plays an important role in the oxidation-reduction status of sickle red blood cells, and that the amino acid had potential to be developed as a treatment for the disease. He saw the suffering of his patients with sickle cell disease, and started Emmaus in Torrance, Calif., in December 2000. Using a combination of National Institutes of Health grant funding and family and friends financing of nearly $5 million, the company was able to initiate Phase II trials, which were completed in 2008.

"The prospect of helping sickle cell patients around the world is what keeps us going. I would much rather be a university professor, but I decided to put this aside, and go around the world to raise money so we can continue this work," Niihara told BioWorld Today.

That first family and friends round got the company through Phase II trials; a second family and friends round raised a little more than $20 million.

That consortium includes more than 300 investors ranging from individuals to middle-sized businesses.

Emmaus is hoping to provide a return to those investors and has filed for an initial public offering. Given near-term potential growth drivers, including the company's efforts to partner, Niihara is carefully weighing the timing in order to maximize valuation.

Sickle cell disease is an inherited disorder most common in West and Central Africa, and in people of African descent in the U.S. and South America. It causes red blood cells to deform into a rigid "sickle" shape, bringing pain, infection and organ damage throughout life.

Sickle disease takes several forms, including sickle cell anemia, sickle-hemoglobin C disease, sickle ß⁰ thalassemia, and sickle ß⁺ thalassemia.

The current standard-of-care treatments for sickle cell disease include hydroxyurea, pain medication and hydration, and treatment costs topped $1.1 billion in 2008 in the U.S.

In some parts of Africa, as many as one person out of 50 suffers from sickle cell disease, and approximately 90 percent die by age 5, and 99 percent are dead by 20.

Niihara and Zerez approached sickle cell disease from the perspective of oxidative stress. They zeroed in on nicotinamide adenosine dinucleotide (NAD) because of its role as an antioxidant in red blood cells.

Sickle red blood cells have a lower NAD redox potential than normal cells, but an increased rate of NAD synthesis, possibly as a way to compensate for oxidant stress.

Niihara and Zerez reasoned that providing the cells with more raw materials to produce NAD could relieve symptoms of sickle cell disease. That theory was supported by a 1997 study showing that sickle red cells have increased transport and use of glutamine, an amino acid precursor of NAD.

Patients treated with L-glutamine (levoglutamide), a pharmaceutical grade nutritional supplement approved for short bowel syndrome under the name Nutrestore, showed improvements in pain symptoms and energy, and in vitro studies showed that L-glutamine reduced adhesion of sickle red blood cells.

A 57-week randomized, double-blind Phase II trial in 30 patients showed a major trend toward reduced frequency of sickle cell crises and a decreased frequency of hospitalization.

Patients in the placebo group had sickle cell crises at a frequency of 30 percent to 149 percent more than those receiving L-glutamine, and their hospitalization rate was 31 percent to 52 percent higher.

Emmaus also noted an anecdotal trend toward healing of chronic skin ulcers.

There were no major side effects, adverse events or deaths attributable to L-glutamine.

The FDA authorized Emmaus to continue to Phase III at an end-of-Phase II meeting, and that trial began enrollment in 2010.

The Phase III trial design is similar to Phase II: a 57-week study in 225 patients at 30 sites in the U.S.

Niihara is confident in the eventual success of the drug. "We are in a fortunate situation. Most of the opinion leaders in this field are participating in our clinical trial right now."

Emmaus is already looking ahead, past approval, and planning its marketing efforts.

"There is really no other practical treatment for sickle cell disease," Niihara said. Few investigational treatments have progressed to late stage trials.

Players include companies like HemaQuest Pharmaceuticals Inc., bluebird bio and AesRx LLC. AesRx started a Phase I/IIa trial of its orally bio-available Aes-103 anti-sickling agent in patients with sickle cell disease earlier this year. (See BioWorld Today, May 15, 2012.)

In March 2012, HemaQuest Pharmaceuticals Inc. closed a $13 million extension of its Series B financing to fund a randomized, double-blind, placebo-controlled Phase IIb study evaluating lead product candidate HQK-1001 in patients with sickle cell disease.

Bluebird bio, of Cambridge, Mass., which is developing gene therapies for severe genetic disorders including sickle cell disease, completed a $60 million Series D financing to fuel its clinical programs. (See BioWorld Today, July 25, 2012.)

Based on promising early clinical proof-of-concept results, bluebird bio plans to initiate a Phase II/III study in childhood cerebral adrenoleukodystrophy in the U.S. and Europe in 2013, as well as a second U.S.-based Phase I/II study in beta thalassemia next year.