Shares of Array Biopharma Inc. hit a 52-week high of $7.20 Tuesday morning after the company reported positive findings from its randomized Phase II trial of oral CRTh2 antagonist ARRY-502 in mild to moderate persistent allergic asthma. The compound hit the primary endpoint – significant improvement in pre-bronchodilator forced expiratory volume in one second (FEV1), compared to placebo – across the study population and in a predefined Th2 biomarker subset that represented half of treated patients.

The proof-of-concept study, conducted in the U.S., enrolled 184 patients. ARRY-502, dosed at 200 mg twice daily (N = 93) for four weeks, improved FEV1 by 3.9 percent compared to placebo (N = 91), achieving statistical significance (P = 0.02). Patients in the biomarker cohort achieved statistically significant enhanced improvement in FEV1 – 6.8 percent compared to placebo (P = 0.008) – using the median baseline value of the undisclosed Th2 biomarker.

Array expects to see an enhanced response when ARRY-502 moves to a 12-week study period, Kevin Koch, the company's president and chief scientific officer, said on a conference call.

The Phase II trial also demonstrated statistical significance in key secondary efficacy endpoints, including reduced use of short-acting beta agonists and improvements in asthma control, symptom-free days during treatment, quality of life and other spirometry measures.

ARRY-502 also showed a good safety profile, with a lower overall number of adverse events than in the placebo arm, including fewer asthma exacerbations. All treatment-related adverse events were mild or moderate.

Asthma affects some 8 percent of the U.S. population, and many patients are poorly managed, said Array CEO Ron Squarer. He pointedly observed on the conference call that Merck & Co. Inc.'s oral asthma drug Singulair (montelukast sodium) generated approximately $5.5 billion in global sales in 2011, the last full year before its patent expired.

"ARRY-502 is the first oral drug since Singulair was introduced 15 years ago to demonstrate clinically meaningful activity in allergic asthma," Squarer said.

ARRY-502's target, the CRTh2 receptor, is expressed on Th2 T cells, basophils and eosinophils; the CRTh2 ligand, prostaglandin D2 (PGD2), is released by mast cells. Study findings suggest that the PGD2/CRTh2 axis plays a key role in the migration and activation of inflammatory cells that lead to many asthma symptoms, including coughing, breathing difficulty and exacerbations, Squarer explained.

Current asthma therapies don't fully target the Th2 pathway, yet that gene signature – present in about half of the asthma population – spans mild, moderate and severe disease, he added. Thus, the findings suggest broad applicability for ARRY-502 not only in asthma but also in Th2-driven diseases such as allergic rhinitis and atopic dermatitis.

"For competitive reasons," Squarer declined repeated questions from analysts to name or characterize the specific Th2 biomarker referenced in the Phase II data, but he said it was unrelated to Singulair's mechanism of action. Array used a number of Th2-related biomarkers to recruit patients for the study.

Squarer said the company will share more complete findings "at relevant scientific forums," though he declined to pinpoint a time frame. Due to the competitive nature of the field, "the standards for releasing data are different" in asthma than in indications such as cancer, he said, adding, "We think partners will wish us to keep as much of this data for them as possible."

Array Seeking 'Right Partnership'

In any event, the findings were sufficiently robust to warrant additional studies – potentially including combination trials with standard-of-care therapies – and to accelerate partnering discussions, Squarer said.

"It's important, really, to find the right partnership, structure and deal for the product," he pointed out, noting that Array is looking for an experienced biopharma that can enhance the asset's value.

"We have had discussions with a number of key players in the field, and there appears to be substantial interest," Squarer acknowledged.

Array can afford to be patient. The company received $577.9 million in research funding and up-front and milestone payments from partners through June 30, 2012, including $174 million in initial payments from strategic collaborations with Amgen Inc., Genentech Inc. (a unit of Roche AG) and Novartis AG. (See BioWorld Today, Dec. 16, 2009, Aug. 10, 2011, and April 21, 2010.)

Earlier this month, Array entered a deal with newly formed Loxo Oncology Inc. to advance a preclinical candidate developed by Array and to find more small-molecule drugs for oncology targets. The arrangement could garner up to $434 million in milestone payments plus royalties on resulting products for Array, which also received shares of Loxo. (See BioWorld Today, July 11, 2013.)

In May, Oncothyreon Inc., of Seattle, plunked down $10 million up front to collaborate with Array around ARRY-380, a small-molecule HER2 inhibitor. (See BioWorld Today, May 31, 2013.)

Array reported cash and equivalents of $87 million as of March 31.

Analysts were uniformly positive. Piper Jaffray & Co. analyst Edward Tenthoff increased Array's price target to $10 from $7, noting the company "could have as many as [six to eight] pivotal trials under way in 2014 with first product sales/royalties by 2016."

Wells Fargo Securities LLC analyst Matthew Andrews added, "Overall we see the current dataset as very encouraging and believe its profile could be attractive to a well-established large pharma company with a commercial presence in asthma."

Array's shares (NASDAQ:ARRY) ended the day high with a gain of 58 cents, or 10.4 percent, closing at $6.14. Volume was 7.5 times higher than average.