Citing a higher-than-expected placebo response and pointing to “encouraging” data in a subset of Crohn’s disease patients did little to assuage investor fears Monday as Coronado Biosciences Inc. reported that CNDO-201, its pig whipworm egg-based candidate, missed its endpoint in the Phase II TRUST-1 study.

Top-line data from the 250-patient study showed that CNDO-201, better known as Trichuris suis ova (TSO), failed to improve response, defined as a 100-point decrease in the Crohn’s Disease Activity Index (CDAI). It also missed the key secondary endpoint of remission, defined as achieving CDAI 150 points. In other overall population, data showed no difference between the treatment and placebo groups, though Coronado reported a non-significant improvement in the TSO group over placebo for patients whose baseline CDAI was greater than 290.

About half the patients enrolled fit that criterion, but that number was not large enough to allow for statistical powering. But Chairman and CEO Harlan F. Weisman noted that if the result for the over-290 CDAI group had been across the entire trial population, TRUST-1 likely would have achieved statistical significance.

Calling the data “fresh,” Weisman told investors on the morning conference call that the company would need time to review results with study investigators before presenting a more detailed dataset, likely at an upcoming scientific conference. He added that the company also is awaiting results from TRUST-II, a European Phase II study in Crohn’s patients being conducted by partner Dr. Falk Pharma GmbH, of Freiburg, Germany.

That study, which is being conducted under an adaptive trial design, involved an interim analysis in April 2012 noting good safety and a positive efficacy trend, Weisman said. The second and possibly final interim analysis is expected later this year.

TRUST-II is similar though “slightly different” to TRUST-I, Weisman explained. While TRUST-1 enrolled patients with CDAI baselines of 220 to 450, TRUST-II capped CDAI severity at baseline at 350. Patients in TRUST-I also were allowed to continue oral immunosuppressive therapy such as steroids, while those enrolled in TRUST-II were not.

So while the trial was “negative overall,” Weisman told investors, the company did find the activity of TSO in the sicker Crohn’s patients to be encouraging.

Wall Street, however, did not. Shares of the Burlington, Mass-based firm (NASDAQ:CNDO), which had dropped 13.5 percent Friday, lost $3.86, or 66.9 percent, to close Monday at $1.91, by far the lowest Coronado has traded since gaining a Nasdaq listing in 2011, and dropping its market cap to $66 million. More than 20 million shares changed hands, at about 47 times the stock’s average trading volume.

The firm’s chief executive acknowledged the market reaction. “We’re acutely aware that among our investors . . . we’ve put a substantial dent” into their wealth and money, Weisman said, adding that he understands the lack of detailed information is “frustrating.” But he said Coronado needed time to fully analyze the data before deciding if and how to move forward on the TSO program. “The last thing in the world I want to do is take a bad situation and make it worse.” The only bright spot in the data were safety results, showing that TSO, given as 7,500 ova once every two weeks, was safe and well tolerated.

Beyond TSO

If TSO gets taken out of the equation, the firm’s only other program is in early stage development. Founded in 2007 by biotech builder Paramount Biosciences, Coronado originally had three immunotherapy programs in its pipeline – a natural killer (NK) cell technology, a doxorubicin analogue and a pan-Bcl-2 inhibitor. When it later picked up the TSO program in its all-stock acquisition of Asphelia Pharmaceuticals Inc., the firm divested the Bcl2 and doxorubicin programs in favor of focusing on TSO.

Developed at the University of Iowa, TSO is based on the notion that parasites down-regulate the immune system, thereby improving outcomes in autoimmune diseases. Because it’s a pig parasite and not a human pathogen, TSO is eliminated from the body within several weeks without treatment.

Coronado’s approach to Crohn’s is only one of many efforts for developing an oral therapy that could compete with the injectable anti-TNF drugs such as Humira (adalimumab, Abbvie Inc.). And it’s not the only drug to run into trouble in the clinic.

Earlier this year, Chemocentryx Inc.’s CCRP antagonist vercirnon (Traficet-EN) fell short in the first of four Phase III studies in moderate to severe Crohn’s disease, prompting partner Glaxosmithkline plc to return rights to the Mountain View, Calif.-based biotech. (See BioWorld Today, Aug. 26, 2013.)

Other firms are still plugging away. Most recently, a joint venture between Hutchison China Meditech Ltd. and Nestle Health Science SA launched Phase III testing in ulcerative colitis (UC) and Crohn’s disease with HMPL-004, a drug based on traditional Chinese medicine. And Israeli firm Redhill Biopharma Ltd. recently started patient screening for a Phase III study testing RHB-104 a fixed-dose oral combination antibiotic therapy, in patients with moderately to severely active Crohn’s. (See BioWorld Today, Sept. 12, 2013.)

In addition to Crohn’s, Coronado disclosed a study started last month to test CNDO-201 in UC. That study, which is being funded by a grant from the National Institute of Allergy and Infectious Diseases, will test CNDO-201 vs. placebo on clinical response of UC, intestinal mucosal immunological response and inflammatory markers. A total of 120 patients will be enrolled in the 12-week trial, and the primary endpoint is clinical response, as defined by a reduction in the Mayo score of 3 or greater and 30 percent or greater from baseline, along with either a decrease from baseline in the rectal bleeding subscore of greater than 1 point or an absolute rectal bleeding subscore of zero or 1 at week 12.

Earlier in development, Coronado is advancing the NK program. Late last year, it started a Phase I/II dose-escalation study testing the lead candidate, CNDO-109, in patients with acute myeloid leukemia who are at high risk for relapse.

Coronado has been public since mid-2011 when it went the alternative route of a Form-10 filing. As of the end of September, Weisman said it had more than $100 million on its balance sheet. (See BioWorld Today, July 30, 2011.)