After last year’s cuts, Ardelyx loses CSO Caldwell as he becomes CEO at a startup

Mike Raab - Ardelyx
Ardelyx CEO Mike Raab. (Image: Ardelyx)

Ardelyx has faced a tough few years with trial setbacks and axing staffers: Today, it announced chief scientific officer (CSO) Jeremy Caldwell, Ph.D., is heading for the exit, with no replacement yet lined up.

In a very brief release, Ardelyx said he “will be leaving the company, effective February 16, 2018,” and is set to become a CEO of an unnamed “early-stage biotech start-up company based in San Diego.”

The small cap biotech has seen a series of setbacks and spooked investors in recent years, and last fall slashed its workforce by nearly one-third as it looked to sharpen its focus on its phase 3 candidates.

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These phase 3 programs include its irritable bowel syndrome (IBS) candidate tenapanor, which the company is prepping for its first NDA in patients with IBS-C (constipation).

Tenapanor is also gearing up for a new test this year as a treatment for hyperphosphatemia in patients with end-stage renal disease on dialysis.

Tenapanor, which is designed to clear excess sodium from the gastrointestinal tract, has not had the best history, however, as the drug has flunked one trial and is showing a high adverse event rate in other.

In May of 2015, it posted data showing tenapanor failed to hit the primary endpoint among 154 patients with stage 3 chronic kidney disease and Type 2 diabetes, failing to significantly decrease the urinary albumin-creatinine ratio compared to placebo.

Just before this, the drug met its main efficacy goal in a phase 2b trial on dialysis patients with dangerously high phosphate levels, but not without charting alarming rates of diarrhea compared to placebo.

It did also hit the target in a phase 2b study of the drug for IBS, but investors were rattled by signs that the drug triggered serious diarrhea in many patients and led to a rout, with shares plunging 30% when the data were posted.

RELATED: Ardelyx rises on better IBS data and a clearer path to FDA filing

AstraZeneca signed a $272 million partnership pact on the drug back in 2012, but a few years ago pulled out of the deal, giving rights back to Ardelyx after one too many setbacks (at a cost of $25 million to the biotech).

Ardelyx had also been working with Sanofi on preclinical treatments that target NaP2b, a phosphate transporter. Under that deal, signed in 2014, the biotech was eligible for up to $198 million, plus tiered royalties on any approved products.

But this went sour too when the French big pharma backed out of its collaboration, returning a handful of candidate treatments for high phosphates in patients with kidney disease. Both AZ and Sanofi had helped the company get off its $60 million IPO back in 2014.

Ardelyx announced new data back in May that its med had hit its primary endpoint, and most of its secondary endpoints, in a late-stage test of its IBS-C drug, but investors were spooked as its shares spiraled downward premarket.

The top-line results from the T3MPO-1 trial, the first of two phase 3 tests in IBS-C in more than 600 patients, hit its primary endpoint, showing that a greater proportion of tenapanor-treated patients compared to placebo-treated patients (27% vs. 18.7%) had at least a 30% reduction in abdominal pain.

It also hit seven of the eight secondary endpoints, missing the target in bowel movement rates, and there were some AE issues with tenapanor as compared with a dummy treatment, seeing higher rates of diarrhea (14.6% vs. 1.7%) and slightly more for nausea (2.6% vs. 1.7%).

Diarrhea caused 5.9% of tenapanor patients to pull out of the trial, compared to just 0.6% for the placebo group. But the company’s shares were down a major 38% in early trading on the news, potentially on the still higher-than-placebo rates of diarrhea, given its past problems in the area.

But back in October, the NHE3 inhibitor nailed a confirmatory trial achieving all its primary and secondary outcome objectives including a significantly higher combined response rate—defined as a reduction in abdominal pain and an increase in spontaneous bowel movements—compared to placebo, boosting its outlook for this med. 

“Jeremy has been a tremendous asset to Ardelyx, and I am incredibly grateful for his many contributions to the company and our programs over the years," said Mike Raab, president and chief executive of Ardelyx.

“My time with Ardelyx has been extremely rewarding, and I’m proud of the many accomplishments of this team,” added Caldwell.

“Since joining in 2014, we have brought forward several first-in-class programs, culminating in the first New Drug Application for tenapanor for IBS-C planned for submission in the second half of the year. I believe that tenapanor will play a critical role in treating both hyperphosphatemia and IBS-C in the future."