DUBLIN – Shares in Abivax SA rose as much as 20 percent Tuesday on preliminary phase IIa proof-of-concept data for its lead drug candidate, ABX-464, in ulcerative colitis. The same molecule is already in development for targeting reservoirs of infection that persist in HIV patients on highly active retroviral therapy, but its anti-inflammatory mechanism, whose effects include up-regulating MIR124, an anti-inflammatory microRNA species, and interleukin-22 (IL-22), an anti-inflammatory cytokine, has also exhibited positive effects in ulcerative colitis.

The phase IIa study recruited 32 patients with active, moderate-to-severe ulcerative colitis, who had failed or were intolerant to immunomodulators, corticosteroids, TNF-alpha inhibitors or Entyvio (vedolizumab, Takeda Pharmaceutical Co. Ltd.), an alpha-4-beta-7-integrin inhibitor. At baseline, they had a score of 6 to 12 on the 12-point Mayo score.

They were randomized to a 50-mg once-daily active treatment arm (n=23) or a placebo arm (n=9). After eight weeks of therapy, 35 percent of those in the active treatment arm attained clinical remission, while just 11 percent of those in the control arm did. The result was not statistically significant, but the effect of ABX-464 on mucosal healing (as measured by endoscopic imaging) was. Fifty percent of those on drug showed a significant improvement on that measure, whereas just 11 percent of those in the control group did (p<0.03).

A biomarker of inflammation, fecal calprotectin, was also more strongly reduced after four weeks on therapy among those in the active treatment arm than in those in the control arm (4.4-fold reduction vs. 1.6-fold reduction). Seventy percent of those on drug were deemed to be clinical responders vs. 33 percent of those in the control arm.

Only mild to moderate adverse events were observed – for 78.3 percent of patients in the active treatment arm and for 55.6 percent of those in the control arm. One patient, who had been in the active treatment group, withdrew from the study due to elevated transaminases, an indication of liver damage. Those who completed the two-month study were allowed to enroll in a follow-up, 12-month safety study.

"It is clear that the next step is a dose-finding study, possibly with three treatment arms," Hartmut Ehrlich, CEO of Paris-based Abivax told BioWorld. The company employed a 50-mg dose in the study, as that had provided at least some indications of efficacy, while also being safe, in HIV trials. "Is it the optimal dose? We don't know that yet," he said.

The company is currently working on a concept sheet and plans to submit a clinical trial protocol to the regulatory authorities by the fourth quarter, the firm's chief medical officer, Jean-Marc Steens, told BioWorld. It aims to begin the study before the end of the first quarter next year.

It has not yet finalized its recruitment target. "It will be around 180 patients most likely," Steens said.

Busy year ahead

Abivax is gearing up for a very busy 2019. It also plans to move ABX-464 into a phase IIb trial in HIV on roughly the same schedule, while also commencing a phase IIa trial of the same drug in Crohn's disease. The company is funded through the end of 2019, Chief Financial Officer Didier Blondel told BioWorld, but it needs to secure additional financing to ensure that it can complete its planned trials. It exited 2017 with €16.9 million (US$19.6 million) on its balance sheet and recently secured €20 million in debt financing from Kreos Capital.

Its main options for further funding include a fresh equity raise and/or a partnering deal. Ehrlich said the company aims to secure one or more deals during the phase IIb trials. Inflammatory bowel disease and antiviral therapy represent two distinct markets, with little or no overlap. It is certainly unusual – and probably unique – to find a single drug addressing each of them.

Abivax has, since its formation in late 2013, majored in antiviral drug and vaccine development, but ABX-464's mechanism is indirect and immunomodulatory rather than being directly antiviral. Its molecular target is the cap binding complex, which is involved in the protection and processing of newly transcribed RNA molecules. ABX-464, Ehrlich said, accelerates the splicing of a long untranslated RNA molecule involved in miRNA production, resulting in the anti-inflammatory effects it has reported.

The company's stock price has been declining steadily since it reported phase IIa proof-of-concept data in HIV in May 2017. Before Tuesday's news, it had been changing hands for about one-third of what it was worth back then, making an equity raise difficult. Right now, the company is valued at little more than €70 million, which implies existing shareholders would be diluted significantly if the company sought a large amount of cash through a share issue. The stock, which closed Tuesday at €7.71, is trading well below its 2015 IPO price of €21.30 per share.