Confident Abivax aims to disrupt IBD landscape

Marc de Garidel, chief executive of French clinical-stage biotech Abivax (Nasdaq: ABVX), has good reason for his belief in the company’s pioneering lead asset, obefazimod.

The highly differentiated oral drug candidate, a small molecule, with a novel mechanism of action based on the expression of a single microRNA, miR-124, to stabilize the immune response, has generated impressive data in several preclinical and clinical studies. It has demonstrated safety, profound and maintained anti-inflammatory activities, and today is undergoing a Phase III clinical study in patients with moderately to severely active ulcerative colitis (UC).

Importantly, the data so far suggest that it is well-tolerated, with a long-lasting efficacy in a field where currently available treatments come with a significant risk of adverse events and patients are often refractory to conventional medications.

A Phase IIb trial in Crohn’s disease is set to begin later this year and Abivax is also exploring combination therapy opportunities with obefazimod in UC.

It is no wonder the fast-growing company has attracted significant investment, including via the largest ever US initial public offering (IPO) on the Nasdaq by a French-listed biotech company.

Fundamentally, what’s very attractive about obefazimod is the new mechanism of action (MoA), viewable via this link and via the image below.

“Obefazimod is a first-in-class drug candidate that increases the expression of miR-124, a natural regulator of the inflammatory response,” de Garidel explained.

Pre-clinical studies showed that under dysregulated inflammatory conditions, enhanced expression of miR-124 resulted in stabilized levels of multiple cytokines and chemokines, bringing them back to homeostatic levels.

Spectacular trial data

“Initially, obefazimod was developed to prevent the replication of HIV, in a collaboration between Abivax - which was officially created in 2013 - and the CNRS (Centre national de la recherche scientifique) in France,” de Garidel added.

However, in pre-clinical studies obefazimod showed promise as an immune stabilizer that also could work in UC. A Phase IIa trial, involving around 40 patients with moderately to severely active UC being treated with obefazimod, confirmed the initial trend seen in mice that it did indeed reduce inflammation.

Encouraged by this, Abivax decided to change the focus of development of obefazimod, turning to the field of inflammatory bowel diseases.

Abivax started a much bigger Phase IIb program in UC patients to establish an effective dose, and to evaluate if and when tolerability issues would appear.

The Phase IIb study was conducted in Eastern Europe. “The first good news about that study was that there were very few, manageable side-effects, proving a strong safety profile,” Mr de Garidel said.

But even more important, the clinical results of the 254-patient study in moderately to severely active UC were compelling. “The data showed significant clinical efficacy in the overall patient population on primary and key secondary endpoints,” Mr de Garidel explained.

There was total clinical remission in several cases and investigators were particularly impressed by the efficacy in severe patients who previously failed biologic and/or JAK inhibitors treatment, along with durable and increasing efficacy during maintenance treatment.

Indeed, with obefazimod, patients are seeing prolonged efficacy over time. After two years, nearly two thirds of the patients are in continued clinical remission.

Positioned to become a first-line treatment option: convenient, safe and long-term effective

“After eight weeks of treatment, we saw a very good response in this challenging disease,” de Garidel said. “Then, more striking, over time, after one year — now we have two years of
data — we see those patients remain controlled.”

“Just to remind you, UC is a very debilitating disease that significantly decreases quality of life. Patients are often diagnosed between the ages of 20 to 40. They have ulcers around the
intestine, the lower intestine in particular. They bleed and become anaemic. In some cases, patients have to go to the bathroom 10 to 20 times per day and have strong abdominal pains. These patients are in high need of an effective, long-lasting therapeutic option and adding a drug that can control the disease is a big deal.”

And this is even more true as patients are often refractory to conventional treatments including corticoids and aminosalicylates. Advanced treatments that are currently on the
market such as TNF inhibitors and IL-23 inhibitors can be highly effective for up to a year or two but, after a while, patients show loss of response, or intolerance, and often start to show symptoms again. They also carry black box warnings over adverse events such as infection and higher risk of cancer and cardiovascular problems.

“Having a safe drug in this young population is really critical,” de Garidel said. “We have to be prudent with our drug because we are only in the middle of our Phase III clinical trial, but
at least from the Phase II program, tracking those patients who have continued with obefazimod for nearly six years, we’re seeing no signs of opportunistic infection or cancer.

“So overall, we’re really excited because we think obefazimod could become the first-line therapy in the future, replacing conventional therapies if we can replicate in Phase III what we saw in Phase II trials.

“Following extensive market research in the USA and Europe, we believe our drug candidate addresses three benefits gastroenterologists want to see in the next generation of drugs for
UC: they want an oral drug for convenience; they want to be sure the drug is safe; and a therapy that shows long term maintenance.

“So, we are very well-positioned to potentially disrupt the landscape.”

A massive opportunity

The opportunity in this area is enormous. In the USA, up to 800,000 patients are estimated to have UC, while in Europe, the total may even be slightly higher. The figures in Crohn’s disease are at least double this and the number of people affected is sadly rising.

But pursuing such an opportunity is a huge task for a small company. Once obefazimod is approved in the USA, Abivax intends to have a commercialization infrastructure in place. The company has strengthened its team in the USA, where it has opened a new office and has a significant management presence, including de Garidel. New executive team members with global expertise in commercializing drug candidates have also been recruited.

“A Phase III clinical trial is very large, with close to 1,200 patients throughout about 600 sites globally,” de Garidel noted. “It’s a very global undertaking for a small company. We were 50 people when I joined last year in early May, now we’re nearly 100 people. But it’s also a big financial investment, 350 million euros ($375 million) for running a Phase III trial.”

Abivax has raised a large amount of capital, including nearly $240 million through the Nasdaq IPO. The company is negotiating a debt facility with a number of lenders to complement that amount.

Investors will closely be watching the first big Phase III data readout, expected from the ABTECT program (see anticipated timeline below) at the end of the first quarter next year, to see how patients are doing after eight weeks of treatment. In early 2026, data from a year’s treatment will come out and, if the results are positive, Abivax will submit filings in the USA and Europe.

At the same time, the company will progress its obefazimod research in Crohn’s disease while also exploring combination therapy opportunities.

Inevitably, big pharma is keeping an eye on Abivax, which does not intend to commercialize everywhere in the world. The company will work with partners outside the USA.

“They are watching us, and we are open for partnering discussions in Europe and other regions.”