Things didn’t go very well today for Sanofi, because it announced that its phase 2 TIDE-Asthma study failed to achieve the primary endpoint of annualized exacerbation rate at week 48, which was not met with statistical significance. Any type of failure, no matter how you put it, is never a good thing at all. Despite the primary endpoint not being met, the big pharma is not yet ready to call it quits with this IgG4 human anti-OX40L monoclonal antibody.

The reason why is because it actually saw a huge reduction of exacerbations in a specific subpopulation of asthma patients. Specifically, this was a subgroup with the presentation of certain biomarkers. These patients had eosinophils ≥300 cells/ml and elevated neutrophils. The bottom line here is that these are severely ill asthma patients. When eosinophils are high, it means that there is an over abundant amount of white blood cells that are in place. This in turn blocks the airways of the patient and results in increased inflammation.

With respect to this Asthma population, it was noted that amlitelimab was able to achieve a reduction of exacerbations by 70% for them. Being that this is a highly underserved patient population [Asthma population with an unmet need], Sanofi believes that it is important to move this program forward into phase 3 clinical testing.

I think I tend to agree with this company that this drug requires further testing for this patient population. Plus, even if a phase 3 study doesn’t succeed with this drug in targeting this subpopulation of Asthma patients, it won’t be the end of this program. The reason why is because this drug is highly versatile in that it could be applied to a wide variety of immune-mediated and inflammatory disorders.

Speaking of which, the primary indication that Sanofi is exploring is Atopic Dermatitis (AD). With positive data released from the phase 2b study STREAM-AD it was shown that amlitelimab achieved sustained improvement of symptoms for 28 weeks in adults with moderate-to-severe disease.

It’s true that there are a lot of drugs approved to treat AD patients but the thing is that a large majority of them still don’t get relief from them. That is, they still have continuous growth of skin lesions and an itch that just keeps persisting. What this company hopes to accomplish is not only to create another solid treatment option for these particular patients, but where they only need to be dosed with amlitelimab once every 12-weeks.

This is not all in terms of the indications that this drug can go after. It is in a phase 2 study for hidradenitis suppurativa. Plus, phase 2 studies are using this monoclonal antibody to target other disorders like: Celiac disease, scleroderma and alopecia. It makes sense why the company wouldn’t want to let the trial failure in Asthma patients rattle it.

That’s because the drug may end up working well for these other disorders. Plus, it had to pay a hefty amount to get its hands on amlitelimab. It spent roughly $1.4 billion to acquire Kymab. It did so in order to get its hands on amlitelimab (known before Kymab acquisition as KY-1005(. Taking it one step further, the company is in a very good spot in terms of targeting inflammatory disorders.

This is because it has other solid drugs in its pipeline for such indications like Lunsekimig for targeting patients with chronic rhinosinusitis, chronic obstructive pulmonary disease (COPD), and asthma. Then, there is Itepekimab being explored for the targeting of patients with chronic rhinosinusitis, COPD and bronchiectasis. Catalysts from these drugs would be the release of data from the phase 3 COPD study in 2nd half of 2025 and the phase 2 readout of treating patients with bronchiectasis in 2026.

The science of this drug or its mechanism of action (MOA) is highly detailed. The basis is that OX40L binds to both T-regulatory cells and antigen-presenting cells (endothelial cells). With this interaction, it brings about T-cell activation and proliferation, which is responsible for T-cells coming about and driving inflammatory disease. Thus, amlitelimab is set in place to block this interaction, which in turn should halt proliferation of such T-cells to cause inflammation.