Today Apogee Therapeutics released positive 16-week data from its phase 2 APEX study using its IL-13 inhibitor APG777 to treat patients with atopic dermatitis (AD). For starters, it showed that its biologic was able to meet the primary endpoint of Part A of the study, which was evaluating the mean percentage change in Eczema Area Severity Index (EASI) score from baseline to week 16. That is, the drug performed better than the placebo in this regard. In part A of this trial, a total of 123 patients were randomized in a 2:1 fashion to take either the drug or placebo. It is important to note that this short 16-week period had patients taking 720 mg of APG777 at weeks 0 and 2, after which patients were moved to a lower dose of 360 mg at weeks 4 and 12.
EASI reduction of APG777 was noted to be 71%; however, it was only 33.8% for patients given the placebo. This primary efficacy endpoint measure was achieved in a statistically significant manner with a p-value of p<0.001. Despite the primary endpoint coming in strong, the share price closed lower today by as much as 17.32%. In essence, it was more than likely a sell-on-the-news type of event because the truth is that this half life-extended IL-13 biologic has the potential to become best-in-class. This has to do with one of the secondary endpoints known as EASI-75, which in essence looks to find the percentage of patients who achieve at least 75% skin clearance of their disease.
It was revealed that 66.9% of patients achieved this secondary endpoint of EASI-75, compared to 24.6% of those on placebo (statistical significance achieved with a p-value of p<0.001). The importance of this is not that APG777 beat placebo because once this drug reaches the market, it is not going to go up against a placebo. Instead, the significance of this outcome is that it is the highest score of this measure for any biologic in terms of absolute and placebo-adjusted EASI-75. While not assured at the moment, as no head-to-head study has been done, it looks thus far that this IL-13 might be superior to that of heavy hitters like Dupixent from Sanofi and Regeneron Pharmaceuticals and Ebglyss from Eli Lilly. With each of these approved drugs holding EASI-75 of 48% and 55%, respectively.
With all that has been mentioned, this was just on the basis of the initial dosing of APG777 that was given to patients. The company is already in the process of evaluating this IL-13 inhibitor in Part B with higher dosing. While not guaranteed, it is possible that higher dosing could achieve an even greater outcome in terms of EASI score, especially as it relates to EASI-75. This brings about a major catalyst in which the company expects to release such high-dose data from Part B of this mid-stage APEX trial in mid-2026. But before then, this company has another trick up its sleeve in terms of Part A of this study. It is expecting in the 1st half of 2026 to release 52 week, 3-month and 6-month dosing data.
The purpose of this is to reduce the amount of injections that these patients with atopic dermatitis must take with other biologics. The four loading doses I described were given in Part A, which was evaluated in a 16-week period, but the ultimate goal is to see if this drug can work for an extended period of time without frequent injections. A major problem is the injection burden of biologics, and if Apogee can solve this problem, then it would gain a huge competitive advantage over the other FDA-approved biologics for atopic dermatitis noted above. There is plenty of expansion opportunity as well because Apogee is looking to advance the use of APG777 for both asthma and eosinophilic esophagitis indications as well.
Even deeper than that, it doesn’t only have Part B with higher dosing of this IL-13 inhibitor to showcase its strength. It is also developing the combination of APG777 together with APG990 to treat patients with AD. This is highly important because the latter subcutaneous, half life-extended monoclonal antibody (mAb) targets OX40L. This is a key thing to note, which is that this specific target is located in a position further upstream compared to IL-13 or IL4Rα, and thus many other inflammatory cascades can be targeted like Type 1, Type 2 and Type 3. Whereas current biologics approved to treat AD only target Type 2 and a lot of patients don’t respond to these treatments. The last item to mention is that APG990 could be further entrenched in a solid position as it may also offer 3-month to 6-month maintenance dosing like APG777 for AD patients.
Hopefully, Apogee Therapeutics proves that this combination actually works in improving clinical outcomes. The truth is that the company has already moved forward in regard to this combination of APG777 + APG990, where this will be pitted up against Dupixent in a head-to-head phase 1b study with data from it expected to be released in the 2nd half of 2026. Again, this provides an additional avenue of overcoming the competition in the use of biologics to treat AD patients. Regardless, the APG777 program remains in good shape, as the company is already entertaining the fact that it will likely initiate a phase 3 study targeting these autoimmune disorder patients in 2026. It definitely has plenty of cash to reach all of the milestones I noted above, with $681.4 million in cash expected to fund its operations into Q1 of 2028.
The beauty of APG777 and other candidates in the pipeline is the extended half-life of each, which provides the potential for infrequent dosing to treat autoimmune disorder patients. The amino acid modifications of this drug are what allows it to have this extended half-life. The mechanism of action (MOA) of IL-13 inhibition is just that of binding to and blocking downstream signaling of the IL-13Rα1/IL-4Rα complex pathways. It remains to be seen if APG777 and other candidates from its pipeline obtain the competitive edge with less frequent dosing of a biologic to treat these patients, but one thing for sure is that it indeed does have the potential to have the best-in-class IL-13 inhibitor with further confirmation from ongoing clinical studies.