Nektar Therapeutics had an amazing trading day today as its stock closed higher by 156% to $24.45 per share after the release of positive results from its phase 2b REZOLVE-AD study, which evaluated the use of its drug rezpeg (rezpegaldesleukin) for the treatment of patients with atopic dermatitis. It was noted that all three doses of this drug were able to beat placebo in terms of the primary endpoint of mean percent change in Eczema Area and Severity Index (EASI) from baseline at week 16. The best response came from the high-dose version of the drug used,24 micrograms/kilograms of rezpeg given once every 2 weeks (Q2W), whereby there was an improvement of EASI over the 16-week period of 61%.
This trial was a very large one, because it recruited a total of 393 patients who were randomized 3:3:3:2 to receive one of three dosing regimens of rezpeg or placebo over this period. It was the goal to see if one of the doses of this drug given in a subcutaneous fashion could help to reduce disease spread and burden. One of the ways that this therapy might be much more ideal is because it takes a completely alternate approach to targeting autoimmune disorders such as this one, atopic dermatitis. Instead of targeting the immune modulation that drives disease, the goal is to restore balance to the immune system with the proliferation (expansion) of regulatory T (Treg) cells.
It is believed that atopic dermatitis and other such immune disorders come about because of an imbalance of Tregs in the patient’s body. Thus, IL-2 is responsible for stimulating an abundant amount of T-regs but at the same time does not have the unintended consequence of generating cytotoxic CD8+ T and CD4+ T cells, which are responsible for the generation of disease. The mechanism of action was proven in the released data, whereby there was a fast onset EASI response along with itch relief achieved with the first few doses of rezpeg. Where the company could fall short is that this T-reg stimulator must be given as a subcutaneous injection, which could result in site reactions on the skin.
The point here being that it is going to be hard to go up against a competing biologic drug known as Dupixent from Sanofi and Regeneron Pharmaceuticals. This particular drug takes the approach of inhibiting the IL-13/IL-4 pathways that drive autoimmune disorders and has already been approved to treat patients with atopic dermatitis. On the flip side, the Treg approach might end up paying off better in terms of safety. Other drugs with different mechanisms of action (MOA) are responsible for an increase in the risk of patients developing other problems such as oral herpes and/or conjunctivitis.
While the stock has gained considerably after the release of results from the phase 2b REZOLVE-AD study, there are two data readouts for investors to look forward to that will act as additional catalysts. The REZOLVE-AD study was also designed with the intention of incorporating a 36-week maintenance period, and with that in mind, these particular results are expected to be released in Q1 of 2026. The beauty of rezpeg is that its mode of action can be applied towards a multitude of other autoimmune disorders as well, which is why the company is also testing the use of it to treat patients with alopecia areata in a phase 2b study.
It also has an extensive preclinical pipeline as well, with additional shots on goal in targeting autoimmune disorders like that of bivalent agonistic antibody targeting TNFR2 NKTR-0165 and polyethylene Glycol (PEG)-modified hematopoietic colony stimulating factor protein NKTR-4222. Although, the former candidate being done in a collaboration agreement with Biolojic. Along with an oncology pipeline boasting the IL-15 inhibitor candidate NKTR-255 for the treatment of patients with hematological malignancies and solid tumors. However, it is not using this drug alone to target such indications but instead combining other drugs such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and tumor-infiltrating lymphocytes (TIL) therapy. It remains to be seen how this program advancement goes, but the company is well established with rezpeg moving forward in the targeting of a variety of autoimmune disorders.