Apogee Therapeutics (NASDAQ:APGE) said its Phase 2 APEX Part B trial of zumilokibart in moderate-to-severe atopic dermatitis met its primary endpoint, supporting the company’s plan to advance the drug into Phase 3 development later this year, pending regulatory alignment.
Chief Executive Officer Michael Henderson said the results give Apogee “a clear path to phase III later this year,” adding that the company believes zumilokibart, or Zumi, could offer a differentiated profile in atopic dermatitis by combining lesion control, itch relief and less frequent dosing than current biologic standards of care.
APEX Part B Meets Primary Endpoint
Chief Medical Officer Carl Dambkowski said APEX Part B enrolled a modified intent-to-treat population of 346 patients randomized to receive low-, mid- or high-dose zumilokibart or placebo. The study was designed to evaluate dose response while maintaining a safety profile consistent with the IL-13 class and reducing injection burden.
Dambkowski said the mid-dose regimen is the planned Phase 3 dose, pending regulatory discussions. At week 16, the mid-dose arm achieved a 65.9% EASI-75 response, while the high-dose arm achieved 61.6% and the low-dose arm achieved 50.5%. He said all zumilokibart treatment arms achieved statistical significance versus placebo beginning at week two.
The mid-dose also showed activity on more stringent endpoints. Apogee reported that 46% of patients receiving the planned Phase 3 dose achieved IGA 0/1 at week 16, 47.4% achieved EASI-90 and 50.5% achieved a four-point or greater reduction from baseline on the itch Numerical Rating Scale. Dambkowski said 16.5% of patients in the mid-dose arm achieved EASI-100, representing completely clear skin, and 20.6% achieved very low disease activity as measured by a composite of EASI-90 and itch NRS of zero or one.
Dambkowski said the Part B results were consistent with earlier Part A data, including on EASI-75 and percentage change from baseline in EASI score. He said Apogee expects to release maintenance data from Part B next year, after patients are re-randomized into every-three-month or every-six-month dosing arms.
Safety and Dosing Profile
Apogee said zumilokibart was well tolerated in the trial, with safety results consistent with expectations for the IL-13 class. Adverse events occurring in at least 5% of patients in one or more zumilokibart treatment arms included nasopharyngitis, headache, non-infective conjunctivitis, upper respiratory tract infection, atopic dermatitis and urinary tract infection.
For the planned Phase 3 dose, Dambkowski said the non-infective conjunctivitis rate was 5.9%, while the pooled rate across conjunctivitis-related preferred terms was 10.6%. He said there was no effect of anti-drug antibodies on pharmacokinetics, clinical activity or safety.
Dambkowski also emphasized zumilokibart’s potential dosing advantage. He said the planned Phase 3 induction regimen requires four dosing days, compared with nine for dupilumab. Based on earlier Part A 52-week results, he said maintenance dosing could require two to four dosing days per year, compared with 26 injections per year for dupilumab.
Dr. Ruth Ann Vleugels of Brigham and Women’s Hospital and Harvard Medical School, who spoke on the call about unmet needs in atopic dermatitis, said patients continue to seek therapies with strong efficacy, a clean safety profile and reduced injection burden. She said dermatologists are comfortable with the IL-4 and IL-13 class and characterized conjunctivitis as a manageable class-related side effect.
Phase 3 Plans and Additional Indications
Kristine Nograles, Apogee’s senior vice president and head of clinical development and medical affairs for dermatology, said the company plans to initiate the Phase 3 ADventure program in the second half of the year, pending regulatory alignment. The program will include three clinical trials.
- ADventure 1 and ADventure 2: Monotherapy studies expected to enroll about 400 patients each with moderate-to-severe atopic dermatitis. Patients will receive mid-dose zumilokibart or placebo during induction, followed by maintenance evaluation of three- and six-month dosing regimens.
- ADventure TCS: A trial of zumilokibart in combination with topical corticosteroids, also expected to enroll about 400 patients. The study will evaluate every-three-month maintenance dosing with topical corticosteroids.
Nograles said EASI-75 and IGA 0/1 will serve as co-primary endpoints in the Phase 3 studies.
Amol Kamboj, Apogee’s senior vice president and head of clinical development for respiratory and GI, outlined plans to study zumilokibart beyond atopic dermatitis. He said Apogee plans to initiate the ASPIRE Phase 2b trial in moderate-to-severe asthma in the first quarter of next year. The randomized, placebo-controlled study will evaluate dosing every three, six or 12 months, with annualized exacerbation rate at week 52 as the primary endpoint.
Kamboj also said Apogee plans to initiate the ELEVATE Phase 2a proof-of-concept study in eosinophilic esophagitis in the coming quarters. That trial is expected to enroll 30 to 50 patients and will assess histologic improvement by eosinophil counts as the primary endpoint, along with endoscopic changes and patient symptoms.
Blackstone Financing and Outlook
Henderson said the Blackstone collaboration provides Apogee with funding flexibility and a potential path to commercialization and profitability. In response to an analyst question, he said the structure was intended to preserve strategic optionality while reducing reliance on equity markets.
Looking ahead, Henderson said Apogee expects multiple catalysts through 2028, including additional data in atopic dermatitis and eosinophilic esophagitis next year. He said the company is also advancing combination programs and expects to share more details later this year.
About Apogee Therapeutics (NASDAQ:APGE)
Apogee Therapeutics, Inc is a clinical-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics that selectively target the nuclear receptor ROR?t, a master regulator of T cell-driven inflammatory pathways. By modulating ROR?t activity, Apogee aims to offer an oral treatment option for patients with autoimmune and inflammatory skin disorders.
The company’s lead candidate, APG-157, is an oral ROR?t inverse agonist currently undergoing early-stage clinical evaluation for moderate to severe plaque psoriasis.
