After Positive Phase 1 Results, Apogee to Test Twice-Yearly Dosing of Atopic Dermatitis Drug Candidate

Apogee Therapeutics announced positive interim phase 1 data from its first-in-human study of APG777, one of its lead product candidates being developed as a frontline treatment for moderate-to-severe atopic dermatitis (AD) and other inflammatory diseases. Pharmacokinetic (PK) data showed a half-life of approximately 75 days across doses tested and pharmacodynamic (PD) data showed deep and sustained inhibition of key AD biomarkers pSTAT6 and TARC for ~3 months (longest follow-up available, with inhibition still ongoing at time of the data cut), according to a company news release.

Results from the trial exceeded the company’s trial objectives and support the potential for APG777, a novel anti-IL-13 antibody, to optimize exposure levels in 16-week induction and be dosed once every 3 or 6 months in maintenance. These findings represent the potential for improved clinical responses from greater exposures in induction and significantly less frequent dosing in maintenance compared to currently approved biologic therapies, which are dosed at every 2 to 4 weeks, a potential major advancement for patients with AD and other inflammatory diseases.

APG777, in single doses up to 1,200mg and multiple doses of 300mg, was well tolerated and showed a favorable safety profile, in line with the existing body of third-party evidence for the safety of the anti-IL-13 class. Based on these data, the company said it plans to initiate a randomized, placebo-controlled, phase 2 clinical trial in patients with moderate-to-severe AD in the first half of 2024 ahead of schedule.

“The positive PK, PD and safety findings from our phase 1 trial mark the first clinical data ahead of schedule from our portfolio of potentially differentiated biologics and underscore the promising potential of APG777 to offer patients a transformational therapy that could drive improved clinical responses than the current standard of care and extend dosing to every 3 or 6 months,” Michael Henderson, MD, Chief Executive Officer of Apogee, said in a company news release. “We are excited to embark on the next phase of development for APG777, with plans to initiate our phase 2 clinical trial in the first half of this year while rapidly progressing the rest of our pipeline forward. At Apogee, we refuse to stop at good enough and are dedicated to advancing innovative solutions for patients. Today’s announcement brings us an important step closer to achieving this goal."

APG777 is a novel, subcutaneous extended half-life monoclonal antibody targeting IL-13 – a critical cytokine in inflammation and a primary driver of AD.

Phase 2 trial in AD

Following today’s positive interim results, Apogee plans to advance APG777 into a randomized, placebo-controlled, 16-week phase 2 clinical trial in patients with moderate-to-severe AD.

• Phase 2 AD trial is expected to initiate in the 1H of 2024 with 16-week topline data from Part A expected in 2H 2025
  • Part A is expected to enroll approximately 110 patients randomized 2:1 to APG777 vs placebo with primary endpoint of mean percentage changes in EASI score from baseline to Week 16
  • Part B of the phase 2 trial is a randomized, placebo-controlled dose optimization with approximately 360 patients randomized 1:1:1:1 to high, medium, or low dose APG777 vs placebo with primary endpoint of mean percentage changes in EASI score from baseline to Week 16
  • All patients benefiting from treatment will continue to APG777 maintenance, which will evaluate 3- to 6-month dosing

• Integrated design expected to provide for significant timeline acceleration by combining Ph2a and Ph2b elements into a single study protocol
  • All Part A sites are also expected to participate in Part B, avoiding delays for site startup between the two parts
• Doses in the Phase 2 trial are enabled by APG777’s potentially best-in-class PK profile, extended half-life, and high-concentration formulation
  • 180 mg/mL formulation enables 44% higher dose of APG777 vs lebrikizumab in the same volume

• APG777 phase 2 induction regimen is designed to exceed lebrikizumab (an IL-13 inhibitor with an overlapping epitope with APG777) exposures by ~30 to 40% with potential for improved clinical responses and maintenance regimen is designed to equal lebrikizumab’s exposures
  • In phase 3 studies, ~30% higher exposure seen in lebrikizumab low bodyweight group resulted in numerically higher efficacy than the overall study population across all key endpoints, including EASI-75 and more stringent endpoints such as EASI-90 and IGA 0/1
  • ~30-40% higher induction exposures for APG777 than lebrikizumab are based on a planned six injection induction regimen given in the first 16 weeks of APG777 treatment. This is approximately half as many of the 11 injections of lebrikizumab given during the same period
  • At 52 weeks, exposures of APG777 dosed every 3 months are designed to exceed those of lebrikizumab and exposures of APG777 dosed every 6 months are designed to equal those of lebrikizumab