Apogee Therapeutics, Inc’s APG990 exceeded trial objectives and demonstrated an approximately 60-day half-life in interim Phase 1 results from its first-in-human trial.
APG990 is a novel, subcutaneous (SQ), half-life-extended monoclonal antibody (mAb) that targets OX40L, which is positioned further upstream in the inflammatory pathway than interleukin (IL)-13.
APG990 interim Phase 1 pharmacokinetic (PK) data showed a half-life of approximately 60 days across doses tested. These PK data support the possibility of every three- and six-month maintenance dosing of APG990 with as little as 50mg, which when considered with APG279 (the anti-IL-13 APG777 + APG990) coformulation data, provides the potential for dosing the combination two to four times per year with a single 2mL co-formulated injection.
The combination also offers the potential for improved clinical outcomes by addressing the heterogeneity of atopic dermatitis (AD) given preclinical data demonstrating deep Type 2 inhibition from the APG777 and broad Type 1-3 inhibition from APG990.
Based on these results, the Company plans on submitting an Investigational New Drug application or foreign equivalent for APG279. Following clearance, it plans to initiate a Phase 1b clinical trial in moderate-to-severe AD of APG279 against dupilumab (Dupixent, Sanofi and Regeneron) in 2025, with data expected in the second half of 2026.
“We’re pleased to report findings from our third clinical program today, APG990, which demonstrated extended PK and a favorable tolerability profile, supporting its potential as a first-in-class combination with APG777 for the treatment of AD and other inflammatory diseases that could address multiple inflammation pathways,” says Michael Henderson, M.D., Chief Executive Officer of Apogee, in a news release. “The interim results as well as the supportive preclinical combination toxicology studies are an important step forward in our combination plans for the program, suggesting strong potential for compatibility with APG777 and supporting our planned APG777 and APG990 co-formulated combination approach, which we have named APG279. With the potential to broadly inhibit Type 1, Type 2 and Type 3 inflammation, APG279 could offer patients a more effective treatment option, while minimizing side effects seen with other available therapies. Based on these findings, we plan to initiate a head-to-head Phase 1b trial of the combination against DUPIXENT this year.”
The APG990 Phase 1 clinical trial is a double-blind, placebo-controlled, first-in-human, single-ascending dose trial evaluating the safety, tolerability, and PK of APG990 in 40 healthy adult participants. Key results include:
- APG990 demonstrated a potential best-in-class PK profile, including a half-life of approximately 60 days, supporting the potential for every three- and six-month maintenance dosing.
- PK profile supports the potential for a single 2mL co-formulated injection of APG279 (APG777 + APG990) administered every three- and six- months.
- APG990 was well tolerated across all five cohorts, with doses up to 1,200mg.
- The most common (≥10%) treatment-emergent adverse events (TEAEs) were headache.
- Fully 53% of participants observed at least one TEAE.
- There were no Grade 3 TEAEs related to study drug or severe adverse events. No adverse events led to study discontinuation.
- There have been no cases of pyrexia or chills.
- The most common (≥10%) treatment-emergent adverse events (TEAEs) were headache.
In addition, preclinical studies of the combination of APG777 and APG990 showed potential for enhanced pharmacologic responses relative to individual agents, and exhibited no safety findings at any dose level, including the highest dose tested of 150mg/kg per agent in a 3-month combination toxicology study.
“With good tolerability at doses up to 1,200mg and a half-life of approximately 60 days, APG990 demonstrated the potential for quarterly or less frequent dosing and was supportive of it as a combination partner with APG777,” adds Carl Dambkowski, MD, Chief Medical Officer of Apogee. “Looking ahead to our planned combination approach, we continue to believe that APG990’s broad inhibition across Type 1, 2, and 3 inflammation, coupled with APG777’s deep and sustained inhibition of Type 2 inflammation, could potentially result in a safe and effective treatment option for people living with atopic dermatitis and other inflammatory diseases.
