AVR-001 Oral IL-23 Gamble: Unproven Delivery Meets Entrenched Injectable Champions

Avere Therapeutics Secures Funding, Advances Oral Psoriasis Drug

Avere Therapeutics, a privately held immunology drug developer, is set to go public through a reverse merger with NextCure, announcing a transaction that will also add $320 million in new funding via a sale of shares and convertible notes led by Fairmount and Hansoh Pharma. This strategic move will enable Avere to advance AVR-001, an experimental long-acting oral psoriasis pill licensed from Hansoh. The company aims for AVR-001 to be a once-weekly oral IL-23 therapy, positioning it to compete with existing and emerging treatments like AbbVie's Skyrizi and Johnson & Johnson's Icotyde. The secured funding is expected to support the completion of Phase 2 testing and the initiation of a global Phase 3 trial for AVR-001.

• Avere Therapeutics is undergoing a reverse merger with NextCure, a strategic transaction that will take the company public and inject $320 million in new capital. This funding, secured through a combination of share sales and convertible notes led by Fairmount and Hansoh Pharma, is crucial for advancing Avere's lead asset, AVR-001, through its next development stages and establishing its market presence.
• The primary focus of Avere's strategy is the development of AVR-001, a long-acting oral drug for psoriasis. This experimental therapy, licensed from Hansoh, is designed to be a once-weekly IL-23 inhibitor, offering a potentially more convenient dosing regimen compared to daily oral competitors like J&J's Icotyde and injectable biologics such as Skyrizi, aiming for best-in-class convenience and competitive efficacy.
• Avere plans to utilize the new funding to complete its ongoing Phase 2b trial for AVR-001 in the U.S., which is expected to commence in 2027, following Hansoh's initiated Phase 2b trial in Chinese patients. The capital also provides a financial runway to initiate a global Phase 3 trial for psoriasis and begin a Phase 2b trial for ulcerative colitis, indicating a broader development pipeline for the IL-23 inhibitor.

Navigating the Evolving Psoriasis Treatment Landscape

Over the past five years, the psoriasis treatment landscape has been reshaped by the emergence and real-world validation of highly targeted biologic agents, particularly IL-17 and IL-23 inhibitors. Bimekizumab, the first monoclonal antibody to dually inhibit both IL-17A and IL-17F, has demonstrated rapid and superior efficacy compared to secukinumab, ustekinumab, and adalimumab in phase II/III trials, with 28.4% of patients achieving PASI 100 as early as week 4 in real-world studies. IL-23 inhibitors have similarly matured: risankizumab showed a mean PASI reduction from 25.49 at baseline to 0.358 by week 52 in registry data, while tildrakizumab achieved PASI75 in over 94% of patients at week 104 in a multicenter Italian study. Guselkumab produced a 94.9% mean PASI improvement at week 48 even in patients with skin of color. Beyond biologics, tapinarof cream 1% demonstrated statistically significant PASI75 responses versus vehicle in Japanese trials, and small molecule inhibitors — including RORγt and ROCK2 inhibitors — have further broadened the therapeutic armamentarium. Biosimilars for adalimumab and etanercept have also demonstrated comparable effectiveness and safety profiles in both pediatric and elderly populations over 72-week follow-up periods.

Long-term real-world data have added critical nuance to the understanding of treatment durability and sequencing. Ixekizumab maintained a drug survival rate of 65.5% at 260 weeks, with PASI ≤3 achieved in 95.5% of observed patients at that timepoint; being a super-responder at week 16 was independently associated with reduced risk of discontinuation. BADBIR registry data spanning 2007–2024 confirm a secular shift in prescribing patterns, with adalimumab remaining the most frequently used first-line biologic (35%) in the later period, followed by ustekinumab (24%) and secukinumab (17%), while patients entering treatment in the 2015–2024 period presented with less severe disease and fewer comorbidities than those in earlier cohorts. Importantly, 55% of biologic-treated patients ultimately required a switch to a second-line agent, underscoring the ongoing challenge of secondary treatment failure. In multi-failure patient populations, bimekizumab demonstrated 12-month drug survival of 85.4% with no discontinuations due to lack of efficacy, suggesting utility in heavily pretreated patients. Brodalumab also showed meaningful rescue responses following IL-17A inhibitor failure, with 70% of patients achieving PASI75 and/or PASI ≤2 at week 12.

Beyond efficacy metrics, the field is increasingly focused on access disparities, special populations, and treatment personalization. In the United States, advanced therapy utilization remained below 17% across all states between 2015 and 2019, with rural patients facing profound access barriers — 75% sought care outside their local area, and dermatologist access ratios were markedly lower than those for internal medicine or family practice physicians. In elderly patients (≥65 years), real-world evidence from Czech, Turkish, and Polish cohorts confirms generally comparable biologic efficacy to younger adults, though drug survival was lower — particularly with adalimumab — and comorbidity burden, including latent tuberculosis and anti-HBc positivity, was substantially higher. A newly characterized "flip-flop phenomenon," identified across 17 centers in six countries, highlights the immunological complexity of biologic therapy: 68.2% of affected patients developed eczematous features while being treated for psoriasis under IL-17 or IL-23 inhibitors, while 31.8% developed psoriasiform disease during type 2 inflammation biologics, predominantly dupilumab. JAK inhibitors have emerged as the most frequently employed strategy for managing these phenotypic switches in both directions, reflecting a growing recognition that precision immunological profiling will be essential to optimizing outcomes in this evolving landscape.