Avalo Therapeutics CEO Teases Q2 Top-Line Data for AVTX-009 Phase 2b HS LOTUS Trial at Conference
by Doug Wharley · The Cerbat GemAvalo Therapeutics (NASDAQ:AVTX) CEO Garry Neil said the company expects to report top-line data in the second quarter from its completed Phase 2b LOTUS trial of AVTX-009 in hidradenitis suppurativa (HS), outlining what he described as operational execution milestones in 2025 and the rationale for targeting interleukin-1 beta (IL-1β) in the disease.
Company focus and near-term catalyst
Speaking at the Leerink Partners Global Healthcare Conference, Neil described Avalo as a small immunology and inflammation company based outside Philadelphia with a single lead program, AVTX-009. He said LOTUS, the company’s Phase 2b study in HS, has completed enrollment and follow-up, with the last patient enrolled by the end of October. Data are expected in the second quarter, which he characterized as an upcoming near-term event.
Neil said the trial was initiated at the end of 2024 and that a key 2025 highlight was rapid execution, including enrollment and an increase in planned sample size to support subgroup analyses.
Mechanistic rationale: IL-1β “in the middle” of HS inflammation
Neil positioned IL-1β as a central cytokine in HS, describing HS as a neutrophilic dermatosis in which neutrophils play a “central role.” He said IL-1β is important for attracting neutrophils into lesions and stimulating them to release enzymes that damage tissue, and that it is upstream of both tumor necrosis factor alpha (TNF-α) and IL-17. He referenced existing marketed agents that target those pathways, including HUMIRA (TNF-α) and COSENTYX and BIMZELX (IL-17).
He also described the disease process, stating that HS lesions originate in hair follicles, can progress to abscesses and deeper lesions such as tunnels and fistulas, and can be painful, disfiguring, and socially isolating.
Differentiation versus AbbVie’s lutikizumab and the IL-1α question
Neil contrasted AVTX-009 with AbbVie’s lutikizumab program in HS. He said lutikizumab is an antibody targeting IL-1β and IL-1α (a bispecific), and that AbbVie had reported strong Phase 2 data in a difficult population that included patients who were TNF-α failures, with a large share at Hurley stage 3. He cited HiSCR75 responses around 45% on drug versus placebo in that dataset and said AbbVie has advanced lutikizumab into Phase 3, with data expected toward the end of the year.
Neil argued that Avalo’s “pure anti-IL-1β” approach could offer advantages versus a bispecific strategy. He said AVTX-009 is not “sidetracked” by binding IL-1α and, as a non-bispecific antibody, could have a longer half-life, better bioavailability, and a lower risk of anti-drug antibodies. He also said AVTX-009 has higher affinity for IL-1β than lutikizumab and suggested that affinity could drive therapeutic benefit and enable a more patient-friendly dosing regimen, such as once every four weeks rather than weekly induction dosing.
On IL-1α specifically, Neil described IL-1α as constitutively expressed on normal epithelial cells and functioning as an “alarmin” involved in signaling damage and supporting repair. He said IL-1α does not appear to be meaningfully increased in HS lesions, in contrast to IL-1β, which he said can be elevated by more than 100-fold in lesions. He also referenced a prior Phase 2 HS study of a pure anti-IL-1α antibody (bermekimab) that he said did not show activity, and he suggested that targeting IL-1α could divert drug toward normal epithelial tissues rather than lesions.
LOTUS trial design and efforts to reduce placebo variability
Neil said LOTUS enrolled more than 250 patients, making it “one of the largest” HS trials to date. He said the study was originally planned for 180 patients, increased to 222 to support subgroup analyses due to enrollment of patients with prior exposure to TNF and IL-17 therapies, and ultimately exceeded 250 when additional screening patients were allowed to enroll.
Key elements of the LOTUS design described by Neil included:
- Randomization: 1:1:1 to two active arms and placebo
- Doses: 300 mg every four weeks and 150 mg every two weeks
- Loading doses: used in both active arms to reach therapeutic levels early
- Duration: 16-week endpoint with 6-week safety follow-up
- No long-term extension: no long-term safety extension included
The primary endpoint is HiSCR75, which Neil said was selected to maximize signal-to-noise and limit placebo effects. He described typical placebo rates at HiSCR75 as generally in the 13% to 18% range, with some exceptions. He added that Avalo will also assess HiSCR50, HiSCR90, and HiSCR100, as well as IHS4, quality-of-life measures, and skin pain scores.
Neil highlighted operational steps intended to reduce variability, including use of Parexel as the CRO (which he said had experience in HS studies), selection of board-certified dermatologists with HS trial experience, and investigator training focused on the primary endpoint. He also described monitoring practices, use of scribes during examinations, and efforts to ensure the same investigator performed key assessments at baseline and endpoint visits.
Safety expectations and patient mix
On safety, Neil said IL-1β inhibitors should be viewed as anti-inflammatory rather than broadly immunosuppressive, and he said he would not expect opportunistic infections, viral reactivation, fungal infections, or cancer risk typical of immunosuppressants. He discussed the possibility of neutropenia, describing it as typically grade 1 or 2 and generally not associated with neutropenic infections in the IL-1β inhibitor experience. He also said there may be an increased risk of bacterial infections, but characterized them as usually mild and treatable with antibiotics.
Neil also pointed to observations from prior IL-1β inhibitor work that he said could influence physician perceptions, including reductions in hemoglobin A1C seen when the drug was studied in type 2 diabetes, and cardiovascular outcomes and cancer observations from the large CANTOS study. He emphasized these points as part of the broader safety perception rather than label claims.
Regarding LOTUS enrollment, Neil said Avalo expects roughly one-third of patients to be biologic-experienced, including TNF failures and IL-17-experienced patients. He said the company expects IL-1β targeting to be effective in both biologic-experienced and biologic-naïve groups, citing what he described as similar outcomes in such subgroups in other programs.
Looking beyond HS, Neil said Avalo has evaluated potential additional indications but has intentionally kept focus on HS ahead of the imminent LOTUS readout. He said the company plans to discuss what comes next after releasing the Phase 2b data, noting interest in diseases across gastroenterology, dermatology, and rheumatology where IL-1β is a validated mechanism with clinical proof of concept.
About Avalo Therapeutics (NASDAQ:AVTX)
Avalo Therapeutics is a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for cardiometabolic, fibrotic and inflammatory diseases. The company’s proprietary drug-design platform enables the creation of long-acting prodrugs with optimized pharmacokinetic profiles, aiming to improve efficacy, safety and patient adherence. By leveraging this technology, Avalo seeks to address key drivers of disease progression that remain underserved by existing treatments.
Its lead programs include AVTX-002, a first-in-class prodrug candidate designed to inhibit angiotensinogen for the treatment of hypertension and related cardiovascular disorders, and AVTX-006, an early-stage candidate targeting pathways implicated in fibrosis and metabolic dysfunction.