Avalo Therapeutics (NASDAQ:AVTX) used a presentation at its 46th Annual Healthcare Conference appearance to outline its strategy for AVTX-009, a high-affinity human monoclonal antibody designed to neutralize interleukin-1 beta (IL-1β), and to discuss how upcoming Phase II data in hidradenitis suppurativa (HS) could position the program in what management described as a rapidly expanding market.
AVTX-009 strategy centered on IL-1β in HS
CEO Garry Neil said the company believes IL-1β sits at the “bullseye” of HS inflammation, characterizing AVTX-009 as a “very high-affinity” antibody with a favorable half-life and dosing regimen. Neil said the aim is to be “best in disease” by sustaining suppression of IL-1β below inflammation-driving levels.
How management framed competing IL-1 approaches
Neil described prior experience with first-generation IL-1 agents as “validating” for IL-1β in HS, while also emphasizing limitations in practicality and potency.
- Anakinra: Neil said anakinra binds the IL-1 receptor and indirectly blocks IL-1β, with efficacy seen in small trials, but he called it impractical due to cost and a short half-life.
- Canakinumab (ILARIS): He said there have not been formal HS studies, but case series and anecdotal use show mixed results, including some dramatic patient responses, which he said supports the IL-1β hypothesis.
- Novartis’ MAS825: Neil described MAS825 as a bispecific targeting IL-1β and IL-18, while stating IL-18 is not prominent in HS and that the program is “mostly about the IL-1β moiety.” He said the patent suggests the construct uses ILARIS complementarity-determining regions (CDRs) and argued that bispecific design could reduce half-life. Based on the dose and schedule discussed (300 mg every four weeks in a 13-week trial), he suggested the IL-1β component would be effectively lower and said he viewed MAS825 data as another positive signal for IL-1β but from a drug he believes is not optimized to suppress IL-1β.
- Sanofi IL1RAP approach: Neil said IL1RAP strategies represent additional validation of IL-1’s importance in HS but described them as more complex and indirect versus directly targeting IL-1β.
The conversation also focused on AbbVie’s lutikizumab, which Neil called the strongest IL-1β data set in HS to date. He pointed to results shown in a severe population that included early Stage 3 patients and individuals who had failed Humira, and later data in bio-naive patients that he said were comparable. Neil noted AbbVie has advanced lutikizumab into Phase III and expects it to be a “player” in HS.
Why Avalo believes AVTX-009 could be differentiated
Neil argued AVTX-009’s potential advantage is driven by binding affinity, half-life, and bioavailability. He stated AVTX-009 is “7x-10x more avid” for IL-1β than lutikizumab and has a longer “off time,” which he said should translate into tighter binding and lower trough IL-1β levels.
He also emphasized a mechanistic reason affinity could matter in HS lesions. Neil described HS lesions as “pus under pressure,” which he said creates a pressure gradient that can repel drug entry, particularly for large molecules like monoclonal antibodies. He said antibody penetration is supported by an “affinity gradient,” where binding to the ligand pulls antibody into the lesion, making higher affinity a potential competitive advantage.
Phase II execution, powering, and timing
Neil spent time detailing efforts to optimize trial conduct. He said Avalo selected Parexel as its CRO based on experience in HS trials and used only board-certified dermatologists as investigators. He also said the company recruited Alexa Kimball as principal investigator and that training was designed with input from academic experts, including a program requiring investigators to pass an exam on the primary endpoint, with monitoring and remediation when needed. He added that patients and physicians were also trained on the placebo effect.
On endpoints, Neil said the company selected HiSCR 75 as the primary measure to improve signal-to-noise, citing historical placebo rates in the 13% to 18% range at that threshold. He said Avalo increased planned enrollment from 180 to 222 to support subpopulation analyses as more biologic-experienced patients enrolled, and ultimately enrolled “something over 250,” which he said left the trial “very adequately powered” under the original assumptions.
Regarding timing, Neil said the company was 17 weeks past announcing full enrollment, with a 16-week clinical period and a six-week safety follow-up. He said investors could “deduce” participants were through the clinical portion and in safety follow-up, with the last patient expected to be out by the end of March, followed by four to eight weeks for database cleaning and analysis.
Safety expectations and plans after Phase II
Neil described IL-1β inhibition as potentially having a differentiated safety profile compared to TNF and IL-17 approaches. He said the company does not expect opportunistic infections, abnormal liver tests, depression/suicidality, or skin rash associated with those classes, while acknowledging IL-1β’s role in innate immunity may lead to some increase in bacterial infections that are typically manageable with antibiotics.
He also discussed neutropenia, saying it can occur because IL-1β affects G-CSF signaling and neutrophil trafficking, but that it is usually low grade and rarely clinically relevant. He cited CANTOS trial figures for severe neutropenic infection (0.3 per 100 patient-years on drug versus 0.2 on placebo) and argued HS patients are generally younger and have high neutrophil counts, making it less concerning.
After Phase II, Neil said Avalo plans to compile its data and request an End-of-Phase II meeting with the FDA. He said the company has begun early CRO outreach and is targeting Phase III enrollment to begin in the early part of 2027.
On commercial opportunity, Neil said Avalo’s analysis suggests the HS market could exceed $10 billion over the next five to six years, citing company-referenced expectations for existing biologics and noting low biologic penetration and diagnosis delays. He also said the company is interested in evaluating AVTX-009 in other IL-1β-validated indications across dermatology, rheumatology, and gastrointestinal disease, referencing external data readouts from AbbVie programs that could serve as catalysts.
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.
