Akebia Therapeutics (NASDAQ:AKBA) used its R&D Day presentation to outline a strategy centered on expanding its commercial anemia franchise while advancing three kidney disease pipeline programs: praliciguat in focal segmental glomerulosclerosis (FSGS), the tissue-targeted complement inhibitor AKB-097 (abribafisp) in complement-mediated kidney diseases, and AKB-9090 in cardiac surgery-associated acute kidney injury (CSA-AKI).
Commercial backdrop: Vafseo growth and evidence-building
President and CEO John Butler said the company is pursuing three “imperatives,” led by an effort to “drive Vafseo to become the standard of care for patients on dialysis treating their anemia.” Butler characterized Vafseo (vadadustat) as “the revenue engine that drives our ability to invest in our pipeline,” while noting that prior revenue from Auryxia is expected to decline due to generic competition.
Operationally, Butler highlighted increased patient access and adherence improvements. He said the number of patients with prescribing access to Vafseo rose from about 40,000 a year ago to about 290,000 today. He also pointed to improved adherence in dialysis centers that moved from daily dosing to observed dosing three times weekly, with first-fill adherence increasing from “70%-75% to about 87% today.”
On clinical evidence, Butler said Akebia conducted a “win statistics analysis” from INNO2VATE showing that patients treated with Vafseo versus darbepoetin had a lower risk of death or hospitalization, and said the analysis is pending publication in the Journal of the American Society of Nephrology. He also outlined additional planned data generation through the VOCAL trial with DaVita, expected by the end of 2026, and the VOICE trial, expected in early 2027.
Praliciguat in FSGS: rationale, preclinical work, and Phase 2 design
External nephrologist Dr. James Tumlin (Emory University School of Medicine) provided an overview of FSGS, emphasizing that it is “purely a descriptive term” encompassing many underlying causes and that prevalence has increased over time. He presented historical and registry data underscoring that lowering proteinuria is associated with better long-term renal outcomes, including partial remissions.
Tumlin described praliciguat as a nitric oxide-dependent soluble guanylate cyclase (sGC) stimulator that increases cyclic GMP signaling downstream, which he said is relevant to podocyte function and fibrotic pathways in kidney disease. He reviewed preclinical data suggesting praliciguat reduced features of TGF-β–driven glomerulosclerosis and fibrosis in models discussed during the presentation, including effects on proteinuria and tissue injury markers.
Chief Medical Officer Dr. Stephen Burke said Akebia reviewed the nonclinical package it acquired from Cyclerion and added two additional studies before selecting FSGS as a development target: an Adriamycin mouse model and a 5/6 nephrectomy rat model. In both, Burke said praliciguat showed the strongest effect when combined with enalapril, an ACE inhibitor. In the Adriamycin model, he said praliciguat alone did not reduce proteinuria, but the combination with enalapril produced a reduction greater than enalapril alone, alongside improvements in glomerulosclerosis and tubulointerstitial fibrosis/degeneration. In the 5/6 nephrectomy model, Burke said the combination reduced proteinuria, lowered serum creatinine versus vehicle, and decreased glomerulosclerosis.
Burke also revisited Cyclerion’s Phase 2 diabetic nephropathy study, describing a reanalysis of 156 subjects randomized to placebo or praliciguat 20 mg or 40 mg for 12 weeks. He said urine albumin-to-creatinine ratio (UACR) decreased by approximately 20%–25% with praliciguat. He also described a modified intent-to-treat analysis (excluding one site where subjects had “negligible blood levels”) and noted that the proportion of subjects achieving UACR <0.5 increased from 34.8% on placebo to 51.2% on praliciguat, an absolute increase of 16.4% and a relative risk of 1.47.
Burke said Akebia initiated a Phase 2 randomized, double-blind, placebo-controlled, dose titration study in adults with biopsy-confirmed FSGS. The trial plans to enroll up to 60 subjects for 24 weeks, with placebo patients crossing over to praliciguat afterward. Primary efficacy measures include change in urine protein-to-creatinine ratio (UPCR) and the percentage of patients achieving partial remission, with additional analyses at UPCR cut points including 0.7 g/g.
AKB-097 (abribafisp): tissue-targeted complement inhibition and a 2026-start basket approach
Akebia’s second program, AKB-097—recently assigned the generic name abribafisp—was in-licensed from Q32 Bio, Butler said. The company expects to initiate an open-label Phase 2 rare kidney disease basket trial in IgA nephropathy, lupus nephritis, and C3 glomerulopathy (C3G) in the second half of 2026, according to the presentation.
Dr. Michael Holers (University of Colorado) described AKB-097 as a “novel tissue-targeted complement inhibitor” designed to bind C3d at sites of complement activation and deliver factor H activity to inhibit convertases locally. Holers argued that a key aim is to separate local efficacy from systemic complement inhibition, potentially reducing infection risk associated with deeper systemic pathway blockade.
Holers reviewed preclinical data he said demonstrated durable tissue binding and prolonged suppression of C3 activation at disease sites, including in a C3G model where complement activation decreased for up to 14 days. In a rat membranous nephropathy model, he described reduced proteinuria alongside what he characterized as a dissociation between local complement inhibition and systemic complement activity at effective doses.
Burke then summarized Phase 1 results in healthy volunteers evaluating intravenous and subcutaneous dosing. He said higher IV doses produced systemic alternative pathway inhibition, while subcutaneous dosing produced much lower systemic inhibition. Burke identified a 450 mg once-weekly subcutaneous regimen as the intended Phase 2 basket dose, stating it did not significantly decrease systemic alternative pathway activity in Phase 1 while achieving exposures he said should be sufficient for tissue-level complement inhibition based on preclinical studies. Burke also reported “no serious or severe AEs,” no discontinuations due to adverse events, “no AEs related to immunogenicity,” and “minimal anti-drug antibodies.”
Dr. Jonathan Barratt, a nephrologist and IgA nephropathy trial leader, said the approach could be attractive in conditions where intra-renal complement activation drives injury, particularly because emerging therapies may need to be administered long term. He said tissue-level inhibition without systemic complement suppression could support chronic use and combination with other immunomodulatory therapies by potentially lowering infection risk. As trial readouts, Barratt highlighted monitoring proteinuria, GFR, pharmacokinetics, and urinary soluble C5b-9 as a biomarker of kidney terminal complement pathway activation, with biopsies discussed as a way to demonstrate tissue localization.
AKB-9090: HIF-PHI approach to cardiac surgery-associated AKI
Burke also introduced AKB-9090, which he said is the first product from Akebia’s internal discovery efforts and is being developed initially to prevent or treat CSA-AKI. He described AKB-9090 as a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) intended to stabilize HIF in the kidney and activate multiple adaptive pathways, including those related to cell survival, metabolism, reactive oxygen species reduction, and inflammation.
In preclinical rat ischemia-reperfusion experiments, Burke said AKB-9090 given at the start of surgery reduced the rise in serum creatinine and improved kidney histology, including reductions in tubular epithelial and vascular damage, in certain IV dosing regimens. He said a Phase 1 study has initiated in New Zealand, with Akebia expecting Phase 1 data before the end of 2026. A planned Phase 2 study would enroll higher-risk elective cardiac surgery patients requiring cardiopulmonary bypass and assess AKI incidence, duration, and severity, along with additional biomarkers.
In Q&A, Burke contrasted AKB-9090 with vadadustat, saying vadadustat is taken up by organic anion transporters and primarily acts in the liver, while AKB-9090 is “not acted upon by the OATs,” enabling higher kidney tissue penetration and target engagement.
Upcoming milestones highlighted by management
In closing remarks, Butler pointed to a series of planned catalysts, including continued execution on Vafseo, the ongoing Phase 2 praliciguat study (initiated in December), initiation of the AKB-097 basket trial in the second half of 2026, and near-term first-in-human dosing for AKB-9090.
- Praliciguat: Phase 2 in FSGS underway; endpoints include UPCR change and partial remission rates.
- AKB-097 (abribafisp): Open-label Phase 2 basket trial planned in IgA nephropathy, lupus nephritis, and C3G in 2H 2026.
- AKB-9090: Phase 1 initiated; Akebia expects Phase 1 data before the end of 2026.
- Vafseo evidence: Butler cited pending JASN publication for the INNO2VATE win-statistics analysis, and future readouts from the VOCAL and VOICE trials in 2026 and 2027, respectively.
About Akebia Therapeutics (NASDAQ:AKBA)
Akebia Therapeutics, Inc, a clinical-stage biopharmaceutical company headquartered in Cambridge, Massachusetts, is focused on the development and commercialization of therapies for patients with kidney disease. The company’s lead product candidate, vadadustat, is an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor designed to treat anemia associated with chronic kidney disease in both dialysis-dependent and non-dialysis patients. Akebia’s research and development efforts also extend to preclinical programs targeting nephrology and related metabolic disorders.
Since its founding in 2007, Akebia has pursued strategic collaborations to advance its clinical pipeline and expand its market reach.
