SCYNEXIS (NASDAQ:SCYX) outlined a new corporate strategy focused on autosomal dominant polycystic kidney disease (ADPKD) following what CEO Dr. David Angulo described as a “transformative asset acquisition” of SCY-770 (previously PXL-770) and the completion of a financing intended to support development activities into mid-2029.
Strategic shift centers on SCY-770 for ADPKD
Angulo said the company’s strategic review began more than a year ago as SCYNEXIS looked to expand beyond its antifungal portfolio by leveraging its development capabilities in severe and rare diseases with high unmet need. That process led it to SCY-770, an oral, direct AMPK activator the company plans to advance into a Phase 2 ADPKD study.
SCYNEXIS acquired global rights and will control development activities, with Angulo saying the company structured the transaction to limit near-term cash outlay and focus resources on accelerating clinical development.
Scientific rationale: AMPK activation and preclinical data
Jeremy Duffield, a nephrologist and physician scientist presented as SCYNEXIS’ chief scientific officer during the call, reviewed the disease landscape and the rationale for targeting AMPK. Duffield described ADPKD as a genetic disorder driven by PKD1 or PKD2 mutations that leads to progressive cyst-filled kidney enlargement and declining kidney function, with up to 50% of patients progressing to end-stage renal disease by age 60.
Duffield said reduced AMPK activity is associated with polycystin loss, contributing to metabolic dysregulation that accelerates cyst growth, fluid secretion, inflammation, and fibrosis. He described SCY-770 as a “potent direct allosteric activator of AMPK” that acts on the beta subunit and “predominantly binds” to AMPK versions found in the kidney, which he said could provide efficacy and safety advantages.
Duffield also highlighted preclinical results in a PKD1-deletion mouse model, stating SCY-770 produced a survival benefit with “90% of treated mice surviving at the point when 50% of untreated controls had died.” He added that renal function improved based on blood urea levels, and kidney weight was reduced by about 35%, which he said reflected suppression of cyst burden.
Clinical plan: Phase 1 dose support, Phase 2 early readout, and regulatory pathway
Management said it plans to open an IND for ADPKD and conduct an additional small Phase 1 study with three arms and approximately 24 participants to confirm food effect and steady-state exposures for selected doses to support Phase 2 dose selection.
The planned Phase 2 study will enroll ADPKD patients at risk of rapid disease progression, described as Mayo categories 1C, 1D, and 1E. The company expects to evaluate two doses initially, with a plan to roll participants into one dose after 16 weeks of therapy. Angulo said the company anticipates an early efficacy analysis at 16 weeks, based on prior ADPKD studies suggesting kidney volume changes can be measurable in 12 to 16 weeks.
SCYNEXIS emphasized two key endpoints for ADPKD development: total kidney volume (TKV) and glomerular filtration rate (GFR). The company said the FDA has endorsed TKV as a surrogate endpoint suitable for accelerated approval, with a subsequent pathway toward full approval based on GFR outcomes. Angulo said the Phase 2 study is expected to begin by the end of 2026, with an early efficacy readout in the second half of 2027 and study completion in 2028. He also stated that “only one phase III study is required” in the intended development plan.
Commercial and market backdrop
Rosana Ferrara-Pontoriero, vice president of business development, characterized ADPKD as a “large orphan indication” with a prevalence of 140,000 diagnosed cases in the U.S. She said the broader addressable population could be about 500,000 cases including diagnosed and undiagnosed, citing increased diagnosis driven by imaging and genetic testing.
Ferrara-Pontoriero pointed to the economic burden of disease, citing a U.S. study estimating ADPKD’s incremental annual cost to the healthcare system at $7 billion to $9 billion. She also discussed patient quality-of-life impacts and said most patients ultimately progress to end-stage renal disease requiring dialysis or transplant.
The company contrasted its opportunity with Jynarque (tolvaptan), which it described as the only FDA-approved ADPKD therapy. Ferrara-Pontoriero said U.S. annual sales peaked at $1.5 billion in 2024 despite “relatively low real-world uptake” around 10%, attributing limited penetration to safety and tolerability constraints. She referenced hepatotoxicity concerns including a black box warning and monitoring requirements, and said discontinuations are often driven by polyuria, with patients producing “6-10 liters” of urine per day; Angulo later described this as requiring urination 10 to 20 times daily.
During the Q&A, Angulo said the 140,000 diagnosed patient estimate is “a relatively solid number” because ADPKD is genetic and patients are typically treated at concentrated centers, though he noted some early-stage patients may be undiagnosed. Duffield added that beyond tolvaptan, current options are supportive care such as antihypertensives (including ACE inhibitors and angiotensin receptor blockers) and management until dialysis or transplant.
Financing, runway, and remaining antifungal programs
CFO Ivor Macleod said the company’s cash position was strengthened by proceeds from a PIPE financing, extending its runway into mid-2029. He said the forecast “excludes” potential milestones and royalties tied to GSK, noting SCYNEXIS could collect “up to approximately $146 million in annual sales milestones plus royalties” following GSK’s relaunch of Brexafemme.
Angulo said SCYNEXIS will continue work on its antifungal portfolio, including completing a Phase 1 study of an intravenous formulation of SCY-247 later in 2026, with an eye toward partnering or non-dilutive funding. He added that other earlier-stage antifungal programs will continue under an NIH-funded program.
On safety considerations for SCY-770, Angulo said the company has more than 270 individuals exposed across multiple Phase 1 studies and a Phase 2 study, and that adverse events observed to date have mainly been mild gastrointestinal effects such as nausea and diarrhea. He also discussed historical concerns about cardiac hypertrophy with other AMPK activators, but said SCY-770’s binding to heart-associated AMPK activators is “extraordinarily high” and that preclinical and clinical data have not shown such risk so far.
About SCYNEXIS (NASDAQ:SCYX)
SCYNEXIS, Inc is a late?stage biopharmaceutical company focused on developing and commercializing novel anti?infective therapies. Headquartered in Jersey City, New Jersey, the company’s primary research and development efforts center on combating invasive and chronic fungal infections, an area of high unmet medical need. SCYNEXIS’s scientific platform is built around its proprietary triterpenoid class of antifungals, which are designed to address resistance and safety limitations associated with existing treatments.
The company’s lead product candidate, ibrexafungerp, represents the first oral glucan synthase inhibitor to reach clinical development.
