Jeune Aesthetics, a wholly-owned subsidiary of Krystal Biotech (NASDAQ: KRYS), announced positive results from its PEARL-2 Phase 1 study of KB304, a novel gene therapy for treating moderate to severe décolleté wrinkles. The randomized, double-blind, placebo-controlled trial demonstrated unprecedented efficacy rates, with 100% of patients showing investigator-assessed improvement at all measured time points.
Breakthrough Efficacy Results
The PEARL-2 study enrolled 19 subjects, with 12 randomized to KB304 and seven to placebo. Following one subject dropout, 18 participants completed the three-month assessment period. The results showed remarkable consistency in treatment response, with investigators reporting at least one-point improvement on the Global Aesthetic Improvement Scale (GAIS) in 100% of KB304-treated patients at one, two, and three months post-treatment, compared to just 28.6% of placebo patients at the three-month mark.
Patient-reported outcomes were similarly impressive, with 72.7% of KB304 recipients showing at least one-point GAIS improvement at three months versus 14.3% in the placebo group. The Subject Satisfaction Questionnaire revealed that 81.8% of KB304-treated patients reported improved satisfaction with their wrinkles' appearance at three months, compared to 14.3% receiving placebo.
Comprehensive Skin Improvement
Beyond wrinkle reduction, KB304 demonstrated broad aesthetic benefits across multiple skin attributes. Investigators reported 100% of treated subjects showed improvement in elasticity, crepiness, hydration, and radiance at all assessment points throughout the three-month follow-up period.
"We are very excited to share today's data update. We are pleased that both the investigator and subjects reported high rates of improvements across a variety of skin attributes when treated with KB304," said Marc Forth, Chief Executive Officer of Jeune. "We believe that KB304 has the potential to revolutionize the treatment of wrinkles and skin quality by directly addressing the underlying biology of aging skin."
Novel Gene Delivery Mechanism
KB304 employs Krystal's replication-defective, non-integrating HSV-1-based vector system to deliver genetic material directly to skin cells. The therapy carries two copies of the COL3 gene encoding type III collagen and one copy of the elastin gene, enabling the body's own cells to produce these essential structural proteins naturally.
"This study is the first randomized, double-blind, placebo-controlled trial to investigate the potential combinatorial benefits of COL3 and elastin supplementation when produced by the body's own skin cells," explained Suma Krishnan, President of Research & Development at Krystal Biotech.
Addressing Unmet Medical Need
The décolleté represents a significant gap in aesthetic medicine, with no FDA-approved injectable treatments currently available for this anatomical area. Forth emphasized this market opportunity, noting that KB304 would be "the first product candidate to directly address elastin and by doing so in the décolleté where there are no injectable products approved."
Safety Profile and Development Timeline
The safety profile remained consistent with previous clinical experience from KB301 studies. Adverse events were characterized as mild-to-moderate, occurring primarily after the first dose and substantially decreasing with subsequent treatments. No severe or drug-related serious adverse events were reported throughout the study period.
Jeune has completed development and validation of a décolleté-specific photonumeric scale (JDWS) and plans to submit this assessment tool to the FDA. The company intends to align on Phase 2 study protocols in the second half of 2025, with the goal of initiating Phase 2 trials in the first half of 2026.
"On the basis of the strong results and broad improvements across multiple skin aesthetic attributes, we will be progressing KB304 into Phase 2 development for the treatment of wrinkles in the décolleté," Krishnan stated. "We plan to prioritize the development of KB304 and will be meeting with the FDA in the coming months to enable initiation of the Phase 2 study."
