Jeune Announces Positive Results and Significant Aesthetic Improvements from Phase 1 Study of KB304 for Moderate to Severe Wrinkles of the Décolleté
Jeune Aesthetics (NASDAQ: KRYS) announced positive Phase 1 results from the PEARL-2 study evaluating KB304 for treating décolleté wrinkles. The randomized, double-blind, placebo-controlled trial demonstrated significant aesthetic improvements in 19 subjects, with 100% of KB304-treated patients showing improvement at three months according to investigator assessments.
The study showed substantial benefits across multiple skin attributes, including elasticity, crepiness, hydration, and radiance. 81.8% of KB304-treated subjects reported improved satisfaction with wrinkle appearance versus 14.3% for placebo. The safety profile was consistent with prior clinical experience, showing only mild-to-moderate adverse events.
Following these positive results, Jeune plans to advance KB304 to Phase 2 development, targeting initiation in the first half of 2026 after FDA consultation.
Jeune Aesthetics (NASDAQ: KRYS) ha annunciato risultati positivi della Fase 1 dello studio PEARL-2, che ha valutato KB304 per il trattamento delle rughe del décolleté. Lo studio randomizzato, in doppio cieco e controllato con placebo ha mostrato miglioramenti estetici significativi in 19 soggetti, con il 100% dei pazienti trattati con KB304 che ha mostrato miglioramenti a tre mesi secondo le valutazioni degli investigatori.
Lo studio ha evidenziato benefici rilevanti su molteplici caratteristiche della pelle, tra cui elasticità, fragilità, idratazione e luminosità. Il 81,8% dei soggetti trattati con KB304 ha riportato una maggiore soddisfazione riguardo all'aspetto delle rughe rispetto al 14,3% del gruppo placebo. Il profilo di sicurezza è risultato coerente con le esperienze cliniche precedenti, con eventi avversi da lievi a moderati.
In seguito a questi risultati positivi, Jeune intende procedere con lo sviluppo di KB304 in Fase 2, con avvio previsto nella prima metà del 2026 dopo consultazione con la FDA.
Jeune Aesthetics (NASDAQ: KRYS) anunció resultados positivos de la Fase 1 del estudio PEARL-2, que evaluó KB304 para el tratamiento de arrugas en el escote. El ensayo aleatorizado, doble ciego y controlado con placebo demostró mejoras estéticas significativas en 19 sujetos, con un 100% de los pacientes tratados con KB304 mostrando mejoría a los tres meses según las evaluaciones de los investigadores.
El estudio mostró beneficios sustanciales en múltiples atributos de la piel, incluyendo elasticidad, flacidez, hidratación y luminosidad. El 81,8% de los sujetos tratados con KB304 reportaron mayor satisfacción con la apariencia de las arrugas frente al 14,3% del placebo. El perfil de seguridad fue consistente con experiencias clínicas previas, presentando solo eventos adversos leves a moderados.
Tras estos resultados positivos, Jeune planea avanzar con KB304 a la Fase 2, con inicio previsto en la primera mitad de 2026 tras consulta con la FDA.
Jeune Aesthetics (NASDAQ: KRYS)는 데콜테 주름 치료를 위한 KB304의 PEARL-2 1상 시험에서 긍정적인 결과를 발표했습니다. 무작위 배정, 이중 맹검, 위약 대조 시험에서 19명의 대상자에게서 유의미한 미용 개선이 나타났으며, 조사자 평가에 따르면 KB304를 투여받은 환자 전원(100%)이 3개월 후 개선을 보였습니다.
본 연구는 탄력성, 주름, 수분 공급, 광채 등 여러 피부 특성에서 상당한 개선 효과를 입증했습니다. KB304 투여 대상자의 81.8%가 주름 외관에 대한 만족도가 향상되었다고 보고한 반면, 위약군은 14.3%에 그쳤습니다. 안전성 프로필은 이전 임상 경험과 일치하며, 경증에서 중등도의 부작용만 나타났습니다.
이러한 긍정적 결과를 바탕으로 Jeune는 FDA와 협의 후 2026년 상반기를 목표로 KB304의 2상 개발을 진행할 계획입니다.
Jeune Aesthetics (NASDAQ : KRYS) a annoncé des résultats positifs de la Phase 1 de l'étude PEARL-2 évaluant KB304 pour le traitement des rides du décolleté. L'essai randomisé, en double aveugle et contrôlé par placebo a démontré des améliorations esthétiques significatives chez 19 sujets, avec 100 % des patients traités par KB304 montrant une amélioration à trois mois selon les évaluations des investigateurs.
L'étude a montré des bénéfices importants sur plusieurs attributs cutanés, notamment l'élasticité, la fragilité, l'hydratation et l'éclat. 81,8 % des sujets traités par KB304 ont déclaré une satisfaction accrue concernant l'apparence des rides contre 14,3 % pour le placebo. Le profil de sécurité était conforme aux expériences cliniques antérieures, ne montrant que des effets indésirables légers à modérés.
Suite à ces résultats positifs, Jeune prévoit de faire progresser KB304 vers la Phase 2, avec un démarrage prévu dans la première moitié de 2026 après consultation avec la FDA.
Jeune Aesthetics (NASDAQ: KRYS) gab positive Phase-1-Ergebnisse der PEARL-2-Studie bekannt, in der KB304 zur Behandlung von Dekolleté-Falten untersucht wurde. Die randomisierte, doppelblinde, placebokontrollierte Studie zeigte signifikante ästhetische Verbesserungen bei 19 Probanden, wobei 100 % der mit KB304 behandelten Patienten nach drei Monaten laut Untersucherbewertungen eine Verbesserung zeigten.
Die Studie zeigte erhebliche Vorteile bei mehreren Hautmerkmalen, darunter Elastizität, Fältchenbildung, Feuchtigkeitsgehalt und Ausstrahlung. 81,8 % der mit KB304 behandelten Probanden berichteten von einer höheren Zufriedenheit mit dem Faltenbild im Vergleich zu 14,3 % der Placebogruppe. Das Sicherheitsprofil entsprach den bisherigen klinischen Erfahrungen mit nur milden bis moderaten Nebenwirkungen.
Aufgrund dieser positiven Ergebnisse plant Jeune, KB304 in die Phase 2 zu bringen, mit einem Start im ersten Halbjahr 2026 nach Rücksprache mit der FDA.
- 100% of KB304-treated subjects showed improvement in wrinkles at 3 months vs 28.6% for placebo
- 81.8% of subjects reported improved wrinkle satisfaction vs 14.3% for placebo
- 100% improvement across multiple skin attributes including elasticity, crepiness, hydration, and radiance
- Safety profile showed only mild-to-moderate adverse events with no severe or serious events reported
- Potential first-in-class treatment for décolleté wrinkles where no FDA-approved injectables exist
- Adverse events were reported, primarily after first dose
- Small sample size with only 19 total subjects in the trial
- One subject dropped out before completing KB304 treatments
Insights
Positive Phase 1 results for Krystal's KB304 décolleté wrinkle treatment show promising efficacy and safety profile, advancing to Phase 2.
Jeune's Phase 1 PEARL-2 study results for KB304 demonstrate a compelling efficacy signal in a first-of-its-kind approach targeting the underlying biology of aging skin. The data revealed 100% investigator-reported improvement in wrinkles at three months post-treatment versus just 28.6% for placebo – a remarkable treatment effect size for an early-stage aesthetic trial. The 72.7% subject-reported improvement further validates real-world perceptible benefits.
What makes KB304 particularly innovative is its dual mechanism targeting both collagen and elastin production. Unlike conventional dermal fillers that provide temporary volume, KB304 leverages Krystal's gene delivery platform to induce the body's own cells to produce these structural proteins, potentially offering more natural and sustainable results.
The technology appears well-tolerated with only mild-to-moderate adverse events that diminished with subsequent doses – a crucial consideration for aesthetic treatments where safety profiles directly impact commercial adoption. The consistent 100% investigator-reported improvements across multiple skin attributes (elasticity, crepiness, hydration, and radiance) points to a comprehensive rejuvenation effect rather than just wrinkle reduction.
While promising, the small sample size (only 11 completed KB304 treatments vs. 7 placebo) warrants caution when interpreting these results. However, the strength of the efficacy signal, combined with the strategic targeting of the décolleté – an area with no FDA-approved injectable treatments – creates a potential first-mover advantage in an unmet aesthetic need. The company's development of a proprietary assessment scale (JDWS) also demonstrates regulatory foresight for the upcoming Phase 2 program expected to begin in H1 2026.
KB304 designed to deliver collagen and elastin to restore skin naturally
Conference call to discuss results scheduled for Thursday, July 24, 2025 at 4:30pm ET
PITTSBURGH, July 24, 2025 (GLOBE NEWSWIRE) -- Jeune Aesthetics, Inc. (“Jeune”), a wholly owned subsidiary of Krystal Biotech, Inc. (“Krystal”) (NASDAQ: KRYS) leveraging Krystal’s clinically validated gene-delivery platform to fundamentally reverse the biology of aging skin, announced today positive safety and efficacy results, including significant improvements in key skin aesthetic attributes such as wrinkles and elasticity, in PEARL-2, a randomized, double-blind, placebo-controlled Phase 1 study evaluating KB304, for the treatment of wrinkles of the décolleté.
Meaningful aesthetic improvements were reported following KB304 treatment with clear and statistically significant advantages over placebo as evaluated by both the investigator and subjects using the Global Aesthetic Improvement Scale (GAIS). GAIS assesses the overall aesthetic change in appearance as a result of a treatment. Subjects also reported increased satisfaction with the appearance of wrinkles, as measured by the Subject Satisfaction Questionnaire (SSQ). The SSQ is a tool to gather subject-reported outcomes providing valuable insights on the impact of treatment beyond clinical observations.
Topline Efficacy Results
A total of 19 subjects were enrolled, 12 were randomized to KB304 and seven to placebo. One subject dropped out before completing KB304 treatments. The remaining 18 subjects were assessed for aesthetic improvement out to three months following KB304 injections in the décolleté.
The study investigator and subjects reported a clinically meaningful improvement in wrinkles one, two, and three months after treatment, as assessed by GAIS among KB304-treated subjects.
| Investigator Reported: At Least One-Point Improvement for Subjects Receiving: | Subject Reported: At Least One- Point Improvement for Subjects Receiving: | |||||||
| KB304 | Placebo | KB304 | Placebo | |||||
| At Three Months | ||||||||
| At Two Months | ||||||||
| At One Month | ||||||||
As assessed by SSQ,
Improvements in subjects receiving KB304 were also seen across multiple additional skin attributes, as assessed by GAIS, including elasticity, crepiness, hydration, and radiance, for which the investigator reported that
“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. 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. KB304 is a truly unique product candidate, which we think will address a massive gap in the market two ways…being the first product candidate to directly address elastin and by doing so in the décolleté where there are no injectable products approved. Consumers are yearning for a solution that delivers natural looking results, and KB304 has the potential to restore the skin to a more youthful appearance,” said Marc Forth, Chief Executive Officer of Jeune.
The KB304 safety profile was consistent with prior clinical experience in KB301. Adverse events were mild-to-moderate and mostly reported after the first dose but substantially tapered off with subsequent doses. No severe or drug-related serious adverse events were reported.
“We are extremely excited by the promising data from the Pearl-2 study,” said Suma Krishnan, President of Research & Development at Krystal Biotech. “We believe KB304 has the potential to be a first-in-class treatment to deliver collagen and elastin directly to the skin. 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. 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, a priority aesthetic site for which no FDA-approved injectables exist. 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.”
Jeune has recently completed development and validation of a décolleté-specific photonumeric scale (“JDWS”). Jeune intends to submit the JDWS to the FDA and align on the Phase 2 study protocol in the second half of 2025 with the goal of initiating the Phase 2 study in the first half of 2026.
Conference Call and Webcast
Jeune and Krystal will host a conference call and webcast today, Thursday, July 24, 2025, at 4:30pm ET, to discuss the results of the PEARL-2 study, the KB304 clinical development program, Jeune’s pipeline product candidates, and the strategic vision for Jeune.
Investors and the general public can access the live webcast at: https://www.webcaster4.com/Webcast/Page/3018/52758.
For those unable to listen to the live webcast, a replay will be available on the Investor’s section of the Krystal website at www.krystalbio.com.
About KB304
KB304 is an investigational aesthetic therapy employing Krystal’s novel replication-defective, non-integrating HSV-1-based vector to deliver two copies of the gene encoding COL3 transgene and one copy of the gene encoding elastin to increase their levels in skin and address signs of skin aging associated with damage to the skin’s extracellular matrix. KB304 is formulated as a solution for direct intradermal injection to aesthetic priority areas.
About the PEARL-2 Study
PEARL-2 is a Phase 1 Study of KB304, a replication-defective, non-integrating vector expressing human type III collagen (COL3) and elastin for the treatment of moderate to severe wrinkles of the décolleté. Details of the Phase 1 study can be found at www.clinicaltrials.gov under NCT identifier NCT06724900.
About Jeune Aesthetics, Inc.
Jeune Aesthetics, Inc., a wholly-owned subsidiary of Krystal Biotech, Inc., is a biotechnology company leveraging a clinically validated gene-delivery platform to fundamentally address – and reverse – the biology of aging skin. For more information, please visit http://www.jeuneinc.com.
About Krystal Biotech, Inc.
Krystal Biotech, Inc. (NASDAQ: KRYS) is a fully integrated, commercial-stage, global biotechnology company focused on the discovery, development and commercialization of genetic medicines to treat diseases with high unmet medical needs. VYJUVEK®, the Company’s first commercial product, is the first-ever redosable gene therapy, and the first genetic medicine approved by the FDA and EMA for the treatment of dystrophic epidermolysis bullosa. The Company is rapidly advancing a robust preclinical and clinical pipeline of investigational genetic medicines in respiratory, oncology, dermatology, ophthalmology, and aesthetics. Krystal Biotech is headquartered in Pittsburgh, Pennsylvania. For more information, please visit http://www.krystalbio.com, and follow @KrystalBiotech on LinkedIn and X (formerly Twitter).
Forward-Looking Statements
Any statements in this press release about future expectations, plans and prospects for Krystal Biotech, Inc., or its wholly-owned subsidiary, Jeune Aesthetics, Inc., including statements about the clinical utility of KB304; KB304’s ability to deliver collagen and elastin to restore the skin naturally to a more youthful appearance and potentially revolutionize the treatment of wrinkles and skin quality; KB304’s potential to address a massive gap in the market; Krystal’s and Jeune’s plans to prioritize the development of KB304 and progress KB304 into a Phase 2 study for the treatment of wrinkles of the décolleté, including timing of meeting with the FDA and the goal of initiating the Phase 2 study in the first half of 2026; and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “likely,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: preliminary clinical data from a Phase 1 trial with a small sample size and limited follow-up may not predict results in later-stage studies; uncertainties associated with regulatory review of clinical trials, the availability or commercial potential of KB304, and such other important factors as are set forth under the caption “Risk Factors” in Krystal’s annual and quarterly reports on file with the U.S. Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent Krystal’s and Jeune’s views as of the date of this press release. Krystal and Jeune anticipate that subsequent events and developments will cause their views to change. However, while Krystal and Jeune may elect to update these forward-looking statements at some point in the future, they specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing Krystal’s and Jeune’s views as of any date subsequent to the date of this press release.
CONTACT
Investors and Media:
Stéphane Paquette, PhD
Krystal Biotech
spaquette@krystalbio.com
Nishant Saxena
Jeune Aesthetics
nsaxena@krystalbio.com
FAQ
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