Nektar Announces Publication in Nature Communications of Results from Phase 1b Studies of Rezpegaldesleukin in Two Inflammatory Skin Diseases
Nektar Therapeutics (NKTR) published peer-reviewed data from two Phase 1b studies in Nature Communications showing promising results for rezpegaldesleukin in treating atopic dermatitis (AD) and psoriasis (PsO). The studies demonstrated that the drug safely increased regulatory T cells (Tregs) and improved disease outcomes, with effects lasting up to 36 weeks after treatment cessation. High-dose AD patients showed an 83% improvement in EASI score after 12 weeks, with EASI-75 and vIGA-AD responses maintained in 71% and 80% of week 12 responders respectively for 36 weeks post-treatment.
Nektar Therapeutics (NKTR) ha pubblicato dati peer-reviewed provenienti da due studi di fase 1b su Nature Communications, mostrando risultati promettenti per rezpegaldesleukin nel trattamento della dermatite atopica (AD) e della psoriasi (PsO). Gli studi hanno dimostrato che il farmaco ha aumentato in modo sicuro le cellule T regolatorie (Tregs) e ha migliorato gli esiti della malattia, con effetti che si sono protratti fino a 36 settimane dopo la cessazione del trattamento. I pazienti con AD ad alta dose hanno mostrato un miglioramento dell'83% nel punteggio EASI dopo 12 settimane, con le risposte EASI-75 e vIGA-AD mantenute nel 71% e nell'80% rispettivamente per i rispondenti della settimana 12 per 36 settimane post-trattamento.
Nektar Therapeutics (NKTR) publicó datos revisados por pares de dos estudios de fase 1b en Nature Communications que muestran resultados prometedores para rezpegaldesleukin en el tratamiento de la dermatitis atópica (AD) y la psoriasis (PsO). Los estudios demostraron que el fármaco aumentó de manera segura las células T reguladoras (Tregs) y mejoró los resultados de la enfermedad, con efectos que duraron hasta 36 semanas después de la interrupción del tratamiento. Los pacientes con AD de alta dosis mostraron una mejora del 83% en la puntuación EASI tras 12 semanas, con respuestas EASI-75 y vIGA-AD mantenidas en el 71% y el 80% de los respondedores de la semana 12, respectivamente, durante 36 semanas post-tratamiento.
Nektar Therapeutics (NKTR)는 Nature Communications에 두 개의 1b 기초 연구에서 동료 검토된 데이터를 발표하며, 아토피 피부염 (AD) 및 건선 (PsO) 치료를 위한 rezpegaldesleukin의 유망한 결과를 보여주었습니다. 이 연구들은 약물이 안전하게 조절 T세포 (Tregs)를 증가시키고 질병 결과를 개선했으며, 치료 중단 후 최대 36주까지 효과가 지속됨을 증명했습니다. 고용량 AD 환자들은 12주 후 EASI 점수가 83% 개선되었습니다, 치료 후 36주 동안 12주 응답자의 71%와 80%가 각각 EASI-75 및 vIGA-AD 반응을 유지했습니다.
Nektar Therapeutics (NKTR) a publié des données évaluées par des pairs provenant de deux études de phase 1b dans Nature Communications, montrant des résultats prometteurs pour rezpegaldesleukin dans le traitement de la dermatite atopique (AD) et du psoriasis (PsO). Les études ont démontré que le médicament augmentait en toute sécurité les cellules T régulatrices (Tregs) et améliorait les résultats de la maladie, avec des effets durables jusqu'à 36 semaines après l'arrêt du traitement. Les patients atteints d'AD à forte dose ont montré une amélioration de 83 % du score EASI après 12 semaines, avec des réponses EASI-75 et vIGA-AD maintenues respectivement chez 71 % et 80 % des répondants de la semaine 12 pendant 36 semaines après le traitement.
Nektar Therapeutics (NKTR) hat in der Fachzeitschrift Nature Communications peer-reviewed Daten aus zwei Phase-1b-Studien veröffentlicht, die vielversprechende Ergebnisse für rezpegaldesleukin bei der Behandlung von atopischer Dermatitis (AD) und Psoriasis (PsO) zeigen. Die Studien haben gezeigt, dass das Medikament sicher regulatorische T-Zellen (Tregs) erhöhte und die Krankheitsverläufe verbesserte, wobei die Wirkungen bis zu 36 Wochen nach Behandlungsende anhielten. AD-Patienten in der Hochdosisgruppe zeigten eine Verbesserung von 83 % im EASI-Score nach 12 Wochen, wobei die EASI-75- und vIGA-AD-Reaktionen bei 71 % bzw. 80 % der Behandler der Woche 12 über 36 Wochen nach der Behandlung aufrechterhalten wurden.
- High efficacy with 83% improvement in EASI score for AD patients after 12 weeks
- Durable treatment effects lasting up to 36 weeks after discontinuation
- Strong response maintenance with 71% EASI-75 and 80% vIGA-AD responses at 36 weeks post-treatment
- Drug demonstrated safety and good tolerability in Phase 1b trials
- None.
Insights
The publication in Nature Communications reveals significant clinical progress for rezpegaldesleukin in treating inflammatory skin conditions. The 83% improvement in EASI score for atopic dermatitis patients and 71% maintenance of EASI-75 response for 36 weeks post-treatment are particularly impressive efficacy metrics.
The drug's novel mechanism targeting regulatory T cells (Tregs) demonstrates potential advantages over existing treatments by addressing multiple inflammatory pathways simultaneously. This could position rezpegaldesleukin as a valuable treatment option in the $15+ billion atopic dermatitis market.
The sustained efficacy duration of 36 weeks post-treatment is a key differentiator, potentially reducing treatment frequency and improving patient compliance. Phase 2b trial results expected next year will be important for validating these findings at a larger scale.
This peer-reviewed publication significantly strengthens Nektar's position in the inflammatory skin disease space. The dual indication potential (atopic dermatitis and psoriasis) expands the drug's commercial opportunity. The safety profile and durability of response could provide competitive advantages against established treatments like Dupixent.
For investors, the upcoming Phase 2b data in 2025 represents a major catalyst. Success could drive partnership opportunities or increase acquisition interest, particularly valuable for a small-cap biotech. However, it's important to note that larger trials are needed to confirm these early results and competition in the inflammatory skin disease market is intense.
- Data from multiple Phase 1b studies in inflammatory skin conditions demonstrate durable dose-dependent improvements in physician-assessed disease activity and patient-reported outcomes -
- Biomarker analyses demonstrate plurality of Treg-mediated pathways with potential effect on tissue resident memory T cell populations resulting in sustained efficacy seen in the antigen challenged mouse model and in clinical trials -
Rezpegaldesleukin is a first-in-class interleukin-2 receptor (IL-2R) agonist that enhances the activity of regulatory T cells (Tregs) with promising dose-dependent clinical activity across multiple physician-assessed and patient-reported endpoints for AD and PsO.
Results from the Phase 1b studies showed that rezpegaldesleukin safely and dose-dependently increased Tregs and rapidly improved measurable exploratory disease outcomes that are largely durable for at least 36 weeks after ceasing treatment.
"These promising findings clinically validate, for the first time, the Treg hypothesis – that restoring Treg function through a central pathway of IL‑2R-driven Treg rescue can have disease remittive potential across a variety of chronic inflammatory skin diseases," said Jonathan Silverberg, M.D., Ph.D., Professor of Dermatology at George Washington University School of Medicine and lead study author. "Newer evidence suggests that diseases like atopic dermatitis are not exclusively Th2-mediated. These results show that rezpegaldesleukin can act on multiple disease-driving pathways and is uniquely poised to address a diversity of immunopathologies."
"The exciting clinical cross-indication efficacy here is buttressed by serum biomarker analysis demonstrating that rezpegaldesleukin can modulate multiple immunoregulatory pathways to provide rapid onset and duration of efficacy" said Jonathan Zalevsky, Ph.D., Chief Research & Development Officer at Nektar. "These findings further validate our therapeutic approach of using a Treg stimulator to dampen inflammatory responses and simultaneously restore immune balance in patients with chronic inflammatory skin diseases. We look forward to reporting topline data next year from our two Phase 2b rezpegaldesleukin studies in atopic dermatitis and alopecia areata."
Key findings are summarized below:
- Rezpegaldesleukin was evaluated in two randomized, double-blind, placebo-controlled Phase 1b trials in patients with moderate-to-severe atopic dermatitis (AD) (NCT04081350) or chronic plaque psoriasis (PsO) (NCT04119557)
- Rezpegaldesleukin is safe and well-tolerated and demonstrates consistent pharmacokinetics in participants receiving subcutaneous doses of 10 to 12 μg/kg or 24 μg/kg once every 2 weeks for 12 weeks, meeting the primary and secondary objectives of each study
- AD patients receiving high dose rezpegaldesleukin demonstrate an
83% improvement in EASI score after 12 weeks of treatment EASI improvement of ≥75% (EASI-75) and vIGA-AD responses are maintained for 36 weeks after treatment discontinuation in71% and80% of week 12 responders, respectively - The clinical improvements are accompanied by sustained increases in CD25bright Tregs
- Serum proteomic biomarkers demonstrated rezpegaldesleukin's ability to engage multiple immunoregulatory mechanisms to facilitate immune homeostasis, which may indicate a potential mechanism of attenuating Th1, Th2, and Th17 responses by restoring the balance of Tregs.
- Results validate the role of IL-2-induced Treg proliferation and activation in the AD treatment paradigm, and support the advancement of rezpegaldesleukin in the Phase 2b study in AD.
- The delayed-type hypersensitivity (DTH) mouse model and the profound reduction in serum IL-15 levels in atopic dermatitis patients treated with rezpegaldesleukin provides mechanistic insight for the durable efficacy that persists for months following treatment
The full citation of this article can be accessed at: https://rdcu.be/dX8lr.
About Rezpegaldesleukin
Autoimmune and inflammatory diseases cause the immune system to mistakenly attack and damage healthy cells in a person's body. A failure of the body's self-tolerance mechanisms enables the formation of the pathogenic T lymphocytes that conduct this attack. Rezpegaldesleukin is a potential first-in-class resolution therapeutic that may address this underlying immune system imbalance in people with many autoimmune and inflammatory conditions. It targets the interleukin-2 receptor complex in the body in order to stimulate proliferation of powerful inhibitory immune cells known as regulatory T cells. By activating these cells, rezpegaldesleukin may act to bring the immune system back into balance.
Rezpegaldesleukin is being developed as a self-administered injection for a number of autoimmune and inflammatory diseases. It is wholly-owned by Nektar Therapeutics.
About Nektar Therapeutics
Nektar Therapeutics is a clinical-stage biotechnology company focused on developing treatments that address the underlying immunological dysfunction in autoimmune and chronic inflammatory diseases. Nektar's lead product candidate, rezpegaldesleukin (REZPEG, or NKTR-358), is a novel, first-in-class regulatory T cell stimulator being evaluated in two Phase 2b clinical trials, one in atopic dermatitis and one in alopecia areata. Our pipeline also includes a preclinical candidate NKTR-0165, which is a bivalent tumor necrosis factor receptor type II agonist antibody. Nektar, together with various partners, is also evaluating NKTR-255, an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer, in several ongoing clinical trials. Nektar is headquartered in San Francisco, California. For further information, visit www.nektar.com and follow us on LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements which can be identified by words such as: "will," "can," "expect," "develop," "potential," "advance," "anticipate," and similar references to future periods. Examples of forward-looking statements include, among others, statements regarding the therapeutic potential of, and future development plans for rezpegaldesleukin. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results to differ materially from those indicated in the forward-looking statements include, among others: (i) our statements regarding the therapeutic potential of rezpegaldesleukin are based on preclinical and clinical findings and observations and are subject to change as research and development continue; (ii) rezpegaldesleukin is an investigational agent and continued research and development for this drug candidate is subject to substantial risks, including negative safety and efficacy findings in future clinical studies (notwithstanding positive findings in earlier preclinical and clinical studies); (iii) rezpegaldesleukin is in clinical development and the risk of failure is high and can unexpectedly occur at any stage prior to regulatory approval; (iv) the timing of the commencement or end of clinical trials and the availability of clinical data may be delayed or unsuccessful due to challenges caused by regulatory delays, slower than anticipated patient enrollment, manufacturing challenges, changing standards of care, evolving regulatory requirements, clinical trial design, clinical outcomes, competitive factors, or delay or failure in ultimately obtaining regulatory approval in one or more important markets; (v) patents may not issue from our patent applications for our drug candidates, patents that have issued may not be enforceable, or additional intellectual property licenses from third parties may be required; and (vi) certain other important risks and uncertainties set forth in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2024. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
Contact:
For Investors:
Vivian Wu of Nektar Therapeutics
628-895-0661
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