Nektar Therapeutics Announces Multiple Presentations for Rezpegaldesleukin at EADV 2024
Nektar Therapeutics announced multiple presentations for rezpegaldesleukin (REZPEG) at the 2024 European Academy of Dermatology and Venereology Congress. New proteomic analyses show that REZPEG increases immune-regulating pathways while reducing specific serum proteins elevated in atopic dermatitis patients. REZPEG is a novel regulatory T cell stimulator designed to address immune system imbalance in autoimmune disorders.
Two Phase 2b studies are ongoing: one in moderate-to-severe atopic dermatitis and another in severe to very severe alopecia areata. Topline data is expected in the first half of 2025 for the AD study and mid-2025 for the AA study. The presentations highlighted REZPEG's unique proteomic profile, its effect on immunoregulatory pathways, and its potential to offer durable effects and long-term remission in atopic dermatitis treatment.
Nektar Therapeutics ha annunciato molteplici presentazioni per rezpegaldesleukin (REZPEG) al congresso 2024 dell'Accademia Europea di Dermatologia e Venereologia. Nuove analisi proteomiche mostrano che REZPEG aumenta i percorsi di regolazione immunitaria riducendo al contempo specifiche proteine sieriche elevate nei pazienti con dermatite atopica. REZPEG è un innovativo stimolatore delle cellule T regolatorie progettato per affrontare lo squilibrio del sistema immunitario nei disturbi autoimmuni.
Due studi di Fase 2b sono attualmente in corso: uno su dermatite atopica da moderata a grave e un altro su alopecia areata da grave a molto grave. I dati principali sono attesi nella prima metà del 2025 per lo studio sulla dermatite atopica e a metà del 2025 per lo studio sull'alopecia areata. Le presentazioni hanno messo in evidenza il profilo proteomico unico di REZPEG, il suo effetto sui percorsi immunoregolatori e il suo potenziale per offrire effetti duraturi e remissione a lungo termine nel trattamento della dermatite atopica.
Nektar Therapeutics anunció múltiples presentaciones sobre rezpegaldesleukin (REZPEG) en el congreso de la Academia Europea de Dermatología y Venereología 2024. Nuevos análisis proteómicos muestran que REZPEG aumenta las vías de regulación inmunitaria mientras reduce proteínas séricas específicas elevadas en pacientes con dermatitis atópica. REZPEG es un novedoso estimulador de células T reguladoras diseñado para abordar el desequilibrio del sistema inmunitario en trastornos autoinmunes.
Actualmente se están llevando a cabo dos estudios de Fase 2b: uno en dermatitis atópica moderada a grave y otro en alopecia areata grave a muy grave. Se esperan datos preliminares para la primera mitad de 2025 para el estudio de AD y a mediados de 2025 para el estudio de AA. Las presentaciones destacaron el perfil proteómico único de REZPEG, su efecto en las vías inmunoreguladoras y su potencial para ofrecer efectos duraderos y remisión a largo plazo en el tratamiento de la dermatitis atópica.
Nektar Therapeutics는 2024 유럽 피부과 및 비뇨기학 아카데미 congress에서 rezpegaldesleukin (REZPEG)에 대한 여러 발표를 발표했습니다. 새로운 단백질 분석 결과, REZPEG가 면역 조절 경로를 증가시키고 아토피 피부염 환자에서 높아진 특정 혈청 단백질을 감소시킨다는 것이 밝혀졌습니다. REZPEG는 자가 면역 질환에서 면역 체계 불균형을 해결하기 위해 설계된 새로운 조절 T 세포 자극제입니다.
현재 두 개의 2b 상 임상 시험이 진행 중입니다: 하나는 중등도에서 중증의 아토피 피부염에 관한 것이고, 다른 하나는 중증에서 매우 중증의 원형 탈모증에 관한 것입니다. AD 연구의 주요 데이터는 2025년 상반기에, AA 연구는 2025년 중반에 발표될 예정입니다. 발표에서는 REZPEG의 독특한 단백질 프로파일, 면역 조절 경로에 미치는 효과 및 아토피 피부염 치료에서 지속적인 효과와 장기적인 관해를 제공할 잠재력이 강조되었습니다.
Nektar Therapeutics a annoncé plusieurs présentations sur rezpegaldesleukin (REZPEG) lors du congrès de l'Académie Européenne de Dermatologie et de Vénéréologie 2024. De nouvelles analyses protéomiques montrent que REZPEG augmente les voies de régulation immunitaire tout en réduisant certaines protéines sériques élevées chez les patients atteints de dermatite atopique. REZPEG est un nouvel activateur de cellules T régulatrices conçu pour traiter le déséquilibre du système immunitaire dans les maladies auto-immunes.
Deux études de Phase 2b sont actuellement en cours : l'une sur la dermatite atopique modérée à sévère et l'autre sur l'alopecia areata sévère à très sévère. Les résultats préliminaires sont attendus au cours de la première moitié de 2025 pour l'étude sur la DA et à la mi-2025 pour l'étude sur l'AA. Les présentations ont mis en lumière le profil protéomique unique de REZPEG, son effet sur les voies immunorégulatrices et son potentiel à offrir des effets durables et une rémission à long terme dans le traitement de la dermatite atopique.
Nektar Therapeutics kündigte mehrere Präsentationen zu rezpegaldesleukin (REZPEG) beim Kongress der Europäischen Akademie für Dermatologie und Venerologie 2024 an. Neue proteomische Analysen zeigen, dass REZPEG immunregulierende Wege erhöht und gleichzeitig spezifische Serumproteine senkt, die bei Patienten mit atopischer Dermatitis erhöht sind. REZPEG ist ein neuartiger Regulator-T-Zell-Stimulator, der entwickelt wurde, um Ungleichgewichte im Immunsystem bei Autoimmunerkrankungen anzugehen.
Zwei Phase-2b-Studien sind derzeit im Gange: eine bei moderater bis schwerer atopischer Dermatitis und eine andere bei schwerer bis sehr schwerer Alopecia areata. Die wichtigsten Daten werden in der ersten Hälfte von 2025 für die AD-Studie und Mitte 2025 für die AA-Studie erwartet. Die Präsentationen hoben das einzigartige proteomische Profil von REZPEG hervor, seine Wirkung auf immunregulatorische Wege und sein Potenzial, dauerhafte Effekte und langfristige Remissionen bei der Behandlung von atopischer Dermatitis zu bieten.
- REZPEG shows promising results in increasing immune-regulating pathways
- Two Phase 2b studies are ongoing for atopic dermatitis and alopecia areata
- REZPEG demonstrates a unique serum proteomic profile in AD patients
- Potential for durable effects and long-term remission in atopic dermatitis treatment
- Topline data for Phase 2b studies not expected until 2025
Insights
The proteomic analyses presented at EADV 2024 provide valuable insights into rezpegaldesleukin's (REZPEG) mechanism of action in atopic dermatitis (AD). Key findings include:
- REZPEG increases proteins in immune-regulating pathways while reducing specific serum proteins elevated in AD patients
- It induces important immunoregulatory pathways, particularly IL-10, a key anti-inflammatory cytokine
- REZPEG reduces cytokines and chemokines known to be elevated in AD, including IL-15, CCL22, CX3CL1 and IL-19
These results help explain the dose-dependent efficacy and rapid onset of action observed in the Phase 1b study. The data also suggest potential for sustained efficacy even after treatment cessation, which could be a significant advantage in AD management.
The ongoing Phase 2b studies in AD and alopecia areata will be important in confirming REZPEG's efficacy and safety profile. With topline data expected in 2025, these trials could potentially position REZPEG as a novel treatment option for patients who don't respond to current biologics and small molecules.
While the scientific data presented is promising, investors should consider several factors:
- Market potential: The atopic dermatitis market is projected to reach
$24 billion by 2027, offering significant opportunity if REZPEG proves successful. - Competition: REZPEG faces competition from established treatments and other pipeline candidates. Its differentiated mechanism of action could be a key advantage.
- Timeline: With topline data from Phase 2b studies expected in 2025, REZPEG is still years away from potential commercialization. This extended timeline impacts near-term revenue prospects.
- Financial position: Nektar's market cap of
$215 million suggests investor caution. The company's cash runway and ability to fund ongoing clinical development are important considerations.
While the news is scientifically positive, investors should balance the long-term potential against near-term financial challenges and clinical development risks.
- New proteomic analyses show that rezpegaldesleukin increases the protein levels of immune-regulating pathways while reducing specific serum proteins known to be elevated in patients with atopic dermatitis -
"As an agonist, REZPEG has a differentiated mechanism of action which is demonstrated by its unique proteomic profile presented today at EADV 2024," said Jonathan Zalevsky, Ph.D., Senior Vice President and Chief Research & Development Officer at Nektar. "The data show that REZPEG induces important immunoregulatory pathways, such as IL-10, a key anti-inflammatory cytokine. In addition, REZPEG reduced specific cytokines and chemokines which are known to be elevated in patients with atopic dermatitis and other atopy diseases, including IL-15, CCL22, CX3CL1, and IL-19. These data provide a greater mechanistic understanding of how treatment with REZPEG led to dose-dependent efficacy in the Phase 1b study over the 12-week treatment period, including its rapid onset of action, and it also provides insight into pathways that could result in the sustained efficacy that was observed in that study even after treatment was removed."
REZPEG is a novel first-in-class regulatory T (Treg) cell stimulator designed to address the imbalance in the immune system underlying autoimmune disorders and chronic inflammatory conditions. REZPEG works by targeting the IL-2 receptor complex and preferentially stimulating the proliferation of Treg cells without stimulating cytotoxic CD8+ T and CD4+ T cells, which drive autoimmune disease, to restore immune balance. REZPEG is currently being evaluated in two Phase 2b studies, one in moderate-to-severe AD and one in severe to very severe alopecia areata (AA). Nektar expects topline data from the AD study in the first half of 2025 and topline data from the AA study in the middle of 2025.
"In recent years, significant progress has been made in the treatment of atopic dermatitis. However, some patients still do not respond to the available biologics and small molecules. Therefore, there is a strong need for molecules with different mechanisms of action, particularly those that are immunoregulatory rather than immunosuppressive," said Spyridon Gkalpakiotis, M.D., Ph.D., MBA, a principal investigator on the Phase 2b study of rezpegaldesleukin in atopic dermatitis and Professor in the Department of Dermatovenerology 3FM CU and UHKV at the University Hospital Královské Vinohrady,
The poster presentations are available for download at www.nektar.com/science/scientific-posters-and-presentations.
Key details and takeaways from the presentations are as follows:
Abstract 5560/ePoster P0662: "Serum proteomic biomarker analysis of the interleukin-2 receptor pathway agonist rezpegaldesleukin in patients with atopic dermatitis", Yu, et al.
- Patients with moderate-to-severe AD received 12 or 24 µg/kg REZPEG or placebo once every two weeks for 12 weeks. The Olink proteomics platform was used to measure the levels of soluble serum proteins from patients at baseline and throughout the induction period.
- REZPEG modulated Treg pathways and those involving lymphocyte immune homeostasis, MHC expression and regulation, ectodomain shedding of cell surface receptors, as well as cellular migration and adhesion processes.
- As an IL-2 receptor pathway agonist, REZPEG demonstrated a unique serum proteomic profile in AD patients, reducing the expression of serum proteins known to be elevated in patients with AD and demonstrated an effect on the expression levels of known targets for current AD therapy.
Abstract 4505/ePoster P0600 (Trial in Progress): "A Phase 2b, Randomized, Double-Blinded, Parallel-Group, Placebo-Controlled, International, Multicenter, Study to Evaluate the Efficacy and Safety of Rezpegaldesleukin in Adults with Moderate-to-Severe Atopic Dermatitis", Gkalpakiotis, et al.
- The Phase 2b trial is enrolling biologic and JAK-inhibitor naïve adults with moderate-to-severe AD. The primary outcome is reduction in Eczema Area and Severity Index (EASI) score from baseline at the end of the treatment induction phase. Secondary and exploratory endpoints include reduction in Investigator's Global Assessment (IGA) AD score, affected total body surface area (BSA) improvement, as well as safety and tolerability.
Abstract 2459/ePoster P2080 (Trial in Progress): "A Phase 2b Study Evaluating the Efficacy and Safety of Single Agent Rezpegaldesleukin, an Interleukin-2 Receptor (IL-2R) Pathway Agonist, in the Treatment of Severe to Very Severe Alopecia Areata", Reich, et al.
- The Phase 2b trial is enrolling JAK-inhibitor naïve patients with severe to very severe alopecia areata. The primary endpoint is percent change from baseline in Severity Alopecia Tool (SALT) score at the end of the treatment period. Secondary and exploratory endpoints include percent change from baseline in SALT score at other assessed timepoints, safety and tolerability, as well as various patient reported outcomes.
About REZPEG
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. REZPEG 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, REZPEG may act to bring the immune system back into balance.
REZPEG 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 (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," "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 are investigational agents and continued research and development for these drug candidates 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 health epidemics, including the COVID-19 pandemic, 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) we may not achieve the expected cost savings we expect from our 2022 corporate restructuring and reorganization plan or our 2023 cost restructuring plan and we may undertake additional restructuring and cost-saving activities in the future, (vi) 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 (vii) 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
For Media:
David Rosen of Argot Partners
646-461-6387
david.rosen@argotpartners.com
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