Werewolf Therapeutics Presents New Preclinical Data Further Characterizing its IL-10 INDUKINE Molecule, WTX-921, for the Treatment of Inflammatory Bowel Disease (IBD) at AAI Annual Meeting
Werewolf Therapeutics (NASDAQ: HOWL) presented new preclinical data for WTX-921, its IL-10 INDUKINE molecule, at IMMUNOLOGY2025. The data demonstrates WTX-921's efficacy in treating Inflammatory Bowel Disease (IBD) through a mouse colitis model.
Key findings show that WTX-921 effectively prevents weight loss and reduces Disease Activity Index scores in the ACT animal model over 4 weeks. The treatment decreased immune cell infiltration and inflammatory cytokine levels in the colon. Importantly, WTX-921's optimized blocking domain prevents peripheral off-tissue effects of IL-10, addressing previous toxicity challenges in IL-10 therapies.
With an estimated 7 million people worldwide affected by IBD in 2024, WTX-921 represents a potential breakthrough as a first-of-its-kind targeted IL-10 therapy designed to overcome systemic toxicity issues while delivering anti-inflammatory benefits to inflamed colon tissue.
Werewolf Therapeutics (NASDAQ: HOWL) ha presentato nuovi dati preclinici per WTX-921, la sua molecola INDUKINE IL-10, durante IMMUNOLOGY2025. I dati dimostrano l'efficacia di WTX-921 nel trattamento della Malattia Infiammatoria Intestinale (IBD) utilizzando un modello murino di colite.
I risultati principali evidenziano che WTX-921 previene efficacemente la perdita di peso e riduce i punteggi dell'Indice di Attività della Malattia nel modello animale ACT per un periodo di 4 settimane. Il trattamento ha ridotto l'infiltrazione delle cellule immunitarie e i livelli di citochine infiammatorie nel colon. È importante sottolineare che il dominio di blocco ottimizzato di WTX-921 previene gli effetti periferici fuori dal tessuto dell'IL-10, risolvendo le precedenti problematiche di tossicità associate alle terapie con IL-10.
Con circa 7 milioni di persone colpite da IBD nel mondo nel 2024, WTX-921 rappresenta una possibile svolta come prima terapia mirata IL-10 di questo tipo, progettata per superare i problemi di tossicità sistemica offrendo al contempo benefici anti-infiammatori al tessuto infiammato del colon.
Werewolf Therapeutics (NASDAQ: HOWL) presentó nuevos datos preclínicos de WTX-921, su molécula INDUKINE de IL-10, en IMMUNOLOGY2025. Los datos demuestran la eficacia de WTX-921 para tratar la Enfermedad Inflamatoria Intestinal (EII) mediante un modelo de colitis en ratones.
Los hallazgos clave muestran que WTX-921 previene eficazmente la pérdida de peso y reduce los índices de actividad de la enfermedad en el modelo animal ACT durante 4 semanas. El tratamiento disminuyó la infiltración de células inmunitarias y los niveles de citoquinas inflamatorias en el colon. Es importante destacar que el dominio de bloqueo optimizado de WTX-921 evita los efectos periféricos fuera del tejido del IL-10, solucionando los problemas previos de toxicidad de las terapias con IL-10.
Con aproximadamente 7 millones de personas afectadas por EII en todo el mundo en 2024, WTX-921 representa un posible avance como la primera terapia dirigida con IL-10 diseñada para superar los problemas de toxicidad sistémica y al mismo tiempo proporcionar beneficios antiinflamatorios al tejido inflamado del colon.
Werewolf Therapeutics (NASDAQ: HOWL)는 IMMUNOLOGY2025에서 자사의 IL-10 INDUKINE 분자인 WTX-921에 대한 새로운 전임상 데이터를 발표했습니다. 이 데이터는 쥐 대장염 모델을 통해 WTX-921이 염증성 장질환(IBD) 치료에 효과적임을 보여줍니다.
주요 결과에 따르면 WTX-921은 4주간 ACT 동물 모델에서 체중 감소를 효과적으로 방지하고 질병 활동 지수 점수를 낮춥니다. 이 치료는 대장에서 면역 세포 침윤과 염증성 사이토카인 수치를 감소시켰습니다. 특히 WTX-921의 최적화된 차단 도메인은 IL-10의 말초 조직 외 효과를 막아 IL-10 치료제의 이전 독성 문제를 해결합니다.
2024년 전 세계적으로 약 700만 명이 IBD에 영향을 받는 가운데, WTX-921은 전신 독성 문제를 극복하면서 염증이 있는 대장 조직에 항염증 효과를 제공하도록 설계된 최초의 표적 IL-10 치료제로서 잠재적 돌파구를 나타냅니다.
Werewolf Therapeutics (NASDAQ: HOWL) a présenté de nouvelles données précliniques pour WTX-921, sa molécule INDUKINE IL-10, lors d'IMMUNOLOGY2025. Ces données démontrent l'efficacité de WTX-921 dans le traitement de la maladie inflammatoire de l'intestin (MII) à travers un modèle murin de colite.
Les résultats clés montrent que WTX-921 prévient efficacement la perte de poids et réduit les scores de l'indice d'activité de la maladie dans le modèle animal ACT sur une période de 4 semaines. Le traitement a diminué l'infiltration des cellules immunitaires et les niveaux de cytokines inflammatoires dans le côlon. Il est important de noter que le domaine de blocage optimisé de WTX-921 empêche les effets périphériques hors tissu de l'IL-10, répondant ainsi aux précédents défis de toxicité des thérapies à base d'IL-10.
Avec environ 7 millions de personnes atteintes de MII dans le monde en 2024, WTX-921 représente une avancée potentielle en tant que première thérapie ciblée IL-10 conçue pour surmonter les problèmes de toxicité systémique tout en offrant des bénéfices anti-inflammatoires au tissu colique enflammé.
Werewolf Therapeutics (NASDAQ: HOWL) stellte auf der IMMUNOLOGY2025 neue präklinische Daten zu WTX-921, seinem IL-10 INDUKINE-Molekül, vor. Die Daten zeigen die Wirksamkeit von WTX-921 bei der Behandlung von entzündlichen Darmerkrankungen (IBD) anhand eines Maus-Colitis-Modells.
Wichtige Ergebnisse zeigen, dass WTX-921 effektiv Gewichtsverlust verhindert und die Disease Activity Index-Werte im ACT-Tiermodell über 4 Wochen reduziert. Die Behandlung verringerte die Infiltration von Immunzellen und die Spiegel entzündlicher Zytokine im Dickdarm. Wichtig ist, dass die optimierte Blockierdomäne von WTX-921 periphere, außertissue IL-10-Effekte verhindert und damit frühere Toxizitätsprobleme bei IL-10-Therapien adressiert.
Mit geschätzten 7 Millionen Menschen weltweit, die 2024 an IBD leiden, stellt WTX-921 einen potenziellen Durchbruch als erste zielgerichtete IL-10-Therapie dar, die systemische Toxizitätsprobleme überwindet und gleichzeitig entzündungshemmende Vorteile für das entzündete Darmgewebe bietet.
- Demonstrated efficacy in mouse colitis model with reduced Disease Activity Index scores
- Successfully prevented weight loss in animal trials over 4 weeks
- Showed reduced inflammation and immune cell infiltration in treated animals
- Achieved effective masking of IL-10 to prevent off-tissue effects, addressing previous therapy limitations
- Still in preclinical stage, requiring further studies before human trials
- Results limited to animal models, human efficacy yet to be proven
Insights
Werewolf's preclinical IL-10 therapy shows promise for IBD by reducing inflammation in mice, but remains years from potential clinical use.
Werewolf Therapeutics has presented compelling preclinical data for their WTX-921 program, a conditionally-activated IL-10 therapy designed to treat Inflammatory Bowel Disease (IBD). The data from the mouse colitis model demonstrates three key efficacy markers: prevention of weight loss, reduced Disease Activity Index scores, and decreased inflammatory markers in colon tissue. This builds logically on their earlier proof-of-concept work presented in 2024.
What makes this approach scientifically noteworthy is the conditional activation mechanism. The INDUKINE platform incorporates an optimized blocking domain that masks IL-10 activity systemically, only releasing the active cytokine when disease-specific enzymes in inflamed tissues cleave the specialized linker. This directly addresses the fundamental challenge that has limited IL-10 therapeutics historically – dose-dependent adverse events that narrow the therapeutic window.
The molecular design shows mechanistic elegance: their data confirms both the masking function (preventing "off-tissue" effects) and preferential activation in inflamed environments. The immunological impact appears comprehensive, reducing both adaptive (CD4+ T cells) and innate (myeloid cells) immune components while decreasing inflammatory cytokine production.
Contextually, IBD affects approximately
However, this program remains in early development – typical drug development timelines would place potential human trials at least 1-2 years away, with commercialization several years beyond that if successful. The key technical hurdle will be demonstrating that the conditional activation functions as effectively in human IBD pathology as it does in controlled animal models.
The preclinical data for WTX-921 reveals a sophisticated approach to harnessing IL-10's anti-inflammatory properties while potentially avoiding its systemic limitations. The primary finding – that their conditionally-activated IL-10 molecule reduced inflammation in the ACT colitis model – aligns with our understanding of IL-10's biological function in suppressing inflammatory cascades.
What's mechanistically interesting is the dual impact observed: WTX-921 reduced both inflammatory cell infiltration (particularly CD4+ effector T cells) and inflammatory cytokine production in colonic tissue. This suggests comprehensive modulation of the inflammatory microenvironment rather than affecting just a single pathway.
The optimization of the IL-10 blocking domain represents a critical engineering achievement. Previous IL-10 therapeutic attempts showed initial promise but were hampered by narrow therapeutic windows due to IL-10's potent immunomodulatory effects when administered systemically. By effectively masking activity until the molecule reaches inflamed tissues, Werewolf's approach could potentially expand this window.
The validation using actual human IBD tissue samples to demonstrate preferential cleavage of their disease-specific linkers adds clinical relevance that pure animal models often lack. This translational element strengthens the scientific rationale.
From an immunopathology perspective, IBD represents dysregulated immune responses where pro-inflammatory cascades overwhelm regulatory mechanisms in genetically susceptible individuals. IL-10's natural role as an anti-inflammatory cytokine makes it a logical therapeutic target, but previous direct administration approaches struggled with achieving sufficient local concentration without systemic effects.
While these results support continued development, several questions remain unanswered: will the engineered specificity maintain sufficient targeting across heterogeneous human IBD pathology? Will the magnitude of anti-inflammatory effect be sufficient for clinical benefit? And importantly, will long-term IL-10 delivery to inflamed intestinal tissues have unintended consequences on mucosal immunity?
- Data reveal WTX-921 is efficacious in a mouse colitis model, resulting in reduced tissue damage and inflammatory cytokine production -
- Findings offer a more detailed understanding of WTX-921’s anti-inflammatory impact on the immune landscape in the inflamed colon -
WATERTOWN, Mass., May 05, 2025 (GLOBE NEWSWIRE) -- Werewolf Therapeutics, Inc. (the “Company” or “Werewolf”) (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions, today announced a poster presentation further characterizing its conditionally-activated IL-10 INDUKINE molecule, WTX-921, at IMMUNOLOGY2025, the annual meeting of the American Association of Immunologists (AAI) taking place May 3-7 in Honolulu, Hawaii.
Werewolf’s findings are summarized in a poster titled, “Development of WTX-921, A Conditionally Active IL-10 INDUKINETM Molecule for the Treatment of Inflammatory Bowel Disease” (Board #1230). The results build on initial data presented at the 2024 AAI Annual Meeting, which revealed preliminary proof-of-concept for its IL-10 INDUKINE molecule as a potential prodrug for IBD treatment.
The data corroborate the preferential cleavage of inflammatory disease linkers by inflamed human IBD tissue samples and reduced colitis in a murine IBD model as previously observed. New results also highlight WTX-921’s effective masking of IL-10 via its optimized IL-10 blocking domain, which prevents the peripheral off-tissue pharmacodynamic effects of IL-10. The CDC estimates that 7 million people worldwide had IBD in 2024, and while clinical studies in IBD involving IL-10 have shown promise, they are consistently hampered by dose-dependent adverse events.
“Our findings validate the potential of WTX-921, a first-of-its-kind targeted IL-10 therapy, to modulate disease-driving innate and adaptive immune responses implicated in IBD,” said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf Therapeutics. “WTX-921 is a novel IL-10 INDUKINE molecule specifically engineered to overcome the significant toxicities associated with systemic IL-10 therapy and deliver this potent anti-inflammatory agent to inflamed colon tissue, which has clear implications for IBD patients in need of better treatment options.”
WTX-921 treatment demonstrated efficacy in the ACT animal model of colitis over a duration of 4 weeks, preventing weight loss and resulting in reduced Disease Activity Index (DAI) scores. WTX-921 also inhibited inflammation, evidenced by a decrease in the infiltration/expansion of immune cells (including CD4+ effector T cells and myeloid cells) and reduced RNA levels of inflammatory cytokines within the colon of treated animals.
The poster can be viewed in person on Tuesday, May 6, 2025, on board number 1230, with Werewolf delegates present from 1:15-2:30pm to answer questions. The poster will also be available on our website at https://investors.werewolftx.com/news-and-events/scientific-resources.
About WTX-921:
WTX-921 is a novel, first-of-its-kind IL-10 INDUKINE™ molecule being developed for the treatment of Inflammatory Bowel Disease (IBD) and other inflammatory diseases. Engineered to overcome the significant toxicities associated with systemic IL-10 delivery, WTX-921 is conditionally activated and is specifically designed for the selective delivery of native IL-10 to inflamed tissues, providing therapeutically-relevant exposure while minimizing systemic toxicity in preclinical models. Preclinical data demonstrate that WTX-921 has the potential to block several disease-driving effector molecules and cytokines, eliciting a multipronged effect by inhibiting disease-driving innate and adaptive immune cell populations.
About Werewolf Therapeutics:
Werewolf Therapeutics, Inc., is an innovative biopharmaceutical company pioneering the development of therapeutics engineered to stimulate the body’s immune system for the treatment of cancer and other immune-mediated conditions. The Company is leveraging its proprietary PREDATOR® platform to design conditionally activated molecules that stimulate both adaptive and innate immunity with the goal of addressing the limitations of conventional proinflammatory immune therapies. Werewolf’s INDUKINE molecules are intended to remain inactive in peripheral tissue yet activate selectively in the tumor microenvironment. The Company’s most advanced clinical stage product candidates, WTX-124 and WTX-330, are systemically delivered, conditionally activated Interleukin-2 (IL-2) and Interleukin-12 (IL-12) INDUKINE molecules, respectively, for the treatment of solid tumors. Werewolf is advancing WTX-124 in multiple tumor types as a single agent and in combination with an immune checkpoint inhibitor and WTX-330 in multiple tumor types or Non-Hodgkin Lymphoma as a single agent. To learn more visit www.werewolftx.com.
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617.430.7576
daniel@lifesciadvisors.com
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Deerfield Group
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