rytvela / Maternica Therap - LARVOL DELTA

Maternal and Postnatal Effects of Poly I:C-Induced Intrauterine Inflammation and Rytvela, a Non-Competitive IL-1R Antagonist, in the Pregnant Spiny Mouse. (PubMed, Dev Neurobiol) - "In conclusion, rytvela attenuated the primary inflammatory response to Poly(I:C), promoting earlier postnatal growth recovery despite persistent cytokine gene expression. Reduced locomotor activity after prenatal rytvela exposure warrants further investigation."

Journal • Preclinical • Infectious Disease • Inflammation • IL1B • IL6 • TLR3

Time-Dependent Inflammatory Cytokine Responses in a Human Fetal Membrane Dual-Compartment Model. (PubMed, In Vivo) - "The dual-compartment fetal membrane model enables time-resolved analysis of inflammatory responses under physiologically relevant conditions. Preceding administration of rytvela was associated with lower IL-1β levels compared to simultaneous or delayed treatment, whereas IL-6 responses were not consistently affected. These findings suggest that timing and pathway-specific regulation may influence inflammatory responses in fetal membranes."

Journal • Inflammation • IL1B • IL6

Mitigating the fetal inflammatory response syndrome (FIRS): modulating fetal membrane interleukin (IL)-1 and 6 receptors protect the fetus from bacterial and viral inflammatory stimuli (PAS 2026) - "We tested the efficacy of blocking proinflammatory responses with Rytvela (IL-1R antagonist) and HSJ633 and HSJ639 (IL-6R antagonists).Objective: We hypothesized that stimulation with LPS or Poly I:C would initiate inflammation in hFM, and Rytvela, HSJ633, or HSJ639 treatments would suppress this inflammation.Design/ hFM explants from term, non-labouring placentas were pretreated with Rytvela, HSJ633, or HSJ639 (1uM) for 30min, followed by addition of increasing doses of LPS for 24h or Poly I:C for 6h... LPS 10ng/mL (optimal dose, n=5) induced a 4x, 1.6x, & 1.7x increase in mRNA abundance of IL1b, IL6, & TNFa, respectively, and 60x, 25x, & 286x increases in protein, respectively (p < 0.05). HSJ633 most consistently suppressed cytokine mRNA expression, causing reductions of 47% in IL1b, 49% in IL6, & 47% in TNFa, (n=8). HSJ633 suppressed LPS-induced IL1b protein output by 69%, but was ineffective in suppressing the output of IL6 & TNFa (n=8).."

Infectious Disease • Inflammation • IL1B • IL6R • TNFA

Modulation of Interleukin (IL) -1 and -6 receptors prevents mouse preterm birth and newborn death due to a viral mimic. (PAS 2026) - "Poly I:C induced PTB in 25% of dams and death in 22% of the neonates by PND7. Rytvela reduced PTB to 10%, HSJ639 to 9%, and combined completely prevented PTB. Neonatal mortality was significantly reduced in all treatment groups: rytvela 10%, HSJ639 2.7%, and combined 1.5%, n = 81-148 pups/group, p< 0.0001."

Preclinical • Prematurity • Infectious Disease • Inflammation • CCL2 • IL1B • IL6 • TLR3 • TNFA

Arrested alveolar organogenesis in a newborn mouse inflammation model: protection by the interleukin (IL)-1 receptor antagonist rytvela (PAS 2026) - "48% of pups from LPS-treated dams were alive on PND1. They were significantly smaller than pups from saline-treated dams (1.56 +/-0.02g, n=82, vs. 1.77+/-0.02g, n=85, p< 0.05)."

Preclinical • Bronchopulmonary Dysplasia • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases

Rytvela, an allosteric modulator of the interleukin-1 receptor, prevents preterm birth and neonatal complications in mice while nifedipine is ineffective. (PubMed, J Immunol) - "Administration of rytvela in a treatment mode after the onset of preterm labor curbed the inflammatory surge and mitigated adverse outcomes, surpassing the effects of nifedipine. Rytvela represents a promising treatment approach for preventing preterm birth complications and addressing this unmet medical need unfulfilled by current tocolytics."

Journal • Preclinical • Inflammation • IL1B

Role of Cellular Senescence in IUGR: Impact on Fetal Morbidity and Development. (PubMed, Cells) - "We also introduce Rytvela, an interleukin-1 (IL-1) receptor modulator developed in our laboratory, which selectively attenuates pro-inflammatory signaling while preserving essential immune responses, which in turn mitigate senescence. By addressing senescence-related dysfunctions, such interventions may improve placental performance and fetal outcomes, opening up new directions for the clinical management of IUGR."

Journal • Review • Inflammation • Metabolic Disorders

Impact of an Interleukin-1 Receptor Antagonist on Preterm Labor and Bacterial Trafficking in a Pregnant Nonhuman Primate Model (ASRI 2025) - "Gene Set Analysis of total RNA-Seq data from the chorioamniotic membranes revealed upregulation of IL-1B,IL-1A,CASP1 andNFKB2 expression in the GBS only and Cefazolin groups; in contrast, expression of these genes and gene sets related to IL-1 signaling were similar between the Rytvela and uninfected control group. This data is promising that Rytvela treatment is downregulating IL-1 pathways in the placental chorioamniotic membranes, a major driver of preterm labor."

Preclinical • Prematurity • Infectious Disease • Inflammation • IL1A • IL1B • NFKB2

Rytvela Outperforms Nifedipine in Preventing Preterm Birth and Neonatal Tissue Injury When Administered after the Induction of Preterm Labor (ASRI 2025) - "Administration of rytvela after the onset of PTL effectively curbed the inflammatory surge and mitigated adverse gestational and neonatal outcomes; no comparable effects were observed with nifedipine. Highlighting the efficacy of rytvela as a relevant treatment option for preventing complications caused by PTB, these findings substantiate a major preclinical development for addressing this unmet medical need unfulfilled by tocolytic agents."

Prematurity • Inflammation • IL1R1

Inhibition of interleukin-1 signaling protects against Group B streptococcus-induced preterm birth and fetal loss in mice. (PubMed, J Reprod Immunol) - "These data show that activation of IL1-mediated signaling in response to Group B streptococcus triggers an inflammatory cascade that causes preterm parturition and fetal inflammatory injury, and that rytvela can suppress inflammatory mediators to substantially improve pregnancy and fetal outcomes. Our findings add to accumulating evidence supporting clinical investigation of rytvela for fetal protection and delaying preterm birth."

Journal • Preclinical • Inflammation • IFNG • IL1B • IL6 • PACERR • PTGS2

Interleukin-1 Receptor Antagonists Partially Inhibited Histological Injury but Not Tissue Inflammation in a Sheep Model of Pregnancy. (PubMed, Reprod Sci) - "In conclusion, fetal intramuscular administration of anakinra and rytvela did not effectively resolve intrauterine inflammation but showed potential in reducing tissue invasion and brain injury markers. These findings suggest that modest inflammation reduction may protect against brain injury and preterm birth, though no additional benefit was observed compared to intraamniotic IL-1RA treatment."

Journal • CNS Disorders • Hematological Disorders • Inflammation • Leukopenia • Oncology • Solid Tumor • Vascular Neurology • CCL2 • CXCL8 • IL1B • TNFA

Evaluation of interleukin-1 and interleukin-6 receptor antagonists in a murine model of acute lung injury. (PubMed, Exp Physiol) - "In COVID-19 ARDS patients, interleukin (IL)-1 and IL-6 receptor antagonists (IL-1Ra and IL-6Ra, kineret and tocilizumab, respectively) have shown some efficacy. Moreover, we have previously developed novel peptides modulating IL-1R and IL-6R activity (rytvela and HSJ633, respectively) while preserving immune vigilance and cytoprotective pathways...Finally, IL-1Ra and IL-6Ra failed to alleviate the inflammatory status of the mice, as indicated by cytokine levels and alveolar neutrophil infiltration. Altogether, these results indicate a lack of beneficial effects of IL-1R and IL-6R antagonists on key parameters of ALI in the bleomycin mouse model."

Journal • Preclinical • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • IL1R1 • IL6R

Fetal Intramuscular Administration of Rytvela Partially Resolved LPS-Induced Inflammation in Preterm Sheep (SRI 2024) - No abstract available

Prematurity • Inflammation

Rytvela Prevents Preterm Birth and Neonatal Tissue Injury When Administered After the Onset of Preterm Labor While the Tocolytic Agent Nifedipine is Ineffective (SRI 2024) - No abstract available

Prematurity

Pharmacological blockade of the Interleukin-1 receptor suppressed E. coli lipopolysaccharide-induced neuroinflammation in preterm fetal sheep. (PubMed, Am J Obstet Gynecol MFM) - "Intraamniotic administration of rytvela or anakinra significantly inhibited fetal brain inflammation and chorioamnionitis in preterm fetal sheep exposed to intraamniotic lipopolysaccharide. In addition, anakinra treatment was associated with potential negative impacts on the developing fetus."

Journal • Inflammation • IGF1 • MPO

Efficacy of Rytvela, an allosteric Anti-IL-1R modulator, to prevent preterm birth and neonatal tissue injury after onset of preterm labor (ASRI 2023) - "Rytvela presents a maximal efficacy in preventing PTB, inhibiting inflammatory upregulation, and promoting neonatal development when administered up to 2 h after inducing PTL in vivo. Taking inter-species allometric variables into account, Rytvela exhibits desirable properties for the safe treatment of PTL to prevent PTB and neonatal tissue injury."

Clinical • Prematurity • Inflammation • IL1R1

HMGB1-Induced Inflammatory Amplification in Human Fetal Membranes is Mediated by IL-1β and Suppressed by Rytvela, a Novel Allosteric Antagonist of the IL-1 Receptor. (SRI 2023) - "HMGB1 stimulated several cytokines in hFM explants, and antagonism of IL-1β using Rytvela attenuated this response. These results suggest that IL-1β is a key mediator of HMGB1 action, contributing to HMGB1-induced inflammatory amplification through secondary stimulation of numerous cytokines. This includes a significant contribution to IL-6 and smaller contributions to IL-1β and TNFα stimulation."

Inflammation • CCL2 • CXCL10 • CXCL8 • HMGB1 • IL1B • IL6 • MMP9 • TNFA

Efficacy of an Allosteric Anti-IL-1R Therapeutic, Rytvela, to Prevent Preterm Birth and Neonatal Tissue Injury After Onset of Preterm Labor. (SRI 2023) - "Rytvela presents a maximal efficacy in preventing PTB, inhibiting inflammatory upregulation, and promoting neonatal development when administered 2 hours after inducing PTL in vivo. Taking inter-species allometric variables into account, Rytvela exhibits desirable properties for the safe treatment of PTB and fetal protection."

Clinical • Prematurity • Inflammation • IL1R1

Intraamniotic Injection of Rytvela Partially Resolved Fetal Brain Injury in a Sheep Model of Chorioamnionitis. (SRI 2023) - "IA rytvela significantly reduced systemic inflammation and brain injury in the preterm ovine fetus, but was unable to resolve pulmonary inflammation. A dose-optimized treatment regimen has a potential to protect the fetal brain from damage in the setting of chorioamnionitis."

CNS Disorders • Oncology • Pneumonia • Solid Tumor • Vascular Neurology • CCL2 • MPO • TNFA

Chemoattraction Between Maternal Peripheral Leukocytes and Human Fetal Membranes is Suppressed by the Interleukin 1 Receptor Antagonist Rytvela. (SRI 2023) - "In summary, the chemoattractant effect of CM to both TNL and TL leukocytes did not increase significantly with IL1β but was reduced by rytvela. While rytvela suppressed IL1β-induced cytokines/chemokines in CMs, it did not affect basal outputs. Rytvela has considerable potential to prevent leukocyte migration and prolong pregnancy in women."

Late-breaking abstract • IL1B