roneparstat (LB401) / Leadiant Biosci - LARVOL DELTA

Design of aminoglycosides as sulfated and hydrophobic glycans to target heparanase-driven tumor progression and metastasis (ACS-Fall 2025) - "In in vivo models of melanoma and myeloma, the lead compound reduced metastatic burden by 97% and exhibited superior tumor growth inhibition (TGI = 83.1%) compared to SST0001, a clinically tested HPSE inhibitor (TGI = 58.6%), and was comparable to Bortezomib, a frontline anti-myeloma drug. Importantly, the lead inhibitor demonstrated favorable tolerability in vivo, with no significant toxicity. These findings validate HPSE as a viable therapeutic target in oncology and highlight aminoglycoside-based inhibitors as a promising class of targeted therapeutics for treating metastatic cancers."

Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor

Heparanase-Inhibiting Polymeric Heparan Sulfate Mimetic Attenuates Myeloma Tumor Growth and Bone Metastasis. (PubMed, ACS Appl Bio Mater) - "Additionally, the glycopolymer exhibited promising efficacy against metastatic CAG human myeloma, comparable to bortezomib, a widely used proteasome inhibitor for MM treatment. A combined treatment further reduced tumor burden. These results highlight the remarkable potential of HS-mimicking glycopolymer as a promising therapeutic option for MM."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Design of Paromomycin and Neomycin as Sulfated and Hydrophobic Glycans to Target Heparanase-Driven Tumor Progression and Metastasis. (PubMed, J Med Chem) - "In vivo, the lead candidate significantly reduced metastatic burden in B16 melanoma and MPC-11 myeloma models, showing tumor growth inhibition (TGI = 83.1%) versus SST0001 (TGI = 58.6%) and matching bortezomib. Importantly, the compound was well-tolerated with no notable toxicity. These results support HPSE as a cancer target and highlight aminoglycoside-based HS mimetics as promising therapeutics for metastatic cancer."

Journal • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Solid Tumor

A Heparan Sulfate Mimetic RAFT Copolymer Inhibits SARS-CoV-2 Infection and Ameliorates Viral-Induced Inflammation. (PubMed, Adv Sci (Weinh)) - "Of particular note, HMSA-06 demonstrated more potent anti-SARS-CoV-2 effects than PG545 and Roneparstat...The HMSA-06's inflammation inhibitory function is further confirmed using a LPS/ATP-stimulated THP-1 macrophage model. Altogether, this study has identified a promising HS mimetic to combat SARS-CoV-2-associated diseases by inhibiting viral infection and attenuating viral-induced inflammatory reaction, providing insights into the development of novel anti-coronavirus drugs in the future."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CASP1 • IL1B • NLRP3

Involvement of heparanase in the pathogenesis of acute pancreatitis: Implication of novel therapeutic approaches. (PubMed, J Cell Mol Med) - "Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice...Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease."

Journal • Gastroenterology • Gastrointestinal Disorder • Inflammation • Pancreatitis

Radiation-Induced Nephropathy in the Murine Model Is Ameliorated by Targeting Heparanase. (PubMed, Biomedicines) - "Given the well-documented anti-cancer effects of heparanase inhibition, our findings attest this enzyme to be a unique target in cancer therapy due to its dual action. Targeting heparanase exerts not only direct anti-tumor effects but protects against radiation-induced kidney damage-the backbone of cancer therapy across a range of malignancies."

Journal • Preclinical • Nephrology • Oncology • Renal Disease

A positive feedback loop of heparanase/syndecan1/nerve growth factor regulates cancer pain progression. (PubMed, Korean J Pain) - "The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment."

Journal • Melanoma • Oncology • Pain • Solid Tumor • NGF • SDC1

Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury. (PubMed, Int J Mol Sci) - "Moreover, cleaved caspase-3 was attenuated in H podocytes exposed to Adriamycin, indicating lower apoptotic cell death in H vs. V podocytes. Collectively, these findings suggest that in podocytes, elevated levels of heparanase promote cytoprotection."

Journal • Glomerulonephritis • Lupus Nephritis • Nephrology • Renal Disease • ATG12 • CASP3

Heparin-Superparamagnetic Iron Oxide Nanoparticles for Theranostic Applications. (PubMed, Molecules) - "Their inhibitory activity on the heparanase enzyme was measured, showing an effective inhibition at concentrations comparable to G4000 (N-desulfo-N-acetyl heparin, a non-anticoagulant and antiheparanase heparin derivative; Roneparstat). The LMWH@SPION encapsulation of paclitaxel (PTX) enhanced the antitumor effect of this chemotherapeutic on breast cancer cells, likely due to an improved internalization of the nanoformulated drug with respect to the free molecule. Lastly, time-domain NMR (TD-NMR) experiments were conducted on LMWH@SPIONs obtaining relaxivity values within the same order of magnitude as currently used commercial contrast agents."

Journal • Breast Cancer • Oncology • Solid Tumor

Targeting of Heparanase in the Murine Model Protects against Radiation-Induced Nephropathy (ASTRO 2022) - "Given the well-documented anti-cancer effects of heparanase inhibition, our present findings attest this enzyme as a unique target in the landscape of cancer therapy due to its dual action. Indeed, targeting of heparanase exerts not only direct anti-tumor effects but also protects from kidney damage induced by radiation - the backbone of cancer therapy across a broad range of abdominal/pelvic malignancies."

Preclinical • Oncology • Renal Disease • EGR1

Heparanase Inhibition Prevents Liver Steatosis in E Mice. (PubMed, J Clin Med) - "Heparanase inhibition significantly attenuates the development of liver steatosis by decreasing tissue lipid content and by affecting the mRNA expression of key lipid metabolism regulators."

Journal • Preclinical • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease

Heparanase Blockade as a Novel Dual-Targeting Therapy for COVID-19. (PubMed, J Virol) - "In addition, HPSE blockade with Roneparstat significantly attenuated SARS-CoV-2 S1 protein-induced inflammatory cytokine release from human macrophages through disruption of NF-κB signaling. Together, this study provides a proof of principle for the use of Roneparstat as a dual-targeting therapy for COVID-19 to decrease viral infection and dampen the proinflammatory immune response mediated by macrophages."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CCL2 • CD68 • IL1B • IL6

Upregulation of ERK-EGR1-heparanase axis by HDAC inhibitors provides targets for rational therapeutic intervention in synovial sarcoma. (PubMed, J Exp Clin Cancer Res) - "The present study provides preclinical rationale and mechanistic insights into drug combinatory strategies based on the use of ERK pathway and heparanase inhibitors to improve the efficacy of HDACi-based antitumor therapies in SS. The involvement of classes of agents already clinically available, or under clinical evaluation, indicates the transferability potential of the proposed approaches."

Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • EGR1 • SS18

Combination of Trehalose and Heparanase Inhibitors Treatment Ameliorates Cerulein-Induced Acute Pancreatitis in a Murine Model (ACG 2021) - "Cerulein-induced AP in WT mice was associated with significant rises in the serum levels of amylase (X3) and lipase (X3.5), enhancement of pancreatic edema index, tissue inflammation, and autophagy response. All types of responses were more profound in Hpa-TG mice, as was evident by 4 and 7.5 fold increases in amylase and lipase levels, respectively. Importantly, pretreatment with PG545, Roneparstat, Aspirin or Trehalose reduced pancreatic inflammatory response, autophagy, along remarkable reduction in amylase and lipase serum levels in both WT and Hpa-Tg mice."

Preclinical • Immunology • Inflammation • Pancreatitis

[VIRTUAL] Discovery of Glycopolymers as Potent Inhibitors of Heparanase for Cancer Therapeutics (ACS-Fall 2021) - "The effect of glycopolymer was comparable to that exerted by bortezomib (Velcade), the leading drug in the treatment of myeloma patients...The results indicate that treatment with the glycopolymer markedly attenuated myeloma tumor growth. The effect of the glycopolymer was comparable to that exerted by Roneparstat (= SST), a well-characterized N-acetylated, glycol-split heparin that recently completed phase I clinical trial in myeloma patients"

Breast Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Heparanase Inhibitors in Cancer Progression: Recent Advances. (PubMed, Curr Pharm Des) - "HPIns can be a better target to be explored against various cancers."

Journal • Immunology • Inflammation • Oncology

Heparanase in Acute Pancreatitis. (PubMed, Adv Exp Med Biol) - "Further support for the involvement of Hpa in the pathogenesis of AP emerged from our observation that treatment of experimental AP with PG545 or SST0001(= Ronepastat), two potent Hpa inhibitors, markedly attenuated the biochemical, histological and immunological manifestations of the disease. Hpa, therefore, emerges as a potential new target in AP, and Hpa inhibitors are hoped to prove beneficial in AP along with their promising efficacy as anti-cancer compounds."

Journal • Gastroenterology • Immunology • Oncology • Pancreatitis

Roneparstat: Development, Preclinical and Clinical Studies. (PubMed, Adv Exp Med Biol) - "However, Roneparstat antitumor activity activity has been documented in other cancers, and in non-oncological conditions.In addition, assessing Roneparstat activity in different experimental models contributed to understanding heparanase role and the biological factors that may be affected by heparanase inhibition in more detail. Finally, some studies elucidated the molecular mechanisms regulating the enzyme-inhibitor kinetics, thus providing important data for the identification and design of new inhibitors.The objective of this chapter is to provide a comprehensive overview of the most significant studies involving Roneparstat and discuss its potential role in therapy."

Journal • Fibrosis • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

[VIRTUAL] Heparanase in myeloma related renal dysfunction: Role in promoting nephrotoxicity and potential as a novel biomarker for early detection. (ASCO 2020) - "HPSE causes kidney cellular injury which can be detected early by the measurement of high sensitivity biomarkers and can be prevented by treatment with HPSE inhibitors, Roneparstat and OGT-2115. Further studies are ongoing to investigate the association between HPSE activity and renal dysfunction in a larger cohort of MM patients which have been accrued as a part of the UAB-Integrative Molecular And Genetic Epidemiology (IMAGE) Study of Myeloma. Research Funding: U.S. National Institutes of Health"

Biomarker • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Disease • KIM1

Novel N-acetyl-Glycol-split heparin biotin-conjugates endowed with anti-heparanase activity. (PubMed, Eur J Med Chem) - "In vitro these novel derivatives maintain the anti-heparanase activity without induced toxicity. The newly synthesized compounds retained the ability to attenuate the growth of CAG myeloma tumors in mice with potency similar, or in one case even higher than that of the reference compound Roneparstat as well as inhibited metastatic dissemination (lung colonization) of murine B16-F10 melanoma cells in vivo."

Journal

Phase I study of the heparanase inhibitor Roneparstat: an innovative approach for multiple myeloma therapy. (PubMed, Haematologica) - No abstract available.

Journal • P1 data

Combination of Heparanase Inhibitors and Aspirin Or Trehalose Alleviate Experimental Pancreatitis (DDW 2019) - "Aims The current study examines whether the combination of Aspirin or Trehalose with Pixatimod (PG545) or Roneparstat (SST0001), two inhibitors of Hpa, exerts a superior protective effect in cerulein- induced AP in mice, vs each compound alone. Administration of either Aspirin, Trehalose or Hpa inhibitor exerts a protective effect against Cerulein- induced AP. Interestingly, combination of Aspirin or Trehalose and Hpa inhibitors completely abolished AP, providing a rational basis for the treatment of this clinical setting."