Drive more therapy deep inside tumors for improved response.

Improved therapy delivery was demonstrated with Pressure-Enabled Drug Delivery (PEDD) across species and therapeutics

Clinical

PEDD improved tumor targeting in liver radioembolization with resin microspheres.

PEDD Significantly Increased Both Tumor to Normal Liver Ratio (T/N) and Dose Delivery Compared to a Standard Endhole Microcatheter6

Study Design

A retrospective analysis of 61 patients with liver cancer (190 lesions). All patients underwent an MAA planning procedure delivered via a standard EH catheter. Resin Y90 was delivered via either an EH catheter (control group) or via PEDD, followed by PET/CT imaging. Each patient’s post-Y90 PET/CT was co-registered to their post-MAA SPECT/CT to compare the tumor to normal liver ratio and tumor dose.6

Achieved greater on-target distribution of beads.

PEDD With SmartValve Delivered a Significantly Higher Concentration of Therapy in the Tumor vs Endhole Microcatheters1

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Study Design

A retrospective, single-center study included 88 treatment-naive patients with solitary HCC tumors <6.5 cm who underwent treatment utilizing either PEDD (n = 18) or standard EH microcatheters (n = 70).* 1

Target the tumor. Spare normal tissue.

PEDD With SmartValve Has Been Shown to Increase Targeting While Reducing Nontarget Embolization2

Same day, same patient, same tumor,
same catheter location

33%-90% (mean=68%)
increase in tumor deposition
when using PEDD
vs microcatheter (P < 0.05)

24%-89% (mean=58%)
decrease in nontarget embolization
when using PEDD vs microcatheter (P < 0.05)

Study Design

A prospective study included 9 patients with unresectable liver cancer who were enrolled for the treatment of HCC (n = 6), liver-dominant metastatic disease (n = 2), or intrahepatic cholangiocarcinoma (n = 1). Each patient was treated via standard EH microcatheter or PEDD.2

Shown to drive therapy delivery.

PEDD Resulted in a >5-fold Increased Chimeric Antigen Receptor (CAR)-T Penetration in Both Tumor and Liver vs Endhole Microcatheter3

Study Design

This small, investigational study was an exploratory Phase 1b clinical trial using biopsy to assess CAR-T activity of a second generation (IgCD28TCR) anti-CEA CAR-T (Sorrento Therapeutics) administered using HAI via PEDD in five patients with stage IV, chemotherapy resistant, CEA+ adenocarcinoma liver metastases (LM).3

Preclinical

Pancreatic Retrograde Venous Infusion with PEDD increased drug delivery to the pancreas 3.6-fold vs systemic infusion.

Oxaliplatin Levels in Porcine Pancreas Increased With PEDD5

Tissue levels achieved with 50 mg oxaliplatin via PEDD SEAL (n=6) are greater than 130 mg systemic (high-end therapeutic, n=5).

Drug delivery increased 360%.5

Study Design

Access to the portal vasculature was achieved via a percutaneous transhepatic approach in a porcine model. A TIS-21120-60 infusion system was tracked into a pancreatic vein and deployed. A solution containing oxaliplatin was administered to the tissue using retrograde venous infusion (RVI). After infusion, tissue and blood samples were collected and oxaliplatin concentration was determined. Tissue concentrations were compared to animals receiving systemic administration of oxaliplatin.5

PRVI With PEDD Increased Tumor Vasculature Pressures and Improved Gemcitabine Delivery 7-Fold4

Mice administered therapeutic by PRVI had greater tumor gemcitabine concentrations (127 vs 19 ng/mg; P < 0.01) than mice receiving systemic infusion.4

Study Design

3 groups of 15 orthotopic murine models were evaluated for tumor volume following a PRVI delivery of gemcitabine, PRVI delivery of saline, or systemic delivery of gemcitabine.4

Improved response by delivering greater concentrations of therapy deep into difficult tumors.1,3,7

Improved Tumor Response Was Observed Across
Therapeutics and Species in Clinical and Preclinical Studies1-5

Clinical

PEDD significantly enhanced drug penetration and improved response in HCC.1

Image for reference only.

Drug-eluting microspheres transarterial chemoembolization (DEM-TACE) procedures with PEDD were associated with improved tumor response.1

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Study Design

A retrospective, single-center study included 88 treatment-naive patients with solitary HCC tumors <6.5 cm who underwent treatment utilizing either PEDD (n = 18) or standard EH microcatheters (n = 70).‡1

Several patients demonstrated a complete response to therapy in the liver.3,7

HITM-SURE + CEA-001 Phase 1 Studies of PEDD With CAR-T for Secondary Liver Cancer3,7

Patients: early 50s with poorly differentiated pancreatic adenocarcinoma and synchronous liver mets received 3 doses of anti-CEA CAR-T delivered regionally via hepatic artery infusion (HAI) using the PEDD approach to optimize the therapeutic index.

HITM-SURE
2/5 CR in liver lesions on PET3†

CEA-001
1/2 CR in liver lesions on PET7‡

CAR-T Therapy Delivered With PEDD Resulted in a Sustained Reduction in Tumor Markers7

Post treatment, PET demonstrated complete metabolic response within the liver, which was durable and sustained for 13 months.7

Study Design

†Small, investigational study was an exploratory Phase 1b clinical trial using biopsy to assess CAR-T activity of a second generation (IgCD28TCR) anti-CEA CAR-T (Sorrento Therapeutics) administered using HAI via PEDD in five patients with stage IV, chemotherapy resistant, CEA+ adenocarcinoma liver metastases (LM).3

‡Small, investigational, open-label, single arm, Phase 1b study to confirm clinical responses in patients with CEA-expressing pancreatic adenocarcinoma liver metastases (LM) with anti-CEA CAR-T cells delivered using the HAI via PEDD. Study focused on patients who had pancreatic adenocarcinoma liver metastases not amenable to R0 surgical resection.7

Preclinical

PRVI With PEDD Increased Tumor Vasculature Pressures and Increased Tumor Response4

Mice administered therapeutic by PRVI had smaller tumor volumes
(274 vs 629 mm3; P < 0.01) than mice receiving systemic infusion.4

Study Design

3 groups of 15 orthotopic murine models were evaluated for tumor volume following a PRVI delivery of gemcitabine, PRVI delivery of saline, or systemic delivery of gemcitabine.4

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Study Designs

*A retrospective, single-center study included 88 treatment-naive patients with solitary HCC tumors <6.5 cm who underwent treatment utilizing either PEDD (n = 18) or standard EH microcatheters (n = 70). Twenty-three patients (5 PEDD, 18 EH) received a liver transplant during the study, with 1 PEDD and 6 EH patients excluded from the tumor necrosis analysis for receiving subsequent therapies prior to transplant. A pathologist performed a blinded review of the liver explant specimens to assess tumor necrosis and treatment distribution. Percentage necrosis was defined as the volume of necrotic areas divided by the total tumor volume.1

References

1. Titano JJ, Fischman AM, Cherian A, et al. End-hole Versus Microvalve Infusion Catheters in Patients Undergoing Drug-Eluting Microspheres-TACE for Solitary Hepatocellular Carcinoma Tumors: A Retrospective Analysis. Cardiovasc Intervent Radiol. 2019;42(4):560-568. doi:10.1007/s00270-018-2150-6. 2. Pasciak AS, McElmurray JH, Bourgeois AC, Heidel RE, Bradley YC. The impact of an antireflux catheter on target volume particulate distribution in liver-directed embolotherapy: a pilot study. J Vasc Interv Radiol. 2015;26(5):660-669. doi:10.1016/j.jvir.2015.01.029. 3. Katz, et al. “HITM-SURE: Phase Ib CAR-T hepatic artery infusion trial for stage IV adenocarcinoma using Pressure-Enabled Drug Delivery technology.” SITC (2018) Poster Presentation. 4. Shankara Narayanan JS, Vicente DA, Ray P, et al. Pressure-enabled delivery of gemcitabine in an orthotopic pancreatic cancer mouse model. Surgery. 2020;168(3):448-456. 5. Data on file, Porcine Animal Model, TriSalus Life Sciences®, 2019. 6. d’Abadie P, Walrand S, Goffette P, et al. Antireflux catheter improves tumor targeting in liver radioembolization with resin microspheres. Diagn Interv Radiol. 2021;27:768–773. 7. Katz SC, Moody AE, Guha P, et al. HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery. J Immunother Cancer. 2020;8(2):e001097.