PIPELINE

Candidate nelitolimod

TriSalus is investigating nelitolimod (also known as SD-101) as a therapeutic candidate to re-activate the immune system within the liver and pancreas and to enable deeper and more durable responses to other immunotherapeutics (e.g., checkpoint inhibitors) resulting in better patient outcomes.

Nelitolimod is in clinical development and has not been approved in the US or globally.

Left: Scientific illustration of TriSalus’ investigational candidate SD-101, a single stranded oligonucleotide-based therapy Right: Scientific illustration of SD-101 Mechanism: SD-101 binds to a plasma membrane and is endocytosed. In a late endosome, SD-101 binds to and activates TLR9 which initiates a cascade of events through NF-κB phosphorylation. Gene expression changes reprogram MDSCs to produce and release cytokines.
Top: Scientific illustration of TriSalus’ investigational candidate SD-10, a single stranded oligonucleotide-based therapy Scientific illustration of SD-101 Method Of Action: SD-101 binds to a plasma membrane and is endocytosed. In a late endosome, SD-101 binds to and activates TLR9 which initiates a cascade of events through NF-κB phosphorylation. Gene expression changes reprogram MDSCs to produce and release cytokines. Bottom: Scientific illustration of SD-101 Method Of Action: SD-101 binds to a plasma membrane and is endocytosed. In a late endosome, SD-101 binds to and activates TLR9 which initiates a cascade of events through NF-κB phosphorylation. Gene expression changes reprogram MDSCs to produce and release cytokines.

Nelitolimod Mechanism of Action to Enable Immunotherapy

Nelitolimod, an investigational agent in development, is a toll-like receptor 9 (TLR9) agonist which is believed to bind to the TLR9 receptors found on suppressive immune cells including myeloid-derived suppressor cells (MDSCs), antigen-presenting immune cells and other immune cells. Toll-like receptors play a key role in the innate immune system and create a bridge to adaptive immunity.1 It is believed that activating TLR9 primes immune cells to promote anti-tumor T-cell function.1,2

Overcoming Immunosuppression
TLR9 agonists have the potential to reprogram and eliminate MDSCs.

Prior Clinical Trials with Nelitolimod

Nelitolimod has been studied in combination with pembrolizumab (Keytruda®) and other agents in over 300 patients enrolled in various Phase 1 and Phase 2 studies of melanoma, lymphoma, and head and neck squamous cell carcinoma.3,4 It was also studied in the I-SPY2 Trial for patients with high-risk, Stage II/III breast cancer.

Publications & Presentations

Prior clinical trials show immunomodulatory properties of nelitolimod.

Locally Targeted Delivery 0f Nelitolimod

Traditionally, TLR9 agonists like nelitolimod have not been administered intravenously but by direct injection into superficial tumors, making treatment of tumors in deep locations, like the liver and pancreas, difficult. TriSalus will utilize its proprietary Pressure-Enabled Drug Delivery™ (PEDD™) method for intravascular regional delivery of nelitolimod to reach these locations.

By infusing nelitolimod via our technology, we can administer it to visceral organs and directly to the site of disease. The goal of this approach is to enhance nelitolimod’s therapeutic index, increase anti-tumor immune activity intended to slow tumor progression and restore, enable or improve responses to immunotherapies for treatment of liver metastases and pancreatic cancer.

Overcoming Intratumoral Pressure

Our intravascular regional delivery technology overcomes physical barriers to delivery.

Ongoing Clinical Trials with Nelitolimod

TriSalus will initially evaluate nelitolimod for the treatment of uveal melanoma with liver metastases, hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We intend to develop additional programs looking at a combination of nelitolimod and other immuno-oncology agents delivered with Pressure-Enabled Drug Delivery™ (PEDD™) in a range of liver and pancreatic cancers for which limited therapeutic options exist.

Clinical Trials

We are committed to developing treatments to improve outcomes for patients with liver and pancreatic tumors.

CITATIONS

  1. Melisi D, et al. Biomedicines. 2014;2(3):211-228.
  2. Humbert M, et al. Cancer Res. 2018 Jun 15;78(12):3280-3292.3.
  3. Ribas A, et al. Cancer Discov. 2018;8(10):1250-1257.
  4. Frank MJ, et al. Cancer Discov. 2018;8(10):1258-1269.

IMPORTANT NOTICE

You are now leaving the Trisalus life Sciences corporate website.

We encourage you to read and evaluate terms of use, privacy, security and other similar policies of the destination site as they may differ from TriSalus’ standards.

Third Party Sites

TriSalus assumes no responsibility nor does it control, endorse or guarantee any aspect of your use of any third party sites. Additionally, the presence of this link does not imply the third party site’s endorsement of TriSalus or this website.

Thank you for visiting our site.

CANCEL