Research Collaboration Aims to Bring TLR9 Agonist SD-101 to Patients With Pancreatic and Liver Cancer

Pipeline Report | <b>Pipeline Report: May 2021</b>

The University of Texas MD Anderson Cancer Center and the immuno-oncology company TriSalus™ Life Sciences announced a strategic research collaboration to evaluate SD-101 in pancreatic cancer and hepatocellular carcinoma.

The University of Texas MD Anderson Cancer Center and the immuno-oncology company TriSalus™ Life Sciences announced a strategic research collaboration to evaluate SD-101, an investigational toll-like receptor 9 (TLR9) agonist, in combination with checkpoint inhibitors for the treatment of patients with pancreatic cancer and hepatocellular carcinoma (HCC).1

The initial study of the collaboration will enroll patients with uveal melanoma–related liver metastases, with other studies planned in metastatic pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. Additional trials in HCC and locally advanced PDAC are being developed.

“Tumors in the pancreas and liver are notoriously difficult to treat effectively, and these patients need new therapeutic options. Our collaboration with TriSalus provides a unique opportunity to evaluate immunotherapy in combination with a novel delivery approach,” said Sapna Patel, BA, MD, an associate professor, uveal melanoma program director, fellowship program director, and director of online media in the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center.1 “We look forward to our work together to advance new treatments aimed at improving clinical outcomes and the lives of our patients.”

The TLR9 agonist is thought to bind to the TLR9 receptors present on suppressive immune cells, including myeloid-derived suppressor cells and antigen-presenting immune cells.2 These receptors contribute to the innate immune system and provide a bridge to adaptive immunity. As such, activating TLR9 may prime immune cells to promote antitumor T-cell function.

SD-101 is delivered intravascularly via TriSalus™ Life Sciences’s FDA cleared, proprietary Pressure-Enabled Drug Delivery™ (PEDD™) technology. PEDD™ offers the potential to deliver SD-101 in a way not previously possible with standard direct injection delivery.1,2

Small prospective and retrospective studies reported that more therapy was able to be delivered into the vasculature of liver metastases and pancreatic solid tumors with PEDD™ technology vs standard end-hole microcatheters.3 The novel approach has the potential to overcome barriers of the tumor microenvironment, such as abnormal vascularity, interstitial fluid pressure, and solid stress.

Moreover, this approach could make treating certain solid tumor malignancies, such as pancreatic cancer and HCC, more feasible.2

Previously, SD-101 in combination with pembrolizumab (Keytruda) demonstrated early efficacy signals and tolerability in phase 1b/2 studies for patients with PD-1 inhibitor–naïve recurrent or metastatic head and neck squamous cell carcinoma (NCT02521870)4, PD-1/PD-L1 inhibitor–resistant advanced or metastatic melanoma (NCT02521870)5, and PD-1/PD-L1 inhibitor–naïve advanced melanoma (NCT02521870)6.

Notably, these data suggest that SD-101 can stimulate innate immune cells and favorably program T cells to enhance responses to checkpoint inhibitors.

“We’re pleased to collaborate with MD Anderson in pursuit of our collective goal to improve outcomes for patients with tumors of the liver and pancreas. The goal of these studies is to augment the potential of existing therapies through novel drug delivery technology and to investigate the strategic modulation of immune microenvironments with investigational candidate SD-101,” said Steven Katz, MD, chief medical officer of TriSalus™ Life Sciences.1

References

  1. TriSalus Life Sciences and MD Anderson announce strategic research collaboration to evaluate treatment of solid tumors. Business Wire. News release. April 8, 2021. Accessed May 21, 2021. https://bwnews.pr/3ytUtqN.
  2. SD-101 an investigational TLR9 agonist. TriSalus™ Life Sciences. 2021. Accessed May 21, 2021. https://trisaluslifesci.com/pipeline-overview/sd-101/.
  3. Proprietary drug delivery technology. TriSalus™ Life Sciences. 2021. Accessed May 21, 2021. https://trisaluslifesci.com/drug-delivery/.
  4. Cohen EEW, Nabell L, Wong DJL, et al. Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2019;37(suppl 15):6039. doi:10.1200/JCO.2019.37.15_suppl.6039
  5. Amin A, Milhem MM, Long GV, et al. Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced/metastatic melanoma resistant to anti-PD-1/PD-L1 therapy. J Clin Oncol. 2019;37(suppl 15):9555. doi:10.1200/JCO.2019.37.15_suppl.9555
  6. Milhem MM, Long GV, Hoimes CJ, et al. Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy. J Clin Oncol. 2019;37(suppl 15):9534. doi:10.1200/JCO.2019.37.15_suppl.9534