nelitolimod (SD-101) / Dynavax, TriSalus Life Sci, UT MD Anderson Cancer Center - LARVOL DELTA

Serum immune markers are associated with pathological complete response and immune-related adverse events in immuno-oncology arms of the I-SPY2 breast cancer trial (AACR 2025) - "Patients received paclitaxel with anti-PD-1 (N=49) or anti-PD-1 plus SD-101 (N=65), followed by anthracycline/cyclophosphamide. Serum immune markers may influence tumor immune cell infiltration, potentially affecting the likelihood of achieving pCR and systemic immune activity linked to irAEs. Serum levels of CRP, CXCL10, sCD25, G-CSF, and IFNγ could be used to monitor and predict clinical benefit from anti-PD-1 and immunomodulatory agents. This study also suggests that VEGF-C and granzyme B can be possible candidate prognostic biomarkers for irAEs in patients receiving anti-PD-1 therapy."

Adverse events • Clinical • Immuno-oncology • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CCL2 • CD163 • CRP • CSF3 • CXCL10 • CXCL11 • CXCL13 • CXCL8 • CXCL9 • GZMB • HER-2 • IFNG • IL10 • IL6 • LAG3 • PD-L1 • TNFA • VEGFC

TriSalus Life Sciences Announces $22.0 Million Private Placement… (Businesswire) - "TriSalus Life Sciences, Inc...announces...that it has entered into a securities purchase agreement with certain investors for shares of its common stock to raise approximately $22.0 million in gross proceeds."

Financing • Oncology

TriSalus Life Sciences Reports Q4 and Full Year 2024 Financial Results and Provides Business Update (Businesswire) - "Enrollment was completed in the PERIO-03 Phase 1 trial investigating nelitolimod in locally advanced pancreatic cancer. Final data are expected mid-2025, with next steps to be determined based on results."

Enrollment closed • P1 data • Pancreatic Cancer

A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies. (PubMed, Clin Cancer Res) - "Clinical results of T cell costimulatory receptor agonism have now repeatedly been inferior to the motivating preclinical results. Our study highlights potential barriers to clinical translation, particularly differences in preclinical and clinical reagents and the complex biology of these coreceptors in heterogenous T cell subpopulations, some of which may antagonize immunotherapy."

IO biomarker • Journal • P1 data • Preclinical • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Cryoablation and Arterial Infusion of SD-101 in Combination with Durvalumab and Tremelimumab (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of California, San Diego | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor

A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies (Clin Cancer Res) - P1 | N=14 | NCT03410901 | "We treated 14 patients with low-dose radiation, intratumoral SD101, and intratumoral and intravenous BMS986178, an agonistic anti-OX40 antibody....Adverse events were consistent with prior experience with low-dose radiation and SD101. No synergistic or dose-limiting toxicities were observed. One patient had a partial response, and nine patients had stable disease, a result inferior to our experience with TLR9 agonism and low-dose radiation alone. Flow cytometry and single-cell RNA sequencing of serial tumor biopsies revealed that T and NK cells were activated after treatment."

P1 data • B Cell Lymphoma • Non-Hodgkin’s Lymphoma

TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Ronald Levy | Active, not recruiting ➔ Completed

Combination therapy • Trial completion • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Waldenstrom Macroglobulinemia

Pembrolizumab +/- SD-101 in Hormone-Naïve Oligometastatic Prostate Cancer With RT and iADT (clinicaltrials.gov) - P2 | N=23 | Active, not recruiting | Sponsor: David Oh | Trial completion date: Oct 2024 ➔ Aug 2025 | Trial primary completion date: Oct 2024 ➔ Aug 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Cryoablation and Arterial Infusion of SD-101 in Combination With Durvalumab and Tremelimumab (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: University of California, San Diego

Combination therapy • Metastases • New P1 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Challenges in translating preclinical mouse results to human patients: insights from a clinical trial combining OX40 agonism with in situ vaccination (SITC 2024) - P1 | "Fourteen patients were enrolled and treated with low-dose radiation (2 x 2Gy), intratumoral SD101, and intratumoral and intravenous BMS986178,2 a fully human agonistic anti-OX40 antibody (figure 1). TREG, FoxP3+ regulatory T. TFH, T follicular helper. TR1, T regulatory type 1 cellsDownload figure Open in new tab Download powerpoint Abstract 990 Figure 3 On-treatment (Day 8 and Week 6) soluble OX40 plasma levels between patients with progression free survival (PFS) 6 months (6M)"

IO biomarker • Preclinical • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • FOXP3 • TNFRSF9

Hepatic artery pressure enabled drug delivery (PEDD) of nelitolimod combined with checkpoint inhibition (ICI) in uveal melanoma liver metastases (UM-LM) in ICI-naïve and -refractory patients (pts) (SITC 2024) - P1 | "Cohorts included monotherapy (Cohort A, n=13), together with nivolumab (Cohort B, n=34), or with nivolumab + ipilimumab (Cohort C, n=20)...Median age was 65, 30% were HLA-A*02:01 positive, 43% were female, and 69% were pre-treated with systemic therapy (45% with ICI and 18% with tebentafusp)...Clinical benefit was associated with MDSC reprogramming. Ethics Approval The study obtained ethics approval from the institutional review boards of all participating centers."

Checkpoint inhibition • Clinical • Late-breaking abstract • Eye Cancer • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A • IL15 • IL18

PERIO Trial Update (Businesswire) - P1 | N=80 | PERIO-01 (NCT04935229) | Sponsor: TriSalus Life Sciences, Inc. | "TriSalus presented Phase 1 results from the PERIO-01 clinical trial at the recent SITC meeting. This dose escalation trial investigated the use of the PEDD method of nelitolimod in patients with UM-LM. The results suggested that PEDD-administered nelitolimod, combined with immune checkpoint inhibitors, provides promising clinical benefits and durable survival in heavily pretreated patients with UM-LM and a favorable safety profile. The Company is actively exploring strategic partnerships to advance this indication further...The Company also completed enrollment of 13 patients in its PERIO-03 Phase 1 dose escalation study of nelitolimod in locally advanced pancreatic cancer....The Company will outline the next steps once the final data are available in mid-2025."

Enrollment status • P1 data • Eye Cancer • Gastrointestinal Cancer • Ocular Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • Uveal Melanoma

Impact of Pressure-Enabled Drug Delivery (PEDD) of Nelitolimod (SD-101) into the Liver with Systemic Immune Checkpoint Inhibitor (ICI) for Treating Metastatic Uveal Melanoma with Liver Metastases (MUM-LM) (ACS-CLINCON 2024) - P1 | " PERIO-01 is a phase 1 trial of nelitolimod via PEDD in MUM-LM (NCT04935229), with dose-escalation cohorts as monotherapy (Cohort A), with nivolumab (Cohort B), or nivolumab + ipilimumab (Cohort C). Delivery of nelitolimod via PEDD with systemic ICI in MUM-LM patients resulted in promising clinical activity. The intrahepatic and systemic immune effects observed were consistent with tumor microenvironment (TME) changes supportive of ICI activity in MUM-LM. Overall, nelitolimod was shown to activate the TLR9 signaling pathway as observed by the biphasic NFΚB signaling effect, inhibit MDSC expansion via the JAK/STAT3 pathway and promote a broader anti-tumorigenic TME in LM."

Checkpoint inhibition • Metastases • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • CD8

Regional lymph node changes on breast MRI in patients with early-stage breast cancer receiving neoadjuvant chemo-immunotherapy. (PubMed, Breast Cancer Res Treat) - "The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

TriSalus Life Sciences Announces Appointment of Riad Salem, M.D., to its Scientific Advisory Board - "TriSalus Life Sciences...an oncology company dedicated to enhancing outcomes for patients with liver and pancreatic cancer through its advanced delivery technology and novel immunotherapy, nelitolimod, has announced the addition of Riad Salem, M.D., to its Scientific Advisory Board (SAB)."

Announcement

TriSalus Reports Q2 2024 Financial Results and Business Update (Businesswire) - "The final results for the PERIO-01 Phase 1 trial are expected in Q4 2024...PERIO-03 is a Phase 1 dose-escalation study of nelitolimod in locally advanced pancreatic cancer...Phase 1 results for this study are anticipated in Q4 2024."

P1 data • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor • Uveal Melanoma

Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases. (PubMed, J Immunother Cancer) - "The SQ route of CPI delivery was equivalent to Sys in combination with nelitolimod, suggesting SQ-CPI may be a rational choice in combination with PEDD of nelitolimod for liver tumor treatment."

Checkpoint inhibition • Journal • Myeloid-derived suppressor cells • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • ITGAM • ITGAX • PTPRC

What Happens to Frailty in the First Year After Lung Transplantation? (PubMed, Clin Transplant) - "Participants in a structured post-LTx rehabilitation program improved in functional exercise capacity (6MWD), GS, depression, and anxiety. For frail participants exercise capacity, depression, anxiety, and GS were well managed in rehabilitation with no significant differences between those who were not frail. Pre-LTx frailty may be reversible post-LTx and should not be an absolute contraindication to LTx."

Journal • Chronic Obstructive Pulmonary Disease • CNS Disorders • Depression • Immunology • Mood Disorders • Psychiatry • Pulmonary Disease • Respiratory Diseases • Transplantation

First Report of Pantoea ananatis causing leaf streak disease on wheat (Triticum aestivum) in the United States of America. (PubMed, Plant Dis) - "We named the culture SD101...2020), this is the first report of its pathogenicity on wheat in the United States. The prevalence, and incidence of BLS disease caused by P. ananatis in wheat is needed to estimate its threat to wheat production and to develop management strategies."

Journal • Infectious Disease

Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial. (ASCO 2024) - P2 | "Treatment included weekly paclitaxel (T) plus ICI-based tx x 4 cycles, followed by doxorubicin/cyclophosphamide (AC) every 2-3 weeks x 4. 6 completed investigational arms included ICIs: T+pembro x 4, T+pembro x 8 (+/- AC), T+pembro+SD101 (TLR9 agonist), T+durvalumab+olaparib, T+cemiplimab (cemi), and T+cemi+REGN3767 (anti-LAG-3)... The incidence of AI in EBC is higher than has previously been reported in advanced disease, with higher rates observed in those tx with dual immune modulation. No correlation was observed with age; correlation of AI with response predictive subtype and other clinicopathologic features is ongoing and will be presented. Given the high incidence of AI in EBC, close monitoring in the peri/postoperative setting and education of pts and providers is critical, as risk persists even after completion of tx."

IO biomarker • Breast Cancer • Endocrine Disorders • Fatigue • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Immune Modulation • Immunology • Nephrology • Oncology • Renal Disease • Solid Tumor • Triple Negative Breast Cancer • HER-2

PERIO-02: Phase 1b pressure enabled regional immuno-oncology trial of nelitolimod (SD-101), a class C TLR9 agonist, delivered via hepatic artery infusion +/- checkpoint inhibition in intrahepatic cholangiocarcinoma and hepatocellular carcinoma. (ASCO 2024) - P1/2 | "Nelitolimod was dose-escalated without ICI (Cohort A), with pembrolizumab (Cohort B), or with nivolumab + ipilimumab (Cohort C). HAI of nelitolimod has been well tolerated and associated with encouraging immunologic activity in HCC and ICC. Clinical and biologic activity in cohort C at 4mg is supportive of further enrollment in this cohort."

Checkpoint inhibition • Immuno-oncology • IO biomarker • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD4 • CD8 • IFNG • IL17A

TriSalus Life Sciences Highlights Clinical Data from Phase 1b PERIO-02 Trial, Studying Delivery of Nelitolimod via Pressure-Enabled Drug Delivery in Patients with Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma at 2024 ASCO Annual Meeting (Businesswire) - P1b/2 | N=89 | PERIO-02 (NCT05220722) | Sponsor: TriSalus Life Sciences, Inc. | "TriSalus Life Sciences, Inc...announced that data from its Phase 1b PERIO-02 clinical trial was presented in a poster session at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, taking place May 31-June 4, 2024, in Chicago, Illinois....At the 4 mg dose in cohort C, three of three patients had disease control as best on-treatment response, with one complete response (CR) in the liver (5L ICC), one partial response (PR) (-31%), and one stable disease (SD)....Median progression-free survival (PFS) in the Cohort C 4 mg dose level is > 120 days. Median overall survival (OS) for this group has not been reached (range 120-170 days)."

P1 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Responders to combination radiation and PD-1 blockade demonstrate reduced myeloid immunosuppression and enhanced interferon signaling in oligometastatic prostate cancer patients (AACR 2024) - P2 | "Patients were randomized to receive anti-PD-1 x 13 cycles (pembrolizumab, Arm 1, n=12), or anti-PD-1 with intraprostatic injections of TLR9 agonist SD-101 (Arm 2, n=11). All patients received SBRT to the prostate tumor during cycle 1, and concomitant hormonal therapy with a GnRH agonist and abiraterone... Responders to combination radiation and anti-PD-1 blockade have decreased myeloid immunosuppression and enhanced IFN activity prior to treatment in oligometastatic prostate cancer. This may identify patients likely to respond, and baseline immune setpoints that can be enhanced with improved immunotherapy strategies."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD63 • LAMP3 • SPP1

TriSalus Reports Q4 and Full Year 2023 Financial Results and Business Update (Businesswire) - "Completed Enrollment in Multiple Phase 1 Clinical Trials (100 Patients) in Uveal Melanoma Liver Metastases, Hepatocellular Cancer, and Intrahepatic Cholangiocarcinoma in Leading Academic Oncology Centers Across the U.S. to Determine Which Indication to Progress; Full Data Set Will be Analyzed in the Second Half of 2024 to Facilitate the Final Decision."

Enrollment closed • P1 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Eye Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Ocular Melanoma • Oncology • Solid Tumor • Uveal Melanoma

TriSalus Life Sciences Technology Featured in Two Presentations at the Society of Interventional Radiology Annual Scientific Meeting (Businesswire) - P1/1b | N=60 | PERIO-03 (NCT05607953) | Sponsor: TriSalus Life Sciences, Inc. | "Technology from TriSalus Life Sciences Inc...was featured in two oral presentations at the Society of Interventional Radiology Annual Scientific Meeting....Early safety and feasibility data from the PERIO-03 trial for locally advanced pancreatic adenocarcinoma showed technical success in all five patients who had received eight treatment interventions at data cutoff. There were no immediate complications from the procedure, and there was no evidence of hemorrhage or thrombosis. This follows a previous report indicating evidence of encouraging immune signals such as decreases in myeloid derived suppressor cells (MDSC) in the treated pancreatic tumors with evidence of T-cell activation."

P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor