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

Pneumonitis but not other immune related adverse events (irAEs) associate with pre-treatment immune signatures in early-stage breast cancer patients receiving neoadjuvant immunotherapy (IO): results from 5 IO arms in I-SPY2 (SABCS 2025) - "Methods 356 patients (206 HR+HER2- and 150 TN) across 5 IO arms (69 pembrolizumab (Pembro), 76 Pembro/SD101, 73 durvalumab/olaparib, 62 cemiplimab (Cemi), and 78 Cemi/LAG3) with irAE and pCR data were analyzed. This association was observed exclusively in patients with ImPrint+ tumors, where PD1 mRNA levels predicted pneumonitis. mRNA signatures may help enable early identification and treatment of IO patients likely to develop pneumonitis."

Adverse events • Clinical • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • LAG3 • PD-1 • PD-L1

The Impact of Pausing Bruton Tyrosine Kinase Inhibitor Therapy and Responsiveness of Vaccination in Blood Cancer Patients: Primary Outcome Result for the Randomised Improve Trial (ASH 2023) - "At baseline, the geometric mean anti-spike RBD antibody titre was 71.6 U/mL (SD 101.3) in the suspend BTKi group and 132.9 U/mL (SD 82.2) in the continue BTKi group. Between Oct 10, 2022 and June 30, 2023, 99 participants with CLL were randomly assigned to continue BTKi (n=49) or pause BTKi (n=50). Mean age of participants was 70.5 years and 71/99 (72%) were male. 63/99 (64%) were on first line CLL therapy, and 51 (52%) were taking Ibrutinib, with the remaining participants taking Acalabrutinib."

Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Respiratory Diseases

Loss of the OX40 Target in Lymphoma Patients after Combining an Anti-OX40 Agonist Antibody with in Situ Vaccination (ASH 2023) - P1 | "STUDY: Fourteen patients with low-grade lymphoma received low-dose (2Gy x 2) radiotherapy to a single tumor site followed by 5 weekly intratumoral injections of 2 mg CpG-ODN (SD-101, TriSalus Life Sciences) and 3.75 mg anti-OX40 antibody into the same site...This loss was reproduced by in vitro assays where activated blood CD4 T cells exhibited a loss of cell surface OX40 when cultured with BMS-986178... Our observations suggest that treatment with an agonistic anti-OX40 antibody induced a loss of OX40 on the cell surface of effector CD4 T cells in the tumor microenvironment. Fewer molecules of OX40 receptor may have constrained the efficacy of subsequent anti-OX40 infusions and may explain why the clinical responses observed in this study were lower than observed in our past clinical trials of in situ vaccination."

Clinical • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Oncology • Solid Tumor • CD4

Short-term efficacy and safety of intravitreal brolucizumab in diabetic macular edema: A retrospective interventional study. (PubMed, Oman J Ophthalmol) - "The study findings in this cohort demonstrated statistically significant improvement in BCVA and a substantial decrease in SFMT. However, more real-world studies are required to enhance the validation of this study's findings."

Journal • Retrospective data • Cardiovascular • Diabetic Macular Edema • Inflammation • Ophthalmology

PERIO-02: Pressure Enabled Delivery of SD-101 With Checkpoint Blockade for Primary Liver Tumors (clinicaltrials.gov) - P1/2 | N=23 | Terminated | Sponsor: TriSalus Life Sciences, Inc. | N=89 ➔ 23 | Active, not recruiting ➔ Terminated; The decision was made to terminate the study after the completion of Phase 1b enrollment and not proceed with Phase 2. Trial termination was not due to patient safety or data concerns.

Checkpoint inhibition • Enrollment change • Trial termination • Biliary Cancer • Cholangiocarcinoma • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • FGFR2

PERIO-01: Intrahepatic Delivery of SD-101 by Pressure-Enabled Regional Immuno-oncology (PERIO), With Checkpoint Blockade in Adults With Metastatic Uveal Melanoma (clinicaltrials.gov) - P1 | N=67 | Terminated | Sponsor: TriSalus Life Sciences, Inc. | Active, not recruiting ➔ Terminated; The decision was made to terminate the study after the completion of Phase 1 enrollment and not proceed with Phase 2. Trial termination was not due to patient safety or data concerns.

Checkpoint inhibition • Trial termination • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine and murine liver tumor models. (PubMed, Front Oncol) - "Transgenic pigs (oncopigs) with liver tumors received intra-arterial infusions of fluorescently labeled ODN2395 or nelitolimod either via PEDD with a specialized infusion device or with conventional microcatheter delivery in both lobar and selective infusions. PEDD of nelitolimod significantly reduced immunosuppressive MDSCs and an increase in cytotoxic CD8 + T cells within the LM. In conclusion, use of PEDD enhanced targeted therapeutic delivery in swine liver tumors and reduced tumor progression by promoting anti-tumor immunity in murine LM in association with suppressive myeloid cell elimination."

Journal • Preclinical • Cutaneous Melanoma • Hepatocellular Cancer • Liver Cancer • Melanoma • Oncology • Solid Tumor • CD8 • PTPRC

INFINITIVE: ImmuNotherapy For PatIeNts wIth colorecTal LIVer MEtastases (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Northwell Health

New P1 trial • Colorectal Cancer • Oncology • Solid Tumor

Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Advanced Melanoma. (PubMed, Clin Cancer Res) - "In patients with anti-PD-1/PD-L1 treatment-naive advanced melanoma, nelitolimod plus pembrolizumab induced objective responses, including in PD-L1-negative tumors. The treatment combination warrants further study in advanced melanoma."

Clinical • Journal • P2 data • Melanoma • Oncology • Solid Tumor

PERIO-03: Pressure Enabled Intrapancreatic Delivery of SD-101 With Checkpoint Blockade for Locally Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: TriSalus Life Sciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2024 ➔ Sep 2027

Checkpoint inhibition • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

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

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

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