– New data from PERIO-01 clinical trial
indicates PEDD™ method resulted in modulation of the tumor
microenvironment by enabling performance of the TLR9 agonist,
SD-101, in metastatic uveal melanoma, consistent with an earlier
presentation from pancreatic adenocarcinoma trial –
– Median Progression-Free Survival was 11.7
months, with an 81% Disease Control Rate with the optimal biologic
dose of SD-101 (2 mg) in combination with nivolumab –
TriSalus Life Sciences® Inc., (Nasdaq: TLSI), an oncology
company integrating its novel delivery technology with
immunotherapy to transform treatment for patients with liver and
pancreatic tumors, today presented additional Phase 1 clinical data
during the late-breaker oral presentation session at the Society of
Immunotherapy for Cancer (SITC) 2023 Annual Meeting.
The PERIO-01 Phase 1 study for uveal melanoma with liver
metastases (UMLM), studied SD-101 delivered via PEDD with the
TriNav® Infusion System in combination with intravenous checkpoint
inhibitors. The data presented today at SITC demonstrate that
SD-101 is well tolerated when given by the PEDD method and is
associated with immunologic effects both within the liver and
systemically, which may enable better outcomes with systemic
checkpoint inhibition. The Progression-Free Survival (PFS), Disease
Control Rate (DCR), and ctDNA molecular response data in PERIO-01
patients in combination with nivolumab are encouraging for UMLM and
for other indications under development. At the optimal biologic
dose of SD-101 (2 mg) in combination with nivolumab (n=7), the
median PFS was 11.7 months with an 81% DCR.
“We are encouraged to see that SD-101 is well tolerated when
given by PEDD, in association with immunologic effects within the
liver and systemically, which may enable better outcomes with
systemic checkpoint inhibition,” said Steven C. Katz, M.D., FACS,
Chief Medical Officer at TriSalus. “The PFS and ctDNA molecular
response data in PERIO-01 patients in combination with nivolumab
are promising for UMLM and as well as for other indications that we
are pursuing.”
“The results of PERIO-01 highlight the importance of getting the
biology right and not just pushing a drug to its maximum tolerated
dose. The biological effects of SD-101 are best at the lowest dose
tested, revealing tumor microenvironment reprogramming and
inflammatory cell trafficking from normal to metastatic liver
tumors,” said Sapna Patel, M.D., director of the uveal melanoma
program at The University of Texas MD Anderson Cancer Center. “This
is not seen at higher doses of SD-101, and these findings ensure we
are entering the next phase with the optimal dose in combination
with checkpoint inhibition, for patients with metastatic uveal
melanoma.”
PERIO-01 is an open-label, first-in-human Phase 1 trial of
SD-101, administered by hepatic arterial infusion with TriNav using
PEDD in UMLM. The study consists of dose-escalation cohorts of
SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition.
At the data cutoff as of September 29, 2023, 56 patients were
enrolled, with each having received at least one dose of SD-101. Of
the patients with available data, 16 patients (29%) were
treatment-naïve and 40 (71%) had failed at least one prior line of
therapy, including 8 patients (14%) on 3rd or greater line of
treatment. SD-101 infused via PEDD in combination with systemic
checkpoint inhibition was well tolerated, with an overall serious
grade 3/4 adverse event rate related to treatment of 11% (n=56),
and no such events at the optimal SD-101 dose level of 2 mg in
combination with nivolumab (n=7). The most common adverse events
overall were gastrointestinal (41%), fatigue (30%), and skin
toxicity (27%), with the majority being minor.
Encouraging early efficacy signals were noted in the UMLM
patients treated in PERIO-01. Overall, the ctDNA molecular response
rate was 65% using specified time points (n=20), and 82% when
analyzing the best on-treatment response (n=26). Clearance of ctDNA
was noted in 59% of subjects when assessing the best on-treatment
response. There was an 81% disease control rate at 2 mg SD-101 via
PEDD with nivolumab (n=7). Across all subjects, two partial
responses (≥30% decrease) and five minor responses
(10-29% decrease) were documented as the best on-treatment
response. The median progression free survival at the optimal dose
of SD-101 via PEDD (2 mg) in combination with nivolumab was 11.7
months with a 1-year overall survival rate of 86% (n=7).
Among PERIO-01 patients who received SD-101 via PEDD in
combination with intravenous nivolumab, there was evidence of
increases in CD8+ T cells, CD4+ T cells, and natural killer cells
within their liver metastases. Gene expression analysis by
Nanostring revealed increased TLR signaling, interferon signaling,
cytokine signaling, Th1 T cell activation, and lymphocyte
activation. At the optimal SD-101 dose of 2 mg in combination with
nivolumab, decreases in monocytic myeloid derived suppressor cells
(MDSC), M2 macrophages, and regulatory T cells were found in liver
metastases. Along with predicted immune changes within liver
metastases, encouraging peripheral immune signals were detected.
Increases in IFNγ, soluble IL2-receptor, IL-15, IL-18, T cell
activation, and NK cell proliferation were found in the blood.
Dr. Katz added, “These data reflect additional validation of our
innovative immunotherapy approach for liver and pancreas tumors.
SD-101 was selected based on its mechanism of action, which has the
potential to reverse immunosuppression in the liver and pancreas
through depletion of MDSC in concert with broad stimulation of
immune cells in the tumor microenvironment. TriSalus delivery
systems, which use the PEDD method, are designed to overcome
mechanical barriers to immunotherapy success, which may be
underappreciated factors in limiting performance of TLR agonists in
liver and pancreas tumors.”
Overall, the data emerging from the PERIO-01 and PERIO-03 also
presented at SITC indicate immunologic changes are occurring within
the liver and pancreas, with favorable safety profiles. Patients
with liver metastases in the PERIO-01 study have had favorable
outcomes despite pre-treatment.
All TriSalus presentations from SITC is available here following
their respective sessions.
About Pressure-Enabled Regional Immuno-Oncology (PERIO)
clinical trials
The Pressure-Enabled Regional Immuno-Oncology (PERIO) clinical
trials are studying an investigational class C toll-like receptor-9
agonist, SD-101, delivered intravascularly by TriSalus’ TriNav®
Infusion System (TriNav) using the Company’s proprietary
Pressure-Enabled Drug Delivery™ (PEDD™) method of administration in
three Phase 1 trials.
The PERIO-01 Phase 1 clinical study for uveal melanoma with
liver metastases (UMLM), is studying SD-101 delivered via PEDD with
the TriNav in combination with intravenous checkpoint
inhibitors.
The PERIO-02 trial is evaluating whether this same platform
approach (PERIO-01) with SD-101 and PEDD can improve the
performance of systemic checkpoint inhibitors in treating patients
with hepatocellular carcinoma or intrahepatic
cholangiocarcinoma.
The PERIO-03 study is an open-label, Phase 1/1b study of the
pressure-enabled intrapancreatic infusion of SD-101, a TLR 9
agonist, alone or in combination with intravenous checkpoint
blockade in adults with locally advanced pancreatic cancer.
About TriSalus Life Sciences
TriSalus Life Sciences® is an oncology company integrating novel
delivery technology with immunotherapy to transform treatment for
patients with liver and pancreatic tumors.
The Company’s platform includes devices that utilize a
proprietary drug delivery technology and a clinical stage
investigational immunotherapy. The Company’s two FDA-cleared
devices use its proprietary Pressure-Enabled Drug Delivery™ (PEDD™)
approach to deliver a range of therapeutics: the TriNav® Infusion
System for hepatic arterial infusion of liver tumors and the
Pancreatic Retrograde Venous Infusion System™ for pancreatic
tumors. PEDD is a novel delivery approach designed to address the
anatomic limitations of arterial infusion for the pancreas. The
PEDD approach modulates pressure and flow in a manner that delivers
more therapeutic to the tumor and is designed to reduce undesired
delivery to normal tissue, bringing the potential to improve
patient outcomes. SD-101, the Company’s investigational
immunotherapeutic candidate, is designed to improve patient
outcomes by treating the immunosuppressive environment created by
many tumors and that can make current immunotherapies ineffective
in the liver and pancreas. Patient data generated during
Pressure-Enabled Regional Immuno-Oncology™ (PERIO) clinical trials
support the hypothesis that SD-101 delivered via PEDD may have
favorable immune effects within the liver and systemically. The
target for SD-101, TLR9, is expressed across cancer types and the
mechanical barriers addressed by PEDD are commonly present as well.
SD-101 delivered by PEDD will be studied across several indications
in an effort to address immune dysfunction and overcome drug
delivery barriers in the liver and pancreas.
In partnership with leading cancer centers across the country –
and by leveraging deep immuno-oncology expertise and inventive
technology development – TriSalus is committed to advancing
innovation that improves outcomes for patients. Learn more at
trisaluslifesci.com and follow us on Twitter and LinkedIn.
For Patients To learn more about the clinical trial treatment
protocol and enrollment, visit http://www.periotrial.com or
http://www.clinicaltrials.gov and search NCT04935229, NCT05220722,
and NCT05607953.
Forward Looking Statements Statements made in this press
release regarding matters that are not historical facts are
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. Because such statements
are subject to risks and uncertainties, actual results may differ
materially from those expressed or implied by such forward-looking
statements. Such statements include, but are not limited to,
statements regarding the benefits and potential benefits of the
Company’s PEDD drug delivery technology and SD-101 investigational
immunotherapy. Risks that could cause actual results to differ from
those expressed in these forward-looking statements include risks
associated with clinical development and regulatory approval of
drug delivery and pharmaceutical product candidates, including that
future clinical results may not be consistent with patient data
generated during the Company’s PERIO clinical trials, and other
risks described in the Company’s filings with the Securities and
Exchange Commission under the heading “Risk Factors.” All
forward-looking statements contained in this press release speak
only as of the date on which they were made and are based on
management’s assumptions and estimates as of such date. The Company
undertakes no obligation to update such statements to reflect
events that occur or circumstances that exist after the date on
which they were made except as required by law.
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For Media and Investor Inquiries: Argot Partners
212.600.1902 TriSalus@argotpartners.com
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