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By systematically addressing these barriers, we aim to improve response to therapies and to enable improved patient outcomes.
−Removed: Many solid tumors, especially desmoplastic tumors like pancreatic ductal adenocarcinoma (PDAC), have high interstitial fluid pressure which creates a physical barrier preventing therapeutics from penetrating the tumor.
+Added: Many solid tumors, especially desmoplastic tumors like pancreatic ductal adenocarcinoma ("PDAC"), liver tumors and various other tumor types have high interstitial fluid pressure which creates a physical barrier preventing therapeutics from penetrating the tumor.
Beyond penetration issues, the blood vessels that supply these tumors are leaky and disorganized, leading to poor distribution of the therapeutic within the tumor.
−Removed: We have developed a platform approach to address the unique challenges of drug delivery to solid tumors with the goal of overcoming the two primary barriers described above that limit therapeutic delivery and inhibits treatment success:
+Added: We have developed a platform approach to address the unique challenges of drug delivery to solid tumors with the goal of overcoming the primary barriers described above that limit therapeutic delivery and inhibits treatment success.
PEDD & TriNav- Device Business with Potential for Growth:
−Removed: Our delivery method — Pressure-Enabled Drug Delivery (PEDD TM ) (“PEDD”) — modulates pressure and flow within blood vessels to improve intravascular therapeutic delivery into tumors thereby increasing the likelihood of tumor response in comparison to conventional delivery technologies.
−Removed: Our on-market, 510(k) cleared PEDD device, the TriNav Infusion System (“TriNav”) is currently being used for a number of interventional radiology procedures, most commonly transarterial radioembolization (“TARE”) and transarterial chemoembolization (“TACE”) in patients with primary liver cancer or in patients with liver metastases.
−Removed: TriNav is a highly innovative and novel device that is FDA-cleared and has undergone peer-reviewed studies at multiple clinical sites.
+Added: Our delivery method, Pressure-Enabled Drug Delivery (“PEDD”), modulates pressure and flow within blood vessels to improve intravascular therapeutic delivery into tumors thereby increasing the likelihood of tumor response in comparison to conventional delivery technologies.
+Added: Our on-market, 510(k) cleared device, the TriNav Infusion System (“TriNav”) using PEDD technology is currently being used for interventional radiology procedures, most commonly transarterial radioembolization (“TARE”) and transarterial chemoembolization (“TACE”) in patients with primary liver cancer or in patients with liver metastases.
+Added: TriNav is a highly innovative device with a novel (PEDD) delivery method.
+Added: At the core of the TriNav system is SmartValve technology , a self-expanding mechanism that:
+Added: • Modulates pressure and flow of the vasculature feeding the tumor to physiologically open collapsed blood vessels,
+Added: • Creates consistent turbulent flow to promote more uniform and repeatable distribution of particles or drugs,
+Added: • Self-centers the catheter tip within the vessel for precise delivery.
+Added: This design represents a meaningful departure from traditional end-hole catheter designs by actively controlling flow dynamics and positioning to improve therapeutic outcomes.
+Added: Food and Drug Administration ("FDA")-cleared and has undergone peer-reviewed studies at multiple clinical sites.
The PEDD method has now been used in over 31,000 procedures, primarily TACE and TARE.
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the previous year.
−Removed: We also have developed a separate 510(k) cleared PEDD device for infusions into the pancreas (Pancreatic Retrograde Venous Infusion ("PRVI") device) to treat pancreatic tumors.
−Removed: TriSalus developed a novel way to access the pancreas via the venous vasculature where the vessels are larger, easier to access and PRVI is designed to address many of the limitations inherent to arterial infusions in the pancreas.
−Removed: The PRVI device is currently being studied in a clinical trial for nelitolimod delivery into pancreatic tumors and has completed enrollment in a Phase 1 clinical trial.
+Added: Additionally, our PEDD technology has proven to demonstrate improved drug delivery in a range of other non-malignant tumor embolizations such as Thyroid Artery embolization for treatment of Multi-nodular goiters, uterine artery embolization ("UAE") for treatment of fibroid tumors, prostate embolization for treatment of prostate cancer and an emerging new application for treatment of osteoarthritis and genicular artery embolization.
+Added: These tumor types share common procedural and drug delivery challenges as oncologic embolization such as tortuosity and small caliber target vessels, variable floor and collateral circulation, risk of off target embolization and the need for deeper penetration of embolic particles into the abnormal tissues.
+Added: TriSalus is currently marketing our PEDD technology and generating clinical data in thyroid embolization, uterine artery embolization, and genicular artery embolization.
+Added: We also have developed a separate 510(k) cleared device for infusions into the pancreas, Pancreatic Retrograde Venous Infusion device, ("PRVI") to treat pancreatic tumors.
+Added: TriSalus developed a novel way to access the pancreas via the venous vasculature where the vessels are larger, easier to access and PRVI with its use of PEDD, is designed to address many of the limitations inherent to arterial infusions in the pancreas.
+Added: The PRVI device is currently being studied in a Phase I dose escalation trial for nelitolimod delivery into pancreatic tumors that has completed enrollment.
Although FDA-cleared, the PRVI device has not yet been commercialized and commercial sale is not anticipated before 2026.
We are currently studying the ability of nelitolimod, an investigational class C TLR9 agonist, to reactivate the immune system within the liver and pancreas by broadly reprogramming immune cells and reducing myeloid derived suppressor cells (“MDSCs”), cells which cause immunosuppression, to enable more durable responses to immune checkpoint inhibitors (“CPIs”), thereby improving patient outcomes.
−Removed: We believe that the combination of PEDD with nelitolimod creates a platform approach with the potential to address common therapeutic barriers across numerous cancer indications affecting the liver and pancreas and that this approach could provide a meaningful benefit to patients.
−Removed: There is also the potential that this platform may not only enable CPIs or other classes of immunotherapeutics, such as cell therapeutics, and, based on published clinical and preclinical data, may prove beneficial when co-administered with currently approved chemotherapeutics and radiation.
−Removed: We are in the early stages of our development efforts and have only one product candidate, nelitolimod, in early clinical development.
−Removed: We have initiated Phase 1 and Phase 1b clinical trials for nelitolimod, each of which are focused on a different target indication, specifically:
−Removed: uveal melanoma, intrahepatic cholangiocarcinoma and hepatocellular carcinoma ("UMLM", "ICC" and "HCC", respectively), and pancreatic cancer.
−Removed: We expect that any continued investigation for ICC and HCC may continue through Investigator Initiated Trials (IITs).
−Removed: Based on the changing landscape for second line treatment of UMLM, we do not intend to proceed to Phase II trials for that indication on our own, but we are looking for potential partners to advance that indication.
−Removed: Our Phase I PERIO-03 clinical trial in pancreatic cancer is enrolled and we anticipate data from the study will be available by the end of 2025, depending on when treatment is completed.
+Added: We believe that the combination of PEDD with nelitolimod creates a platform approach with the potential to address common therapeutic barriers across numerous solid tumor indications, including those affecting the liver and pancreas and that this approach could provide a meaningful benefit to patients.
+Added: There is also the potential that this platform may not only enable CPIs or other classes of immunotherapeutics, such as cell therapeutics, but also will prove to be beneficial when co-administered with currently approved chemotherapeutics and radiation, based on published clinical and preclinical data.
+Added: We are in the early stages of our development and have completed Phase I nelitolimod dose escalation (Uveal Melanoma with Liver Metastases ("UMLM") and LA-PDAC) and Phase Ib (Intrahepatic Cholangiocarcinoma ("ICC")/Hepatocellular Carcinoma ("HCC")) clinical trials.
+Added: Due to physician and investigator interest, we are supporting two Investigator Initiated Trials of nelitolimod, one in patients with advanced HCC in combination with cryoablation, durvalumab and tremelimumab and another in patients with resectable colorectal liver metastases.
+Added: TriSalus may seek to partner nelitolimod in recognition of the significant opportunity within the med-tech platform, while strategically leveraging a partner’s established drug development infrastructure.
+Added: Following the completion of data analysis from the the studies mentioned above, we will explore potential partners to advance nelitolimod development to Phase II trials in one or more chosen indications.
+Added: Results of these early trials will be available in 2026 and we will begin discussions with potential partners on further clinical development.
Overcoming Barriers to Effective Drug Delivery with PEDD
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The end result of these factors creates barriers to the systemic administration of chemotherapeutic agents and nanomedicines to tumors, reducing treatment efficacy.
−Removed: PEDD Delivery Technology is a technological solution to this intratumoral pressure barrier that can enable more effective delivery of therapeutic agents to liver and pancreatic tumors.
+Added: PEDD Delivery Technology is a technological solution to this intratumoral pressure barrier that can enable more effective delivery of therapeutic agents to solid tumors.
PEDD devices are engineered to overcome high intratumoral pressure through creation of a favorable pressure gradient, causing increased blood flow to the tumor while constricting blood flow to normal tissue minimizing systemic exposure and decreasing toxicity.
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The aim of the treatment is to target tumor cells with a high dose of radiation while limiting exposure to healthy tissue.
+Added: This treatment is used commonly when the tumor can’t be surgically removed, the patient’s disease is liver dominant and their liver function is still reasonably preserved.
The PEDD approach is designed to provide a reliable method to maximize the tumor to normal liver ratio (“T/N ratio”).
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Another study at the Saint Luc University Hospital and King Albert II Cancer Institute in Brussels, Belgium confirmed the superiority of PEDD devices in improving tumor deposition in liver radioembolization with resin microspheres.
−Removed: In patients undergoing TARE, augmenting the T/N ratio for the delivery of therapeutic micro spheres has the potential to increase therapeutic response as a direct positive relationship between absorbed dose and tumor response.
−Removed: In addition to the potential for improved response, an increased T/N ratio reduces radiation exposure to normal liver parenchyma and reduces the risk of associated liver toxicity.
+Added: In patients undergoing TARE, augmenting the Tumor /Normal (T/N) ratio for the delivery of therapeutic micro spheres has the potential to increase therapeutic response as a direct positive relationship between absorbed dose and tumor response.
+Added: In addition to the potential for improved response, an increased T/N ratio reduces radiation exposure to normal liver parenchyma and reduces the risk of associated liver toxicity and patient complications.
Treatment of Liver Tumors with Transarterial Chemoembolization ("TACE")
−Removed: TACE is an image-guided, locoregional therapy that involves hepatic artery embolization with intra-arterial infusion of a chemotherapeutic agent and is used most commonly for treatment of HCC and hepatic metastases of colorectal and neuroendocrine tumors in the U.S.
+Added: TACE is an image-guided, locoregional therapy that involves hepatic artery embolization with intra-arterial infusion of a chemotherapeutic agent and is used most commonly for treatment of HCC and hepatic metastases of colorectal and neuroendocrine tumors.
As with TARE, the goal of TACE procedures is to deliver chemotherapeutic agents (in either an emulsion or as part of a drug-eluting bead system) with the goal of complete tumor coverage while avoiding delivery of therapeutic or embolic beads to normal tissue.
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For instance, such studies have shown that:
−Removed: • PEDD has improved tumor targeting in liver radioembolization with resin 90Y microspheres and significantly increased both T/N ratio and dose delivery compared to a standard endhole microcatheter in head-to-head comparisons between PEDD devices and standard catheters in the two studies summarized below:
−Removed: ◦ A prospective company sponsored study included 9 patients with a variety of tumor types who were referred for Y90 radioembolization treatment of their liver tumors.
+Added: • PEDD has improved tumor targeting in liver radioembolization with resin Y90 microspheres and significantly increased both T/N ratio and dose delivery compared to a standard endhole microcatheter in head-to-head comparisons between PEDD devices and standard catheters in the studies summarized below:
+Added: ◦ A prospective company sponsored study included nine patients with a variety of tumor types who were referred for Y90 radioembolization treatment of their liver tumors.
Prior to treatment via PEDD, each patient received two same-day sequential lobar infusions of macroaggregated albumin ("MAA") via endhole microcatheter and PEDD.
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and increased on target deposition in 100% of the tumors.
−Removed: ◦ A retrospective independent study of 61 patients with liver cancer (190 lesions) treated with resin Y90 radioembolization.
+Added: ◦ A retrospective independent study of 61 patients with liver cancer (190 lesions) treated with Y90 radioembolization.
All patients in the study underwent an MAA planning procedure delivered via a standard endhole ("EH") catheter.
−Removed: Resin Y90 was then delivered via either an EH catheter (control group) or via PEDD, followed by PET/CT imaging.
+Added: Y90 was then delivered via either an EH catheter (control group) or via PEDD, followed by PET/CT imaging.
Each patient’s post-Y90 PET/CT was co-registered to their post- MAA SPECT/CT to compare the T/N ratio and tumor dose ("TD").
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The results showed that PEDD significantly improved both tumor targeting and dose delivery across multiple tumor types.
−Removed: • PEDD achieved greater on-target distribution of chemotherapy eluting beads, delivering a significantly higher concentration of therapy in the tumor as compared to standard microcatheters and delivered higher radiographic and pathologic response rates in a head-to-head comparison between the PEDD device and standard catheters in the study summarized below;
◦ A retrospective, single-center study, included 88 treatment-naive patients with solitary HCC tumors <6.5cm who underwent treatment using either PEDD (n = 18) or a standard microcatheter (n = 70).
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p=0.026) as well as a significantly higher concentration of therapy in tumor compared to the standard EH catheter (88.7 ± 10.6% vs 55.3 ± 32.7 %;
−Removed: Real-world Support
−Removed: TriSalus recently published a Health Economic and Outcome Research ("HEOR") study looking at real-world data capturing both safety and clinical complications for TriNav as compared to conventional catheters over the 2020-2022 time period.
+Added: • TriSalus is collaborating with leading academic sites to expand the clinical evidence for PEDD in TACE and TARE procedures.
+Added: The studies include:
+Added: (1) a prospective, randomized study to compare PEDD versus standard microcatheter and T/N ratios in hypovascular and hypervascular liver tumors, (2) a study to measure concordance of MAA mapping and Y90 radioembolization using PEDD, (3) a prospective, randomized study to compare PEDD versus standard microcatheter to deliver TACE neuroendocrine tumors, (4) a prospective, randomized study to compare PEDD versus standard microcatheter for delivery of Y90 embolization in liver metastases, and (5) a prospective, randomized study to compare PEDD versus standard microcatheter for delivery of Y90 radioembolization for large liver tumors.
+Added: Real-world Evidence
+Added: TriSalus recently presented a Health Economic and Outcomes Research ("HEOR") study looking at real-world data capturing both safety and clinical complications for TriNav as compared to conventional catheters over the 2020-2023 time period.
This study utilized a large, 300 million patient datasets covering 98% of US payers.
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Key findings include that TriNav patients, despite a higher baseline disease burden and clinical complexity as compared to non-TriNav patients, showed overall clinical results comparable to the patients with lower disease burden.
−Removed: The study also revealed that:
−Removed: • TriNav patients showed reduced rates of post-procedure fatigue compared to non-TriNav patients
+Added: The study also revealed that in propensity matched cohort analysis:
+Added: • TriNav patients showed reduced rates of post-procedure fatigue compared to non-TriNav patients (p < 0.05)
• In TACE procedures, interventional radiologists were able to deliver significantly more chemotherapeutic to the tumor when using TriNav vs.
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• TriNav TACE patients had fewer 30-day inpatient visits post-procedure vs.
−Removed: non-TriNav patients in matched cohort comparison.
−Removed: • TriNav HCC patients were more likely to have a liver transplant in matched cohort comparison.
−Removed: • TriNav TARE patients with liver metastases had fewer clinical complications post-procedure vs.
−Removed: non-TriNav patients in matched cohort comparison.
−Removed: • In patients with HCC, TriNav patients showed lower rates of post-procedural gastric ulcers and jaundice.
+Added: non-TriNav patients in matched cohort comparison (p<0.05)
+Added: • TriNav patients with had fewer clinical complications post-procedure vs.
+Added: non-TriNav patients in matched cohort comparison (p = 0.07)
These study data demonstrate that TriNav is preferentially selected to treat the complex patient with a higher burden of disease vs.
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Furthermore, post-embolization syndrome, characterized by pain, fever and liver dysfunction, impacts patient quality of life and may delay subsequent treatments.
−Removed: TriNav is focused on improved therapeutic delivery and reduction of off target effects on a range of liver tumors including HCC, colorectal liver metastasis and neuro endocrine tumors.
+Added: TriNav is focused on improved therapeutic delivery and reduction of off-target effects on a range of liver tumors including HCC, colorectal liver metastasis and neuroendocrine tumors.
The incidence of primary and metastatic liver tumors has been increasing, presenting a large opportunity given the poor outcomes associated with liver cancers, whether primary or metastatic.
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The liver is also one of the most common sites for metastases, which is cancer that has spread from another site, and according to the National Cancer Institute and recent epidemiological data, there are at least 96,000 individuals diagnosed annually with liver metastases, primarily from colorectal cancer or non-small cell lung cancer, for a total of more than 137,000 new liver cancer diagnoses per year.
−Removed: We estimate that 60% of these patients are eligible for TACE or TARE procedures and that between 75% and 80% are appropriate candidates for our current TriNav device, representing a potential market opportunity of approximately 62 thousand units, or approximately $494.0 million, based on our current price of $7,983.
−Removed: TriSalus recently expanded its portfolio of PEDD devices with the launch of the TriNav LV Infusion System ("TriNav LV") and TriGuide Guiding Catheter to optimize therapeutic delivery for patients with larger vessels.
−Removed: The TriNav LV is suitable for patients with vessels sized between 3.5 and 5.0mm and is expected to allow us to meaningfully expand our addressable liver embolization market.
−Removed: The TriGuide Guiding Catheter has a larger inner diameter, lubricious inner lining, and reverse curve design to support femoral access for the TriNav LV, which we believes will enhance procedural efficiency.
+Added: We estimate that 60% of these patients are eligible for TACE or TARE procedures and that between 75% and 80% are appropriate candidates for our current TriNav portfolio of devices, representing a potential market opportunity of approximately 62 thousand units, or approximately $494 million, based on our current unit price of $7,983.
+Added: TriSalus has expanded its portfolio of PEDD devices with multiple product launches in 2025 providing interventional radiologists ("IR") a choice of TriNav devices customized to specific patient anatomy and expanding the use in additional applications.
+Added: These include the launch of TriNav FLX, a device with a more flexible distal tip for easier navigation of tortuous vascular anatomy and the launch of TriNav XP, a device with the more flexible distal tip and an increased internal diameter ensuring compatibility with the larger embolic beads commonly used in certain procedures such as uterine artery embolization.
These new products are eligible for the same Healthcare Common Procedure Coding System ("HCPCS") reimbursement codes as existing TriNav products, enabling seamless integration into current billing structures.
−Removed: One potential new application for TriNav LV is the use of the technology for uterine fibroid embolizations ("UFEs").
−Removed: Roughly 10% of women aged 18-65 lives with uterine fibroid today and current treatment approaches include hysterectomy, endometrial ablation and uterine fibroid embolizations.
−Removed: We estimate TriNav LV is applicable for 20 thousand UFEs per year, expanding the market opportunity by approximately $160.0 million.
−Removed: TriSalus also initiated a registry study called PROTECT (Pressure Enabled Retrograde Occlusive Therapy with Embolization for Control of Thyroid Disease) and intends to enroll 100 patients across at least five leading academic sites.
−Removed: It is estimated that approximately 5% of adults have multinodular goiters, and the prevalence in adults over 50 is estimated to be up to 50%.
−Removed: We estimate that this could expand the addressable market for TriNav by approximately 50 thousand procedures, representing an incremental $400.0 million market opportunity.
−Removed: This new procedure utilizing the TriNav system is also eligible for the same HCPCS reimbursement code allowing for seamless integration into current billing approaches.
Additionally, through our pancreas infusion technology we believe we can deliver to the site of disease (pancreatic tumor) in combination with systemic therapy allowing for maximum concentration of the therapeutic directly to the tumor with potential reduced toxicity.
−Removed: We believe that this technology potentially could treat 2 thousand patients annually adding an additional market expansion of $400.0 million.
−Removed: Another potential application of TriNav is for the use in prostate embolization’s.
+Added: We believe that this technology potentially could treat two thousand patients annually adding an additional market expansion of $400 million.
+Added: In addition to the use of our technology for treatment of liver and pancreatic tumors, Interventional Radiologists have initiated its use in a range of other non-malignant tumor applications which include uterine artery embolization, thyroid artery embolization, prostate artery embolization and an emerging treatment for osteoarthritis, genicular artery embolization.
+Added: All represent significant market opportunities for the use of the PEDD technology.
+Added: In regards to UAE, roughly 10% of women aged 18-65 lives with uterine fibroid today and current treatment approaches include hysterectomy, endometrial ablation and uterine artery embolizations.
+Added: We estimate TriNav XP is applicable for 20 thousand UAEs per year, expanding the market opportunity by approximately $160.0 million.
+Added: TriSalus also initiated a registry study called PROTECT (Pressure Enabled Retrograde Occlusive Therapy with Embolization for Control of Thyroid Disease) and is enrolling up to 100 patients across several leading academic sites.
+Added: It is estimated that approximately 5% of adults have multinodular goiters and the prevalence in adults over 50 is estimated to be up to 50%.
+Added: This new procedure for thyroid goiters utilizing the TriNav system is eligible for the same HCPCS reimbursement code allowing for seamless integration into current billing approaches.
+Added: Another potential application of TriNav is for the use in prostate embolizations.
Current treatment options for men with enlarged prostate include prostatectomy, trans-urethral prostate resection, alpha blockers and 5-alpha reductase inhibitors and other options.
−Removed: Prostate embolization’s offer a minimally invasive alternative to pharmaceutical side effects or surgical complications.
+Added: Prostate embolizations offer a minimally invasive alternative to pharmaceutical side effects or surgical complications.
We estimate that TriNav has potential in 25 thousand patients of the 100 thousand patients diagnosed with the disease.
+Added: An emerging new application of TriNav is for the use of our PEDD technology is for genicular artery embolization.
+Added: This procedure aims to treat the chronic knee pain from osteoarthritis, especially for patients who aren’t ready for or want to avoid knee replacement surgery.
+Added: This procedure offers significant pain reduction for many patients, improved function and mobility and offers an alternative to other treatments.
+Added: We estimate that TriSalus has the potential in 100,000 patients of the 33 million people who suffer from this disease.
The estimated total addressable market for TriSalus PEDD technology in the U.S.
is project to exceed >$2.3 billion annually.
−Removed: The market is divided into a current market valued at $900.0 million and an additional market opportunity estimated at $700.0 million.
−Removed: The analysis is based on patient population estimates for various conditions where PEDD may be applicable, including liver cancer, multinodular goiter, locally advanced pancreatic cancer, UFEs and prostate embolization.
−Removed: TriNav Positioning
−Removed: Multiple clinical studies, both in TACE and in TARE, have demonstrated that the PEDD™ approach can increase therapeutic delivery to the tumor while decreasing delivery of radioembolics or chemoembolics to healthy tissue.
−Removed: Our recently published HEOR study clearly demonstrates that TriNav is used in patients with a high burden of disease, and in patients who are more advanced in their disease progression as evidenced by higher comorbidities, greater levels of liver-related adverse events prior to their embolization procedures, higher rates of previous embolization, and higher rates of previous systemic therapy.
−Removed: Given that TriNav patients have achieved outcomes similar to patients with lesser burden of disease overall, and trends towards better outcomes (successful liver transplant) and lower rates of clinical complications, we believe that TriNav is positioned to become the standard of care for the complex patient who may benefit from liver embolization.
−Removed: We believe that a significant majority of embolization patients are "complex patients” defined by one or more of the following:
−Removed: • Previous embolization and/or systemic therapy;
−Removed: • Multi-nodal or bilobar lesions – (Significant tumor burden);
−Removed: • Large tumors ( > 5 cm);
−Removed: • Multiple comorbidities;
−Removed: • Hypovasular tumors.
−Removed: Given this evidence base, we are positioning TriNav to become standard of care for complex patients and are instructing our sales organization to focus interventional radiologists’ utilization of TriNav on these complex patients where TriNav has been shown to provide benefit when compared to standard catheters.
+Added: The market is divided into a current market valued at $1B million and an additional market opportunity estimated at $1.3 Billion.
+Added: The analysis is based on patient population estimates for various conditions where PEDD may be applicable, including liver cancer, multinodular goiter, locally advanced pancreatic cancer, uterine artery embolization, genicular artery embolization and prostate artery embolization.
Reimbursement
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The C9797 code brings significant benefit vs.
−Removed: previous CMS coverage as the new code is not restricted to use in conjunction with specific CPT codes, which was the case under TPT status.
−Removed: Effective April 1, 2025, TriNav received a second unique and permanent HCPCS code from CMS, C8004, which has been assigned to APC 5193 (Level 3
−Removed: Endovascular Procedures) for the calendar year 2025 with a payment rate of $11,341.
+Added: previous CMS coverage as the new code is not restricted to use in conjunction with specific CPT codes, which was the case under transitional pass-through payments (“TPT”) status.
+Added: Effective April 1, 2025, TriNav received a second unique and permanent HCPCS code from CMS, C8004, which has been assigned to APC 5193 (Level 3 Endovascular Procedures) for the calendar year 2025 with a payment rate of $11,341.
This new code provides reimbursement clarity for mapping procedures conducted prior to TARE.
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We aim to enhance awareness among patient communities regarding the array of available treatment options, including participation in our technology and nelitolimod clinical trials.
−Removed: Receiving a diagnosis such as liver or pancreatic cancer is devastating and overwhelming to patients.
−Removed: Our commitment is to provide patients, their clinicians and advocacy organizations with information regarding the benefits of our technology and platform approach with nelitolimod.
Sales and Marketing
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TriSalus utilizes a direct sales model to hospitals and ambulatory surgery centers nationwide.
−Removed: Our current sales focus is on targeting hospitals and major academic medical centers with the highest levels of TACE and TARE procedures.
−Removed: Our sales representatives and sales managers have substantial medical device sales experience and market our products directly to interventional radiologists who perform TACE and TARE procedures.
−Removed: We are focused on developing strong relationships with our physicians and hospital customers in order to educate them on the use and benefits of our products.
+Added: Our current sales focus is on targeting hospitals and major academic medical centers with the highest levels of TACE, TARE and other embolization procedures.
+Added: Our sales representatives, clinical specialists and sales leaders have substantial medical device sales experience and market our products directly to interventional radiologists who perform embolization procedures.
+Added: We are focused on developing strong relationships with physicians and hospital in order to educate them on the use and benefits of our products.
Similarly, our marketing team has a significant amount of domain expertise.
Our sales and marketing team totals 43 professionals as of December 31, 2025.
−Removed: The use of TriNav is consistent with the current steps an interventional radiologist utilizes to conduct TACE and TARE procedures.
+Added: The use of TriNav is consistent with the current steps an interventional radiologist utilizes to conduct TACE and TARE and other embolization procedures.
Following instructions from one of our sales representatives on how best to manage optimal functioning of the SmartValve, we believe the TriNav catheter is intuitive, and relatively easy to use.
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• Reduced treatment toxicity – Fine-tuning treatment regimens based on real-time pressure and flow data may help minimize treatment toxicity by delivering therapeutic agents more precisely to the tumor while sparing healthy tissues.
−Removed: Current PEDD™ devices are able to significantly outperform conventional microcatheters in delivering more dose to the tumor while sparing normal tissue (improving the T:N Ration), and we are focused on enhancing this capability.
−Removed: • Real-time monitoring – Continuous monitoring of pressure and flow allows for real-time assessment of optimal therapy delivery.
−Removed: This enables clinicians' ability to adjust treatment strategies promptly based on dynamic changes in the tumor’s vascular characteristics, optimizing therapeutic efficacy while minimizing potential side effects.
−Removed: • Additional applications – TriSalus continues to explore opportunities to improve patient outcomes in interventional radiology procedures beyond the liver and pancreas.
−Removed: Potential areas where PEDD™ devices may be able to improve outcomes and/or reduce post-embolization complications include benign goiter, UFE, geniculate artery embolization for osteoarthritis of the knee, and prostate embolization for prostatic hyperplasia, among others.
−Removed: We are committed to enhancing our technology by incorporating new technologies that provide meaningful improvements in treatment outcomes and where we can gather new data to support continued product development.
−Removed: Most importantly, we are focused on improving personalized treatment strategies and improving patient outcomes in a range of disease areas.
+Added: Current PEDD devices are able to significantly outperform conventional microcatheters in delivering more dose to the tumor while sparing normal tissue (improving the T/N Ratio), and we are focused on enhancing this capability.
Research and development efforts are currently underway on a variety of different technologies with plans for future product launches within the next several years.
Pancreatic Retrograde Venous Infusion Device
−Removed: Additionally, we are advancing our PRVI, which is currently 510(k) cleared by the FDA and in a Phase 1 clinical trial for locally advanced pancreatic cancer.
+Added: We are advancing our PRVI device, which is currently 510(k) cleared by the FDA and in a Phase 1 clinical trial for locally advanced pancreatic cancer.
Our PRVI approach seeks to address many of the key challenges associated with delivering therapeutics to pancreas tumors.
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• Enabling a therapeutic index that is efficacious while limiting toxicity compared to systemic dosing.
−Removed: The Pancreatic Retrograde Venous Infusion Device has not been commercialized and commercial sales are not anticipated before 2026.
−Removed: Pre-clinical pancreatic cancer model experiments indicated that using the PRVI method of PEDD™ improved drug delivery 3.6-7.0-fold.
+Added: The PRVI device has not been commercialized and commercial sales are not anticipated before 2027.
+Added: Pre-clinical pancreatic cancer model experiments indicated that using our PRVI method of PEDD improved drug delivery 3.6-7.0-fold.
We studied PRVI in an orthotopic murine model of PDAC and demonstrated that PRVI delivery of gemcitabine increased intra-tumoral drug concentrations and enhanced the subsequent tumor responses to treatment.
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It was found that PRVI administration of a 2mg dose of oxaliplatin resulted in a significant decrease in tumor size while preserving nerve conduction velocity and nerve tissue morphology as compared to standard delivery methods under histopathological analysis.
+Added: We believe our pancreatic infusion technology with PEDD offers a potential platform opportunity due to its ability to enable targeted controlled delivery of a broad range of therapeutics directly to the tumor microenvironment.
+Added: By overcoming the vascular and stromal barriers that have historically limited effective drug penetration in pancreatic cancer, the system has the potential to enhance local drug concentration while minimizing systemic exposure.
+Added: This approach is modality-agnostic supporting administration of small molecules, biologics, viral vectors, immunotherapies and combination regimens and can be adapted across multiple treatment paradigms.
+Added: As a result, our goal is to scale this platform across a wide array of therapeutic delivery to improve patient outcomes.
Other Commercialization Growth Opportunities
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In July 2020, we acquired nelitolimod, a class C TLR9 agonist, from Dynavax Technologies Corporation (“Dynavax”).
−Removed: Prior to acquiring nelitolimod, we embarked on a comprehensive landscape assessment evaluating assets currently or formerly in clinical development that would fit the criteria for optimal immunomodulation of the TME in the liver and pancreas.
+Added: Prior to acquiring nelitolimod, we embarked on a comprehensive landscape assessment evaluating assets currently or formerly in clinical development that would fit the criteria for optimal immunomodulation of the tumor microenvironment ("TME") in the liver and pancreas.
Our selection criteria included the identification of an immunotherapeutic with a potential mechanism of action to specifically address immunosuppressive mechanisms in the liver and/or pancreas;
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In the melanoma and head and neck carcinoma studies, nelitolimod in combination with anti-programmed cell death protein 1 (“PD-1”) therapy produced response rates that are higher than those reported for anti-PD 1 therapy alone.
−Removed: See (12) Dynavax Purchase to our consolidated financial statements included elsewhere in this Annual Report for more information.
−Removed: Since acquiring the worldwide rights to nelitolimod, we have initiated three Phase 1/1b Pressure Enabled Regional Immuno-oncology (PERIO TM ) (“PERIO”) studies which are focused on four indications where we are testing the ability of the nelitolimod /PEDD therapeutic platform to enable systemic CPIs in the following Phase 1 clinical trials:
+Added: See Note 10 to our consolidated financial statements included elsewhere in this Annual Report for more information.
+Added: Since acquiring the worldwide rights to nelitolimod, we have initiated three Phase 1/1b Pressure Enabled Regional Immuno-oncology (“PERIO”) studies which are focused on four indications where we are testing the ability of the nelitolimod /PEDD therapeutic platform to enable systemic CPIs in the following Phase 1 clinical trials:
• Uveal melanoma with liver metastases (PERIO-01, NCT04935229);
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• Locally advanced pancreatic carcinoma (PERIO-03, NCT05607953).
−Removed: We have initiated Phase 1 and Phase 1b clinical trials for nelitolimod, each of which are focused on a different target indication, specifically UMLM, ICC and HCC, and pancreatic cancer.
−Removed: We expect that any continued investigation for ICC and HCC will only continue through IITs.
−Removed: Based on the changing landscape for second line treatment of uveal melanoma, we do not intend to proceed to Phase II trials for that indication on our own, but we are looking for potential partners to advance that indication.
−Removed: Our Phase I PERIO-03 clinical trial in pancreatic cancer is enrolled and we anticipate data from the study will be available in sometime in 2025, depending on when treatment is completed.
−Removed: We are collaborating with leading cancer centers across the country to help leverage our deep immuno-oncology expertise and our unique, proprietary platform to improve patient responses to CPI therapy and potentially allow a greater number of cancer patients to benefit from immunotherapy advances.
+Added: Results of our three Phase 1 nelitolimod studies will be available in 2026 and we will begin discussions for a pharmaceutical partner for further clinical development in the most promising indication(s).
+Added: Investigation for HCC is continuing through an IIT.
We believe our approach in combination with CPI therapy has the potential to extend and improve the lives of patients battling liver and pancreatic tumors.
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Based on published clinical and preclinical data, TLR9 agonists may also have beneficial effects when combined with chemotherapeutics and/or radiation.
−Removed: Cancer Types in Clinical Studies
−Removed: Locally Advanced Pancreatic Adenocarcinoma (“LA-PDAC”)
−Removed: LA-PDAC is associated with rapid progression, resistance to conventional therapies, deterioration in quality of life, significant morbidity, and a high mortality rate.
−Removed: PDAC tumors are characterized by dense desmoplastic stroma with limited effector immune cells, rendering both drug delivery and stimulation of immune responses very challenging.
−Removed: Immuno-oncology approaches in general and CPI therapy have been highly successful in certain other malignancies, but PDAC is a particularly aggressive disease which has proven resistant to immuno-oncology regimens.
−Removed: Poor responses to CPI therapy in PDAC patients may be due to the presence of suppressive immune mediators such as MSDCs, scarcity of effector T cells, and drug delivery challenges due to a highly desmoplastic stroma creating high tumor pressures.
−Removed: Response rates to CPI in patients with PDAC are routinely below 10% and new therapeutic options capable of addressing the delivery and immunologic barriers are urgently needed.
−Removed: LA-PDAC immunotherapy success may be limited due to challenges with drug delivery and a deeply immunosuppressive TME driven by MDSC.
−Removed: The PERIO programs are designed to test delivery technology and class C TLR9 agonist with the potential to enhance immunotherapy performance in intrapancreatic indications.
−Removed: Uveal Melanoma Liver Metastases
−Removed: With fewer than three thousand new diagnoses per year in the U.S., uveal melanoma is a rare solid organ malignancy in which metastatic spread to the liver results in rapidly progressive and often fatal disease.
−Removed: Uveal melanoma arises from melanocytes within the uveal tract, but it is a unique disease with distinct genetic, chromosomal, and biologic features not observed in cutaneous melanoma.
−Removed: Metastatic disease occurs in more than 50% of patients and involves the liver in up to 90% of metastatic patients.
−Removed: The recent regulatory approval of Kimmtrak®, a bispecific T-cell receptor engager, which had a 1-year OS rate of 73% offers promise for patients with stage IV uveal melanoma and demonstrates that immunotherapy has potential application in addressing this disease.
−Removed: However, approximately 50% of patients are ineligible due to human leukocyte antigen (“HLA”) type.
−Removed: While the OS data was positive, progression-free survival at one year was only approximately 19%, with a median progression-free survival of 3.3 months.
−Removed: Despite representing a crucial clinical advance, the unmet need in the stage IV uveal melanoma space persists.
−Removed: For patients not eligible for tebentafusp (Kimmtrak), CPIs that target CTLA-4, such as ipilimumab, and those that target PD-1, such as nivolumab and pembrolizumab are often used off-label.
−Removed: However, they have had limited efficacy in metastatic uveal melanoma.
−Removed: An important contributor to the failure of current therapies to effectively treat uveal melanoma is the profoundly immunosuppressive intrahepatic environment.
Market Opportunity for Investigational Therapeutic Nelitolimod
−Removed: Nelitolimod Market Opportunity
+Added: Nelitolimod Market Opportunities
According to the American Cancer Society, the National Cancer Institute and our most up-to-date epidemiology, there are approximately 137 thousand new cases of primary and secondary liver cancers diagnosed annually in the U.S.
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is more than 64 thousand annually with more than 90% of these being pancreatic ductal adenocarcinoma (“PDAC”).
−Removed: PDAC and liver cancers are areas of very high unmet medical need and represent large market opportunities.
−Removed: We are currently evaluating data from our Phase 1 clinical studies and determining which indication(s) we will progress into further clinical studies.
−Removed: A chosen indication would be one in which we believe there is evidence supportive of commercial success, and such progression would require us to raise additional capital.
−Removed: Nelitolimod Potential Indications:
−Removed: Pancreatic Cancer
PDAC is a prevalent, highly lethal cancer, with a five-year survival rate of 13% across all stages.
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Both locally advanced and metastatic PDAC face similar challenges with respect to drug delivery and deep immunosuppression.
−Removed: The National Comprehensive Cancer Network recommends consideration of clinical trials as the preferred option in the first-line setting for metastatic PDAC, emphasizing the broad recognition that current therapies are failing.
−Removed: First-line therapy for advanced or recurrent disease patients is FOLFIRINOX, a chemotherapy regimen, often delivered in concert with radiotherapy.
−Removed: A hallmark of PDAC TME is the abundance of noncancer cell components, collectively designated as the stroma, including MDSCs.
−Removed: This stroma can account for up to 90% of the tumor mass.
−Removed: The stroma has been shown to inhibit both spontaneous and therapeutically inducted antitumor immunity making it difficult to treat.
−Removed: Higher CPI response rates in mismatch repair (“MMR”) deficient PDAC patients suggest promise for CPI in combination with immune reprogramming agents, although fewer than 5% of PDAC patients are MMR deficient.
−Removed: The success of immunotherapy in PDAC may hinge on successful management of two critical barriers:
−Removed: (1) PDAC tumors are densely desmoplastic, with the stroma and high tumor pressures posing a major barrier to drug delivery and (2) PDAC tumors foster deep immunosuppression, which is driven in part by MDSCs.
−Removed: We are initially focusing on locally advanced PDAC due to the potential of the PRVI device to deliver nelitolimod into pancreatic tumors with the PRVI approach.
+Added: Both PDAC and liver cancers are areas of very high unmet medical need and represent large market opportunities for nelitolimod, and for our TriNav device portfolio.
+Added: We have initially focused on locally advanced PDAC due to the potential of the PRVI device to deliver nelitolimod into pancreatic tumors with the PRVI approach.
Drug delivery to pancreatic tumors is more challenging than to the liver, given the more complicated arterial anatomy for the pancreas.
We believe that the potential to administer an immunomodulatory drug, such as nelitolimod, into pancreatic tumors with PEDD creates a highly differentiated clinical approach.
−Removed: Nelitolimod Potential Indications:
−Removed: Uveal melanoma is a malignant tumor derived from melanocytes.
−Removed: Despite similarities between cutaneous and uveal melanoma with respect to cell of origin, the genetic, molecular, and clinical features are entirely distinct.
−Removed: In particular, uveal melanoma has a unique metastatic pattern, with the liver being the dominant site of spread.
−Removed: Uveal melanoma is more aggressive and resistant to current therapies than cutaneous melanoma.
−Removed: Up to 50% of patients develop metastatic disease, with 90% of stage IV patients developing liver metastases.
−Removed: The highly suppressive immune environment in the liver may prevent immunotherapies such as CPIs from achieving success in this patient population.
−Removed: Currently, there are limited treatments for uveal melanoma.
−Removed: Immunocore’s Kimmtrak® is indicated for the treatment of HLA-A*02:01 positive adults with unresectable or metastatic uveal melanoma.
−Removed: Although an improvement over previous therapeutic options, it is only available to approximately 50% of uveal melanoma patients due to its HLA restriction.
−Removed: Kimmtrak was approved by the FDA with median overall survival of 21.7 months and 1-year overall survival of 73% in first line patients.
−Removed: Approximately 50% of the population who are HLA-A*02:01 negative still have not approved treatment option with limited late-stage clinical trials ongoing (Ideaya’s Darovasertib is being studied in combination with crizotinib, is currently in a trial that is potentially registrational).
−Removed: In these patients, dual agent CPI treatment is commonly used with median overall survival of approximately 19 months demonstrated in a small Phase 2 trial.
−Removed: Hepzato TM from Delcath was also recently approved and is available through a Risk Evaluation and Mitigation Strategy program.
−Removed: Use of Hepzato TM requires placement of three catheters (two in the groin and one in the neck) to deliver a chemotherapeutic.
−Removed: We are seeking to create a TME more amenable to checkpoint inhibition, which we believe may potentially be achievable due to direct delivery of nelitolimod to the liver with PEDD, the dual mechanism effect of broad intratumoral immune stimulation coupled with elimination of MDSCs, and the absence of HLA restrictions.
−Removed: Based on the changing landscape of second line treatment of uveal melanoma, we do not intend to proceed to Phase II trials for that indication on our own, but we are looking for potential partners to advance that indication.
+Added: We are currently evaluating data from our Phase 1 clinical studies and determining which indication(s) we will progress into further clinical studies.
+Added: A chosen indication would be one in which we believe there is evidence supportive of commercial success, and such progression would require us to raise additional capital.
Clinical Site Partnership
MD Anderson Cancer Center
−Removed: We have been engaged with top academic sites and leading clinicians in the liver and pancreas cancer spaces.
−Removed: All three PERIO programs have been centered on a 5-year Alliance Program with the University of Texas MD Anderson Cancer Center (“MDACC”) which we entered into in March 2021 (the “MDACC Agreement”).
−Removed: Pursuant to the MDACC Agreement, investigators at MDACC agreed to serve as the lead clinicians for the PERIO-01, PERIO-02, and PERIO-03 studies and we agreed to pay $10.0 million in collaboration funding to MDACC to conduct preclinical and clinical studies as mutually agreed by the parties.
−Removed: To date, we have paid an aggregate of $8.0 million towards these studies.
−Removed: The term of the agreement is for the later of (i) five years or (ii) until the applicable studies are completed.
+Added: In 2021, we entered into a five-year Alliance Program (the “MDACC Agreement”) with the University of Texas MD Anderson Cancer Center (“MDACC”) to serve as the lead investigators for the PERIO-01, PERIO-02, and PERIO-03 studies.
+Added: We agreed to pay MDACC $10 million in collaboration funding for MDACC to conduct preclinical and clinical studies as mutually agreed to by the parties.
+Added: To date, we have paid an aggregate $9.4 million towards these studies.
+Added: The term of the agreement was for the later of (i) five years or (ii) until the applicable studies are completed.
Prior to the expiration of the term of the MDACC Agreement, either party may terminate the MDACC Agreement if the other party commits a material breach of the agreement and fails to cure such breach within 30 days of receiving notice of such breach.
−Removed: We have the right to terminate a study (and the corresponding study order) upon 30 days prior notice to MDACC, provided that the joint steering committee (which is composed of three representatives of each party and oversees the collaboration) has approved such termination and that all reasonable study costs and fees associated with wind-down activities and final monitoring visit shall be paid by us.
−Removed: Termination of one or more study orders will not automatically result in the termination of the MDACC Agreement or termination of any other study orders.
−Removed: Under the terms of the MDACC Agreement, each party retains all right, title and interest in and to its own background intellectual property and no license to use such background intellectual property is granted to the other party except for MDACC’s use of the study drug and study devices, as applicable, in a study as set forth in the MDACC Agreement.
−Removed: Within fifteen days after our receipt of an invention disclosure covering any invention, representatives from each party shall meet to assess whether, taking into consideration the intellectual property limits outlined in the MDACC Agreement, the applicable invention in which MDACC has an ownership interest can be assigned to us in full and exclusive ownership.
−Removed: If such assignment would not violate the intellectual property limits agreed to, MDACC assigns to us the sole and exclusive ownership in and to the applicable invention and we shall reimburse MDACC for reasonable patent costs, if any, incurred by MDACC prior to the date of assignment.
−Removed: No intellectual property has been developed or transferred to date.
+Added: Effective February 25, 2025, we modified our payment terms and extended the MDACC Agreement for an additional year.
Nelitolimod Competition
−Removed: We expect nelitolimod to compete primarily with a number of therapeutics that are now, or will soon be, approved for use in UMLM with liver metastases and locally advanced PDAC.
−Removed: These therapeutics include a range of immunotherapeutics (e.g., tebentafusp for HLA-A*02:01 positive metastatic uveal melanoma patients.
−Removed: Uveal Melanoma
−Removed: There are currently two FDA-approved therapies for uveal melanoma liver metastases, Immunocore's Kimmtrak® (tebentafusp) and Delcath's Hepzato Kit TM .
−Removed: Kimmtrak is a bispecific fusion protein that recognizes two targets, with one target present on melanoma cells, and the second target present on T cells.
−Removed: As with all T-cell receptor products, only patients with specific HLA types are eligible for treatment.
−Removed: As a result, only approximately 50% of stage IV uveal melanoma patients are eligible to receive tebentafusp, and a significant unmet need still remains.
−Removed: Hepzato Kit is designed to deliver high-dose chemotherapy to the liver while limiting systemic exposure.
−Removed: Hepzato Kit carries several black box warnings, is only available at select institutions through a Risk Evaluation and Management Strategy ("REMS"), and is associated with a high rate of Grade 3 or 4 adverse events.
−Removed: We believe that even with the availability of the Hepzato Kit, as an alternative for some uveal melanoma liver metastases patients, significant unmet needs remains for these patients.
−Removed: Ideaya’s Darovasertib, in combination with crizotinib, is currently being studied in HLA:A*02:01 negative patients in a potential registrational trial.
−Removed: We believe that nelitolimod delivered with PEDD to the site of disease with its believed dual mechanism effect of broad intratumoral immune stimulation coupled with elimination of MDSCs, combined with systemic checkpoint inhibition, has the potential to outperform current treatment options.
−Removed: Nelitolimod, if approved, would address the entire stage IV uveal melanoma patient population, with no limitations based on HLA typing.
−Removed: Pancreatic Ductal Adenocarcinoma
−Removed: Current preferred therapy for PDAC is either a clinical trial or chemotherapy (commonly the FOLFIRINOX regimen, + subsequent chemoradiation with a more recent approval of NALIRIFOX which uses liposomal irinotecan rather than standard irinotecan).
−Removed: These chemotherapeutic treatments have significant toxicities and limited efficacy, leaving significant unmet medical need in this disease.
−Removed: In December 2024, the FDA approved BIZENGRI (Zenocutuzamab )for pancreatic adenocarcinoma that harbors NRG1 gene fusions and are advanced unresectable or metastatic.
−Removed: Revolution Medicine is in a Phase 3 registrational trial for RMC-6236, a RAS multi-selective inhibitor.
−Removed: Revolutions trial is anticipated to enroll approximately 460 patients who have received prior PDAC therapy and harbor RAS mutations.
−Removed: Other clinical trials for PDAC are early stage and are evaluating combinations of targeted therapies and immunotherapy.
+Added: We expect nelitolimod to compete primarily with a number of therapeutics that are now, or will soon be, approved for use in liver metastases, liver cancers and locally advanced PDAC.
+Added: These therapeutics include a range of immunotherapies and chemotherapeutics, some already approved and some of which are currently in development.
Dynavax Asset Purchase Agreement
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As of December 31, 2025 and 2024, we have made three milestone payments of $1.0 million each, totaling $3.0 million.
−Removed: no payments were made in the twelve months ended December 31, 2024.
+Added: No payments were made in the years ended December 31, 2025 and 2024.
We also are obligated to pay Dynavax certain royalty payments equal to 10% of aggregate net sales of products containing the nelitolimod compound acquired during each fiscal year up to and including $1.0 billion and 12% for the portion of aggregate net sales during a fiscal year greater than $1.0 billion, subject to certain adjustments.
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Manufacturing
−Removed: Manufacturing
−Removed: We manufacture TriNav at our facility in Westminster, Colorado, and have adequate capacity to meet anticipated commercial and clinical demands through the next several years.
+Added: We manufacture TriNav at our facility in Westminster, Colorado, and through a recent expansion of our clean room we have adequate capacity to meet anticipated commercial and clinical demands through the next several years.
We are continually strengthening our supply chain and are currently qualifying additional third-party suppliers for select components of TriNav.
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As of December 31, 2025, we owned at least 82 registered patents expiring between 2030 and 2040, with at least an additional 11 pending patent applications.
−Removed: For our TriNav device, we are the sole owner of five granted U.S.
−Removed: patents, five pending U.S.
−Removed: patent applications, eight foreign patents (counting national validations in Europe) and two pending foreign patent applications in Canada and Europe relating to a dynamic reconfigurable microvalve protection device and the PEDD method for infusing an immunotherapy agent to a solid tumor and method for selective pressure-controlled therapeutic delivery.
−Removed: The five granted U.S.
+Added: For our TriNav device, we are the sole owner of eight granted U.S.
+Added: patents, three pending U.S.
+Added: patent applications, 13 foreign patents (counting national validations in Europe) and two pending foreign patent applications in Canada and Europe relating to a dynamic reconfigurable microvalve protection device and the PEDD method for infusing an immunotherapy agent to a solid tumor and method for selective pressure-controlled therapeutic delivery.
+Added: The eight granted U.S.
patents expire between 2031 and 2038.
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patents, five pending U.S.
−Removed: patent applications, 12 granted foreign patents (counting national validations in Europe) and two pending foreign patent applications in China and Europe relating to closed tip dynamic microvalve protection device, atraumatic occlusive system with compartment for measurement of vascular pressure change, method for selective pressure-controlled therapeutic delivery and the PRVI method for pressure-controlled retrograde venous therapeutic delivery.
−Removed: The five granted U.S.
+Added: patent applications, 14 granted foreign patents (counting national validations in Europe) and two pending foreign patent applications in Europe and Hong Kong relating to atraumatic occlusive system with compartment for measurement of vascular pressure change The six granted U.S.
patents expire between 2034 to 2039.
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Some patents and applications relating to the TriSalus Infusion System overlap with those identified for the TriNav device.
−Removed: For nelitolimod, we are awaiting three pending U.S.
−Removed: patent application, two pending PCT patent applications, 16 pending foreign patent applications relating to immunostimulatory sequence oligonucleotides and methods of using the oligonucleotides and specifically nelitolimod.
+Added: For nelitolimod, we are the sole owner of five pending U.S.
+Added: patent applications, two pending Patent Cooperation Treaty ("PCT") patent applications, and 34 pending foreign patent applications relating to methods of using immunostimulatory sequence oligonucleotides and specifically nelitolimod.
However, we jointly own with Merck Sharp & Dohme LLC two granted US and 12 granted foreign patents (counting national validations in Europe) that expire in 2036 and related to nelitolimod, which is a CPG-C type oligonucleotide, as discussed further below.
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Any patents issuing from the pending patent applications (if issued from future national phase applications that we file) are expected to expire between 2041 and 2043, without accounting for potential terminal disclaimers or potentially available patent term adjustments or extensions.
−Removed: Upon regulatory approval of nelitolimod in the U.S., we expect to be granted five years of regulatory exclusivity in the U.S.
−Removed: We also intend to apply for orphan drug designation which, if granted, would extend the exclusivity period for an additional two years.
+Added: Successful approval of nelitolimod in the U.S., would provide an opportunity for five years of regulatory exclusivity in the U.S.
+Added: We are studying nelitolimod in orphan indications and intend to apply for orphan drug designation which, if granted, would extend the exclusivity period for an additional two years.
Trade Secrets and Other Proprietary Information
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TriNav, SmartValve, and TRISALUS LIFE SCIENCES are registered trademarks of ours in the U.S, and we have pending applications for U.S.
−Removed: trademarks for TRISALUS, SMARTSENSE, TRIGUIDE, TRISALUS CLINICAL ESSENTIALS.
+Added: trademarks for TRISALUS, SMARTSENSE, TRIGUIDE and TRISALUS CLINICAL ESSENTIALS.
Government Regulation
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These agencies review our design and manufacturing practices, labeling, record keeping, and manufacturers’ required reports of adverse experiences and other information to identify potential problems with marketed products.
−Removed: We are also subject to periodic inspections for compliance with applicable manufacturing and quality system regulations, which govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging,
−Removed: and servicing of finished drugs and medical devices intended for human use.
+Added: We are also subject to periodic inspections for compliance with applicable manufacturing and quality system regulations, which govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, and servicing of finished drugs and medical devices intended for human use.
In addition, the FDA and other regulatory bodies, both within and outside the U.S.
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Some Class I devices may require premarket notification to the FDA.
−Removed: Class II devices are moderate risk devices and are subject to the FDA’s general controls, and special controls as deemed necessary by the FDA to ensure the safety and effectiveness of the device.
+Added: TriSalus has Class II devices that are moderate risk devices and are subject to the FDA’s general controls, and special controls as deemed necessary by the FDA to ensure the safety and effectiveness of the device.
These special controls can include performance standards, post-market surveillance, patient registries and FDA guidance documents.
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The Food and Drug Administration Modernization Act of 1997 established a new route to market for low to moderate risk medical devices that are automatically placed into Class III due to the absence of a predicate device, called the “Request for Evaluation of Automatic Class III Designation,” or the de novo classification procedure.
−Removed: This procedure allows a manufacturer whose novel device is automatically classified into Class III to request
−Removed: down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA.
+Added: This procedure allows a manufacturer whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA.
If the manufacturer seeks reclassification into Class II, the manufacturer must include a draft proposal for special controls that are necessary to provide a reasonable assurance of the safety and effectiveness of the medical device.
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The FDA may condition PMA approval on some form of post-market surveillance when deemed necessary to protect the public health or to provide additional safety and efficacy data for the device in a larger population or for a longer period of use.
−Removed: In such cases, the manufacturer might be required to follow certain patient groups for a number of years and to make periodic reports to FDA on the clinical status of those patients.
Failure to comply with the conditions of approval can result in material adverse enforcement action, including withdrawal of the approval.
Certain changes to an approved device, such as changes in manufacturing facilities, methods, or quality control procedures, or changes in the design performance specifications, which affect the safety or effectiveness of the device, require submission of a PMA supplement.
−Removed: PMA supplements often require submission of the same type of information as a PMA, except that the supplement is limited to information needed to support any changes from the device covered by the original PMA and may not require as extensive clinical data or the convening of an advisory panel.
+Added: A PMA supplement may not require as extensive clinical data or the convening of an advisory panel.
Certain other changes to an approved device require the submission of a new PMA, such as when the design change causes a different intended use, mode of operation, and technical basis of operation, or when the design change is so significant that a new generation of the device will be developed, and the data that were submitted with the original PMA are not applicable for the change in demonstrating a reasonable assurance of safety and effectiveness.
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If the device presents a “significant risk” to human health, as defined by the FDA, the FDA requires the device sponsor to submit an IDE application to the FDA, which must become effective prior to commencing human clinical trials.
−Removed: A significant risk device is one that presents a potential for serious risk to the health, safety or welfare of a patient and either is implanted, used in supporting or sustaining human life, substantially important in diagnosing, curing, mitigating or treating disease or otherwise preventing impairment of human health, or otherwise presents a potential for serious risk to a subject.
−Removed: An IDE application must be supported by appropriate data, such as animal and laboratory test results, showing that it is safe to test the device in humans and that the testing protocol is scientifically sound.
−Removed: The IDE will automatically become effective 30 days after receipt by the FDA, unless the FDA notifies the manufacturer that the investigation may not begin or is subject to a clinical hold.
−Removed: the FDA determines that there are deficiencies or other concerns with an IDE for which it requires modification, the FDA may permit a clinical trial to proceed under a conditional approval.
−Removed: In addition, clinical studies must be approved by, and conducted under the oversight of, an Institutional Review Board (“IRB”) for each clinical site.
+Added: Clinical studies must be approved by, and conducted under the oversight of, an Institutional Review Board (“IRB”) for each clinical site.
The IRB is responsible for the initial and continuing review of the IDE and may pose additional requirements for the conduct of the trial.
If an IDE application is approved by the FDA and one or more IRBs, human clinical trials may begin at a specific number of investigational sites with a specific number of patients, as approved by the FDA.
−Removed: If the device presents a non-significant risk to the patient, a sponsor may begin the clinical trial after obtaining approval for the trial by one or more IRBs without separate approval from the FDA, but must still follow abbreviated IDE requirements, such as monitoring the investigation, ensuring that the investigators obtain informed consent, and labeling and record-keeping requirements.
−Removed: An IDE supplement must be submitted to, and approved by, the FDA before a sponsor or investigator may make a change to the investigational plan.
During a clinical trial, the sponsor is required to comply with the applicable FDA requirements, including, for example, trial monitoring, selecting clinical investigators and providing them with the investigational plan, ensuring IRB review, adverse event reporting, record keeping, and prohibitions on the promotion of investigational devices or on making safety or effectiveness claims for them.
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Drug Development and Approval
−Removed: Under the FD&C Act, FDA approval of an NDA is required before any new drug can be marketed in the U.S.
+Added: Under the FD&C Act, FDA approval of an NDA (or BLA, for biologics) is required before any new drug can be marketed in the U.S.
NDAs require extensive studies and submission of a large amount of data by the applicant.
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Before testing any compound in human patients in the U.S., a company must generate extensive preclinical data.
−Removed: Preclinical testing generally includes laboratory evaluation of product chemistry and formulation, as well as toxicological and pharmacological studies in several animal species to assess the toxicity and dosing of the product.
−Removed: Certain animal studies must be performed in compliance with the FDA’s Good Laboratory Practice (“GLP”) regulations and the U.S.
+Added: Preclinical testing generally includes laboratory evaluation of product chemistry and formulation, as well as toxicological and pharmacological studies in several animal species to assess the toxicity and dosing of the product, some of which may require compliance with the FDA’s Good Laboratory Practice (“GLP”) regulations and the U.S.
Department of Agriculture’s Animal Welfare Act.
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Unless the FDA raises concerns, the IND becomes effective 30 days following its receipt by the FDA, and the clinical trial proposed in the IND may begin.
−Removed: Either before or after human clinical trials commence, the FDA may stop a clinical trial by placing it on “clinical hold” because of concerns about the safety of the product being tested or for other reasons.
+Added: TriSalus opened an IND in 2021, under which it launched three (3) Phase 1 studies.
+Added: TriSalus also obtained three additional INDs when it licensed nelitolimod from Dynavax.
Clinical Trials.
−Removed: Clinical trials involve the administration of a drug to healthy human volunteers or to patients, under the supervision of a qualified investigator.
−Removed: The conduct of clinical trials is subject to extensive regulations, including compliance with the FDA’s Good Clinical Practice (“GCP”) requirements, which establish standards for conducting, recording data from, and reporting the results of, clinical trials, and are intended to assure that the data and reported results are credible and accurate and that the rights, safety, and well-being of study participants are protected.
−Removed: The conduct of clinical trials is subject to the FDA’s Bioresearch Monitoring (“BIMO”) program, a comprehensive program of on-site inspections, data audits, and remote regulatory assessments.
−Removed: Clinical trials must be conducted under protocols that detail the study objectives, parameters for monitoring safety, and the efficacy criteria, if any, to be evaluated.
−Removed: Each protocol is reviewed by the FDA as part of the IND.
−Removed: In addition, each clinical trial must be reviewed and approved by, and conducted under the auspices of, an Institutional Review Board (“IRB”) for each clinical site.
−Removed: Companies sponsoring the clinical trials, investigators, and IRBs also must comply with, as applicable, regulations and guidelines for obtaining informed consent from the study patients, following the protocol and investigational plan, adequately monitoring the clinical trial, and timely reporting of adverse events (“AEs”).
−Removed: Foreign studies conducted under an IND must meet the same or comparable requirements as those that apply to studies being conducted in the U.S.
+Added: Clinical trials must be conducted by qualified investigators, and are subject to extensive regulations, including compliance with the FDA’s Good Clinical Practice (“GCP”) requirements, which establish standards for conducting, recording data from, and reporting the results of, clinical trials, and the well-being of study participants.
+Added: Clinical trials are subject to the FDA’s Bioresearch Monitoring (“BIMO”) program, a comprehensive program of on-site inspections, data audits, and remote regulatory assessments.
+Added: Either before or after human clinical trials commence, the FDA may stop a clinical trial by placing it on “clinical hold” because of concerns about the safety of the product being tested or for other reasons.
+Added: Clinical trials are conducted under protocols reviewed by the FDA, that detail the study objectives, parameters for monitoring safety, and the efficacy criteria, if any, to be evaluated., Each clinical trial must be reviewed and approved by , an Institutional Review Board (“IRB”) for each clinical site.
+Added: Companies sponsors, investigators, and IRBs must comply with, as applicable, regulations and guidelines for obtaining informed consent from the study patients, following the protocol and investigational plan, adequately monitoring the clinical trial, and timely reporting of adverse events (“AEs”).
+Added: Foreign studies conducted under an IND must meet the same or comparable requirements as those being conducted in the U.S.
Data from a foreign study not conducted under an IND may be submitted in support of an NDA if the study was conducted in accordance with GCP and U.S.
regulations and the FDA is able to validate the data.
−Removed: A study sponsor is required to publicly post specified details about certain clinical trials and clinical trial results on government or independent websites (e.g., http://clinicaltrials.gov).
+Added: A company or study sponsor is required to publicly post specified details about certain clinical trials and l results on government or independent websites (e.g., http://clinicaltrials.gov).
Human clinical trials typically are conducted in three sequential phases, although the phases may overlap, be combined, or be subdivided.
In some cases, particularly in the development of therapies to treat orphan or rare disease or diseases with unmet medical need, development is limited to one or two phases.
−Removed: • Phase 1 clinical trials involve the initial administration of the investigational drug to humans, typically to a small group of healthy human subjects, but occasionally to a group of patients with the targeted disease or disorder.
−Removed: Phase 1 clinical trials generally are intended to evaluate the safety, metabolism and pharmacologic actions of the drug, the side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.
+Added: • Phase 1 clinical trials involve the initial administration of the investigational drug to humans, typically to a small group of healthy human subjects, but occasionally to a group of patients with the targeted disease or disorder to primarily establish safety before proceeding to additional phase of drug development.
• Phase 2 clinical trials generally are controlled studies that involve a relatively small sample of the intended patient population, and are designed to develop initial data regarding the product’s effectiveness, to determine dose response and the optimal dose range, and to gather additional information relating to safety and potential AEs.
−Removed: • Phase 3 clinical trials are conducted after preliminary evidence of effectiveness has been obtained and are intended to gather the additional information about safety and effectiveness necessary to evaluate the drug’s overall risk-benefit profile and to provide a basis for physician labeling.
+Added: • Phase 3 clinical trials are conducted to gather the additional information about safety and effectiveness necessary to evaluate the drug’s overall risk-benefit profile and to provide a basis for physician labeling.
Generally, Phase 3 clinical development programs consist of expanded, multi-site, large-scale studies of patients with the target disease or disorder to obtain statistical evidence of the efficacy and safety of the drug at the proposed dosing regimen.
Phase 3 data often form the core basis on which the FDA evaluates a drug’s safety and effectiveness when considering the product application.
−Removed: The sponsoring company, the FDA or the IRB may suspend or terminate a clinical trial at any time on various grounds, including a finding that the patients are being exposed to an unacceptable health risk.
−Removed: Further, success in early-stage clinical trials does not assure success in later-stage clinical trials.
+Added: Success in early-stage clinical trials does not ensure success in later-stage clinical trials.
Data obtained from clinical activities are not always conclusive and may be subject to alternative interpretations that could delay, limit or prevent regulatory approval.
NDA Submission and Review.
−Removed: The FD&C Act provides two pathways for the approval of new drugs through an NDA.
−Removed: An NDA under Section 505(b) of the FD&C Act is a comprehensive application to support approval of a product candidate that includes, among other things, data and information to demonstrate that the proposed drug is safe and effective for its proposed uses, that production methods are adequate to ensure its identity, strength, quality, and purity of the drug, and that proposed labeling is appropriate and contains all necessary information.
−Removed: A 505(b)(1) NDA contains results of the full set of preclinical studies and clinical trials conducted by or on behalf of the applicant to characterize and evaluate the product candidate.
−Removed: Section 505(b)(2) of the FD&C Act provides an alternate regulatory pathway to obtain FDA approval that permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference.
−Removed: We plan to seek FDA approval of nelitolimod delivered via PEDD through the 505(b)(1) regulatory approval pathway, as part of a combination regimen with other therapeutics.
+Added: An NDA is submitted under Section 505(b) of the FD&C Act, and includes, among other things, preclinical and clinical study data sufficient to demonstrate that the proposed drug is safe and effective for its proposed uses, that production methods are adequate to ensure its identity, strength, quality, and purity of the drug, and that proposed labeling is appropriate and complete A 505(b)(1) NDA contains results of the full set of preclinical studies and clinical trials conducted by or on behalf of the applicant to characterize and evaluate the product candidate.
+Added: A 505(b)(2) of the FD&C Act provides an alternate regulatory pathway to obtain FDA approval that permits the filing of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference.
+Added: We plan to seek FDA approval of nelitolimod delivered via PEDD through the submission of an 505(b)(1) NDA as part of a combination regimen with other therapeutics.
A combination regimen requires data demonstrating the contribution of each drug in the regimen to the treatment of the disease under study.
−Removed: For nelitolimod to obtain approval, we will be required to produce data to confirm its contribution to the regimen improves the efficacy of the therapeutic regimen.
−Removed: There is FDA precedent for this data to be obtained from a number of sources, including, a comparator in a controlled trial, prior FDA approvals, historic data from other clinical trials or meta-analysis of clinical practice or “real world” data.
+Added: Approval will require us to produce data to confirm nelitolimod’s or any other therapeutic contribution improves the efficacy of the therapeutic regimen.
+Added: FDA precedent indicates that these data may be obtained from a number of sources, including, a comparator in a controlled trial, prior FDA approvals, historic data from other clinical trials or meta-analysis of clinical practice or “real world” data.
In addition to a combined therapy, the inclusion of a drug (nelitolimod) and a cleared device component (TriNav) in the platform is likely to be considered a “combination product” under FDA regulations.
−Removed: For nelitolimod, we expect that the FDA’s Center for Drug Evaluation and Research (“CDER”) will have primary jurisdiction for review of the NDA, and the drug and cleared device will be reviewed as a combination product under one marketing application.
−Removed: For a drug-device combination product, CDER typically consults with the FDA’s Center for Devices and Radiological Health in the NDA review process.
−Removed: For TriNav to become part of a combination product, we may be required to produce data supporting TriNav or PEDD’s contribution to the efficacy of nelitolimod in the targeted indications beyond the original data used in support of 510(k) clearance of the TriNav device.
−Removed: In addition, our PRVI device is currently being studied in combination with nelitolimod in the PERIO-03 trial.
−Removed: The PRVI device has received 510(k) clearance and may in the future also meet the definition of a “combination product” under FDA regulations.
−Removed: For the PRVI device to become part of a combination product, we may be required to produce data supporting PRVI or PEDD’s contribution to the efficacy of nelitolimod in the targeted indications beyond the original data used in support of 510(k) clearance of the PRVI device.
−Removed: The submission of an NDA generally requires payment of a substantial user fee to the FDA, however a drug that has received an Orphan Drug Designation is not subject to this user fee.
−Removed: Moreover, under section 736(d)(1)(D) of the FD&C Act, an applicant is eligible for a waiver of the application fee if the applicant is a small business submitting its first human drug application to the Agency for review and does not have another product approved under a human drug application and introduced or delivered for introduction into interstate commerce.
+Added: We expect that the FDA’s Center for Drug Evaluation and Research (“CDER”) will have primary jurisdiction for review of the NDA, and that FDA’s Center for Devices and Radiological Health will be consulted during the NDA review process.
+Added: As part of a combination product, we may be required to produce data supporting TriNav or PEDD’s contribution to the efficacy of the regimen in the targeted indications beyond the original data used in support of 510(k) clearance.
+Added: The same is true for our PRVI device currently being studied in combination with nelitolimod in the PERIO-03 trial.
+Added: For the PRVI device to become part of a combination product, we may be required to produce data supporting PRVI or PEDD’s contribution to the efficacy of the regimen in the targeted indications beyond the original data used in support of 510(k) clearance of the PRVI device.
+Added: An NDA submission to the FDA generally requires payment of a substantial user fee, however a drug that has received an Orphan Drug Designation is not subject to this user fee.
+Added: Moreover, under section 736(d)(1)(D) of the FD&C Act, a small business submitting its first human drug application to the Agency without another approved human drug application introduced or delivered into interstate commerce is eligible for a waiver.
The FDA reviews applications to determine, among other things, whether a product is safe and effective for its intended use and whether the manufacturing controls are adequate to assure and preserve the product’s identity, strength, quality, and purity.
−Removed: For some NDAs, the FDA may convene an advisory committee to seek insights and recommendations on issues relevant to approval of the application.
−Removed: Although the FDA is not bound by the recommendation of an advisory committee, the FDA considers such recommendations carefully when making decisions.
−Removed: Additional regulatory requirements may be implicated.
−Removed: The FDA may determine that a Risk Evaluation and Mitigation Strategy (“REMS”) is necessary to ensure that the benefits of a new product outweigh its risks prior to approving a new product.
−Removed: A REMS may include various elements, ranging from a medication guide or patient package insert to limitations on who may prescribe or dispense the drug, depending on what the FDA considers necessary for the safe use of the drug.
−Removed: Under the Pediatric Research Equity Act, as amended by the FDA Reauthorization Act of 2017, certain molecularly targeted oncology drugs require early evaluation.
−Removed: Specifically, if an original NDA or Biologics License Application for a new active ingredient for adults is directed at a molecular target FDA determines to be substantially relevant to the growth or progression of a pediatric cancer, study of the molecularly targeted pediatric cancer must be submitted with the marketing application, unless FDA waives or defers the requirement.
−Removed: FDA also inspects the facility or facilities where the product is manufactured prior to approving an NDA.
−Removed: The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with current Good Manufacturing Practice (“cGMP”) requirements and an adequate quality system to assure consistent production of the product within required specifications.
−Removed: Once the FDA accepts an NDA submission — which occurs, if at all, within 60 days after submission of the NDA — the FDA’s goal for a non-priority review of an NDA is ten months.
−Removed: The review process can be and often is significantly extended, however, by FDA requests for additional information, studies, or clarification.
−Removed: After review of an NDA and the facilities where the product is manufactured, the FDA either issues an approval letter or a complete response letter (“CRL”) outlining the deficiencies in the submission.
−Removed: The CRL may require additional testing or information, including additional preclinical or clinical data.
−Removed: Even if such additional information and data are submitted, the FDA may decide that the NDA still does not meet the standards for approval.
−Removed: Data from clinical trials are not always conclusive and the FDA may interpret data differently than the sponsor.
+Added: The FDA may occasionally convene an advisory committee to seek insights and recommendations on issues relevant to approval of the application, although the FDA is not bound by the recommendation of an advisory committee when making decisions.
+Added: FDA accepts (or rejects) an NDA submission — which occurs within 60 days after submission of the NDA — with a non-priority review goal of ten months.
FDA’s goal for the review of an application granted priority review is six months after the 60-day acceptance period.
−Removed: Developing a drug and obtaining regulatory approval often takes a number of years, involves the expenditure of substantial resources, and depends on a number of factors, including the severity of the disease in question, the availability of alternative treatments, and the risks and benefits demonstrated in clinical trials.
−Removed: Additionally, as a condition of approval, the FDA may impose restrictions that could affect the commercial success of a drug or require post-approval commitments, including the completion within a specified time period of additional clinical studies, which often are referred to as “Phase 4” or “post-marketing” studies.
−Removed: Post-approval modifications to the drug or its use, such as changes in indications, labeling, or manufacturing processes or facilities, may require a sponsor to develop additional data or conduct additional preclinical studies or clinical trials, to be submitted in a new or supplemental NDA, which would require FDA approval.
+Added: The review process can be somewhat or significantly extended, however, by FDA requests for additional information, studies, or clarification.
+Added: Upon completion of its review and manufacturing inspection, , the FDA either issues an approval letter or a complete response letter (“CRL”) outlining the deficiencies in the submission.
+Added: A CRL may require additional information or additional clinical data.
+Added: Even with submission of additional information and data, FDA may interpret the data differently from the sponsor and decide that the NDA still does not meet the standards for approval.
+Added: Drug development and regulatory approval often takes a number of years, involves the expenditure of substantial resources, and depends on a number of factors, including the severity of the disease in question, the availability of alternative treatments, and the risks and benefits of the candidate as demonstrated in clinical trials.
+Added: Even upon approval, the FDA may require post-approval commitments, including the completion within a specified time period of additional clinical studies, which often are referred to as “Phase 4” or “post-marketing” studies which could affect the commercial success of a drug.
Post-Approval Regulation
−Removed: Once approved, drug and medical device products are subject to continuing regulation by the FDA.
−Removed: If ongoing regulatory requirements are not met, or if safety or manufacturing problems occur after the product reaches the market, the FDA may at any time withdraw product approval/clearance or take actions that would limit or suspend marketing.
−Removed: Additionally, the FDA may require post-marketing studies or clinical trials, changes to a product’s approved labeling, including the addition of new warnings and contraindications, or the implementation of other risk management measures, including distribution-related restrictions, if there are new safety information developments.
+Added: Drug and medical device products are subject to continuing regulation following approval.
+Added: Failure to meet ongoing regulatory requirements or safety or manufacturing problems may cause the FDA to to take actions that would limit or suspend marketing.
+Added: Post-approval changes in indications, labeling, manufacturing processes or facilities may require a sponsor to develop additional data or conduct additional preclinical or clinical studies and the submission of a supplemental NDA.
+Added: Changes to the product’s approved labeling could include the addition of new warnings and contraindications, or the implementation of other risk management measures, if new safety information develops.
Good Manufacturing Practices.
−Removed: Companies engaged in manufacturing drug products or their components must comply with applicable cGMP requirements and product-specific regulations enforced by the FDA and other regulatory agencies.
+Added: Companies engaged in manufacturing drug products or their components must comply with applicable current Good Manufacturing Practices ("cGMP") requirements and product-specific regulations enforced by the FDA and other regulatory agencies.
Compliance with cGMP includes adhering to requirements relating to organization and training of personnel, buildings and facilities, equipment, control of components and drug product containers and closures, production and process controls, quality control and quality assurance, packaging and labeling controls, holding and distribution, laboratory controls, and records and reports.
−Removed: The FDA regulates and inspects equipment, facilities, and processes used in manufacturing pharmaceutical products prior to approval.
−Removed: If, after receiving approval, a company makes a material change in
−Removed: manufacturing equipment, location, or process (all of which are, to some degree, incorporated in the NDA), additional regulatory review and approval may be required.
−Removed: The FDA also conducts regular, periodic visits to re-inspect equipment, facilities, and processes following the initial approval of a product.
+Added: The FDA regulates and inspects equipment, facilities, and processes used in manufacturing pharmaceutical products prior to approval and may conduct periodic visits post-approval.
+Added: If, after receiving approval, a company makes a material change in manufacturing equipment, location, or process (all of which are, to some degree, incorporated in the NDA), additional regulatory review and approval may be required.
Failure to comply with applicable cGMP requirements and conditions of product approval may lead the FDA to take enforcement action or seek sanctions, including fines, issuance of warning letters, civil penalties, injunctions, suspension of manufacturing operations, operating restrictions, withdrawal of FDA approval, seizure or recall of products, and criminal prosecution.
Although we periodically monitor the FDA compliance of our third-party manufacturers, we cannot be certain that our present or future third-party manufacturers will consistently comply with cGMP and other applicable FDA regulatory requirements.
−Removed: We also need to comply with some of the FDA’s manufacturing and safety regulations for devices.
−Removed: In addition to cGMP, the FDA requires that devices or drug-device combination products comply with the QSR, which sets forth the FDA’s manufacturing quality standards for medical devices.
−Removed: The FDA also requires that we comply with certain device safety reporting requirements for device or a drug-device combination product.
+Added: FDA also has manufacturing and safety regulations for devices that apply to the Company.
+Added: In addition to cGMP, the FDA requires that devices or drug-device combination products comply with the QSR, which sets forth manufacturing quality standards for medical devices.
+Added: The FDA also requires that we comply with certain device safety reporting requirements for our devices.
Advertising and Promotion.
4 unchanged sentences
However, FDA regulations impose restrictions on manufacturers’ communications regarding off-label uses.
−Removed: Broadly speaking, a manufacturer may not promote a drug for off-label use, but under certain conditions may engage in non-promotional, balanced, scientific communication regarding off-label use.
−Removed: In addition to FDA restrictions on marketing of pharmaceutical products, state and federal fraud and abuse laws have been applied to restrict certain marketing practices in the pharmaceutical industry.
+Added: A manufacturer may not promote a drug or device for off-label use, but under certain conditions may engage in non-promotional, balanced, scientific communication regarding its drugs or devices.
+Added: In addition to FDA restrictions on marketing of pharmaceutical or device products, state and federal fraud and abuse laws have been applied to restrict certain marketing practices.
Failure to comply with applicable FDA requirements and restrictions in this area may subject a company to adverse publicity and enforcement action by the FDA, the Department of Justice, or the Office of the Inspector General of the Department of Health and Human Services, as well as state authorities.
This could subject a company to a range of penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially restrict the manner in which a company promotes or distributes a drug or medical device.
−Removed: Other Requirements.
−Removed: Drug and medical device market authorization holders must comply with other regulatory requirements, including submitting annual reports, reporting information about adverse experiences, and maintaining certain records.
In an NDA, a sponsor must identify patents that claim the drug substance or drug product or a method of using the drug.
7 unchanged sentences
The Hatch-Waxman Act provides periods of regulatory exclusivity for products that would serve as RLDs for an ANDA or 505(b)(2) application.
−Removed: If a product is a “new chemical entity”, commonly referred to as an “NCE”, which generally indicates that the active moiety has never before been approved in any drug, there is a period of five years from the product’s approval during which the FDA may not accept for filing any ANDA or 505(b)(2) application for a drug with the same active moiety.
−Removed: An ANDA or 505(b)(2) application may be submitted after four years, however, if the sponsor of the application makes a Paragraph IV certification.
+Added: If a product is a “new chemical entity”, commonly referred to as an “NCE”, which generally indicates that the active moiety has never before been approved in any drug, there is a period of five years from the product’s approval during which the FDA may not accept any ANDA or 505(b)(2) application for a drug with the same active moiety.
A product that is not an NCE may qualify for a three-year period of exclusivity if the NDA contains new clinical data, other than bioavailability studies, derived from studies conducted by or for the sponsor, which were necessary for approval.
In that instance, the exclusivity period does not preclude filing or review of an ANDA or 505(b)(2) application;
−Removed: FDA is precluded from granting final approval to the ANDA or 505(b)(2) application until three years after approval of the RLD.
−Removed: Additionally, the exclusivity applies only to the conditions of approval that required submission of the clinical data.
−Removed: Once the FDA accepts for filing an ANDA or 505(b)(2) application containing a Paragraph IV certification, the applicant must within 20 days provide notice to the RLD or listed drug NDA holder and patent owner that the application has been submitted and provide the factual and legal basis for the applicant’s assertion that the patent is invalid or not infringed.
+Added: rather, the FDA is precluded from granting final approval until three years after approval of the RLD.
+Added: The exclusivity is limited to the conditions of approval that required submission of the clinical data.
+Added: A Paragraph IV certification filing triggers certain notice requirements for the applicant to notify the NDA or patent holder.
If the NDA holder or patent owner files suit against the ANDA or 505(b)(2) applicant for patent infringement within 45 days of receiving the Paragraph IV notice, the FDA is prohibited from approving the ANDA or 505(b)(2) application for a period of 30 months or the resolution of the underlying suit, whichever is earlier.
If the RLD has NCE exclusivity and the notice is given and suit is filed during the fifth year of exclusivity, the regulatory stay extends until 7.5 years after the RLD approval.
−Removed: The FDA may approve the proposed product before the expiration of the regulatory stay if a court finds the patent invalid or not infringed or if the court shortens the period because the parties have failed to cooperate in expediting the litigation.
Patent Term Restoration.
7 unchanged sentences
Section 505A of the FD&C Act provides for six months of additional exclusivity or patent protection if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.
−Removed: The data do not need to show that the product is effective in the pediatric population studied;
+Added: The data does not need to show that the product is effective in the pediatric population studied.
Rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted.
If reports of requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or Orange Book listed patent protection that cover the drug are extended by six months.
−Removed: This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot approve an ANDA or 505(b)(2) application owing to regulatory exclusivity or listed patents.
+Added: This exclusivity effectively extends the regulatory period during which the FDA cannot approve an ANDA or 505(b)(2) application owing to regulatory exclusivity or listed patents.
When any product is approved, we will evaluate seeking pediatric exclusivity as appropriate.
11 unchanged sentences
Generally, product candidates that are eligible for these programs are those for serious or life- threatening conditions, those with the potential to address unmet medical needs and those that offer meaningful benefits over existing treatments.
−Removed: For example, Fast Track Designation is a process designed to facilitate the development and expedite the review of product candidates to treat serious or life-threatening diseases or conditions and fill unmet medical needs.
−Removed: Priority Review Designation is designed to give a product candidate that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness, an initial review within eight months as compared to a standard review time of within ten months of the
−Removed: date the FDA files the NDA.
−Removed: Although Fast Track Designation and Priority Review Designation do not affect the standards for approval, the FDA will attempt to facilitate early and frequent meetings with a sponsor of a Fast Track Designation product candidate and expedite review of the application for a Priority Review Designation product candidate.
+Added: These designations do not affect the standards for approval, however, the FDA will attempt to facilitate early and frequent meetings with a sponsor and generally seek to expedite the NDA for a promising drug.
+Added: of a Fast Track Designation product candidate and expedite review of the application for a Priority Review Designation product candidate.
Healthcare Reform
28 unchanged sentences
While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.
+Added: Additionally, in April 2025, an executive order was signed directing the Secretary of HHS to take appropriate steps to, among other things, modify certain provisions of the Medicare Drug Price Negotiation Program, develop and implement a payment model to reduce the price of high-cost prescription drugs and biological products covered by Medicare, accelerate approval of generic and biosimilar products, and facilitate the ability of states to import pharmaceuticals from other countries, and in May 2025, an executive order was signed, among other things, directing the Secretary of HHS to propose rules that impose “most-favored-nation” pricing and take other measures to reduce the cost of prescription drugs.
+Added: It is currently unclear whether and to what extent these measures will be implemented and what impact any such implementation would have on our business.
+Added: Further, there can be no assurance that the current administration or future administrations will not pursue different or additional measures, such as those intended to more closely align U.S.
+Added: drug prices with international drug prices (often referred to as “reference” or “international price index” drug pricing).
+Added: Future price controls or other changes in pricing regulation or negative publicity related to the pricing of pharmaceutical drugs could restrict the amount that we are able to charge for our product candidates, which could render our product candidates, if approved, commercially unviable and materially adversely affect our ability to raise additional capital on acceptable terms.
It is possible that other healthcare reform measures may be adopted in the future, which may result in more rigorous coverage criteria and in additional downward pressure on the price that we receive for any approved product, particularly given the recent change in administration.
The current Trump administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.
−Removed: These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create
−Removed: additional uncertainty for our business.
+Added: These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.
These actions may include, for example, directives to reduce agency workforce, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establishing an AI task force and developing a strategic plan, and directing certain federal agencies to enforce existing law regarding hospital and price plan transparency and by standardizing prices across hospitals and health plans.
20 unchanged sentences
There can be no assurance that continuing reimbursement will be available at similar reimbursement rates or at all.
−Removed: TriSalus has been in active discussion with CMS with the goal of clarifying that the current code used for TriNav procedures, C9797, covers both "mapping" or "simulation" procedures.
−Removed: These procedures precede the actual Y90 delivery, usually from several days to several weeks, are critical for determining the optimal dose to be delivered and are an essential component of the treatment plan for patients receiving Y90 therapy.
−Removed: Specifically, we have asked for minor changes in the language of the code to make it clearer that simulation procedures, commonly referred to as mappings, are reimbursed when a TriNav is used.
−Removed: Effective April 1, 2025, TriNav received a second unique and permanent HCPCS code from CMS, C8004, which has been assigned to APC 5193 (Level 3 Endovascular Procedures).
−Removed: This new code provides reimbursement clarity for mapping procedures conducted prior to TARE.
Additional legislative changes, regulatory changes and judicial challenges related to the Affordable Care Act remain possible, as discussed above under the subheading “ U.S.
2 unchanged sentences
Healthcare Fraud and Abuse Laws
−Removed: In addition to FDA restrictions on marketing of pharmaceutical products, our business is subject to healthcare fraud and abuse regulation and enforcement by both the federal government and the states in which we conduct our business.
+Added: Our business is subject to healthcare fraud and abuse regulation and enforcement by both the federal government and the states in which we conduct our business.
These laws include, but are not limited to, the following:
−Removed: • The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration, directly or indirectly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for or recommending the purchase, lease or order of any healthcare item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federally financed healthcare programs.
+Added: • The federal Anti-Kickback Statute prohibiting, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration, directly or indirectly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for or recommending the purchase, lease or order of any healthcare item or service reimbursable, in whole or in part, under Medicare, Medicaid or other federally financed healthcare programs.
The term “remuneration” has been broadly interpreted to include anything of value.
5 unchanged sentences
• HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH”) and its implementing regulations, imposes obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” and their subcontractors that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
−Removed: HITECH also increased the civil and criminal penalties that may be imposed under HIPAA and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA.
+Added: Medical device manufacturers are generally not considered covered entities under HIPAA, but may become subject to HIPAA regulations as business associates with they handle protected health information.
• The majority of states also have statutes or regulations similar to the federal anti-kickback and false claims laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.
−Removed: Several states now require pharmaceutical companies to report expenses relating to the marketing and promotion of pharmaceutical products in those states and to report gifts and payments to individual health care providers in those states.
−Removed: Some of these states also prohibit certain marketing-related activities including the provision of gifts, meals, or other items to certain health care providers.
−Removed: Other states have laws requiring pharmaceutical sales representatives to be registered or licensed, and still others impose limits on co-pay assistance that pharmaceutical companies can offer to patients.
−Removed: In addition, several states require pharmaceutical companies to implement compliance programs or marketing codes.
−Removed: • The Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to direct or indirect payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.
−Removed: Compliance with such laws and regulations requires substantial resources.
−Removed: Because of the breadth of these laws and the narrowness of available statutory exceptions and regulatory safe harbors, it is possible that some of our business activities could be subject to legal challenge and enforcement actions.
−Removed: In the event governmental authorities conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and
−Removed: abuse or other healthcare laws and regulations, they may impose sanctions under these laws, which are potentially significant and may include civil monetary penalties, damages, exclusion of an entity or individual from participation in government health care programs, criminal fines and imprisonment, additional reporting requirements if we become subject to a corporate integrity agreement or other settlement to resolve allegations of violations of these laws, as well as the potential curtailment or restructuring of our operations.
+Added: The regulations differ by state but may require the reporting of certain marketing costs or the reporting of gifts and payments to individual health care providers.
+Added: Other states require the Company to be licensed or registered where it or its sales representatives conduct sales.
+Added: In addition, several states require pharmaceutical or device companies to implement compliance programs or marketing codes.
+Added: • The Physician Payments Sunshine Act, implemented as the Open Payments program, and its implementing regulations, requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to CMS information related to direct or indirect payments and other transfers of value to physicians or other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held in the company by physicians and their immediate family members.
+Added: Because federal and state health care laws and regulations related to compliance are broad and available statutory exceptions and regulatory safe harbors are narrow, it is possible that some of our business activities could be subject to legal challenge and enforcement actions.
+Added: In the event governmental authorities conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations, they may impose sanctions under these laws, which are potentially significant and may include civil monetary penalties, damages, exclusion of an entity or individual from participation in government health care programs, criminal fines and imprisonment, additional reporting requirements if we become subject to a corporate integrity agreement or other settlement to resolve allegations of violations of these laws, as well as the potential curtailment or restructuring of our operations.
Even if we are not determined to have violated these laws, government investigations into these issues typically require the expenditure of significant resources and generate negative publicity.
Foreign Corrupt Practices Act
−Removed: In addition, the U.S.
Foreign Corrupt Practices Act of 1997 prohibits corporations and their intermediaries from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity.
3 unchanged sentences
We have not yet determined if we will exercise the extension option.
−Removed: We also lease office facilities in Bannockburn, Illinois, and laboratory space at Rhode Island Hospital in Providence, Rhode Island.
+Added: We also lease office facilities in Bannockburn, Illinois.
+Added: During 2025, we terminated our lease for the laboratory space at Rhode Island Hospital in Providence, Rhode Island.
We believe our facilities are adequate to meet our current needs, although we may seek to negotiate new leases or evaluate additional or alternate space for our operations.
We believe appropriate alternative space will be readily available on commercially reasonable terms.
−Removed: As of December 31, 2024, we had approximately 110 full-time employees, including six employees who held Ph.D.
+Added: As of December 31, 2025, we had approximately 102 full-time employees,
None of our employees are represented by a labor union or covered under collective bargaining agreement.
10 unchanged sentences
Information contained on or accessible through our website is not a part of this Annual Report, and the inclusion of our website address in this Annual Report is an inactive textual reference only.
−Removed: For additional information, see Item 7- Management’s Discussion and Analysis of Financial Condition and Results of Operations of this Annual Report, and (3) Business Combination of our audited consolidated financial statements for the year ended December 31, 2024, included in Item 8 of this Annual Report.
+Added: For additional information, see Item 7- Management’s Discussion and Analysis of Financial Condition and Results of Operations of this Annual Report for the year ended December 31, 2025.
We and our subsidiaries own or have rights to trademarks, trade names and service marks that they use in connection with the operation of their business.
1 unchanged sentence
Solely for convenience, in some cases, the trademarks, trade names and service marks referred to in this prospectus are listed without the applicable ®, ™ and SM symbols.
+Added: RISK FACTOR SUMMARY
+Added: Below is a summary of material factors that make an investment in our securities speculative or risky.
+Added: Importantly, this summary does not address all of the risks and uncertainties that we face.
+Added: Additional discussion of the risks and uncertainties summarized in this risk factor summary, as well as other risks and uncertainties that we face, can be found in the more detailed discussion in Item 1A in this Annual Report, and the below summary is qualified in its entirety by that more complete discussion of such risks and uncertainties.
+Added: You should carefully consider the risks and uncertainties described herein as part of your evaluation of an investment in our securities:
+Added: • We have a limited operating history, have incurred significant losses since our inception and anticipate incurring increasing expenses and continuing losses for the foreseeable future.
+Added: • Until we are able to generate significant revenues or achieve profitability through product sales, we may require substantial additional capital to finance our operations and continue development of our product candidates.
+Added: We cannot be certain that such additional financing will be available on terms favorable to us, or at all, which could limit our ability to grow and jeopardize our ability to continue our business operations.
+Added: • We may not be able to generate sufficient cash to service our indebtedness or borrow additional funds pursuant to our Loan Facility.
+Added: • The Dynavax Agreement, entered into by Legacy TriSalus in connection with its purchase of nelitolimod requires us to make potentially significant payments to Dynavax before we will have regulatory approval of nelitolimod and be able to generate revenue from sales of nelitolimod.
+Added: • Our revenue is primarily generated from sales of our TriNav device and we are therefore highly dependent on it for our success.
+Added: Failure to achieve continued market acceptance of TriNav for any reason will harm our business and future prospects.
+Added: • Any change to TriNav’s reimbursement status that reduces our level of reimbursement could cause TriNav sales to materially decline and impede market adoption.
+Added: • We are early in our pharmaceutical development efforts for nelitolimod, and if we are unable to advance our product candidates, including nelitolimod in clinical development for any reason (including due to lack of funding), obtain regulatory approval and ultimately commercialize our product candidates, or experience significant delays in doing so, our business, results of operations, financial condition, and prospects may be materially adversely affected.
+Added: • Delays in clinical trials are common and have many causes, and any delay could result in increased costs to us and could jeopardize or delay our ability to obtain regulatory approval and commence future product sales.
+Added: We may also find it difficult to enroll patients in our clinical trials, which could delay or prevent the development of our product candidates.
+Added: • Changes in existing third-party coverage or our inability to secure and maintain favorable reimbursement may impact our ability to sell our products, which would materially and adversely impact our business, results of operations, financial condition and prospects.
+Added: • The business and industry in which we participate are highly competitive.
+Added: If we are unable to compete effectively, we will not be able to establish our products in the marketplace or maintain or grow our products’ market share in the marketplace, and as a result, our business and results of operations will be adversely impacted.
+Added: • We are subject to numerous complex regulatory requirements, and failure to comply with these regulations, or the cost of compliance with these regulations, may harm our business.
+Added: • The complexity of a combination product that includes a drug and a medical device presents additional, unique development and regulatory challenges, which may adversely impact our development plans and our ability to obtain regulatory approval or clearance of our product candidates.
+Added: • Failure to obtain, adequately protect, maintain or enforce our intellectual property rights could substantially harm our business and results of operations.
+Added: • The expiration or loss of patent protection may adversely affect our future revenues.
+Added: • We have incurred and will continue to incur increased costs as a result of operating as a public company, and our management now devotes substantial time to new compliance initiatives and corporate governance practices.
+Added: We may fail to comply with the rules that apply to public companies, including Section 404 of the Sarbanes-Oxley Act, which could result in sanctions or other penalties that would adversely impact our business.
+Added: • Our management has identified material weaknesses in its internal control over financial reporting in prior years and we may identify additional material weaknesses in the future.
+Added: If we fail to establish and maintain effective control over financial reporting, it may adversely affect our ability to accurately and timely report our financial results and may adversely affect investor confidence and business operations.
+Added: • The price of our securities has been and may continue to be volatile.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.