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Item 1. Business

2025-04-15 compared with 2024-04-11 · 194 added, 342 removed, 600 unchanged (47% of the section changed)

We are a growing, oncology focused medical technology business bringing disruptive drug delivery technology with the goal of improving therapeutic delivery to liver and pancreatic tumors.

Additionally, we are exploring the integration of our technology with our investigational immunotherapeutic, nelitolimod, a class C Toll-like receptor 9 agonist, for a range of liver and pancreatic indications.

Our ultimate goal is to transform the treatment paradigm for patients battling liver and pancreatic tumors.

We have developed an innovative organ-specific platform that is designed to overcome two of the most significant challenges that prevent optimal delivery and performance of therapeutics in these difficult-to-treat diseases:

(i) high intratumoral pressure caused by tumor growth and collapsed vasculature restricting the delivery of oncology therapeutics and (ii) the immunosuppressive properties of liver and pancreatic tumor immune cells.

Unless the context indicates otherwise, references in this Annual Report to the “Company,” “TriSalus,” “we,” “us,” “our” and similar terms refer to TriSalus Life Sciences, Inc.

(f/k/a MedTech Acquisition Corp.), a Delaware corporation and its consolidated subsidiaries.

We are a growing, oncology focused medical technology business seeking to transform outcomes for patients with solid tumors by integrating our innovative delivery technology with standard-of-care therapies, and with our investigational immunotherapeutic, nelitolimod, a class C Toll-like receptor 9 ("TRL9") agonist, for a range of different therapeutic and technology applications.

Our ultimate goal is to transform the treatment paradigm for patients battling solid tumors.

We have developed an innovative technology designed to overcome two of the most significant challenges that prevent optimal delivery and performance of therapeutics in these difficult-to-treat diseases:

(i) high intratumoral pressure caused by tumor growth and collapsed vasculature restricting the delivery of oncology therapeutics and (ii) off target delivery.

Nelitolimod, specifically, combined with our technology aims to address the immunosuppressive properties of tumor immune cells in liver, pancreas and other solid tumors.

By systematically addressing these barriers, we aim to improve response to therapies and to enable improved patient outcomes.

Liver and pancreatic cancers are among the world’s most lethal diseases.

Depending on the disease stage, many patients have no curative treatment options and have poor outcomes, with 5-year survival rates ranging from 8-20% for patients with advanced disease.

While immunotherapy represents one of the greatest advancements in cancer treatment over the past 50 years, patients with primary or secondary tumors in the liver or pancreas are less likely to respond to treatment relative to most other cancer types that do not involve these sites of disease.

These patients need new treatment options designed to address the unique challenges specific to liver and pancreatic tumors that limit the success of immunotherapy.

We have developed a platform approach to address the unique challenges of treating tumors in the liver and pancreas by integrating our innovative drug delivery technology with our investigational immunotherapeutic agent, nelitolimod, formerly known as SD-101, with the goal of overcoming the two primary barriers that inhibit treatment success:

intratumoral pressure and immunosuppression, both of which limit therapeutic delivery and efficacy.

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.

Beyond penetration issues, the blood vessels that supply these tumors are leaky and disorganized, leading to poor distribution of the therapeutic within the tumor.

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:

PEDD & TriNav- Device Business with Potential for Growth:

Our delivery method — Pressure-Enabled Drug Delivery (PEDD TM ) (“PEDD”) — modulates pressure and flow within blood vessels to improve intravascular therapeutic delivery into tumors and is designed to increase the likelihood of tumor response in comparison to conventional delivery technologies.

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 either primary liver cancer and in patients with liver metastases.

TriNav is a highly innovative, novel technology, FDA-cleared drug delivery device that has undergone peer-reviewed studies at multiple clinical sites.

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.

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.

TriNav is a highly innovative and novel device that is FDA-cleared and has undergone peer-reviewed studies at multiple clinical sites.

The PEDD method has now been used in over 21,000 procedures, primarily TACE and TARE.

TriNav achieved $18.5 million in revenue in 2023 with fourth quarter growth of 77% vs.

TriNav achieved $29.4 million in revenue in 2024 representing growth of 59.0% vs.

the previous year.

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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.

The PRVI device is currently being studied in a clinical trial for nelitolimod delivery into pancreatic tumors.

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.

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 toll-like receptor 9 (“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.

Nelitolimod has previously been shown in both clinical and non-clinical studies to broadly induce interferon production, dendritic cell activation, and B cell activation.

Through pre-clinical experiments and early clinical experience in patients with liver and pancreatic tumors, we have demonstrated that nelitolimod reduces MDSCs, which are important mediators of immunosuppression in these tumor types, while recruiting T cells which are the target of CPIs.

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.

There is also the potential that this platform may not only enable CPIs, but other classes of immunotherapy as well, such as cell therapeutics.

Currently we are completing phase 1 clinical trials for four indications, in leading academic oncology centers across the United States (“U.S.”).

In these trials, PEDD devices are used to administer our investigational immunotherapy candidate, nelitolimod, through a regional intravascular approach for patients with liver and pancreatic tumors.

We believe this approach will maximize TLR9 stimulation within the liver and pancreas and eliminate immunosuppressive cells to broadly reprogram the tumor microenvironment (“TME”) with the goal of enabling improved efficacy of systemic immunotherapies like CPIs or cell therapy while maintaining a tolerable safety profile.

We are currently evaluating data from these trials and determining which indication we intend to advance.

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.

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.

We are in the early stages of our development efforts and have only one product candidate, nelitolimod, in early clinical development.

We have initiated Phase 1 and Phase 1b clinical trials for nelitolimod, each of which are focused on a different target indication, specifically:

uveal melanoma, intrahepatic cholangiocarcinoma and hepatocellular carcinoma ("UMLM", "ICC" and "HCC", respectively), and pancreatic cancer.

We expect that any continued investigation for ICC and HCC may continue through Investigator Initiated Trials (IITs).

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.

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.

Overcoming Barriers to Effective Drug Delivery with PEDD

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total occlusion) due to its intermittently occlusive design.

This physiologically and traumatically increases local vascular pressure at the target location close to the tumor, infusing therapeutics into resistive tumor vessels to enable deeper perfusion and to improve therapeutic delivery.

This physiologically increases local vascular pressure at the target location close to the tumor, infusing therapeutics into resistive tumor vessels to enable deeper perfusion and to improve therapeutic delivery.

The SmartValve also provides a fixed centro-luminal catheter position, unlike a standard microcatheter where the position of the catheter is in a random, off-centered position.

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The SmartValve has also been shown to reduce or eliminate reflux and has been shown in clinical studies to reduce delivery of therapeutics to non-target tissues.

In independent clinical studies, the PEDD method of delivery has demonstrated the ability to overcome the infusion barriers of the TME and to improve therapeutic delivery.

Additionally, in a recent large Health Economics and Outcome Research ("HEOR") study, (a 300 million patient dataset covering over 98% of US patients), capturing real-world safety and clinical outcomes for TriNav in its launch phase (2020-2022), demonstrated that TriNav patients, despite a higher baseline disease burden and clinical complexity, showed overall clinical results that were comparable to patients with a lower disease burden.

The study also demonstrated that:

• In TACE procedures, interventional radiologists were able to deliver significantly more chemotherapeutic to the tumor when using TriNav vs.

the amount delivered using standard catheters, a critical treatment goal.

• TriNav patients had fewer 30-day inpatient visits post-procedure vs.

non-TriNav patients in matched cohort comparison.

• TriNav HCC patients were more likely to have a liver transplant in matched cohort comparison.

• TriNav TARE patients with liver metastases had fewer clinical complications post-procedure vs.

non-TriNav patients in matched cohort comparison.

◦ TriNav TARE patients with liver metastases had lower rates of post-procedure fatigue vs.

non-TriNav patients.

The results from this HEOR study suggests that TriNav is preferentially selected to treat patients with higher burden of disease than patients treated with standard catheters, yet these patients show comparable results post-treatment when compared to patients with lower disease burden.

In matched cohort comparisons, TriNav patients showed meaningful trends towards better outcomes, including an increased rate of liver transplant.

These results also demonstrate how real-world data complement traditional clinical trials to provide a more robust and timely understanding of the benefits realized by patients.

TriSalus is committed to updating this data set continuously, and to continue reinforcing the benefit TriNav and the PEDD approach have been shown to provide to patients, providers, and payers.

Treatment of Liver Tumors with Transarterial Radioembolization (TARE)

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The PEDD approach is designed to provide a reliable method to maximize the tumor to normal liver ratio (“T/N ratio”).

PEDD devices are designed to not only increase therapeutic delivery to target tumors but also to provide anti-reflux protection to minimize off-target delivery of radioactive micro spheres and the potential complications associated with undesired normal tissue exposure.

PEDD devices are designed to not only increase therapeutic delivery to target tumors but also to provide protection to minimize off-target delivery of radioactive micro spheres and the potential complications associated with undesired normal tissue exposure.

A pilot study of a PEDD catheter not only demonstrated reduced hepatic nontarget embolization but also found a significant increase in tumor deposition of 99m Tc-MAA by a factor of 1.68 (range 1.33 to 1.90, p < 0.05).

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Real-world Support

TriSalus recently published a 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.

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.

This study utilized a large, 300 million patient datasets covering 98% of US payers.

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The study also revealed that:

• TriNav patients were more likely to have received prior systemic therapy and were much more likely to have received prior embolization.

• In TACE procedures, interventional radiologists could deliver significantly more chemotherapeutic to the tumor when using TriNav vs.

the amount delivered using standard catheters, a critical treatment goal for TACE procedures.

• In a matched cohort comparison, TriNav patients had fewer 30-day inpatient visits post-procedure than non-TriNav patients.

• TriNav HCC patients were more likely to have a post-procedure liver transplant in a matched cohort comparison.

• TriNav patients showed reduced rates of post-procedure fatigue compared to non-TriNav patients

• In TACE procedures, interventional radiologists were able to deliver significantly more chemotherapeutic to the tumor when using TriNav vs.

the amount delivered using standard catheters, a critical treatment goal.

• TriNav TACE patients had fewer 30-day inpatient visits post-procedure vs.

non-TriNav patients in matched cohort comparison.

• TriNav HCC patients were more likely to have a liver transplant in matched cohort comparison.

• TriNav TARE patients with liver metastases had fewer clinical complications post-procedure vs.

non-TriNav patients in a matched cohort comparison.

• TriNav TARE patients with liver metastases had lower rates of post-procedure fatigue vs.

non-TriNav patients.

non-TriNav patients in matched cohort comparison.

• In patients with HCC, TriNav patients showed lower rates of post-procedural gastric ulcers and jaundice.

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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TriNav patients showed meaningful trends toward better outcomes in matched cohort comparisons, including an increased rate of liver transplants.

TriSalus is committed to updating this data set continuously and affirming the benefit TriNav and the PEDD approach bring to patients, providers, and payers.

TriNav Market Opportunity

The incidence of primary and metastatic liver tumors has been increasing, presenting a large opportunity for developing technologies and therapeutics given the poor outcomes associated with liver cancers, whether primary or metastatic.

According to the American Cancer Society, primary liver tumors, including intrahepatic cholangiocarcinoma ("ICC") and hepatocellular carcinoma ("HCC"), currently represent more than 41,000 cases annually in the U.S.

TACE and TARE are widely used locoregional therapies for HCC, colorectal liver metastases ("CRLM"), and neuroendocrine tumor ("NET") liver metastases.

However, significant unmet medical needs remain.

One major challenge is inconsistent drug delivery;

traditional embolization techniques often result in suboptimal drug penetration due to high intratumoral pressure and poor perfusion, limiting treatment efficacy.

Additionally, tumor heterogeneity and vascular variability can lead to uneven distribution of therapeutic agents, reducing overall response rates.

Another key limitation is treatment resistance and recurrence, as embolization alone does not fully eradicate microscopic disease, necessitating repeat procedures that may compromise liver function over time.

Furthermore, post-embolization syndrome, characterized by pain, fever, and liver dysfunction, impacts patient quality of life and may delay subsequent treatments.

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.

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.

According to the American Cancer Society, primary liver tumors, including ICC and HCC, currently represent more than 42 thousand cases annually in the U.S.

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.

We estimate that 40% of these patients are eligible for TACE or TARE procedures and that between 25% and 30% are appropriate candidates for our current TriNav device, representing a potential market opportunity of approximately 37,000 units, or approximately $286 million, based on our current price of $7,750.

When TriNav Large, a larger version of TriNav capable of being used in larger vessel size (3.0-5.0 mm), is commercially launched, we expect that our addressable market will increase by approximately 25%, resulting in an aggregate opportunity of 47,500 units or approximately $368 million, based on current TriNav pricing.

Currently, TriNav is used primarily for either TACE or TARE, both of which entail localized therapeutic delivery to HCC or metastatic liver tumors using standard interventional radiology techniques.

We are also exploring additional indications for use, including uterine fibroid embolization, which fall within the present 510(k) clearance.

Potential market impact of additional indications will be determined after clinical data become available.

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.

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.

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.

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.

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.

One potential new application for TriNav LV is the use of the technology for uterine fibroid embolizations ("UFEs").

Roughly 10% of women aged 18-65 lives with uterine fibroid today and current treatment approaches include hysterectomy, endometrial ablation and uterine fibroid embolizations.

We estimate TriNav LV is applicable for 20 thousand UFEs per year, expanding the market opportunity by approximately $160.0 million.

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.

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%.

We estimate that this could expand the addressable market for TriNav by approximately 50 thousand procedures, representing an incremental $400.0 million market opportunity.

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.

We believe that this technology potentially could treat 2 thousand patients annually adding an additional market expansion of $400.0 million.

Another potential application of TriNav is for the use in prostate embolization’s.

Current treatment options for men with enlarged prostate include prostatectomy, trans-urethral prostate resection, alpha blockers and 5-alpha reductase inhibitors and other options.

Prostate embolization’s 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.

The estimated total addressable market for TriSalus PEDD technology in the U.S.

is project to exceed $1.6 billion annually.

The market is divided into a current market valued at $900.0 million and an additional market opportunity estimated at $700.0 million.

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.

TriNav Positioning

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• Multiple comorbidities;

• Hypovasular tumors.

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.

Reimbursement

In December 2023 TriNav received a unique and permanent HCPCS code from CMS, C9797, which has been assigned to APC 5194 (Level 4 Endovascular Procedures) for calendar year 2024 with a payment rate of $16,724.70.

In December 2023 TriNav received a unique and permanent HCPCS code from Centers for Medicare & Medicaid Services (“CMS”), C9797, which has been assigned to APC 5194 (Level 4 Endovascular Procedures) for calendar year 2025 with a payment rate of $17,957.

This code can be used without restriction for any embolization or occlusion procedure consistent with the TriNav Instructions for Use and is reimbursed in the hospital outpatient and ambulatory surgery center settings.

With the provision of this new code, reimbursement for TriNav has continued uninterrupted from the launch year.

The new C9797 code brings significant benefit vs.

With the provision of this code, reimbursement for TriNav has continued uninterrupted from the launch year.

The C9797 code brings significant benefit vs.

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.

In November 2019, TriNav, with its innovative SmartValve technology, received transitional pass-through ("TPT") status for U.S.

reimbursement.

Receiving TPT requires meeting stringent clinical and effectiveness criteria, and TriNav is one of the few technologies to receive this in the Interventional Oncology arena.

The launch of TriNav in February 2020 coincided with the onset of the COVID-19 pandemic, which temporarily limited access to hospitals and impeded the technology’s adoption.

Furthermore, it hindered our ability to gather essential data needed by the Centers for Medicare and Medicaid Services (CMS) for establishing a long-term reimbursement plan.

In late 2022, we collaborated with Congress to include a bi-partisan provision in the consolidated Omnibus Appropriations Act of 2023, P.L.

117-328, which extended the TPT reimbursement for an additional year.

This extension provided us with the opportunity to collect the necessary data to work closely with CMS on developing a long-term reimbursement solution.

Thanks to this additional year, we were able to conduct a HEOR study, a database of over 300 million patient lives, to gain insights into how TriNav with SmartValve is being used, the patient profiles, additional steps involved, and the procedures performed.

This additional year of coverage provided the necessary data propelling CMS to provide the unique and permanent HCPCS code described above.

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.

Our Customers & Stakeholders

We aim to interact closely with all our key stakeholders to ensure a patient’s experience is beneficial.

We view our customers as including the interventional radiologists, IR technicians, medical oncologists, nursing support, and the value

analysis committee staff, who either use our products or recommend the purchase of such products to hospitals and, most importantly, the patients they treat.

Our goal is to establish a high level of engagement and trust with the various clinicians and support individuals in the hospital as well as patients.

We view our customers as including the interventional radiologists, IR technicians, medical oncologists, nursing support, and the Value Analysis Committee ("VAC") staff, who either use our products or recommend the purchase of such products to hospitals and, most importantly, the patients they treat.

Our goal is to establish a high level of engagement and trust with the various clinicians and support individuals in the hospital as well as with patients.

Additionally, we believe that many hospitals are under cost pressure and need education on, and assistance to support and embrace, the use of modern technology.

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Our commercial strategy for TriNav targets hospitals through direct sales engagements with clinicians and the broader medical, hospital and technical staff.

TriSalus utilizes a direct sales model to hospitals and ambulatory surgery centers nationwide, eliminating the need to pay distributor fees and assuring that representatives are trained on TriNav's clinical benefit and use, and are not distracted by other sales priorities as would be the case if we utilized distributors.

TriSalus utilizes a direct sales model to hospitals and ambulatory surgery centers nationwide.

Our current sales focus is on targeting hospitals and major academic medical centers with the highest levels of TACE and TARE procedures.

Our sales representatives and sales managers have substantial medical device experience and market our products directly to interventional radiologists who perform TACE and TARE procedures.

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.

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.

Similarly, our marketing team has a significant amount of domain expertise and a strong track record of success.

Our sales and marketing team totals 41 professionals as of March 10, 2024.

Similarly, our marketing team has a significant amount of domain expertise.

Our sales and marketing team totals 53 professionals as of December 31, 2024.

The use of TriNav is consistent with the current steps an interventional radiologist utilizes to conduct TACE and TARE procedures.

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We believe this provides value to our customers and makes our sales model a source of competitive advantage.

A lower service burden means we can develop a cost-efficient sales model by optimizing a mix of clinical specialists and salespeople.

A lower service burden means we can develop a cost-efficient sales model by optimizing a mix of clinical specialists and sales representatives.

In the U.S., TriNav can be provided to hospitals on a consignment basis whereby title is transferred when the technology is used in clinical procedures.

Other hospitals purchase TriNav directly, and TriNav is sold for a predetermined set fee for each catheter via a predetermined contract or purchase order.

TriNav Design & Specifications

TriNav is a flexible microcatheter that can be used to deliver diagnostic and therapeutic agents into peripheral vasculature beds, with its main clinical use being TACE or TARE procedures.

It is equipped with a SmartValve, which is a one-way microvalve capable of generating infusion pressure greater than mean arterial pressure to help overcome intratumoral pressure and improve distribution of therapeutics.

The SmartValve is designed to provide reflux protection and to maintain a centroluminal position during infusion.

The unique ability of TriNav in generating infusion pressure to drive therapy deeper into solid tumors is driven by the SmartValve at the distal end of the catheter.

It is made of ultra-thin nitinol fibers laid out in a precise braid geometry, which is then overlaid with nanofilaments made of composite polymers — creating a filter valve that allows particles >10µm (for example, red blood cells) to pass through.

The exact geometry of the braid and composition of the polymers have been calibrated to create a soft, pliable valve that can react dynamically to varying pressure and flow conditions in vasculatures, yet that is strong enough to prevent reflux of material and generate sufficient pressure without imposing too much radial force on the vessel walls.

TriNav’s dimensional specifications are as follows:

Dimensional Specifications

Parameter Specification (nominal)

Usable Length 120 cm, 150 cm

Outer Diameter (max) 0.038 in (0.97 mm)

Inner Diameter (Infusion Lumen) 0.021 in (0.53 mm)

Expandable Tip Outer Diameter 3.7 mm

The catheter shaft is made of composite polymer (Pebax) segments of varying softness and reinforced with stainless-steel braid.

The design and material of the shaft have been optimized to provide strength, kink resistance, ease of tracking and flexibility — all of which are important to enable navigation of the catheter over microwires in tortuous vasculature.

At the distal end of the catheter, there are two radiopaque marker bands to help physicians locate the distal end of the catheter as it is being threaded through the vasculature.

The inner lumen of the catheter shaft is lined with polytetrafluoroethylene, a highly inert and lubricious polymer, to minimize friction and maximize compatibility with microwires, chemotherapy, cell therapy products, and other agents used during the procedure.

Finally, the device is coated with a hydrophilic formulation that is thin yet durable, making it even more trackable and capable of accessing the most tortuous vasculature.

Industry and Competition

Our industry is highly competitive and subject to rapid and significant technological change as research provides a deeper understanding of the pathology of diseases and new technologies and treatments are developed.

We believe our scientific knowledge, technology, and development capabilities provide us with substantial competitive advantages, but we face potential competition from multiple sources, including large pharmaceutical, biotechnology, specialty pharmaceutical and, to a lesser degree, medical device companies.

TriNav Competition

The primary competition for TriNav is the standard microcatheter, which is frequently used in minimally invasive procedures for delivering therapeutics or devices.

However, standard microcatheters do not have the ability to modulate pressure and flow nor do they have clinical evidence or data that they can improve therapeutic delivery to liver and pancreatic tumors.

The primary competition for TriNav is the standard microcatheter, which is frequently used in minimally invasive procedures for delivering therapeutics or devices (e.g., Y90).

However, standard microcatheters do not have the ability to modulate pressure and flow or to improve the T:N ratio, nor do they have clinical evidence or data that they can improve therapeutic delivery to liver and pancreatic tumors.

Microcatheters are manufactured by a wide range of medical device manufacturers.

Besides the standard microcatheter, there are two other competitive products:

Embolix’s Sniper and Guerbet’s SeQure.

Embolix’s Sniper and Merit Medical's Swift NINJA.

Some of our competitors are large, well-capitalized companies with significantly larger market shares and resources than we have.

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We also compete with smaller, niche players that have less resources and more limited influence in the market.

Growth Opportunities - TriNav Portfolio Expansion

The next product that we plan to commercialize is a larger version of TriNav capable of being used in larger vessel sizes, 4.0-6.0 mm, which was 510(k) cleared by the FDA in May 2023.

We intend to launch the product commercially once our ongoing market evaluation is completed, which is expected to occur in the second half of 2024.

We believe that by offering additional devices to address a broader range of vessel sizes encountered in TACE and TARE procedures, there is a potential that TriNav and our next-generation of PEDD products could be positioned to be utilized

across the wide range of procedural approaches, disease stages, and patient vasculatures that interventional radiologists encounter.

The SmartValve component, which is embedded into the catheter, is highly dynamic in that is opens and close in sync with the heartbeat to achieve the following:

• Enhances perfusion of the tumor by modulation of the vessel pressure gradient;

• Improves target delivery by redirecting blood flow to the tumor and away from the normal liver;

• Creates turbulence to mix therapeutic with the blood for reliable distribution;

• Reduces reflux to protect normal tissue outside the liver.

TriSalus is committed to enhancing our technology to improve patient outcomes.

A major area of product enhancement underway at the Company is to incorporate machine learning and sensing into our technology to improve patient outcomes through several mechanisms:

• Precision Therapeutic Delivery – By accurately measuring both pressure and flow within blood vessels feeding tumors, healthcare providers can overcome mechanical barriers in the tumor microenvironment with greater precision.

This data can inform more precise and consistent treatment delivery, dosage of chemotherapy, radiation therapy or targeted therapies and ensure optimal tumor perfusion.

Growth Opportunities - TriNav Product Improvements

We are committed to advancing our technology to improve patient outcomes.

Major areas of product enhancement underway at the Company includes incorporation of sensing and machine learning into our technology to improve patient outcomes while also exploring potential new applications outside of our current core focus on liver and pancreatic cancer.

These include:

• Precision therapeutic delivery – By more accurately measuring both pressure and flow within blood vessels feeding tumors, we expect healthcare providers will be able to more efficiently and precisely overcome mechanical barriers in the tumor microenvironment.

• 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.

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.

• Real-time monitoring – Continuous monitoring of pressure and flow allows for real-time assessment of optimal therapy delivery.

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.

• Selection of optimal target vessel location – Changes in pressure and flow patterns can negatively alter therapeutic delivery efficiency before clinically apparent.

Early detection through sensing monitoring enables proactive intervention, allowing for improved therapeutic delivery.

• Personalized Therapy Optimization – Every tumor and vascular network is unique.

By monitoring pressure and flow parameters over time, interventional radiologists can tailor treatment to the patient’s specific vascular dynamics.

This personalized approach enhances treatment efficacy while minimizing unnecessary interventions and risks.

• Reduced treatment toxicity – Fine-tuning treatment regimens based on real-time pressure and flow data can help minimize treatment toxicity by delivering therapeutic agents more precisely to the tumor while sparing healthy tissues.

This has the potential to lead to improved patient tolerance of treatment and overall improved tumor response.

• Enhanced research opportunities – The data collected from pressure and flow sensors can contribute to better understanding of mechanical TME barriers and treatment response.

This data can lead to “smart algorithms” to optimize treatment protocols and develop improved overall patient outcomes.

TriSalus is committed to enhancing our technology, incorporating machine learning and sensing technologies with a range of capabilities to provide valuable clinical insights, improving personalized treatment strategies, and most importantly, improve patient outcomes.

R & D efforts are underway on a variety of different technologies with plans for future product launches within the next several years.

Pancreatic Retrograde Venous Infusion Device (PRVI)

Additionally, we are advancing our Pancreatic Infusion Technology ("PRVI"), which is currently 510(k) cleared by the FDA and in a Phase 1 clinical trial for locally advanced pancreatic cancer.

• Additional applications – TriSalus continues to explore opportunities to improve patient outcomes in interventional radiology procedures beyond the liver and pancreas.

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.

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.

Most importantly, we are focused on improving personalized treatment strategies and improving patient outcomes in a range of disease areas.

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

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.

Our PRVI approach seeks to address many of the key challenges associated with delivering therapeutics to pancreas tumors.

In contrast to the liver, pancreas arteries feeding tumors are small and tortuous, making targeted delivery challenging.

In contrast to the liver, pancreatic arteries feeding tumors are small and tortuous, making targeted delivery challenging.

Venous access affords anatomic advantages due to the presence of larger diameter vessels.

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• Enabling a therapeutic index that is efficacious while limiting toxicity compared to systemic dosing.

The Pancreatic Retrograde Venous Infusion Device has not been commercialized and commercial sales are anticipated to coincide with approval, if any, of nelitolimod in locally advanced Pancreatic cancer.

The Pancreatic Retrograde Venous Infusion Device has not been commercialized and commercial sales are not anticipated before 2026.

Pre-clinical pancreatic cancer model experiments indicated that using the PRVI method of PEDD™ improved drug delivery 3.6-7.0-fold.

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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.

Near-Term Commercial Focus

Our near-term pipeline focus is to improve outcomes with TARE and TACE for patients, while concurrently investigating how nelitolimod may allow more patients with liver tumors to benefit from immunotherapy.

Current evidence for the efficacy of specific locoregional therapies is primarily based on retrospective reports and a large population-based study, as there are few prospective clinical trials.

Given this landscape, along with our PERIO clinical program, we are supporting multiple investigator-initiated trials comparing PEDD with standard catheters for TACE and TARE procedures with respect to therapeutic delivery.

Other Commercialization Growth Opportunities

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to provide broader hospital coverage and increased time for the representative to expand utilization within hospital targets from which we expect to foster deep relationships with physicians and drive revenue growth.

We intend to expand our commercial organization over the next several years to ensure full coverage of the Embolization market in a manner that will maximize shareholder value.

• Expand Internationally Through Distributors :

In addition to growing our direct sales organization in the U.S., we are considering the option of selling to distributors in Europe, where we believe that selling through third-party distributors is the best way to optimize our opportunities and resources.

In addition, certain Asian markets have a very high incidence of both hepatocellular carcinoma ("HCC") and intrahepatic cholangiocarcinoma ("ICC"), and TACE procedures are the standard of care for many patient types.

We currently have a distribution relationship with Hangzhou Ruizhen Therapeutics Co., Ltd.

(“Hangzhou”) in China.

In collaboration with Hangzhou, TriNav has been submitted for National Medical Products Administration (“NMPA”) approval and we expect a final determination regarding such approval sometime in the first half of 2024.

If approved, Hangzhou is expected to have the responsibility to launch in the Chinese market with support from us.

We intend to expand our commercial organization over the next several years to ensure full coverage of the embolization market and drive revenue growth.

• Develop Collaborations with Therapeutic Partners .

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standard approaches.

We may explore opportunities to partner with therapeutics companies at all stages of development and commercialization by reading the delivery of therapies to patients in a manner that can improve outcomes in areas of high unmet medical need.

We may explore opportunities to partner with therapeutics companies at all stages of development and commercialization in collaborations designed to improve targeted delivery of therapies to patients in a manner that can improve outcomes in areas of high unmet medical need

• Continue Partnering with Leading Academic Medical Centers.

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Strategic Acquisition of Nelitolimod

In July 2020, we acquired nelitolimod, a class C Toll-like Receptor 9 (TLR9) agonist, from Dynavax Technologies Corporation (“Dynavax”).

In July 2020, we acquired nelitolimod, a class C TLR9 agonist, from Dynavax Technologies Corporation (“Dynavax”).

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.

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;

the potential to enable systemic checkpoint inhibition in patients with liver or pancreatic tumors to the extent observed in other indications, the ability to broadly reprogram the TME while addressing Myeloid Derived Suppressor Cells, (a key cell type that suppresses the immune system in the liver and pancreas) and a therapeutic where locoregional delivery would be expected to improve outcomes.

the potential to enable systemic checkpoint inhibition in patients with liver or pancreatic tumors to the extent observed in other indications;

the ability to broadly reprogram the TME while addressing Myeloid Derived Suppressor Cells (a key cell type that suppresses the immune system in the liver and pancreas);

and a therapeutic where locoregional delivery would be expected to improve outcomes.

We chose to focus on TLR agonists since they are well known to have broad TME modulating effects with induction of immunity at distal sites and the potential to turn “cold tumors”, such as those affecting the liver and pancreas, “hot”, meaning responsive to immunotherapeutics such as ICIs.

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• Locally advanced pancreatic carcinoma (PERIO-03, NCT05607953).

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.

We expect that any continued investigation for ICC and HCC will only continue through IITs.

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.

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.

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.

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Intratumoral pressure in the TME may result in subtherapeutic drug concentrations at the site of disease.

With systemic intravenous (IV) infusion, it is difficult to achieve therapeutic levels within the tumor due to distribution of cardiac output and high intratumoral pressures, and off-target toxicity is common.

With systemic IV infusion, it is difficult to achieve therapeutic levels within the tumor due to distribution of cardiac output and high intratumoral pressures, and off-target toxicity is common.

Local needle injection, the traditional approach for TLR agonists since they typically cannot be administered systemically, is highly localized at the point of insertion, not uniformly distributed throughout the tissue (particularly in patients with large or multiple tumors), and physically impractical for most tumors, including liver and pancreas.

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In addition, nelitolimod may be able to reduce myeloid suppressor cells in the liver and pancreas.

Based on published clinical and preclinical data, TLR9 agonists may also have beneficial effects when combined with chemotherapeutics and/or radiation.

Cancer Types in Clinical Studies

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Uveal Melanoma Liver Metastases

With fewer than 3,000 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.

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.

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.

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Despite representing a crucial clinical advance, the unmet need in the stage IV uveal melanoma space persists.

For patients not eligible for 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.

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.

However, they have had limited efficacy in metastatic uveal melanoma.

An important contributor to the failure of current therapies to effectively treat uveal melanoma is the profoundly immunosuppressive intrahepatic environment.

HCC and ICC are the most common primary liver tumors, with HCC representing approximately 90% of cases.

While the underlying reasons for the biologic aggressiveness of HCC and ICC are not fully understood, the profoundly immunosuppressive intrahepatic environment is likely an important contributor to both disease progression and failure of current therapies.

Given limited success of single agent CPI therapy for HCC and ICC, these drugs have been used in this patient population, but with less success than other diseases.

Current standard of care in first-line ICC is the combination of gemcitabine/cisplatin (“gem/cis”) in combination with AstraZeneca’s Imfinzi® (durvalumab or “durva”).

Median overall survival in these patients is about 12.7 months.

Some second line patients are eligible for targeted therapies which can provide hope for these patients, but the majority of 2 nd line patients are not eligible for these targeted therapies.

For these patients there are few options, generally receiving FOLFOX/FOLFIRI chemotherapy with median overall survival of around 6 months.

Addressing unmet need in either second line or in first line patients is an attractive market opportunity.

Our Platform Solution:

Addressing the Limitations of Current Approaches in Cancer Immunotherapy

Our proprietary platform approach seeks to address immune dysfunction in liver and pancreatic tumors by combining our drug delivery technology with standard care therapies and immunotherapeutics.

In a number of clinical studies, PEDD has shown the ability to overcome intra-tumoral pressure and enable delivery of therapeutics intravascularly into liver tumors relative to conventional regional delivery.

Platform Components

PEDD Devices :

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.

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.

TriNav is currently being used to deliver nelitolimod to tumors in the liver in our Phase 1 PERIO-01 and PERIO-02 trials.

A second FDA-cleared device, our PRVI is designed for therapeutic delivery into pancreatic tumors and is currently being used to deliver nelitolimod to the pancreas in the Phase 1 PERIO-03 trial.

In July 2020, we acquired nelitolimod, a class C Toll-like Receptor 9 agonist (TLR9 agonist) from Dynavax and are investigating nelitolimod as a therapeutic candidate delivered by PEDD to reactivate the immune system within the liver and pancreas with the goal of enabling deeper, more durable responses to other immunotherapeutics (e.g., CPIs) in liver and pancreatic cancers for which limited therapeutic options currently exist.

Broad immune suppression driven by MDSCs leads to failure of systemic immunotherapeutics in liver and pancreas tumors.

Our phase 1 clinical and pre-clinical data support the concept that nelitolimod primes immune cells to promote anti-tumor T-cell function, induces interferon pathways, reduces MDSCs and broadly activates the local tumor immune system to reverse immunosuppression in the liver and pancreas.

Market Opportunity for TriNav Delivery Technology and Investigational Therapeutic Nelitolimod

Market Opportunity for Investigational Therapeutic Nelitolimod

Nelitolimod Market Opportunity

According to the American Cancer Society, the National Cancer Institute and our most up-to-date epidemiology, there are approximately 137,000 new cases of primary and secondary liver cancers diagnosed annually in the U.S.

alone, and more than 60,000 cases of pancreatic cancer diagnosed each year.

Of these, more than 80,000 may be addressable through our nelitolimod /PEDD platform for liver and pancreas.

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.

alone, and more than 60 thousand cases of pancreatic cancer diagnosed each year.

Of these, more than 80 thousand may be addressable through our nelitolimod /PEDD platform for liver and pancreas.

Additionally, there is a high global incidence in key targeted indications, such as HCC and ICC, providing an additional opportunity outside the U.S.

The incidence of pancreatic cancer in the U.S.

is more than 64,000 annually with more than 90% of these being pancreatic ductal adenocarcinoma (“PDAC”).

is more than 64 thousand annually with more than 90% of these being pancreatic ductal adenocarcinoma (“PDAC”).

PDAC and liver cancers are areas of very high unmet medical need and represent large market opportunities.

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Nelitolimod Potential Indications:

Liver Cancers

Nelitolimod is currently being studied in three liver cancer indications:

ICC, HCC, and UMML.

In liver cancer our focus is currently on ICC and UMML.

ICC is a relatively rare and aggressive form of primary bile duct cancer which carries a poor prognosis since it is typically diagnosed when the disease is already in advanced stages.

Despite growing awareness and education of the disease, outcomes have not improved substantially in the last decade, with a 5-year survival rate of 3-23% depending on stage of diagnosis.

For patients with advanced or metastatic disease, systemic chemotherapy with gemcitabine + cisplatin (“gem/cis”) has been the standard-of-care.

Recently, the FDA approved the PD-L1 inhibitor, durvalumab, in combination with gem/cis, for the treatment of first-line patients with advanced or metastatic biliary tract cancers, including ICC.

In this trial of first-line patients, median OS for durvalumab + gem/cis was 12.8 months, as compared to 11.5 months for gem/cis alone.

The FDA has approved targeted fibroblast growth factor receptor 2 (FGFR2”) and isocitrate dehydrogenase-1 (“IDH1”) inhibitors for second line and third line treatment in CCA, but less than 15% of the patients are eligible.

The results from CPI in microsatellite instability-high CCA (<10% of CCA patients) may suggest the potential for immunotherapy to work if the TME in microsatellite instability-stable patients can be reprogrammed effectively.

Since ICC is typically a desmoplastic tumor with a “cold” TME, direct tumor administration of nelitolimod via PEDD has the potential to enhance patient outcomes.

We currently expect to seek a second-line and beyond indication for ICC for which the current standard of care is systemic chemotherapy for those not eligible for targeted therapy.

Although there is significant clinical development underway with targeted therapies, there is little clinical development ongoing focused on the majority of patients who are not targeted therapy eligible.

Uveal melanoma is a malignant tumor derived from melanocytes.

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Immunocore’s Kimmtrak® is indicated for the treatment of HLA-A*02:01 positive adults with unresectable or metastatic uveal melanoma.

Although an improvement over previous therapeutic options, it is only available to approximately 50% of uveal melanoma patients due to its HLA restriction and with median overall survival of 21.7 months and 1-year overall survival of 73% in first line patients.

Although an improvement over previous therapeutic options, it is only available to approximately 50% of uveal melanoma patients due to its HLA restriction.

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.

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).

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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.

Significant Potential Upside from Nelitolimod Program in Development :

We are investigating nelitolimod as a therapeutic candidate to re-activate the immune system within the liver and pancreas and to enable deeper and more durable responses to systematic immunotherapeutics (e.g., checkpoint inhibitors).

We are initially evaluating nelitolimod for the treatment of uveal melanoma with liver metastases, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and locally advanced pancreatic ductal adenocarcinoma.

We believe delivering nelitolimod through our proprietary FDA cleared device using our PEDD technology creates a potential opportunity to change the paradigm of how liver and pancreatic cancer are treated.

Our current pipeline represents a major market opportunity, particularly for PDAC and ICC given the high unmet need in these indications.

Safety and feasibility data for 5 PDAC patients who received nelitolimod via PRVI was reported at the Society for Interventional Radiology 2024 Annual Meeting and indicated no serious treatment-related complications.

Previous study data released in November 2023 for 3 patients demonstrated immune signals in these patients consistent with what we

reported for liver metastasis patients.

We anticipate reporting the full phase 1 experience in the second half of 2024 and begin phase 1b enrollment in the second half of 2024 if the data remains supportive.

Phase 1 data for the PERIO-01 program was presented at a late-breaking oral session at the Society of Immunotherapy for Cancer meeting in November 2023.

The data presented included safety data on 56 patients, of whom 65% had failed prior therapy.

Grade 3 or greater adverse event rate was 11%.

The disease control rate (“DCR”) was 58% across all dose levels, and at the presumed optimal biologic dose (2mg, N=7), there was a DCR of 81%, median progression free survival of 11.7 months and 1-year overall survival rate of 86%.

Amongst patients with available data ctDNA clearance was 59%, with 86% showing reduction in ctDNA.

We continue to follow ICC patients and expect to report initial data in mid-2024.

Growth Strategies

Our goal is to target the significant unmet medical needs of patients with pancreatic and liver cancers by improving how liver cancer is treated currently, utilizing the TriNav Infusion System to deliver chemoembolization and radioembolization more effectively while working to transforming immunotherapy treatment through using our PEDD method to administer our investigational class C TLR9 agonist, nelitolimod.

• Complete Development and Obtain Approval of Nelitolimod:

Currently, our uveal melanoma, ICC, and pancreas cancer clinical programs are studying the delivery of nelitolimod deep into the vasculature of the liver or pancreatic tumors using our proprietary, FDA-cleared TriNav devices.

Analysis of data expected in the second half of 2024 will be used to support decisions regarding the initiation and timing of next-phase trials.

Related data milestones are dependent on multiple factors, including prioritization of available capital, interactions with regulatory authorities, enrollment rates, and external events which may impact operations at clinical sites.

• Seek Potential Expedited Development Pathway or Accelerated Approval Regulatory Pathway :

Our targeting of orphan indications and rare disease creates an opportunity to expedite development and the potential for an accelerated path to approval and commercialization.

Nelitolimod is being studied for the treatment of ICC, uveal melanoma and HCC, diseases for which potential therapies have previously received orphan drug designations.

However, nelitolimod does not currently have orphan designation, nor have we discussed possible use of the accelerated approval pathway for any indication with the FDA or other comparable regulatory agencies and it is possible that we may never be granted orphan designation or pursue accelerated approval.

For approval of new medicines, the regulatory standard for proving “substantial evidence of efficacy” has often historically required the execution of two randomized, well-controlled clinical trials.

In orphan and ultra-orphan indications with unmet medical need, including many cancer indications, there is significant precedent for FDA approval based on a single pivotal clinical trial.

Further, in FDA’s draft guidance on Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics issued in March 2023, FDA discusses the opportunities, and provides guidance for sponsors on using a single clinical trial to potentially support an accelerated approval and to verify clinical benefit.

Certain drugs in development that have received orphan drug designation have been approved via the accelerated approval regulatory pathway.

It is also possible, however, that in the context of either orphan or non-orphan drug development, the FDA may require more than one clinical study and/or may not accept certain clinical data.

• Conducting Clinical Trials with Checkpoint Inhibitors:

The global current immunotherapy market represents the highest growth therapeutic sector in the pharmaceutical industry.

This growth has been led, and we anticipate that this growth will continue to be led, by the continuing growth of CPIs, innovative new classes and an expanding patient pool.

While immunotherapy targeting CTLA-4 and PD-1/PD-L1 in many cancer types has been introduced, response rates remain low in uveal melanoma, HCC, ICC and pancreatic cancer leaving significant unmet need in these patient groups.

PD-(L)1 therapy has been transformational for a number of cancer types but outcomes with respect to the liver and pancreas have lagged in comparison.

Despite this performance, PD-(L)1 companies have significant clinical programs studying various novel combinations of their PD-(L)1 inhibitors with both on-market and investigational drugs, including investigational immmunotherapeutics in hepatobiliary cancers.

An increasing number of developmental programs are incorporating regional delivery approaches, where PEDD may add additional value.

We intend to use investigator’s choice of anti-PD-1 in the development of nelitolimod in the described indications.

If partnership with or rights of reference from a CPI manufacturer(s) becomes prudent or required, we believe that any such collaboration has the potential to provide any such partner companies with significant growth opportunities and differentiation from competitors.

Clinical Development Program for Nelitolimod

The following table sets forth information pertaining to the clinical trials for nelitolimod.

We are currently advancing PERIO-03 while we evaluate data from the PERIO-01 and PERIO-02 trials.

Initiation and timing of next-phase programs and data milestones are subject to change and dependent on multiple factors including interactions with regulatory authorities, enrollment rates, and external events which may impact operations at clinical sites.

Our anticipated upcoming milestones (which are subject to change based on enrollment, competitive environment, and regulatory feedback) include:

• Release of PERIO-01 Phase 1 overall survival and progression free survival data, with optimal biologic dose confirmation, in Q2 2024;

• PERIO-03 Phase 1 (monotherapy) enrollment completion and data release in Q4 2024 with initiation of Phase 1b (+ CPI);

• PERIO-02 data release and initiation of next-phase enrollment in 2H 2024.

Clinical Progress to Date Using Our Therapeutic Platform

PEDD with nelitolimod:

As of March 10, 2024, across three clinical trials, more than 400 infusions of nelitolimod have been delivered at multiple dose levels as monotherapy and in combination with CPIs in more than 100 patients.

Clinical Sites and Partnerships

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.

Clinical Site Partnership

MD Anderson Cancer Center

We have been engaged with top academic sites and leading clinicians in the liver and pancreas cancer spaces.

All three PERIO programs are 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”).

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”).

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.

To date, we have paid an aggregate of $6.0 million towards these studies and will pay an additional $2.0 million following on each of the fourth and fifth anniversaries of the MDACC Agreement.

To date, we have paid an aggregate of $8.0 million towards these studies.

The term of the agreement is for the later of (i) five years or (ii) until the applicable studies are completed.

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No intellectual property has been developed or transferred to date.

Other Clinic Sites

Other active clinical sites for the PERIO programs include:

University of Colorado Anschutz Medical School, Columbia University, Massachusetts General Hospital, Thomas Jefferson University Hospitals, University of Pittsburgh Medical Center, Stanford University, University of California — Los Angeles, University of Miami and University of Washington Medical Center.

We also entered into an agreement with Lifespan to open the TriSalus Translational Immunotherapy Lab, which is part of a comprehensive, integrated, academic health system with The Warren Alpert Medical School of Brown University.

Nelitolimod Competition

We expect nelitolimod to compete primarily with a number of therapeutics that are now, or will soon be, approved for use in uveal melanoma with liver metastases, cholangiocarcinoma HCC, ICC, and locally advanced PDAC.

These therapeutics include a range of immunotherapeutics (e.g., tebentafusp for HLA-A*02:01 positive metastatic uveal melanoma patients, atezolizumab in combination with bevacizumab for HCC patients), chemotherapeutics (e.g., gemcitabine combined with cisplatin for cholangiocarcinoma) and a limited number of targeted therapies (e.g., sorafenib or lenvatinib for HCC).

Pancreatic Ductal Adenocarcinoma (PDAC)

Current preferred therapy for PDAC is either a clinical trial or chemotherapy (commonly the FOLFIRINOX regimen, + subsequent chemoradiation).

Although there are a number of therapeutics and early stage clinical trials, there are currently no ongoing and active industry sponsored Phase 3 drug trials according to Clinicaltrials.gov.

Intrahepatic Cholangiocarcinoma (ICC)

Most patients at initial presentation of ICC are poor candidates for surgical resection and, in those that undergo surgical resection, recurrence rates are high.

Chemotherapy is the primary treatment approach, although the recent approval of the PD-L1 inhibitor durvalumab in combination with gemcitabine + cisplatin for first-line ICC is likely to lead to this regimen becoming the standard of care.

FGFs and IDH1 inhibitors have been approved by the FDA, but fewer than 15% of ICC patients are eligible to receive such treatment based on mutation presence.

Initially, we will seek approval in previously treated patients.

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.

These therapeutics include a range of immunotherapeutics (e.g., tebentafusp for HLA-A*02:01 positive metastatic uveal melanoma patients.

Uveal Melanoma

Uveal melanoma has only one FDA-approved therapy, tebentafusp (KIMMTRAK).

Tebentafusp is a bispecific fusion protein that recognizes two targets, with one target present on melanoma cells, and the second target present on T cells.

There are currently two FDA-approved therapies for uveal melanoma liver metastases, Immunocore's Kimmtrak® (tebentafusp) and Delcath's Hepzato Kit TM .

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.

As with all T-cell receptor products, only patients with specific HLA types are eligible for treatment.

As a result, only approximately 50% of stage IV uveal melanoma patients are eligible to receive tebentafusp, and a significant unmet need still remains.

Ideaya’s darovasertib, in combination with crizotinib, is currently being studied in HLA:A*02:01 negative patients in a potentially registrational trial.

Hepzato Kit is designed to deliver high-dose chemotherapy to the liver while limiting systemic exposure.

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.

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.

Ideaya’s Darovasertib, in combination with crizotinib, is currently being studied in HLA:A*02:01 negative patients in a potential registrational trial.

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.

Nelitolimod, if approved, would address the entire stage IV uveal melanoma patient population, with no limitations based on HLA typing.

Pancreatic Ductal Adenocarcinoma

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).

These chemotherapeutic treatments have significant toxicities and limited efficacy, leaving significant unmet medical need in this disease.

In December 2024, the FDA approved BIZENGRI (Zenocutuzamab )for pancreatic adenocarcinoma that harbors NRG1 gene fusions and are advanced unresectable or metastatic.

Revolution Medicine is in a Phase 3 registrational trial for RMC-6236, a RAS multi-selective inhibitor.

Revolutions trial is anticipated to enroll approximately 460 patients who have received prior PDAC therapy and harbor RAS mutations.

Other clinical trials for PDAC are early stage and are evaluating combinations of targeted therapies and immunotherapy.

Dynavax Asset Purchase Agreement

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Such commercial milestone payments are valued up to $80.0 million.

As of December 31, 2023, we have made three milestone payments of $1 million each, totaling $3 million.

As of December 31, 2024 and 2023, we have made three milestone payments of $1.0 million each, totaling $3.0 million;

no payments were made in the twelve months ended December 31, 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 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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(i) expiration of the last-to-expire claim of an issued and unexpired patent relating to nelitolimod that claims such product (or compound contained therein) or the manufacture or use thereof in the applicable country of sale, or (ii) 10 years after the first commercial sale of such product in such country.

Manufacturing and Distribution

Manufacturing

We manufacture TriNav at our facility in Westminster, Colorado, and have adequate capacity to meet anticipated commercial and clinical demands throughout the next several years.

Manufacturing

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.

We are continually strengthening our supply chain and are currently qualifying additional third-party suppliers for select components of TriNav.

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Our systems and our contractors are required to comply with these regulations, and we assess this compliance regularly through monitoring of performance and a formal audit program.

Effective January 1, 2023, we became exclusive distributor in the U.S.

for TriNav, which we now distribute directly to our customers.

In May 2019, we entered into a Distribution and Collaboration Agreement with Hangzhou (the “Hangzhou Agreement”) pursuant to which Hangzhou was granted an exclusive, non-transferable and non-sublicensable right to distribute PEDD devices and to develop and commercialize PEDD combination products, if any, in China, Taiwan, Hong Kong and Macau (the “Territory”).

We will collaborate with Hangzhou in the development, manufacture and commercialization of PEDD combination therapies.

We must provide Hangzhou with sufficient quantities of PEDD devices to conduct clinical trials to obtain regulatory approval for each PEDD combination therapy in the Territory and use commercially reasonable best efforts to meet all supply needs to support the commercialization plan (if implemented).

Hangzhou is responsible for (i) developing a commercialization plan, (ii) the cost of development activities to obtain regulatory approval for each PEDD combination therapy in the Territory, (iii) securing all rights to each of its drug candidates as necessary to execute the applicable plan and grant the corresponding U.S.

option to TriSalus, and (iv) developing, commercializing and obtaining regulatory approvals for each PEDD combination therapy for the applicable indication in the Territory.

To date, no clinical trials have commenced nor do we believe such commencement is imminent.

In connection with entering into the Hangzhou Agreement, we issued a convertible promissory note (which has been subsequently fully converted to TriSalus common stock) to an affiliate of Hangzhou for gross proceeds of $10 million.

No other amounts have been paid or received under the Hangzhou Agreement to date.

In collaboration with Hangzhou, we submitted TriNav for NMPA approval and we expect a final determination in the first half of 2024.

The Hangzhou Agreement also requires Hangzhou to deliver to us a marketing plan no less than 12 months prior to the first distribution of any PEDD device.

Such marketing plan has not been delivered to us as of the date of this Annual Report on Form 10-K and accordingly no PEDD devices have been sold pursuant to this Hangzhou Agreement or are expected to be sold in the immediate future.

The Hangzhou Agreement further includes an obligation for Hangzhou to pay us a milestone payment in the amount of $2.5 million for each PEDD combination therapy that receives regulatory approval in the covered jurisdictions and low-single digit royalties for any subsequent sales of such PEDD combination therapy on a country-by-country basis for the later of (i) ten years after the first commercial sale of such therapy in such country or (b) the first commercial sale of a generic version of such therapy by a third party.

No submission for regulatory approval has been made as of the date of this Annual Report and none is expected to be made in the immediate future.

Importantly, under the terms of the Hangzhou Agreement, we will own all intellectual property that is discovered or generated in the course of performance of the collaboration that relates primarily and directly to any PEDD device, including any method of making or using any of the foregoing.

Hangzhou shall own all intellectual property generated in the course of performance of the collaboration that relates primarily and directly to a Hangzhou drug candidate, including the composition, salt, polymorph, formulation of or any method of making or using the foregoing;

except that TriSalus has the option to obtain an exclusive, non-transferable license under the Hangzhou intellectual property to develop, manufacture and commercialize Hangzhou drug candidates as PEDD combination therapies in the United States.

The exercise of such option, or lack thereof, will result in further payment obligations of ours, if exercised, ranging from $0 to $10.0 million dependent on the timing of the exercise, and of Hangzhou in the amount of up to $10.0 million if unexercised.

In the event of a material breach, the Hangzhou Agreement can be terminated by the non-breaching party effective upon (i) 90 days written notice of the breach if uncured, (ii) 30 days written notice if the alleged breach related to failure to make payments under the Hangzhou Agreement and is uncured, or (iii) immediately if such notice pertains to the willful and intentional breach related to compliance with anti-corruption laws, confidentiality obligations, distribution of competing PEDD devices, or violation of material intellectual property rights of the non-breaching party.

Intellectual Property

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and other select countries.

As of March 10, 2024, we owned at least 122 registered patents expiring between 2041 and 2043, with at least an additional 61 pending patent applications and four provisional applications.

As of December 31, 2024, we owned at least 79 registered patents expiring between 2030 and 2040, with at least an additional 86 pending patent applications.

For our TriNav device, we are the sole owner of five granted U.S.

patents, seven pending U.S.

patent applications, one granted patent in Japan and four pending foreign patent applications in Canada, China, Europe, and Hong Kong 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.

patents, five pending U.S.

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.

The five granted U.S.

patents expire between 2031 and 2038.

The one granted patent in Japan expires in 2038.

The eight granted foreign patent expire in 2038.

Any patents issuing from the pending patent applications (or in the case of priority applications, if issued from future non-provisional applications that we file) are expected to expire between 2030 and 2041, without accounting for potential terminal disclaimers or potentially available patent term adjustments or extensions.

For the TriSalus Infusion System, we are the sole owner of five granted U.S.

patents, seven pending U.S.

patent applications, 12 granted foreign patents (counting national validations in Europe) and four pending foreign patent applications in China, Europe, Hong Kong, and India 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.

patents, five pending U.S.

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.

The five granted U.S.

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Some patents and applications relating to the TriSalus Infusion System overlap with those identified for the TriNav device.

For nelitolimod, we are the sole owner of five granted U.S.

patents, three pending U.S.

patent application, three pending U.S.

provisional patent applications, two pending PCT patent applications, 16 pending foreign patent applications, and 61 granted foreign patents in Australia, Canada, China, Europe (counting national validations), Hong Kong, Japan,

South Korea, New Zealand and Singapore relating to immunostimulatory sequence oligonucleotides and methods of using the oligonucleotides and specifically nelitolimod.

All of the granted US and foreign patents that relate to composition of matter for nelitolimod expired in December 2023.

Currently, we do not solely own any granted US or foreign patents relating to nelitolimod that expired past December 2023.

However, we jointly own with Merck Sharp & Dohme LLC one granted US, seven granted foreign patents, and two pending foreign applications that relate to nelitolimod, which is a CPG-C type oligonucleotide, as discussed further below.

For nelitolimod, we are awaiting three pending U.S.

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.

However, we jointly own with Merck Sharp & Dohme LLC two granted US and 14 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.

We also jointly own a pending U.S.

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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.

We also jointly own with third parties one granted U.S.

patent, two pending U.S.

patent applications, and seven granted foreign patents in China, Europe (counting national validations), Hong Kong and Japan and tending foreign applications relating to combinations with CPG-C type oligonucleotides for treating cancer.

The one granted U.S.

patent and seven granted foreign patents in China, Europe (counting national validations), Hong Kong and Japan all expire in 2036.

Any patents issuing from the two (2) pending U.S.

patent applications and the two (2) pending foreign patent applications (or in the case of priority applications, if issued from future non-provisional applications that we file) are expected to expire between 2036 and 2039, without accounting for potential terminal disclaimers or potentially available patent term adjustments or extensions.

Upon regulatory approval of nelitolimod in the U.S., we expect to be granted five years of regulatory exclusivity in the U.S.

We also intend to apply for orphan drug designation which, if granted, would extend the exclusivity period for an additional two years.

Nelitolimod is currently undergoing clinical trials using pressure enabled drug delivery of nelitolimod using TriNav and the TriSalus Infusion System in various cancers, and in combination with systemic checkpoint inhibitor therapy.

Some of the patents and applications described with respect to TriNav and the TriSalus Infusion System are expected to be relevant to the manner nelitolimod is administered in clinical development, and post-marketing if nelitolimod is approved by regulatory authorities to be used in combination with TriNav and the TriSalus Infusion System.

Trade Secrets and Other Proprietary Information

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We expect the global regulatory environment will continue to evolve, which could impact the cost, the time needed to approve, and ultimately, our ability to maintain existing approvals or obtain future approvals for our products.

of the FDA and other regulatory agencies in and outside the U.S.

Regulations of the FDA and other regulatory agencies in and outside the U.S.

impose extensive compliance and monitoring obligations on our business.

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.

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.

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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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.

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.

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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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.

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.

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.

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.

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.

If 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.

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.

In addition, clinical studies must be approved by, and conducted under the oversight of, an Institutional Review Board (“IRB”) for each clinical site.

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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.

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.

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.

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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.

We plan to seek FDA approval of nelitolimod through a 505(b)(1) regulatory approval pathway, as part of a combination regimen with checkpoint inhibitor(s).

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.

A combination regimen requires data demonstrating the contribution of each drug in the regimen to the treatment of the disease under study.

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Orphan Drug Exclusivity .

The Orphan Drug Act provides incentives for the development of drugs intended to treat rare diseases or conditions, which generally are diseases or conditions affecting less than 200,000 individuals in the U.S.

If a sponsor demonstrates that a drug product qualifies for orphan drug designation, the FDA grants orphan drug designation to the product for that use.

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For example, in August 2011, the Budget Control Act of 2011 was signed into law which, among other things, led to aggregate reductions of Medicare payments to providers up to 2% per fiscal year, and, due to subsequent legislative amendments, will remain in effect until 2032 unless additional congressional action is taken.

Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester.

There has been increasing legislative and enforcement interest in the U.S.

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In addition, the IRA, among other things, (1) directs HHS to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions will take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

These provisions began to take effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare drug price negotiation program.

Further, the Biden administration released an additional executive order on October 14, 2022, directing HHS to submit a report within 90 days on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

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It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

Further, on December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

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.

The current Trump administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

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.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors.

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Moreover, we are unable to predict what changes will be made to the reimbursement methodologies used by third-party payors in the future.

For example, CMS awarded TPT payments for TriNav for the two-year period through December 31, 2022.

On December 29, 2022, the Consolidated Appropriations Act of 2023 (H.R.

2617) was signed into law and includes an extension of TPT status for certain devices, including TriNav, through December 31, 2023.

In December 2023, CMS granted a New Technology HCPCS code for procedures involving TriNav.

This new code, C9797, became effective on January 1, 2024, and may be reported by hospital outpatient departments and ambulatory surgical centers.

This code, C9797, became effective on January 1, 2024, and may be reported by hospital outpatient departments and ambulatory surgical centers.

There can be no assurance that continuing reimbursement will be available at similar reimbursement rates or at all.

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.

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.

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.

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).

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.

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The Affordable Care Act, among other things, amended the intent requirement of the federal Anti-Kickback Statute such that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate in order to commit a violation.

• The federal civil and criminal false claims laws, including the False Claims Act, which can be enforced by private individuals on behalf of the government through civil whistleblower or qui tam actions, and civil monetary penalty laws prohibit individuals or entities from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment of government funds, or knowingly making, using, or causing to be made or used, a false record or statement material to an obligation to pay money to the government or knowingly concealing or

knowingly and improperly avoiding, decreasing, or concealing an obligation to pay money to the U.S.

federal government.

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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.

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.

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

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It is illegal to pay, offer to pay or authorize the payment of anything of value to any official of another country, government staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in that capacity.

Our principal office is located in Westminster, Colorado, where we lease approximately 21,000 square feet of office, manufacturing, and warehouse space pursuant to a lease that expires on December 31, 2026.

The lease includes two

extension options, each for five years.

We have not yet determined if we will exercise the extension options.

We also lease office facilities in Bannockburn, Illinois, and Cranston, Rhode Island.

We also lease laboratory space at Rhode Island hospital in Providence, Rhode Island.

Our principal office is located in Westminster, Colorado, where we lease approximately 21 thousand square feet of office, manufacturing, and warehouse space pursuant to a lease that expires on December 31, 2031.

The lease includes one extension option, for five years.

We have not yet determined if we will exercise the extension option.

We also lease office facilities in Bannockburn, Illinois, and 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.

As of March 5, 2024, we had approximately 112 full-time employees, including 10 employees who held Ph.D.

None of our employees is represented by a labor union or covered under collective bargaining agreement.

As of December 31, 2024, we had approximately 110 full-time employees, including six employees who held Ph.D.

None of our employees are represented by a labor union or covered under collective bargaining agreement.

We have not experienced any material work stoppages and we consider our relationship with our employees to be good, healthy and transparent.

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Corporate Information

We were incorporated in Delaware in September 2020.

Our principal executive offices are located at 6272 W.

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Our corporate website address is www.trisaluslifesci.com.

Information contained on or accessible through our website is not a part of this prospectus, and the inclusion of our website address in this Annual Report is an inactive textual reference only.

For additional information, see the “Introductory Statement” to this Annual Report, Item 7- Management’s Discussion and Analysis of Financial Condition and Results of Operations of this Annual Report, and (3) Business Combination of our financial statements for the year ended December 31, 2023, included in Item 8 of this Annual Report for more information regarding the Merger.

We intend to announce material information to the public through filings with the SEC, the investor relations page on our website, press releases, public conference calls and public webcasts.

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.

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.

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.

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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.

What changed 10-K

Item 1. Business