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– New data from PERIO-03 clinical trial indicates PEDD™ method resulted in modulation of the tumor microenvironment by enabling performance of a TLR9 agonist in pancreatic tumors – DENVER & SAN DIEGO--(BUSINESS WIRE)-- TriSalus Life Sciences® Inc., (Nasdaq: TLSI), an oncology company integrating its novel delivery technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors, today announced initial positive safety and feasibility data from a Phase 1 trial at the Society of Immunotherapy for Cancer (SITC) 2023 Annual Meeting. TriSalus is studying an investigational class C toll-like receptor-9 (TLR9) agonist, SD-101, delivered intravascularly using the Company’s proprietary Pressure-Enabled Drug Delivery™ (PEDD™) method of administration in three Phase 1 trials (periotrial.com). In PERIO-03, SD-101 is delivered via PEDD with the TriSalus Infusion System® using a retrograde venous approach, leveraging established interventional radiology access techniques. The TriSalus Infusion System has an expandable SmartValve® and can interface with standard invasive blood pressure transducers for continuous pressure monitoring during infusion of a therapeutic. During infusion, the device blocks retrograde flow and modulates pressure in the vessel, resulting in the perfusion of the venous and capillary network isolated by the device. Early safety and feasibility data from the PERIO-03 locally advanced pancreatic adenocarcinoma trial revealed that in three patients who received SD-101 via retrograde venous infusion PEDD at the lowest dose level (0.5 mg), there were no serious grade 3/4 adverse events related to treatment. This is a first-in-human experience for use of PEDD and retrograde venous infusion for delivery of an immunologic agent into pancreatic tumors. Immune signals pointed to a decrease in myeloid derived suppressor cells (MDSC) activity in the treated pancreatic tumors, with declines in MDSC associated genes, including arginase-1, nitric oxide synthetase-2, and S100A9 (n=3). Signals associated with T cell activation were also noted in pancreatic tumor biopsy specimens. “There is a critical need for novel treatments and approaches in locally advanced pancreatic cancer. The PERIO-03 trial is a highly innovative and multidisciplinary approach of delivery of a novel immunotherapy into the pancreas through pancreatic retrograde venous infusion,” stated Michael S. Lee, M.D., associate professor of Gastrointestinal (GI) Medical Oncology at The University of Texas MD Anderson Cancer Center. “The treatments have been well tolerated and the translational studies show intriguing changes in immune markers. We are excited to continue enrolling patients in this study.” “These data offer additional validation of our innovative immunotherapy approach for pancreatic tumors. SD-101 was selected based on its mechanism of action, which has the potential to reverse immunosuppression in the pancreas through depletion of MDSC in concert with broad stimulation of immune cells in the tumor microenvironment,” said Steven C. Katz, M.D., FACS, Chief Medical Officer at TriSalus. “TriSalus delivery systems, which use the PEDD method, are designed to overcome mechanical barriers to immunotherapy success, which may be underappreciated factors in limiting performance of TLR agonists in liver and pancreas tumors. Pancreatic tumors in particular contain very dense stromal tissue, which may accentuate the mechanical barriers to effective drug delivery in these patients.” Overall, the data emerging from PERIO-03 trials indicate immunologic changes are occurring within the pancreas, with a favorable safety profile. Additionally, pre-clinical data presented by TriSalus at SITC indicates that SD-101 administered via PEDD can enable both intravenously and subcutaneously administered checkpoint inhibitors. TriSalus will also present data from its PERIO-01 trial for uveal melanoma liver metastases at a SITC late breaker session on Saturday, November 4 at 11:25 am PT. All TriSalus presentations from SITC are available here following their respective sessions. About Pressure-Enabled Regional Immuno-Oncology (PERIO) clinical trials The Pressure-Enabled Regional Immuno-Oncology (PERIO) clinical trials are studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly by TriSalus’ TriNav® Infusion System (TriNav) using the Company’s proprietary Pressure-Enabled Drug Delivery™ (PEDD™) method of administration in three Phase 1 trials. The PERIO-01 Phase 1 clinical study for uveal melanoma with liver metastases (UMLM), is studying SD-101 delivered via PEDD with TriNav in combination with intravenous checkpoint inhibitors. The PERIO-02 Phase 1b clinical study for hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is studying SD-101 delivered via PEDD with TriNav in combination with intravenous checkpoint inhibitors. The PERIO-03 Phase 1 clinical study for locally advanced pancreatic adenocarcinoma, is studying SD-101 delivered via PEDD with TriNav in combination with intravenous checkpoint inhibitors. About TriSalus Life Sciences TriSalus Life Sciences® is an oncology company integrating novel delivery technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors. The Company’s platform includes devices that utilize a proprietary drug delivery technology and a clinical stage investigational immunotherapy. The Company’s two FDA-cleared devices use its proprietary Pressure-Enabled Drug Delivery™ (PEDD™) approach to deliver a range of therapeutics: the TriNav® Infusion System for hepatic arterial infusion of liver tumors and the Pancreatic Retrograde Venous Infusion System for pancreatic tumors. PEDD is a novel delivery approach designed to address the anatomic limitations of arterial infusion for the pancreas. The PEDD approach modulates pressure and flow in a manner that delivers more therapeutic to the tumor and is designed to reduce undesired delivery to normal tissue, bringing the potential to improve patient outcomes. SD-101, the Company’s investigational immunotherapeutic candidate, is designed to improve patient outcomes by treating the immunosuppressive environment created by many tumors and that can make current immunotherapies ineffective in the liver and pancreas. Patient data generated during Pressure-Enabled Regional Immuno-Oncology™ (PERIO) clinical trials support the hypothesis that SD-101 delivered via PEDD may have favorable immune effects within the liver and systemically. The target for SD-101, TLR9, is expressed across cancer types and the mechanical barriers addressed by PEDD are commonly present as well. SD-101 delivered by PEDD will be studied across several indications to address immune dysfunction and overcome drug delivery barriers in the liver and pancreas. In partnership with leading cancer centers across the country – and by leveraging deep immuno-oncology expertise and inventive technology development – TriSalus is committed to advancing innovation that improves outcomes for patients. Learn more at trisaluslifesci.com and follow us on Twitter and LinkedIn. For Patients To learn more about the clinical trial treatment protocol and enrollment, visit or and search NCT04935229, NCT05220722, and NCT05607953. Forward Looking Statements Statements made in this press release regarding matters that are not historical facts are “forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward‐looking statements. Such statements include, but are not limited to, statements regarding the benefits and potential benefits of the Company’s PEDD drug delivery technology and SD-101 investigational immunotherapy. Risks that could cause actual results to differ from those expressed in these forward‐looking statements include risks associated with clinical development and regulatory approval of drug delivery and pharmaceutical product candidates, including that future clinical results may not be consistent with patient data generated during the Company’s PERIO clinical trials, and other risks described in the Company’s filings with the Securities and Exchange Commission under the heading “Risk Factors.” All forward‐looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made except as required by law.

Engineers have developed an experimental vaccine that could prevent the spread of metastatic cancers to the lungs. Its success lies in targeting a protein known to play a central role in cancer growth and spread, rather than targeting the primary tumor itself. Engineers at the University of California San Diego have developed an experimental vaccine that could prevent the spread of metastatic cancers to the lungs. The key ingredients of the vaccine are nanoparticles -- fashioned from bacterial viruses -- that have been engineered to target a protein known to play a central role in cancer growth and spread. In mice, the vaccine significantly reduced the spread of metastatic breast and skin cancers to the lungs. It also improved the survival rate in mice with metastatic breast cancer after surgical removal of the primary tumor. The findings were published on Oct. 16 in Proceedings of the National Academy of Sciences. Metastasis is a process involving the migration of cancer cells from their primary site to other parts of the body. Recent studies have identified S100A9, a protein typically released by immune cells, as a key player in this process. Its normal role is to regulate inflammation. However, an excess of S100A9 can attract cancer cells like a magnet, causing them to form aggressive tumors and facilitating their spread to other organs, such as the lungs. A team led by Nicole Steinmetz, a professor of nanoengineering at the UC San Diego Jacobs School of Engineering, developed a vaccine candidate that can modulate the levels of S100A9 when it goes haywire. When injected subcutaneously, the vaccine stimulated the immune system in mice to produce antibodies against S100A9, effectively reducing the protein levels and minimizing cancer metastasis to the lungs. The vaccine also increased the expression of immune-stimulating proteins with anti-tumor properties, while decreasing the levels of immune-suppressing proteins. "S100A9 is known to form what is called a premetastatic niche within the lungs, creating an immunosuppressive environment that allows for tumor seeding and growth," said study first author Young Hun (Eric) Chung, a UC San Diego bioengineering Ph.D. alumnus from Steinmetz's lab. "By reducing S100A9 levels, we can effectively counteract the formation of this premetastatic niche, leading to a reduced attraction and increased clearance of cancer cells to the lungs." "This is a clever, new approach to vaccination in that we are not targeting tumor cells, but rather the tumor microenvironment so that it prevents the primary tumor from making new tumors," said Steinmetz, who is the founding director of the UC San Diego Center for Nano-ImmunoEngineering and co-lead of the university's Materials Research Science and Engineering Center (MRSEC). "We are essentially changing the whole immune system to be more anti-tumor." How it works The vaccine consists of nanoparticles made from a bacterial virus called Q beta. The nanoparticles were grown from E. coli bacteria and isolated. Afterwards, a piece of the S100A9 protein was attached to the surface. How it works is that the Q beta virus nanoparticles act as bait for the immune system. This virus is harmless to animals and humans, but immune cells recognize it as foreign and get fired up to attack to search for a pathogen. When the immune cells see that the virus nanoparticles display a piece of the S100A9 protein, they produce antibodies to go after that protein. An advantage of using antibodies, Steinmetz noted, is that they help keep the levels of the target protein in check. "With this form of immunotherapy, we are not necessarily knocking out all of the protein, but we are reducing the levels everywhere," said Steinmetz. Testing the vaccine candidate The vaccine was tested in metastatic mouse models of melanoma and triple-negative breast cancer, an aggressive and hard-to-treat cancer type. Healthy mice were first administered the vaccine, then challenged with either melanoma or triple-negative breast cancer cells through intravenous injection. Vaccinated mice exhibited a significant reduction in lung tumor growth compared to unvaccinated mice. In unvaccinated mice, the injected cancer cells circulated throughout the body and eventually homed in on the lungs to form metastatic tumors. The researchers note that this vaccine strategy combats tumor spread, not the primary tumor itself. "While S100A9 does get overexpressed in certain primary tumors, it is mainly indicated in metastatic disease and progression," said Chung. "The protein is involved in the formation of immunosuppressive tumor microenvironments. Therefore, we found that our vaccine is much more effective at reducing metastasis, and not in reducing the growth of the primary tumors." Another set of experiments demonstrated the vaccine's potential to offer protection against cancer metastasis after surgical removal of the primary tumor. Mice with triple-negative breast cancer tumors who received the vaccine post-surgery demonstrated an 80% survival rate, while 30% of unvaccinated mice survived after surgery. "These findings are the most clinically relevant, as they closely model what could happen in real-life scenarios," said Steinmetz. "For instance, a patient diagnosed with an aggressive cancer who undergoes surgery to remove their tumor may be at risk of recurrence and metastasis to the lungs. We envision that this vaccine could be administered post-surgery to prevent such recurrence and outgrowth of metastatic disease." Next steps Before the vaccine can progress to human trials, more comprehensive safety studies are needed. "S100A9 is an endogenous protein within the lungs, and there aren't a lot of data out there that demonstrate what happens when S100A9 is abolished," said Chung. "We know that S100A9 is important in the clearance of pathogens, and future studies should better test whether reducing S100A9 levels decreases the patient's ability to fight infections, especially in cancer patients who may have weakened immune systems." Future work will also explore the vaccine's effectiveness when combined with other cancer therapies, with the aim of improving its efficacy against hard-to-treat cancers. This work was supported in part by the National Institutes of Health (R01-CA224605). Disclosure: Nicole Steinmetz is a co-founder of, has equity in, and has a financial interest with Mosaic ImmunoEngineering Inc. Steinmetz serves as director, board member, acting chief scientific officer, and paid consultant to Mosaic. Steinmetz, Young Hun Chung and Oscar. A. Ortega-Rivera have a filed patent in regard to the work presented. The other authors declare no potential conflict of interest.

WESTON, Fla., Aug. 28, 2023 /PRNewswire/ -- Cantex Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions, announced today the initiation of a Phase 2 clinical trial to assess the safety and effectiveness of Cantex's azeliragon combined with stereotactic radiosurgery in patients with brain metastases. Cantex's azeliragon, currently also in Phase 2 development for the treatment of other major cancers, complications of cancer treatment and the treatment of other life-threatening illnesses, inhibits the receptor for advanced glycation end products (known as RAGE), is orally administered and is taken once daily. "We are very excited to initiate enrollment into this important clinical trial. With the initiation of this Phase 2 clinical trial, Cantex expands the cancer indications for which azeliragon is being investigated, which now include active Phase 2 clinical trials in glioblastoma, breast cancer, pancreatic cancer, and a phase 2/3 clinical trial in hospitalized COVID-19 patients to prevent acute kidney injury, accelerating azeliragon's development as a treatment of very aggressive and difficult to treat cancers and other illnesses," said Stephen G. Marcus, M.D., Chief Executive Officer of Cantex. Brain metastases are the most common type of cancer in the brain, with over 150,000 people each year developing brain metastasis from their primary cancer (most commonly from lung and breast cancer). "Brain metastases are a common complication of cancer and often are treated with stereotactic radiosurgery in the upfront setting," said Rupesh Kotecha, M.D., principal investigator of the investigator-initiated trial and Chief of Radiosurgery and Director of Central Nervous System Metastasis at Miami Cancer Institute, part of Baptist Health South Florida. "This investigator-initiated Phase 2 clinical trial of azeliragon, with its differentiated mechanism of action, will offer patients a unique approach to the treatment of brain metastases that may protect against inflammation as well as enhance the effectiveness of radiation therapy." Cantex's azeliragon inhibits RAGE interactions with certain ligands, including HMGB1 and S100 proteins in the cancer microenvironment. S100A9, a protein released from cells within the microenvironment of brain metastasis, binds to RAGE receptors on the surface of cancer cells, making them resistant to the effectiveness of radiation treatments. Azeliragon blocks the interaction of S100A9 with RAGE, potentially restoring sensitivity to radiation therapy. In addition, interaction of RAGE with proteins that bind to it, triggers inflammatory responses, which may worsen brain swelling associated with radiation therapy. This clinical trial is designed to determine whether Cantex's azeliragon, when administered in combination with stereotactic radiosurgery, can prevent or eliminate the need for a powerful steroid, dexamethasone, to control brain swelling as well as improve the effectiveness of radiation therapy to treat brain metastases. About Azeliragon Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of RAGE with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was discovered by and originally under development for Alzheimer's disease by vTv Therapeutics Inc. (NASDAQ:VTVT) from whom Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated. Cantex also has ongoing Phase 2 clinical trials in newly diagnosed glioblastoma, neoadjuvant therapy of breast cancer, and metastatic pancreatic cancer, and an ongoing Phase 2/3 clinical trial in hospitalized COVID-19 patients to prevent acute kidney injury. These trials are based on azeliragon's robust pre-clinical data as well as its extensive clinical safety information from randomized placebo-controlled clinical trials. About Cantex Pharmaceuticals, Inc. Cantex Pharmaceuticals, Inc. is a privately held, clinical stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit . About vTv Therapeutics Inc. vTv Therapeutics Inc. is a clinical stage biopharmaceutical company focused on developing oral, small molecule drug candidates, led by cadisegliatin (TTP399) for the treatment of type 1 diabetes. To learn more please visit vtvtherapeutics.com. Contacts: Tiberend Strategic Advisors, Inc. Investors Daniel Kontoh-Boateng +1 862-213-1398 [email protected] Media Casey McDonald +1 646-577-8520 [email protected] Cantex Pharmaceuticals, Inc.: Stephen G. Marcus, M.D. +1 954-315-3660 [email protected] Juan F. Rodriguez +1 954-315-3660 [email protected] SOURCE Cantex Pharmaceuticals, Inc.