Mr. Chris Seto reports

SPECTRAL MEDICAL AND VANTIVE ANNOUNCE TOPLINE RESULTS FROM SPECTRAL'S TIGRIS TRIAL EVALUATING PMX HEMOADSORPTION THERAPY FOR ENDOTOXIC SEPTIC SHOCK

Spectral Medical Inc. and Vantive, a vital organ therapy company committed to pursuing novel diagnostic and therapeutic options for organ failure, today released top-line results from the Tigris trial. This phase 3 follow-on study sponsored by Spectral evaluated the use of Polymyxin B Hemoadsorption (PMX) in a randomized clinical trial of adults treated for endotoxic septic shock.

• Results exceed prespecified primary end point of 95-per-cent posterior probability of benefit for PMX on 28-day mortality;
• Pooled absolute risk reduction of 8.3 per cent; relative risk reduction of 18 per cent;
• Key secondary end point: 90-day mortality 17.4-per-cent lower with PMX and greater than 99 per cent posterior probability of benefit;
• 38.7-per-cent mortality at 28 days with PMX confirms results of prior trial subset.

Each year, approximately five million to seven million cases of endotoxic septic shock, a particularly deadly form of sepsis, occur worldwide. Today, there is no specific therapy targeting this patient population currently available in the United States. The Tigris trial was a United States-based, multicentre, randomized, controlled phase 3 study evaluating PMX in adults with endotoxic septic shock, defined by an Endotoxin Activity Assay (EAA) level between 0.60 and 0.90. EAA is a Food and Drug Administration-approved, semiquantitative test for measurement of endotoxin activity, allowing for rapid measurements to obtain results in approximately 30 minutes. The treating physician can use these results to help inform timely therapeutic decisions. Eligible patients also had to meet criteria for multiple organ dysfunction, including a multiple organ dysfunction score (MODS) greater than nine or a sequential organ failure assessment (SOFA) score of greater than 11. A total of 157 patients were randomized in a 2:1 ratio to receive either PMX plus standard care (n equals 106) or standard care alone (n equals 51).

The primary end point -- 28-day all-cause mortality -- was evaluated using a prespecified Bayesian statistical model, which evaluates results in the context of prior probability. The model incorporated data from 179 patients in the previously conducted Euphrates trial alongside the data from the Tigris trial. The Euphrates trial was conducted in North America and examined the impact of PMX on mortality in patients with septic shock and endotoxemia. The goal of the Tigris trial was to confirm the benefit of PMX hemoadsorption in patients with endotoxic septic shock, defined by EAA 0.60 but less than 0.90. The Tigris trial's design and analysis plan were aligned with published FDA's Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials.

Key findings of the Tigris trial and Bayesian analysis

The purpose of Bayesian analysis is to update prior evidence with new trial data, producing a "posterior probability" that reflects the most current and complete picture of the treatment effect. Results are presented for adjusted and unadjusted analyses. Consistent with expert recommendations and the FDA's guidance on clinical trials, the adjusted analysis is used to account for baseline prognostic covariates such as severity of illness and comorbidities -- which provides a more precise estimate of the true treatment effect. Unadjusted analyses do not account for these important differences.

Primary end point (28-day mortality):

• Intention to treat cohort showed a posterior probability of benefit of 95.3 per cent at 28 days;
• Adjusted odds ratio 0.67 (0.39 to 1.08):
  • Adjusted posterior probability of benefit from PMX at 28 days exceeds the prespecified 95-per-cent target and thus meets the prespecified primary end point.
• Observed 28-day mortality for Tigris was 38.7 per cent with PMX versus 45.1 per cent with standard of care -- 6.4 per cent absolute difference:
  • Unadjusted absolute risk reduction from the posterior distribution was 8.3 per cent (negative 2.1 per cent, 19.7 per cent) representing a 18-per-cent relative risk reduction, posterior probability 92.3 per cent.
  • Observed 28-day mortality from the modified intention to treat population (includes 100 PMX and 51 control patients receiving any assigned treatment) was 37.0 per cent with PMX versus 45.1 per cent with standard of care -- 8.1 per cent absolute difference.

Key secondary end point (90-day mortality):

• The key secondary end point, mortality at 90 days, showed a greater than 99-per-cent posterior probability of benefit for PMX.
• Adjusted odds ratio 0.54 (0.32 to 0.87):
  • Adjusted posterior probability of benefit from PMX at 90 days was 99.4 per cent.
• Observed mortality at 90 days (Tigris alone): 43.4 per cent with PMX versus 60.8 per cent with standard of care -- 17.4-per-cent absolute difference:
  • Unadjusted absolute risk reduction from the posterior distribution was 12.3 per cent (0.76 per cent, 23.7 per cent) representing a 20.2-per-cent relative risk reduction, posterior probability 98.3 per cent.
  • Resultant number needed to treat (NNT) to save one life at 90 days is 8.1.

Dr. John Kellum, chief medical officer of Spectral Medical, commented: "We are pleased to announce that the fully adjusted Bayesian analysis met our prespecified goal of greater than 95-per-cent posterior probability of benefit for 28-day mortality. As we explained in our Nov. 14, 2023, press release, our published simulations involving over 2,000 potential trial results found an observed absolute risk reduction for mortality in the range of 6 to 7 per cent in Tigris would meet this bar. Final results from Tigris indicate that our observed 6.4-per-cent difference yields a 95.3-per-cent posterior probability and thus exceeds this threshold. Furthermore our 90 days results provide important confirmation that benefits with PMX are persistent."

Professor Claudio Ronco, director of the International Renal Research Institute of Vicenza IRRIV and world-renowned expert in blood purification for sepsis, commented: "The results that we see today are a clear confirmation of what we observed more than 16 years ago with the Euphas trial. Tigris, together with a subset of patients from Euphrates, indicate that hemoadsorption therapy with PMX can be effective if we select the correct population. Like in Euphas, patients in the Tigris trial have a 28-day mortality of approximately 50 per cent unless treated with PMX. The benefit for survival from PMX becomes even more dramatic at 90 days where it exceeds 17 per cent. This is not unexpected as today many patients can be maintained on life support for more than 28 days -- as such, longer-term survival is a more accurate reflection of benefit."

Dr. Danielle Davison, professor of anesthesiology and critical care medicine and director of the Intensive Care Unit, George Washington University, Washington, D.C., commented: "Having participated in both Euphrates and Tigris, it is particularly satisfying to see these final results. We look forward to having this therapy available for our patients."

"Vantive is committed to supporting clinical research to advance therapy innovation and expand access to care for critically ill patients," said Professor Peter Rutherford, head of worldwide medical at Vantive. "We are encouraged by these results, and look forward to continuing to work toward addressing unmet clinical needs and improving outcomes for patients affected by endotoxic septic shock."

"The results from Tigris represent a significant milestone for Spectral as we continue advancing toward our goal of improving outcomes in endotoxic septic shock," said Chris Seto, chief executive officer of Spectral Medical. "When considered alongside prior evidence from the Euphrates trial and real-world global experience, the totality of data supporting PMX continues to strengthen. Importantly, the safety profile observed in Tigris was consistent with PMX's historical use with over 360,000 units sold worldwide. These findings further support our planned FDA PMA submission and our efforts to make this therapy available to the patients who need it most."

Vantive is Spectral's exclusive distributor of PMX in the United States and Canada, and has non-exclusive rights to distribute EAA globally. Spectral Medical intends to submit the final premarket approval (PMA) module (module 3) for PMX to the FDA by end of October, 2025. If approved by the FDA, Vantive plans to commercialize both EAA and PMX, beginning in the United States, to support targeted rapid endotoxin adsorption (TREA) therapy. TREA therapy brings precision medicine to sepsis, delivering rapid, decisive treatment for patients with endotoxic septic shock.

Full results from the Tigris trial will be submitted for presentation at an upcoming major medical conference and for publication in a peer-reviewed journal later this year.

Spectral Medical Tigris trial top-line results call

Chris Seto, chief executive officer, and Dr. John Kellum, chief medical officer, will host the call followed by a question-and-answer session. All interested parties are invited to participate.

conference call details:

Date:  Wednesday, Aug. 13, 2025

Time:  8:30 a.m. ET

Dial-in:  1-877-407-0792 or 1-201-689-8263

Participants can use guest dial-in numbers above and be answered by an operator or click the call me link for instant telephone access to the event.

* Available 15 minutes prior to scheduled start time.

Replay dial-in:  1-844-512-2921 or 1-412-317-6671

Available 1 p.m. ET, Wednesday, Aug. 13, 2025, until 11:59 p.m. ET, Wednesday, Aug. 27, 2025

Conference ID:   13755395

PMX is not approved for use in the United States.

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About Spectral Medical Inc.

Spectral is a phase 3 company seeking United States FDA approval for its unique product for the treatment of patients with septic shock, Toraymyxin (PMX). PMX is a single-use therapeutic hemoperfusion device that removes endotoxin, which can cause sepsis, from the bloodstream and is guided by the company's FDA-cleared Endotoxin Activity Assay (EAA), the clinically available test for endotoxin in blood. EAA is also CE marked and licensed by Health Canada.

PMX is approved for therapeutic use in Japan and Europe, licensed by Health Canada, and has been used safely and effectively with over 360,000 units sold worldwide to date. In March, 2009, Spectral obtained the exclusive development and commercial rights in the U.S. for PMX, and in November, 2010, signed an exclusive distribution agreement for this product in Canada. In July, 2022, the U.S. FDA granted breakthrough device designation for PMX for the treatment of endotoxic septic shock. Approximately 330,000 patients are diagnosed with septic shock in North America each year.

The Tigris trial is a confirmatory study of PMX in addition to standard care versus standard care alone and is designed as a 2:1 randomized trial of 150 patients using Bayesian statistics. Endotoxic septic shock is a malignant form of sepsis.

The trial methods are detailed in "Bayesian methods: a potential path forward for sepsis trials."

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