Mr. Aaron Benson reports

ARCH BIOPARTNERS ANNOUNCES ST. MICHAEL'S HOSPITAL COMMENCES PATIENT DOSING IN THE PHASE II CS-AKI TRIAL OF LSALT PEPTIDE

St. Michael's Hospital (SMH), part of Unity Health Toronto, has commenced patient dosing in Arch Biopartners Inc.'s continuing phase II trial evaluating LSALT peptide for the prevention and treatment of cardiac surgery-associated acute kidney injury (CS-AKI).

St. Michael's Hospital is the third Canadian site to successfully recruit patients in the CS-AKI phase II trial. Along with SMH, Toronto General Hospital, part of University Health Network (Ontario) and the University of Calgary Cumming School of Medicine (Alberta) continue to actively recruit new patients in the trial. At Royal Columbian Hospital (British Columbia), site start-up activities are continuing in advance of commencing patient recruitment.

Update on the CS-AKI phase II trial

The company's blinded review of trial data indicates that AKI has been consistently observed using the protocol-defined criteria, supporting the trial's study design and defined end points.

At this time, investigators and medical monitors have not assessed any adverse events or serious adverse events as related to LSALT peptide. There have been no SUSARs (suspected unexpected serious adverse reactions) reported in the trial.

The company is currently progressing feasibility and start-up discussions with additional leading cardiac surgery centres in Canada and the United States. Expanding to selected U.S. sites is intended to broaden clinical awareness of LSALT peptide among cardiac surgery and kidney care specialists, while also supporting the acceleration of patient recruitment.

Discussions with prospective clinical sites have included site evaluations, investigator commitments to perform the trial, budget development and drafting clinical trial agreements. Three prospective sites in the U.S. and one additional site in Ontario (to participate through Clinical Trials Ontario) are currently under consideration. The addition of new clinical sites to the CS-AKI phase II trial will be subject to the execution of clinical trial agreements.

In Turkey, the company has submitted required annual safety reports to the Turkish Ministry of Health. The clinical team is preparing to commence final close-out visits at the first five sites that participated in the trial, as part of standard trial oversight procedures.

The CS-AKI phase II trial is an international, multicentre, randomized, double-blind, placebo-controlled study of LSALT peptide with a recruitment target of 240 patients. Subjects are randomized to receive either LSALT peptide (10-milligram IV twice daily for five days) or placebo. The primary objective of the trial is to evaluate the percentage of subjects with acute kidney injury (AKI) in each treatment group within seven days following on-pump (heart-lung machine) cardiac surgery, as defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria.

Details of the phase II trial, titled "Phase 2 Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of LSALT peptide for the Prevention or Attenuation of Acute Kidney Injury (AKI) in Patients Undergoing On-Pump Cardiac Surgery," can be viewed at the Clinical Trials website (NCT05879432).

CS-AKI and LSALT peptide

CS-AKI often results from ischemia-reperfusion injury (IRI), which restricts blood flow and oxygen to the kidney (ischemia), leading to kidney cell damage. When blood flow is restored (reperfusion), inflammation is triggered, exacerbating injury to the kidney. There are currently no approved pharmacologic therapies indicated to prevent acute kidney injury of the type commonly experienced by on-pump cardiac surgery patients. In the worst cases of AKI, the kidneys fail, requiring dialysis or a kidney transplant for survival.

LSALT peptide is the company's lead drug candidate for the prevention and treatment of inflammation-related injury in the kidneys, lungs and liver. It binds to the dipeptidase-1 (DPEP1) enzyme, which is primarily expressed in the kidney, to inhibit its role in triggering organ inflammation. Arch scientists and their collaborators have reported that LSALT reduced IRI to the kidneys in preclinical models. This mechanism was first described in the journal Cell (2019), and further characterized in Science Advances (2022), by Lau et al. in a paper titled "Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury."

Findings from an earlier phase II trial evaluating LSALT peptide for acute lung inflammation were published in BMJ Open (2024). In that study, patients received a five-milligram daily dose of LSALT peptide. The results provided first-in-human evidence validating DPEP1 as a therapeutic target for organ inflammation. The publication also reported notable biomarker findings: patients treated with LSALT peptide showed reductions in a range of inflammation-related biomarkers, including a reported statistically significant decrease in CXCL10, a protein linked to inflammation in the lungs and kidneys. These findings are consistent with LSALT's proposed mechanism of action and its continued development for preventing inflammation-related injury in critical organs. Additional peer-reviewed publications related to LSALT peptide and the DPEP1 pathway are available on the company's website.

Update on the PONTiAK phase II trial (Cilastatin)

The phase II PONTiAK study aims to evaluate the efficacy of cilastatin in preventing AKI associated with nephrotoxic pharmaceuticals. These include commonly used drugs such as antibiotics, chemotherapy agents and imaging dyes, some of which are known to cause kidney damage as a side effect. The investigator-led trial is currently recruiting at hospital sites in both Calgary and Edmonton and plans to enroll a total of 698 patients in five hospital sites in Alberta. The trial is registered on the Clinical Trials website (NCT06886464).

To date, no adverse events or serious adverse events have been assessed as related to cilastatin in the PONTiAK trial and new patient recruitment is continuing at both active clinical sites.

The company is working to form a new U.S. arm of the PONTiAK trial to increase the clinical audience of cilastatin as a new treatment to prevent AKI and support patient enrolment.

Incidence of CS-AKI and AKI caused by Nephrotoxic Pharmaceuticals

Acute kidney injury (AKI) is a frequent complication following cardiac surgery, especially in procedures that use a heart-lung machine. Clinical studies report that up to 30 per cent of patients undergoing on-pump cardiac surgery develop CS-AKI, a condition that increases the risk of serious complications, longer hospital stays and increased mortality.

AKI is also common in hospitalized patients exposed to nephrotoxic pharmaceuticals, including certain antibiotics, chemotherapy agents, immunosuppressants and imaging contrast dyes. Published studies have reported that medications are associated with AKI in 14 per cent to 26 per cent of adults in prospective cohort studies, and that AKI can occur in up to 25 per cent of patients exposed to nephrotoxic pharmaceuticals. AKI is associated with adverse long-term outcomes, including progression of chronic kidney disease (CKD), increased cardiovascular risk and higher mortality.

With no approved pharmacologic therapies indicated for prevention of CS-AKI or drug-induced AKI, these conditions remain areas of significant unmet medical need. LSALT peptide is being evaluated as a potential first-in-class therapeutic approach to prevent inflammation-related injury in patients at high risk of developing AKI and cilastatin is being evaluated in the investigator-led PONTiAK phase II trial for nephrotoxin-induced AKI.

About Arch Biopartners Inc.

Arch Biopartners is a therapeutic biotech company developing novel drugs for acute kidney injury (AKI) and chronic kidney disease (CKD). The company is advancing an integrated program that includes new treatments targeting inflammation- and toxin-related kidney injury.

Arch's development pipeline includes:

• LSALT peptide: in a phase II trial targeting cardiac surgery-associated AKI;
• Cilastatin: a repurposed drug in a phase II trial targeting toxin-induced AKI;
• CKD platform: next-generation therapeutics targeting chronic kidney disease.

These assets represent distinct, mechanism-based approaches to treating and preventing common causes of kidney damage. Together, they target serious unmet needs in kidney care across both chronic and acute indications, affecting more than 800 million people worldwide. Both lead programs are currently enrolling patients at Canadian clinical sites, with additional North American sites in development.

The scientific and medical content of this release has been reviewed and approved by the company's chief science officer.

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