Mr. Richard Muruve reports

ARCH BIOPARTNERS CLINICAL TEAM PUBLISHES DATA FROM PHASE II TRIAL FOR LSALT PEPTIDE TARGETING ORGAN INFLAMMATION IN HOSPITALIZED PATIENTS INFECTED WITH SARS-COV-2

Arch Biopartners Inc. has published a peer-reviewed paper in the British Medical Journal Open (BMJ Open) detailing the results of the international phase II human trial for LSALT peptide targeting acute lung and kidney inflammation in hospitalized patients infected with SARS-CoV-2 virus. LSALT peptide is a DPEP-1 inhibitor and the company's lead drug candidate for preventing and treating inflammation injury in the kidneys, lungs and liver.

The paper in BMJ Open describes the clinical highlights, outcomes and biomarker results of the study. The phase II trial was an international, multicentre, randomized, double-blind, placebo-controlled, proof-of-concept study of LSALT peptide for the prevention of organ inflammation such as acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2. The exploratory, adaptive trial was initiated in the early stages of the global pandemic to identify clinical signals of efficacy for LSALT peptide in the treatment of acute lung and kidney inflammation.

The results of the phase II trial provided first-ever evidence validating DPEP-1 as a mediator of organ inflammation and therapeutic target in humans. In addition, LSALT peptide was well tolerated with no safety issues related to the drug.

New biomarker data for LSALT peptide were disclosed for the first time in the BMJ Open publication. An analysis of serum inflammatory biomarkers was performed from blood samples collected from study participants. Biomarkers analyzed which relate to organ inflammation included cytokines and chemokines such as IL-6, CXCL8, CXCL10, IL-1beta and CCL7. Collectively, a greater proportion of inflammatory biomarkers decreased in patients receiving LSALT peptide compared with placebo. In particular, the reduction of CXCL10 in the LSALT peptide group versus the placebo group was statistically significant at the end of treatment.

CXCL10 play a role in facilitating leukocyte recruitment to various vascular beds, including the lungs and kidneys. The reduction of CXCL10 and the other inflammatory biomarkers during LSALT peptide treatment is consistent with LSALT peptide's mechanism of action as an inhibitor of DPEP-1 mediated leukocyte recruitment to the lungs and kidneys.

The new data provide more scientific rationale for Arch to advance LSALT peptide to prevent leukocyte recruitment and organ inflammation for other indications, including a larger phase II trial targeting cardiac surgery-associated AKI, which recently began recruiting patients.

Details of the results from the phase II trial are reported in the peer-reviewed journal BMJ Open. The publication, titled "Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome and Acute Kidney Injury in Patients Infected with SARS-CoV-2 (COVID-19)" by Somayaji et al., can be found at the BMJ Open website.

Quote from Richard Muruve, chief executive officer of Arch Biopartners: "When the pandemic started and hospitals were filling up with patients with respiratory distress caused by inflammation, we postponed our plans to do a CS-AKI trial to urgently perform a phase II trial to treat hospitalized COVID patients and reduce acute organ inflammation. Now that we have published our biomarker and clinical data from the trial, we are more confident today that inhibiting DPEP-1 mediated leukocyte recruitment to the kidneys, lungs and liver is a valid path toward first-ever treatments to prevent acute injury in these organs."

About the phase II trial for LSALT peptide in pandemic patients

The phase II trial was an international, multicentre, randomized, double-blind, placebo-controlled, proof-of-concept study of LSALT peptide for the prevention of organ inflammation such as acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2. Six clinical sites located in Canada, the United States and Turkey participated in the phase II trial in 2021.

The composite primary end point of the phase II trial reflected the severe effects often experienced by hospitalized patients in the early months of the pandemic and deemed appropriate for LSALT peptide's novel mechanism of action in blocking consequential inflammation in the lungs, kidneys and other organs. The exploratory study was designed to detect a clinical signal of efficacy and was not powered for statistical significance.

Previously disclosed in December, 2021, and included in the BMJ Open publication, there were no significant differences in adverse events between LSALT peptide and placebo-treated patients. The study population of the phase II trial did not have enough incidence of ARDS or AKI to detect a conclusion on these two particular clinical outcomes. In a secondary evaluation of patients on ventilation, despite being older by an average of five years, subjects in the LSALT peptide group demonstrated 22.8 ventilation-free days compared with 20.9 days in the placebo group in the unadjusted analysis at 28 days. Ventilation was defined as a need for high-flow oxygen therapy (greater than or equal to six litres/minute), non-invasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation (ECMO). In a post hoc analysis adjusting for age, body mass index (BMI) and PaO2/FiO2 (partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen concentration) ratio (a measure of lung disease severity), the difference in ventilation-free days was 6.7 days favouring the LSALT peptide group compared with the placebo group.

About phase II trial for LSALT peptide targeting CS-AKI

Arch Biopartners is currently sponsoring a phase II trial for LSALT peptide targeting cardiac surgery-associated acute kidney injury (CS-AKI). CS-AKI is often caused by ischemia-reperfusion injury (IRI) that reduces blood flow (ischemia) and thus oxygen in the kidney causing kidney cell damage. Once blood flow is restored to normal (reperfusion), inflammation is triggered and injury to kidney cells is exacerbated. In the worst cases of AKI, kidneys fail, leading to kidney dialysis or kidney transplant. At present, there are no therapeutic treatments available to prevent or treat CS-AKI or IRI.

The CS-AKI phase II trial is an international multicentre, randomized, double-blind, placebo-controlled study of LSALT peptide. The recruitment target for the trial is 240 patients. The primary objective of the trial is to evaluate the percentage of subjects with AKI within seven days following on-pump (heart-lung machine) cardiac surgery, defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria.

Details of the phase II trial, entitled "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 on the ClinicalTrials.gov website.

Recruitment of patients in the CS-AKI trial has begun in three hospital sites in Turkey with a hospital in Canada (University of Calgary) joining the trial last week. Additional sites are expected to be added in Turkey and Canada in the next few weeks.

About LSALT peptide

LSALT peptide is a novel peptide drug candidate and DPEP-1 inhibitor. In August, 2019, a scientific team led by Arch scientists Dr. Donna Senger and Dr. Stephen Robbins published a paper in the journal Cell describing a novel mechanism of action for organ inflammation. In the publication, DPEP-1 was identified, for the first time, as a major leukocyte (white blood cell) adhesion receptor on the lung, liver and kidney endothelium. DPEP-1 was also identified as the target of LSALT peptide, differing from typical anti-inflammatory drugs by targeting this novel adhesion receptor rather than targeting individual cytokines, of which there are many.

The Cell publication, titled "Dipeptidase-1 is an adhesion receptor for neutrophil recruitment in lungs and liver" by Choudhry et al., can be found at the Cell journal's website.

LSALT peptide has been shown by Arch scientists and their collaborators to prevent ischemia-reperfusion injury to the kidneys in preclinical models. Details of their findings were published in a Science Advances publication, titled "Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury" by Lau et al., and can be found at the Science Advances website.

About Arch Biopartners Inc.

Arch Biopartners is a late-stage clinical trial company focused on preventing inflammation and acute organ injury. The company is developing new drug candidates that inhibit inflammation in the lungs, kidneys and liver via the dipeptidase-1 (DPEP-1) pathway and are relevant for common injuries and diseases where organ inflammation is an unmet problem.

We seek Safe Harbor.