At present, the Company is focused on the clinical development of its novel drug platform in the area of targeting dipeptidase-1 mediated organ inflammation in the lungs, liver and kidneys. Organ inflammation often results in organ damage or failure, including in the cases of sepsis and COVID19. The Company’s lead drug candidate is Metablok TM (also known as “LSALT Peptide”).
LSALT Peptide has completed an international Phase II trial targeting organ inflammation often experienced in hospitalized COVID-19 patients. LSALT peptide has recently been accepted into the Canadian Treatments for COVID-19 Phase III trial (CATCO) which is funded by the Canadian Institutes of Health Research. Health Canada provided CATCO a No Objection Letter in February 2022 to proceed with the dosing of LSALT peptide in a new arm of the CATCO trial.
I. MetablokTM - Lead DPEP-1 Inhibitor Drug Candidate Metablok is a new peptide drug candidate and has emerged to be the lead opportunity among the Company’s growing pipeline of DPEP-1 inhibitor drug candidates. Metablok is also referred to as “LSALT peptide” or “LSALT” in Company communications, academic publications and with health authorities such as the U.S. FDA or Health Canada.
LSALT has the potential to be a breakthrough in the treatment of diseases where inflammation plays a major role. The inventors of LSALT published the details of the mechanism of action and efficacy of LSALT. The publication, titled “by Choudhry et. al. was published by the journal Cell in August 2019 and can be found at the following link:
Dipeptidase-1 is an adhesion receptor for neutrophil recruitment in the lungs and liver
In February 2022, Arch scientists and their collaborators published a paper in the journal Science Advances describing the mechanism of action for dipeptidase-1 (DPEP-1) in acute kidney injury (AKI) in a pre-clinical study. Importantly, the study also confirmed the mechanism of action of two DPEP-1 inhibitors (the LSALT peptide and cilastatin) that effectively protected the kidney during ischemia reperfusion injury. These findings provide Arch with the scientific rationale to pursue a Phase II trial for LSALT and/or cilastatin targeting the prevention of cardiac surgeryassociated AKI. The publication, entitled “Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury” by Lau et al. can be found at:
Dipeptidase-1 govern renal inflammation during ischemia reperfusion injury
LSALT was invented by Arch scientists led by Dr. Stephen Robbins and Dr. Donna Senger. The inventors have assigned the intellectual property related to Metablok to the Company. All of the DPEP-1 inhibitors invented by the Arch team, including LSALT, are protected by composition patents held by Arch. Cilastatin, for treatment of kidney inflammation, is protected by methods of use patents also held by Arch, or exclusively licensed to Arch.
The Science Explained:
Animal Studies:
“Using biochemical, genetic, and confocal intravital imaging approaches, we identified dipeptidase-1 (DPEP1) as the target and established its role as a physical adhesion receptor for neutrophil sequestration independent of its enzymatic activity. Importantly, genetic ablation or functional peptide blocking of DPEP1 significantly reduced neutrophil recruitment to the lungs and liver and provided improved survival in models of endotoxemia.”
Phase I In pre-clinical studies, Arch scientists have demonstrated LSALT’s ability to prevent acute kidney injury by blocking the inflammatory response triggered by ischemia/reperfusion and other insults to the kidney. The Arch team has similarly shown LSALT’s ability to prevent acute inflammation injury to the lungs and liver in preclinical in vivo models. Currently, there are no specific or effective treatments to prevent acute organ injury caused by inflammation.
The Company completed initial toxicology, including a maximum tolerable dose and pharmacokinetic studies for LSALT, to support a pre-Investigational New Drug (IND) meeting with the U.S. Food and Drug Administration (FDA) in April 2018. The FDA members addressed questions from the Arch team and confirmed key components of a future IND application for Metablok.
Arch received approval during March 2019 from the Alfred Health Human Research Ethics Committee (HREC) in Melbourne, Australia to conduct a Phase I human trial for LSALT.
The Phase I human trial was a double-blind, placebo-controlled, randomized, single and multiple ascending dose study to evaluate the safety and pharmacokinetic profile of LSALT in 52 healthy, normal participants. The drug was well tolerated by all volunteers and no significant drug related adverse effects were observed.
Phase II In May 2020, Health Canada granted a No Objection Letter to Arch to conduct a Phase II trial to investigate LSALT’s efficacy to prevent organ damage caused by inflammation in patients with COVID-19.
In June 2020, U.S. Food and Drug Administration (FDA) granted permission to the Company to proceed with a Phase II trial in the U.S. and an Investigational New Drug application was activated. The trial began October 2020, at a hospital site in Florida, which was followed by clinical trial sites elsewhere in the U.S., Canada and Turkey. A total of 7 sites were activated into the trial, with two each in Canada and Turkey and three sites in the U.S.
The Phase II trial was an international, multicenter, randomized, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of organ inflammation known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) in patients infected with SARS-CoV-2 (COVID-19).
The composite primary endpoint reflected early global pandemic data from COVID-19 patients that showed the SARS-CoV-2 virus resulted in damage to organs besides the lungs and LSALT’s potential to prevent inflammation injury in multiple organs. Studies have shown that COVID-19 results in mortality with AKI (Hirsch, Kidney Int. 2020) and mortality with cardiomyopathy (Akhmerov, Circ Res. 2020). Further, acute liver injury (Lee, J Chin Med Assoc. 2020) and thrombotic disease (Llitjos, J Thromb Haemost 2020) have resulted in poor outcomes in COVID19 patients.
Secondary endpoints to measure the performance of LSALT included continuous measurements of respiratory, renal, hepatic, cardiac, and blood-clotting function throughout treatment and end of study, hospital stays (floor, ICU, and overall), 28-day mortality, and viral infection (clearance rate, SARS-CoV-2-specific immunoglobulins) compared between the active treatment arm and the placebo group. Exploratory endpoints included changes in cytokines between treatment arms and description of the pharmacokinetics of LSALT peptide.
Patient recruitment into the Phase II trial was completed at the end of April, 2021 and the dosing of the final patients occurred in May, 2021. A total of 65 patients were randomized into the trial with 61 patients receiving at least one dose of treatment.
Phase II Top-Line results and Canadian Treatments for Covid-19 Trial
On December 1, 2021, the Company announced that LSALT peptide will enter the Canadian Treatments for COVID-19 (CATCO) human trial, a multi-centre adaptive, randomized, openlabel, controlled study being conducted in fifty-five hospitals across Canada as of the date hereinabove. The CATCO trial is taking place in conjunction with the World Health Organization’s (WHO) SOLIDARITY trial, in collaboration with countries around the world and with support from the Canadian Institutes of Health Research (CIHR)-funded COVID-19 Network of Clinical Trials Networks.
Based on results of the Phase II study, the primary endpoint of the confirmatory clinical trial will be the difference in the number of respiratory support free days between study groups during the 28-day study period. The control group will receive standard of care and the drug group will receive standard of care plus LSALT. Based on the Phase II results, a total of 320 patients will be required in each study group to detect an unadjusted treatment difference of 3.35 days requiring ventilation with 90% statistical power.
Secondary endpoints include mortality, differences in outcomes involving other organs affected by COVID-19, such as kidney, liver, and heart function, time of hospitalization and intensive care stay, healthcare resource utilization, and late follow-up at 12 months post hospitalization.
Sunnybrook Research Institute (SRI) is the sponsor of the CATCO trial. SRI has entered into a collaboration agreement with Arch Biopartners to use LSALT in a new arm of the CATCO trial. SRI and CATCO leadership have received ethics committee approval and Health Canada approval to commence the dosing of LSALT in the CATCO trial.
The Company’s responsibilities during the trial include supplying LSALT drug vials to support the trial until completion. Arch completed the manufacturing of a new supply of vials during the summer and autumn of 2021 and has enough drug supply on hand for the 320 patients scheduled to be dosed in the CATCO trial.
Overview of Phase II results
LSALT has entered the CATCO trial on the basis of a positive clinical effect observed in the Phase II trial completed earlier this year and funded in part by Innovation Science and Economic Development (ISED) Canada’s Strategic Innovation Fund (SIF) which is part of the Canadian Government’s Plan to mobilize Science to Fight COVID-19
Sixty-one patients were enrolled in the study and randomized 1:1 to receive LSALT or placebo. Despite having older patients and having greater co-morbidities in the LSALT group, the unadjusted analysis of all patients in the trial demonstrated 22.8 ventilation-free days for the LSALT group compared to 20.9 days in the placebo group during the 28-day evaluation period. “Ventilation” was defined as a need for high flow oxygen therapy (≥ 6L/min), non-invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Adjusting for age, body mass index (BMI), and PaO2/FiO2 ratio (a measure of lung disease severity), the average number of ventilation-free days was 6.7 days less in the LSALT group of patients than the placebo group.
There were no unexpected differences in adverse events between LSALT and placebo treated patients. LSALT was well tolerated with no safety issues related to the drug. The exploratory study was designed to detect a clinical signal of efficacy and was not powered for statistical significance. Based on the promising clinical signal observed in the patients who received LSALT in the Phase II trial, 320 patients are scheduled to be dosed in the CATCO trial in order to detect a statistically significant difference.
Full details of the Phase II study are currently under consideration at a peer-reviewed scientific journal and will be released as soon as they are published.
Phase II results provide a first-ever signal towards validating Dipeptidase-1’s role in the mechanism of action of organ inflammation in humans
These Phase II results provide key human data which, in conjunction with extensive preclinical studies, further support DPEP-1 as a relevant therapeutic target for diseases of the lung, liver and kidney where inflammation plays a major role. In addition to evaluating LSALT as a treatment of inflammation complications experienced by hospitalized COVID-19 patients, Arch Biopartners intends to pursue its strategy to develop new DPEP-1 targeting drugs and clinical indications outside of COVID-19. LSALT Peptide and a Potential Path to Drug Registration The path to drug approval for LSALT peptide will depend on additional human data showing efficacy in preventing or treating organ inflammation. Such additional data may result from the CATCO trial, or it may not, and will depend on the outcome of the pandemic in Canada in the future. Arch Biopartners is currently exploring opportunities to generate additional human efficacy data for LSALT peptide to support future drug registration outside of the CATCO trial and the COVID19 indication. One opportunity Arch management is exploring at present is to test LSALT peptide in a Phase II trial targeting the prevention of inflammation of the kidney and acute kidney injury in high-risk patients
Patent Position / Intellectual Property: MetaBlok was invented by Arch scientists Dr. Stephen Robbins, Dr. Donna Senger, Dr. Jennifer Rahn and their University of Calgary colleague, Dr. Paul Kubes. The inventors have assigned the Metablok intellectual property to the Company.
Arch Biopartners files new patent application for novel antibody candidates targeting dpep 1 mediated organ inflammation Q) Does Arch have other drugs that target DPEP-1? A) "The answer is yes, we have been working on this pathway for several years and while LSALT was the lead candidate we have developed a number of other molicules that also target the DPEP pathway. This includes a varariety of novel peptides that have been modified to improve thier pharmacologic properties, we are also developing antibodies that can target DPEP-1. We also have method of use patents on existing small molecules that block the enzymatic activility of DPEP-1. We will be advancing 2 of the small molecules into preclinical pipeline in the next month or two. These 2 molicules are not ready for human clinical studies yet and they still need to undergo the pre clincal testing before advancing into human studies, but we will be advancing a few of our products hopefully before the end of the year" 34:40 Peptides Vs Antibodies
Antibody drugs such as these typically display more specific receptor targeting and longer half-life in the bloodstream compared to peptides or small molecules. The development of DPEP-1 targeting antibody drugs provides the Arch platform with another class of therapeutics for diseases involving the lungs, kidneys and liver where inflammation plays a prominent role.
Market Potential:
- COVID19 - Organ Inflammation
- acute respiratory distress syndrome (ARDS)
- acute kidney injury (AKI)
- Currently, no specific therapies exist to prevent AKI in the world today. Management of AKI is supportive and includes life-sustaining therapy with dialysis. Patients that experience AKI are at high risk of developing chronic kidney disease, adverse cardiovascular outcomes and death.The worldwide market for AKI is estimated to be over $20 billion USD per year. ($325.4 dollars a share)
- Acute Kidney Injury
Share Structure:
- The Company had 47,360,179 Common Shares outstanding as of May 7, 2010. As of the date hereinabove, the Company has 61,862,302 common shares outstanding.
- No warrants outstanding
Previous Financing: - Dec 23, 2020 (One Placee)
announced it has closed the non-brokered private placement the Company disclosed in a press release December 23, 2020 (The “Offering”). Pursuant to the Offering, Arch issued 430,000 common shares priced at CAD $1.50 per common share (the “Common Shares”) for net proceeds of $500,000 USD (approximately $645,000 CAD) (the “Offering”).
- June 30, 2020 (Two Placee)
The Company announced it closed a non-brokered private placement offering of 900,000 common shares priced at $1.50 per common share (the “Common Shares”) for gross and net proceeds of up to $1,350,000 (the “Offering”).
The Company announced it arranged a non-brokered private placement offering of up to 2,500,000 common shares priced at .50 per common share (the “Common Shares”) for gross proceeds of up to $1,250,000 (the “Offering”).
Government Support: - “Our support for Arch Biopartners’ development of their COVID-19 treatment is an important part of our plan to rebuild Canada’s bio-manufacturing and life sciences sector. Today’s announcement highlights how Canadian innovation can contribute to the global race to find treatments for COVID-19 and will help build Canada’s capacity to address future health emergencies.”
– The Honourable Franois-Philippe Champagne, Minister of Innovation, Science and Industry
- “As the world works toward an effective COVID-19 vaccine, we cannot lose sight of the importance of developing treatments to keep those stricken with the virus alive. Today’s contribution will support Arch Biopartners in taking its promising treatment through clinical trials and subsequent approvals. Once approved, this drug has the potential to be an important tool to save lives, improve long-term health and reduce the strain on Canada’s medical system. Investments like these help not only protect and support Canadians through this pandemic but also lay the foundation for a better-prepared, healthier and more prosperous future.”
– The Honourable Navdeep Bains, Minister of Innovation, Science and Industry
- Great to see this made-in-Alberta COVID-19 drug move ahead to national human trial. Once again, Alberta is flexing its research and innovation muscle!
- Premier Kenney
- This drug candidate from Arch Biopartners, Which has the generic name LSALT peptide, was discovered by @UCalgary scientists about five years ago
- Minister Copping
Quote from CEO:
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“Organ inflammation represents an unmet need in the medical world and is also a predictor of critical illness and mortality in COVID-19. A new medical treatment to block acute organ inflammation is urgently needed to improve patient outcomes. We look forward to working with Sunnybrook Research Institute and participating in the CATCO study to help improve outcomes for hospitalized patients who have organ inflammation.”
– Mr. Richard Muruve, Chief Executive Officer, Arch Biopartners
Phase III/Covid Trial Human Clinical Trial:
Organ Inflammation:
This NEW Mechanism of Action works the same in the Lung, Liver and Kidney. With Dipeptidase-1 having the strongest response in the Kidney. With a positive signal in the lung, this leaves potential treatment for acute kidney injury where there is currently no standard of care.
Insider Ownership
CEO owns 8,577,700 Shares = 13%
Last Purchase December 8, 2021
Insider Ownership is currently 56%
Peptides likelihood of approval
Statistically speaking in the report available above, Arch Biopartners has a 52.8% chance of having a drug make it ot the approval process from the regulator. Given that there is no standard of care for the area of medicine being saught, the odds go up dramattically
Phase I to Approval - 8%
Phase II to Approval - 15%
Phase III to Approval - 52.8%
NDA/BLA to Approval - 88.1%
Clinical Development Success Rates and Contributing Factors 2011-2022
Current Market Cap Industry Peers:
Arch - $182,000,000 @ $2.90 Positive Phase II Data ( Organ Inflammation )
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