Arch Biopartners Enters into Worldwide License Agreement with Telara Pharma to Re-Purpose Cilastatin for the Treatment and Prevention of Acute Kidney Injury

Rhea-AI Summary

Arch Biopartners has entered an exclusive global license agreement with Telara Pharma to develop cilastatin, a small-molecule drug aimed at preventing acute kidney injury (AKI). This collaboration unifies existing patents and supports a new Phase II trial targeting AKI, a condition affecting 10-15% of hospitalized patients, with a market valued over $20 billion. Cilastatin, previously used in combination with imipenem, inhibits dipeptidase-1 (DPEP-1), an adhesion receptor linked to inflammation. Arch's Metablok is also in trials addressing similar pathways.

Positive

• Exclusive license agreement with Telara Pharma for cilastatin enhances development pipeline.
• New Phase II trial opportunity targeting acute kidney injury, a significant unmet market needs.
• Cilastatin is one of the only known DPEP-1 antagonists successfully completing Phase I trials.

Negative

• None.

• Arch Biopartners is a clinical stage company developing new drug candidates for treating organ damage caused by inflammation
  
  
• Novel Mechanism of Action - selective dipeptidase-1 (DPEP-1) antagonists that prevent leukocyte adhesion to endothelial cells reducing inflammation and subsequent organ damage
• Cilastatin and Arch drug Metablok are the only known DPEP-1 antagonists that have successfully completed phase I trials
• New license creates opportunity for a new Phase II trial for Metablok and cilastatin targeting acute kidney injury, which is currently an unmet billion dollar market

TORONTO, April 15, 2021 (GLOBE NEWSWIRE) -- Arch Biopartners Inc. (“Arch” or the “Company”) (TSX Venture: ARCH and OTCQB: ACHFF), announced today it has entered into an exclusive worldwide license agreement with Telara Pharma of Spain (“Telara”) to clinically develop and market cilastatin, a small-molecule drug candidate for the treatment and prevention of acute kidney injury (“AKI”).

With this license, Arch secures the commercial rights to the patents around the use of cilastatin that it does not already own. The patents held by Arch and Telara are now unified into one clinical development program to be led by Arch. These patents include method of use claims for the use of cilastatin as a potential drug to prevent AKI from a variety of causes including ischemia-reperfusion injury, sepsis and toxins. 

Cilastatin is a known small molecule inhibitor of the enzyme dipeptidase-1 (DPEP-1) previously developed in the 1980s to prevent the degradation of the antibiotic imipenem in the kidney. In the past, cilastatin was used only as an active ingredient in a dual formulation with imipenem and has yet to be approved or sold as a stand-alone product.

The Arch team recently discovered that DPEP-1 is an adhesion receptor of neutrophil (white blood cell) recruitment in the lungs, liver and kidneys, a pathway that is targeted by Arch’s lead drug candidate Metablok (LSALT peptide). Currently, Arch is nearing completion of a Phase II trial for Metablok targeting this new pathway in the prevention of acute lung injury and AKI in COVID-19 patients.

Cilastatin inhibits DPEP-1 by binding to a different part of the DPEP-1 molecule than Metablok. Although DPEP-1 is expressed by the lungs, liver and kidneys, pre-clinical animal studies to date have shown that cilastatin is effective in preventing AKI induced by sepsis, ischemia-reperfusion injury and drugs/toxins¹. Unlike Metablok, cilastatin is not effective in preventing liver inflammation². Pre-clinical studies to assess cilastatin’s ability to prevent lung inflammation are still ongoing.

As a result, the license with Telara provides Arch a co-lead drug candidate in its next Phase II clinical trial which will target the prevention of AKI in human diseases outside of the COVID-19 pandemic. The new license further adds to the Arch pipeline of DPEP-1 targeting agents, which currently includes several other proprietary drug candidates besides Metablok.

As part of the license agreement and collaboration, the Telara team will provide to Arch the Phase I safety data and the newly established cilastatin drug manufacturing program to support a future Phase II trial application with regulatory agencies in Europe and North America.

CEO of Arch Biopartners, Richard Muruve, commented, “With the license of Telara’s cilastatin patent rights combined with our own, we look forward to doing a significant Phase II trial targeting ischemia reperfusion related AKI. Currently, there are no effective treatments to prevent AKI and Arch now has both Metablok and cilastatin that can be used in separate patient arms of a new Phase II trial. The collaboration with Telara will also facilitate a future drug application in Europe and potential patient recruitment in Spain.”

¹ Lau, A., et al. Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury. J Clin Invest 128, 2894-2913 (2018).
² Choudhury, S.R., et al. Dipeptidase-1 Is an Adhesion Receptor for Neutrophil Recruitment in Lungs and Liver. Cell 178, 1205-1221 e1217 (2019).

Acute Kidney Injury

AKI occurs in approximately 10-15% of all hospitalized patients, 30% of patients undergoing cardiac surgery and more than 50% of those admitted to intensive care units. AKI is caused by a variety of conditions, including ischemia reperfusion injury from shock or cardiac surgery, sepsis, COVID-19 and drugs/toxins such as radiographic contrast dye. It is well known that inflammation plays a major role in all forms of acute kidney injury^3,4.

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.

³ Ronco, C., Bellomo, R. & Kellum, J.A. Acute kidney injury. Lancet 394, 1949-1964 (2019).
⁴ Rosner, M.H. & Okusa, M.D. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 1, 19-32 (2006).

About Metablok (LSALT peptide) and DPEP-1

Metablok (also known as LSALT peptide) is a novel therapeutic agent and the lead DPEP-1 inhibitor in the Arch development pipeline.

A scientific team led by Arch scientists Dr. Donna Senger and Dr. Stephen Robbins first described a novel mechanism of action for organ inflammation in the journal Cell in August, 2019. In the publication, DPEP-1 was identified for the first time as a major neutrophil adhesion receptor on the lung, liver and kidney endothelium. Their findings identified DPEP-1 as a novel therapeutic target for diseases of these organs where inflammation plays a major role.

Metablok is currently in an international, multicenter, randomized, double-blind, placebo-controlled, proof of concept Phase II trial of LSALT peptide (Metablok) as prevention of organ inflammation known to trigger acute respiratory distress syndrome (ARDS) and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19) or new variants of the virus. ARDS is the leading cause of death in COVID-infected patients. AKI has also been observed in approximately 35% of patients admitted to hospital with COVID-19 and is also a leading cause of mortality⁵.

⁵ Hirsch, J.S., et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int 98, 209-218 (2020).

About Telara and Hospital General Gregorio Marañon

The Gregorio Marañon General University Hospital in Madrid, Spain (GMGUH) is a public hospital, which stands out for the high level of training and qualification of its professionals, for its healthcare, teaching and research capacity, and for its state-of-the-art facilities.

From the Nephrology Service at the Gregorio Marañon Health Research Institute, Drs. Alberto Tejedor and Alberto Lazaro began research on the nephroprotective effect of cilastatin, which resulted in the obtainment of a family of patents for the treatment of kidney damage caused by other drugs and sepsis.

Once all the non-clinical studies and the Phase I clinical safety trial were completed, the spin-off company Telara Pharma was created at the GMGUH in 2020 with the aim of bringing cilastatin to clinical use as a kidney protection drug.

With this goal in mind, Telara Pharma has reached a worldwide licensing agreement with Arch Biopartners for the clinical development and marketing of cilastatin.

Telara Pharma is focused on the research, development, and marketing of drugs for the treatment of high prevalence pathologies (mainly kidney injuries and sepsis), as well as providing associated services.

About Arch Biopartners

Arch Biopartners Inc. is a clinical stage company focused on the development of innovative technologies that have the potential to make a significant medical or commercial impact. Arch is developing a pipeline of new drug candidates that inhibit inflammation in the lungs, liver and kidneys via the dipeptidase-1 (DPEP-1) pathway for multiple medical indications.

Continuing under development in the Arch portfolio are: AB569, a potential new treatment for antibiotic resistant bacterial infections in wounds and the lungs; and, ‘Borg’ peptide coatings that increase corrosion resistance and decrease bacterial biofilm on various medical grade metals and plastics.

For more information on Arch Biopartners, its technologies and other public documents Arch has filed on SEDAR, please visit www.archbiopartners.com

The Company has 61,462,302 common shares outstanding.

Forward-Looking Statements

All statements, other than statements of historical fact, in this news release are forward looking statements that involve various risks and uncertainties, including, without limitation, statements regarding the future plans and objectives of the Company. There can be no assurance that such statements will prove to be accurate. Actual results and future events could differ materially from those anticipated in such statements. These and all subsequent written and oral forward-looking statements are based on the estimates and opinions of management on the dates they are made and are expressly qualified in their entirety by this notice. The Company assumes no obligation to update forward-looking statements should circumstances or management’s estimates or opinions change.

Neither TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release

FAQ

What is the significance of Arch Biopartners' recent license agreement with Telara Pharma?

The license enables Arch to develop cilastatin for preventing acute kidney injury, unifying their patent rights for a focused clinical development.

How does cilastatin relate to acute kidney injury?

Cilastatin is a small-molecule drug that inhibits dipeptidase-1, targeting pathways involved in AKI, which currently lacks effective treatments.

What potential market does Arch Biopartners aim to address with cilastatin?

The global market for acute kidney injury is estimated to exceed $20 billion annually, presenting a significant commercial opportunity.

What is the phase of the trial for cilastatin and Metablok?

Arch is preparing for a Phase II trial for cilastatin, while Metablok is nearing completion of its Phase II trial targeting similar pathways.

Why is cilastatin considered a novel treatment option?

Cilastatin is the only known DPEP-1 antagonist that has effectively completed Phase I trials and represents a new approach to treating AKI.