ILIAS Biologics Inc. demonstrated the therapeutic effect of anti-inflammatory exosomes for ischemia-reperfusion-induced acute kidney injury

DAEJEON,South Korea,June 28,2021 -- Anti-inflammatory exosomes could have a place in treating acute kidney injury (AKI) caused by ischemia repercussion injury (IRI),according to a study done by ILIAS Biologics,Inc. in collaboration with Yonsei University of Seoul,South Korea.

ILIAS Research team and Yonsei University research team,led by professor of internal medicine Tae-Hyun Yoo and professor of oral pathology Jong In Yook,published the study result in the official journal of the International Society of Nephrology,Kidney International(Link).

ILIAS Biologics,Inc. secured itsthird proof of concept (POC),demonstrating the therapeutic efficacyof their anti-inflammatory exosomeswith this successful result in IRI-AKI. This study result comes just after itssecond POC in the field of pretermbirth,published in Science Advanceslast January. With its platform technology EXPLOR® (Exosomes engineering for Protein Loading via Optically Reversible protein-protein interaction),ILIAS hasdemonstrated the therapeutic applicability of its anti-inflammatoryexosomes in multipleinflammation-related therapeutic areas,includingsepsis,preterm birth,and IRI-AKI.

AKI affects approximately one million people annually worldwide. It is characterized as a rapid decline in kidney function,and multiple conditions such as acute tubular necrosis and interstitial nephritiscan cause AKI. IRI is a major causeof AKI,often occurring in the aftermath of heart valve surgery.Severe AKI can result in permanent damage and,therefore,dysfunction of the kidney.

"Even thoughAKI is a relatively common disease capable of progressing to permanent kidney dysfunction and threatening the lives of many patients,there has been nodrug with proven clinical efficacy and safety for its treatment. Therefore,this study suggests that exosome therapeutics could be promising clinical intervention for the prevention of IRI-AKI occurring post-heart surgery," says professorTae-Hyun Yoo.

Using ILIAS'unique exosome therapeutics platform technology EXPLOR®,the research team successfully generated NF-κB inhibiting anti-inflammatory exosomes by loading super-repressor of IκBα (srIκB),an engineered dominant active form of NF-κB inhibiting protein IκBα with a prolonged half-life,into exosomes. Systemic administration of anti-inflammatory exosomes into preclinical IRI-AKI mouse models significantly lowered AKI-related biomarker levels in the blood,i.e.,BUN(blood urea nitrogen),creatine,and NGAL(Neutrophil Gelatinase-associated Lipocalin).

This treatment also decreasedNF-κB activation,expressionof adhesion molecules,apoptosis,and release of pro-inflammatory cytokines. Intravital imaging revealed that neutrophils and macrophages were the principal cells that uptook the exosomes after in vivo administration.

The results suggest that intracellular delivery of srIκB to immune cells in the kidney can ameliorate IRI-AKI by reducing excessive inflammation,thus pointing to ILIAS'exosomes as the next potential novel IRI-AKI therapeutic.

"Therapeutic exosomes with EXPLOR® technology have successfully demonstrated itstherapeutic potential in preclinical models representing multipledisease settings,including sepsis,and AKI. Theresults support that our engineered exosomes could be a game-changing novel therapeutics with minimal side effects for the treatment of inflammation-associated diseasesthat are at present incurable," said Chulhee Choi,CEO/CSO of ILIAS Biologics Inc."We will also continue to deepenour therapeutic pipeline by developing first-in-classtherapeuticexosomes for the treatment of other incurable diseases,as well as accelerating open innovation with academia and industry partners."

Basedon these accomplishments,ILIAS plansto submit anapplication to initiate a first-in-human Phase 1 clinical trial atthe end of 2021.

About Acute Kidney Injury (AKI):

Acute Kidney Injury (AKI) is defined as a rapid dysfunction in kidney function and structure,which results from secondary injury caused by multiple conditions such as acute tubular necrosis,glomerulonephritis,vasculitis,ischemia,and drug-induced nephrotoxicity. The pathological outcome of AKI varies widely from minor alteration of kidney function biomarkers to devastating loss of kidney function,which requires renal replacement therapy (RRT)[i].

Approximately one million people are newly diagnosed with AKI worldwide every year,accompanying permanent loss in renal function. In the U.S,a relatively high incidence rate of 10,100 per 1 million peopleis reported.AKI is also showing a rapid increase in occurrence,as newly diagnosed patients in 2011 are 5-foldsmore than that of 2001[ii]. Nearly one-third of people who have undergone heart surgery suffer from AKI,showing an estimated 880,000 newly diagnosed IRI-AKI patients after heart surgery[iii]. The rapid increase of incidence is influenced by 1) increased incidence of diabetes,heart failure,and sepsis due to theagingpopulation,2)increased usage of nephrotoxic contrast agents during operations such as cardiac catheterization,CT scan,and angiography,and 3) increased usageof antibiotics and NSAIDs,thus showing a more rapid increase of incidence in developed countries with high quality of medical infrastructures. The global market size of AKI therapeutics in 2018 is $1,527M,and the estimated compound annual growth rate (CAGR) is 8.1%[iv].Currently,thereis no drug with proven clinical efficacy and safety for AKItreatment,rendering AKI therapeutics a field of high unmet needs to substitute the current RRT.

Exosomes:

Exosomes are a type of extracellular vesicles,sized from 50 to 200nm,released by cells in the body. Exosomes act as intercellular messengers delivering a variety of materials,including RNA,proteins,etc. Due to this unique function as a messenger between cells,exosomes can be developed as treatments and a novel drug delivery system to carry drugs into the target cells in various diseases with significant unmet medical needs.

ABOUT ILIAS Biologics,Inc.:

ILIAS Biologics,Inc. is a biotech company dedicatedto developing a new treatment modality,engineeredexosome therapeutics. ILIAS has successfully created three proprietaryplatform technologies,EXPLOR®,Exo-Target®,and Pure-Exo®. EXPLOR® makes it possible to load large therapeutic molecules into exosomes,which can subsequently target previously undruggable intracellular pathways. Exo-Target® allows active targeting of its engineeredexosomestospecific organs or cells. Pure-Exo® enablesthe manufacturing of high-purity exosomes on a commercial scale.

ILIAS accelerates innovation through two tracks; (a) in-house pipeline development in inflammation and CNS areas,and (b) research collaboration with industry partners interested in leveraging ILIAS's unique platform technology.

For more information,visithttp://www.iliasbio.com.

ABOUT EXPLOR® technology:

EXPLOR® technology is a novel protein-loading method that enables the active loading of large therapeutic cargo proteins as free forms into the lumen of exosomes,nanosized extracellular vesicles,through cellular biogenesis processes.

This process involves controllable and reversible detachment of cargo proteins from the membrane of exosomes once they load into exosomes,which increases the efficiency of delivery of payload proteins into the cytoplasm or nucleus of target cells. While exosomes have been actively studied as novel therapeutic vehicles for intracellular drug delivery,the controllable loading of therapeutic cargo proteins as free forms in the exosomal lumen has remained a technical hurdle.

ILIAS'technology provides a unique solution to overcome this challenge and is expected to treatvarious diseases with significant medical unmet needs. The technology wasfirst published by Nature communication in 2016,and ILIAS has provided its first POC study result in sepsis in Science Advance in Apr. 2020. ILIAS secured the patent for EXPLOR® technology in the United States,Japan,China,and South Korea. In addition,ILIASapplied for the patents in 5 other countries,including India and Europe.

[i]Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group (2012) KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012; 2(Suppl 1):1-138

[ii]Jeremiah B,Michael R,Emily M,Michael M. Hospital Mortality in the United States following Acute Kidney Injury,BioMed Research International,Volume 2016,4278579

[iii]International Journal of Nephrology and Renovascular diseases 2019:12 – 153:166

[iv]Acute Kidney Injury Treatment Market: Global Industry Analysis 2014 – 2018 and Opportunity Assessment,2019 – 2029,Future Market Insights,201

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