Technology

Novel Mechanism of Action

sPLA2 inhibitors represent a novel approach treating inflammation without the safety concerns of current therapies.

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Inhibiting the Inflammation Cascade

sPLA2 inhibitors are designed to inhibit the inflammatory process at its inception rather than after inflammation has occurred.

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Efficacy and Durability

In Phase 2a testing, contact dermatitis patients demonstrated 50+% improvement in mean score from baseline and statistically significant  improvement for each symptom vs. placebo. Clear durability demonstrated following treatment.

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Well Tolerated

No serious adverse effects or discontinuations due to adverse events.

EB01 inhibits sPLA2 from degrading phospholipids to produce arachidonic acid. Arachidonic acid is processed via the LOX-COX pathway to produce several pro-inflammatory signaling molecules.  EB01 exerts its anti-inflammatory activity upstream of currently approved NSAIDs, which target the LOX-COX pathway.

EB01- A Topical Treatment Candidate for Allergic Contact Dermatitis

Image of Topical Cream Being Applied to Rash on Hand

Initial Phase 2 Efficacy Study of EB01

For the treatment of allergic contact dermatitis

Mean Percent Improvement from Baseline in Total PVA Score

The bilateral study (n = 30) was conducted to assess 2.0% EB01 cream applied twice daily for 21 consecutive days in connection with the treatment of allergic contact dermatitis (ACD). To be included in the study, patients had to have bilateral ACD with a PVA** score of at least 10 on each side, with no more than a 1-point difference between lesions. At Day 21, EB01-treated lesions had a mean improvement from baseline of 58%, compared to 24% for those treated with placebo cream (p < 0.001).

Improvements were seen for each of the individual PVA parameters graded (dryness, scaling, redness, pruritus, and fissures), indicating that each aspect contributed to the overall effect of the treatment (as shown in Table 1 below). Efficacy of the 2.0% EB01 cream was maintained through Day 42 (21-days after ending treatment) with a 49% decrease in total PVA score for 2.0% EB01 cream-treated hands, compared to 15% in the vehicle-treated hands (p < 0.001).
Improvements were seen for each of the individual PVA parameters graded (dryness, scaling, redness, pruritus, and fissures), indicating that each aspect contributed to the overall effect of the treatment (as shown in table below). Efficacy of the 2.0% EB01 cream was maintained through Day 42 (21-days after ending treatment) with a 49% decrease in total PVA score for 2.0% EB01 cream-treated hands, compared to 15% in the vehicle-treated hands.

** The Physician’s visual assessment (PVA) is a composite endpoint, which grades each symptom of the disease (dryness, scaling, redness, pruritus, and fissures) scored from 0 (none) to 3 (severe), with a maximum severity score of 15. A diagnosis of ACD was confirmed by a positive patch test deemed to be clinically relevant by the investigator.

Percent Change from Baseline to Day 21
Comparison between treatment groups using Paired T-test/Wilcoxon Rank Sum Test (n = 30)

Endpoint EB01VehicleP-Value
Total Physicians Visual AssessmentMean % Change from Baseline-56%-24%<0.001
Scaling*Mean % Change from Baseline-48%-20%<0.001
Redness*Mean % Change from Baseline-47%-20<0.001
Pruritis*Mean % Change from Baseline-62%-25%<0.001
Fissures*Mean % Change from Baseline-81%-46%<0.001
Dryness*Mean % Change from Baseline-45%-15%<0.001

* Data are not normally distributed — P-Values result from Wilcoxon Rank Sum test.

Novel monoclonal antibodies for immune and inflammatory diseases

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First in Class mAbs

EB05 and EB06 have been engineered to alter inflammatory signaling by binding to and blocking the activation of a specific cytokine pathway target.
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Well Documented Mechanism of Action

EB05 dampens TLR4 signaling by blocking receptor dimerization (and subsequent intracellular signaling cascades) and has been shown to be independent of ligand type and concentration, therefore broadly blocking potentially any TLR4 ligands. EB06 binds specifically and selectively to CXCL10 and inhibits the interaction of CXCL10 with its receptor.

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Powerful Scientific Rationale

EB05 and EB06 could ameliorate proinflammatory cascades in COVID-19 patients, thereby reducing lung injury, ventilation rates and mortality.

Acute Respiratory Distress Syndrome

An Exaggerated Immune Response Leads to Hypoxia & Death

Moderate to severe viral pneumonia triggers exaggerated immune response

  • Cell damage, “cytokine storm” and widespread inflammation
  • Oxygen cannot permeate air sacks leading to death

Cytokine release and inflammatory response due to viral infection is mediated via TLR4.

Activity Data from Phase 1 and Phase 2 Clinical Studies

Compelling Evidence of Activity

EB05 lowered cytokines after in vivo endotoxin challenge

Inhibits “Cytokine Storm”

A single low dose of EB05 provided a measurable protective response to endotoxin (LPS) challenge for 22+ days

In previous Phase 1 and Phase 2 clinical studies, EB05 and EB06 have demonstrated the ability to resolve fever and stabilize heart and breathing rates in subjects administered immune challenges.

Favorable Safety Profile

Our anti-TLR4 and anti-CXCL10 antibody therapies been administered to >120 subjects without any safety signals

EB05 lowered fever and stabilized vital signs after in vivo endotoxin (LPS) challenge

The physiological signs observed are consistent with the biological profile measured

Further Reading

Jiang et al., 2005: TLRs are known to be involved in exaggerated immune responses, with TLR4 shown to induce inflammatory responses that can lead to acute lung injury (ALI) and ARDS

Imai et al., 2008: This study looked at the role of TLR4 in ALI. Mice deficient in TLR4 were resistant to acid-induced ALI and while H5N1 influenza rapidly induced ALI in wild-type mice, TLR4 deficient mice were resistant to H5N1-induced ALI, suggesting a causative role for TLR4 in

Shirey et al., 2016: In this study, an anti-TLR4 antibody protected mice from lethal influenza

Perrin-Cocon et al., 2017: A novel small molecule TLR4 antagonist (FP7) was tested in an in vivo mouse model of influenza. FP7 blocked TLR4 stimulation and protected mice from influenza-induced lethality and reduced inflammatory cytokine expression and

Zhou et al., 2018: An anti-TLR4 monoclonal antibody was studied in a rat model of ARDS. The rats treated with the anti-TLR4 antibody showed lower respiratory frequency, lung permeability, lung edema, inflammatory infiltration, and tumor necrosis factor and interleukin expression levels in lungs along with lower TLR4, TLR9, MyD88, and nuclear factor expression in macrophages.

Domitrovic 2018: TLR4 monoclonal antibodies were evaluated both in vitro and in a rat model of ARDS. Stimulating macrophages with TNF-alpha along with anti-TLR4 antibody eliminated the upregulation and secretion of cytokines. Pre-treating rats with anti-TLR4 antibody prior to ventilation.

Lee et al., 2009: CXCL10 plays a significant role in leukocyte recruitment to inflamed tissues, and because of this it can lead to excessive inflammation and tissue damage. Patients who suffer from ARDS are known to exhibit unusually high levels of CXCL10.

Wang et al., 2013: This study showed that patients suffering from ARDS caused by H1N1 infection had significantly elevated levels of CXCL10 in their serum compared to a control group. An anti-CXCL10 monoclonal antibody increased survival time, reduced lung edema, and significantly decreased ALI in a mouse model of H1N1 infection.

Ichikawa et al., 2013: In this study, ARDS was induced in mice by both non-viral and viral means. Mice deficient in CXCL10 or CXCR3 had improved severity and survival of both viral and non-viral ARDS.

Lang et al., 2017: This study explored the role of CXCL10 in a rat model of LPS-induced ARDS. Expression of CXCL10 and CXCR3 increased after LPS-induction. An anti-CXCL10 antibody decreased the severity of ARDS.

Global Agreement

Edesa has established a strategic global agreement with Light Chain Bioscience, a leading Swiss pharmaceutical development company. Light Chain has been at the forefront of antibody development technology for the last two decades and is a world leader in antibody engineering,

Yissum Collaboration

Edesa collaborates with researchers at Hebrew University of Jerusalem and has a license agreement with the university’s tech transfer agent Yissum Research Development Company for our investigational medicines EB01 and EB02.