Technology-DRAFT

First-In-Class Targets for Immuno-Inflammatory Diseases

We are advancing first-in-class therapies for Medical Dermatology and Respiratory diseases. Our clinical-stage drugs target critical points in inflammatory and innate immune response pathways, such as CXCL10 and TLR4.  Our goal is to transform the lives of patients suffering from acute and chronic diseases.

CXCL10

C-X-C Motif Chemokine Ligand 10 plays an important role in both the innate and adaptive immune responses in patients with vitiligo

TLR4

Toll-like Receptor 4 is key receptor on which both infectious and noninfectious stimuli converge to induce a proinflammatory response

sPLA2

The Secretory Phospholipase A2 enzyme family plays a key role in initiating inflammation associated with many diseases

EB06- Anti-CXCL10 Antibody Candidate for Vitiligo

Vitiligo – Millions Affected Globally

Diagnosed with Vitiligo

Mean Age of Onset

Approved Systemic Treatments

A Life-Altering Disease

2% of the world’s population

  • Chronic, progressive and must be managed for decades
  • Deep emotional impact – especially children & teens
  • Numerous comorbidities

Significant unmet medical need

  • No systematic drugs approved by FDA to re-pigment skin
  • Few effective therapies
  • Millions do not seek treatment

Prominent role of CXCL10

  • CXCL10 is elevated in vitiligo patients

  • Therapeutically targeting this chemokine has been substantiated in third-party preclinical studies
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Novel Mechanism

A fully human monoclonal antibody, EB06 has been shown to trap CXCL10 in the circulatory system and render it biologically inactive.

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Dual Action

EB06 blocks CXCL10 from binding to its receptors, CXCR3A and CXCR3B, which mediates different signaling pathways important to disease progression and maintenance.

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No Daily Dosing

EB06 is being developed as a more effective and conventient treatment, with an improved safety profile compared to current treatments

Target Product Profile – EB06 anti-CXCL10 biologic drug candidate

Addressing Unmet Medical Needs in Vitiligo

Topical JAK Inhibitors

  • Treats lesional skin
  • Treats non-lesional skin
  • Viable for patients with >10% BSA
  • No expected safety precaution (“Black Box”)
  • No Daily Dosing

Oral JAK Inhibitors

  • Treats lesional skin
  • Treats non-lesional skin
  • Viable for patients with >10% BSA
  • No expected safety precaution (“Black Box”)
  • No Daily Dosing

Topical BET Inhibitors

  • Treats lesional skin
  • Treats non-lesional skin
  • Viable for patients with >10% BSA
  • No expected safety precaution (“Black Box”)
  • No Daily Dosing

Biologics

  • Treats lesional skin
  • Treats non-lesional skin
  • Viable for patients with >10% BSA
  • No expected safety precaution (“Black Box”)
  • No Daily Dosing

BSA = Body Surface Area

EB01- A Topical Daniluromer Candidate for Allergic Contact Dermatitis

Image of Topical Cream Being Applied to Rash on Hand

ACD – The Leading Occupational Health Issue Related to Dermatology

Known Contact Allergens

%

Unable to Identify Allergen

No Known Labelled Drugs

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First-in-Class Anti-Inflammatory

EB01 (daniluromer), an sPLA2 inhibitor, is designed to inhibit the inflammatory process at its inception.

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Alternative to Steroids

Due to its non-steroidal mechanism of action, Edesa is evaluating EB01 as a treatment for patients with chronic moderate-to-severe Allergic Contact Dermatitis.
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Broad Potential Opportunities

Potential for treating a diverse range of  inflammatory/allergic conditions.

 

1.0% EB01 Met Primary with Statistical Significance

Phase 2B – Daniluromer Results 

For the treatment of chronic moderate-to-severe allergic contact dermatitis

Total CDSI Score*

Mean Percent Improvement from Baseline

Efficacy

  • 1.0% EB01-treated patients demonstrated a relative improvement of >50% (CDSI) and >80% (ISGA) over placebo/vehicle

Response at 15 Days (CDSI)

  • 44% for 1.0% EB01 vs. 29% for placebo; p=0.05

Response at Follow Up (CDSI)

  • 64% for 1.0% EB01 vs. 44% for placebo; p=0.04

Lowest Efficacious Dose

  • 1.0% EB01 was identified as the lowest efficacious dose over 2.0% and 0.2%

Safety

  • No serious treatment-related adverse events were reported across all doses

 

*Intention to Treat (ITT) population; statistical analysis based on last observation carried forward (LOCF). Placebo (n=84); 1.0% EB01 Cream (n=19). Contact Dermatitis Severity Index (CDSI) at Day 29. Success on the Investigator’s Static Global Assessment (ISGA) is defined as a 2-point reduction and score indicating clear/almost-clear skin.

EB05 (paridiprubart) – An Antibody Candidate for Inflammation and Fibrosis
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First in Class mAb

Our most advanced Respiratory drug candidate is EB05 (paridiprubart), an anti-TLR4 monoclonal antibody developed for acute and chronic disease indications that involve dysregulated innate immunity responses.

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Well Documented Mechanism of Action

TLR4 is one of the most studied innate immune receptors. It mediates of both inflammation and fibrosis.

EB05 binds with a high affinity and blocks the dimerization of TLR4 and its activity.  

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Preclinical and Clinical Evidence

Hundreds dosed in multiple preclinical and clinical studies.

Edesa’s Phase 2 study was stopped early due to a strong survival signal in critically ill patients.

Acute Respiratory Distress Syndrome (ARDS)

A Leading Cause of ICU Admissions Globally

Annual Cases Globally

%

ICU Mortality Rate

$ Cost Per Patient (Average U.S.)

Multiple Causes

ARDS can be caused by both viral and bacterial infections as well as smoke/chemical inhalation and chest injury

Aging Population

Changing demographics increase the risk of developing ARDS. There’s an increasing long-term need for effective ARDS therapeutics.

Co-morbidities and Risk Factors

Increasing incidence of comorbidities and risk factors, including hypertension, diabetes & obesity, can further drive incidence of ARDS

EB05 (Paridiprubart) Decreases Mortality by 84% in Critically Severe Patients

Phase 2 Results

Statistically Significant Mortality Trend in Critical Patients

28-Day Mortality Rate by Treatment Group*

n=33; p=0.04

“Achieving statistical significance in the most difficult-to-treat patients has increased our excitement and belief that Paridiprubart could become a standard-of-care treatment option.”

Par Nijhawan, MD

CEO, Edesa Biotech

Critically ill patient population*

  • 28-day death rate of 7.7% (1/13) in the EB05 (Paridiprubart) arm vs. 40.0% (8/20) in the placebo arm
  • 84% reduction in the risk of dying (HR: 6.12 placebo vs. EB05 (Paridiprubart); 95% CI: 0.77-49.06; p=0.088).
  • All patients received Standard of Care (SOC): ~85% received dexamethasone (or other steroids); >40% received both tocilizumab and a steroid; well balanced

Favorable Safety Profile

  • Paridiprubart, an anti-TLR4 antibody candidate, has been evaluated in multiple clinical studies (with 600+ subjects in total)

*World Health Organization’s Covid-19 Severity Scale Level 7 critically severe patients, receiving extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation plus organ support, or both. ITT= Intend to Treat (i.e., no randomized subjects were excluded).

Additional Opportunities for Paridriprubart in Pulmonary Fibrosis

Current Treatments May Only Slow Disease Progression

Prevalence per 100k

Billion Dollars (Annual Cost U.S.)

$ Cost Per Patient (Average U.S.)

Third Party PreClinical Research Highlights Prominent Role of TLR4 in Fibrosis

Animal models display attenuated fibrosis

  • Knockouts of TLR4 result in attenuated fibrosis in mice

Anti-TLR4 Reduced Fibrosis

  • TLR4 antagonist reduced fibrosis in mouse model in a dose-dependent manner

Reversed Fibrosis

  • Targeting TLR4 leads to a reversal of fibrosis in skin in mouse model

Predict

  • TLR4 agonists are predictors of disease progression and severity

Lung Fibrosis from Various Causes Culminate in a Pathway that is Meditated by TLR4 Activation

Further Reading

El-Domyati et al., 2022: Demonstrated that the chemokine CXCL10 was elevated in both vitiligo patient skin and serum.

Rashighi et al., 2014: In a mouse model of vitiligo, neutralization of CXCL10 in mice with established, widespread depigmentation induced reversal of disease.

Gharib et al., 2021: Serum CXCL10 levels are significantly increased in vitiligo patients compared to controls, suggesting that CXCL10 may play a role in the pathogenesis of vitiligo

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.