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Item 1. Business

2024-12-13 compared with 2023-12-15 · 87 added, 147 removed, 452 unchanged (34% of the section changed)

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We prioritize our efforts on disease indications where there is compelling scientific rationale, no approved therapies or where there are unmet medical needs, and where there are large addressable market opportunities, among other factors.

We have multiple late-stage product candidates in our development pipeline.

Our most advanced drug candidate is EB05 (paridiprubart).

Our clinical pipeline is focused on two therapeutic areas:

Medical Dermatology and Respiratory.

In Medical Dermatology we are developing EB06, an anti-CXCL10 monoclonal antibody candidate, as a therapy for vitiligo, a common autoimmune disorder that causes skin to lose its color in patches.

CXCL10 has been shown to play a key role in the disease, and neutralization of CXCL10 has been demonstrated to both prevent and reverse depigmentation in animal models.

To date, EB06 has demonstrated a favorable safety and tolerability profile.

We have received regulatory approval from Health Canada to conduct a Phase 2 proof of concept study of EB06 in patients with moderate-to-severe nonsegmental vitiligo and we are in discussions with the U.S.

Food and Drug Administration (FDA) for the same study.

Our medical dermatology assets also include EB01 (1.0% daniluromer cream), a Phase 3-ready asset developed for use as a potential therapy for moderate-to-severe chronic Allergic Contact Dermatitis (ACD), a common occupational skin condition.

This asset is at the partnering stage.

Our most advanced Respiratory drug candidate is EB05 (paridiprubart).

Paridiprubart represents a new class of emerging therapies called Host-Directed Therapeutics (HDTs) that are designed to modulate the body’s own immune response when confronted with infectious diseases or even chemical agents.

Importantly, these therapies are designed to work across multiple infectious diseases and threats, and could be stockpiled preemptively ahead of outbreaks.

Because they are threat agnostic, HDTs like paridiprubart have the potential to become standard of care in Intensive Care Units (ICUs) and critical countermeasures for both pandemic preparedness and biodefense.

We are currently evaluating EB05 as a potential treatment for Acute Respiratory Distress Syndrome (ARDS), a life-threatening form of respiratory failure.

Recruitment in a Phase 3 study is ongoing.

In addition to EB05, we are developing product candidates for a number of chronic dermatological and inflammatory conditions.

In November 2023, we reported final results from a Phase 2b clinical study evaluating multiple concentrations of our drug candidate, EB01 (daniluromer), as a monotherapy for moderate-to-severe chronic Allergic Contact Dermatitis (ACD), a common occupational skin condition.

Among the findings, 1.0% EB01 cream demonstrated statistically significant improvement over placebo for the primary endpoint and a key secondary endpoint.

For our EB06 monoclonal candidate, we have received regulatory approval by Health Canada to conduct a future Phase 2 study in patients with moderate to severe nonsegmental vitiligo, a common autoimmune disorder that causes skin to lose its color in patches.

We are also preparing an investigational new drug application (IND) in the United States (U.S.) for our EB07 product candidate to conduct a future Phase 2 study in patients with fibrotic diseases such as systemic sclerosis.

EB05 is currently being evaluated in a U.S.

government-funded platform study investigating three novel threat-agnostic HDTs in hospitalized adult patients with Acute Respiratory Distress Syndrome (ARDS), a life-threatening form of respiratory failure.

Certain development expenses, including manufacturing scale-up, for our EB05 program are also eligible for reimbursement from the Government of Canada under a 2023 grant and funding award.

In addition to EB05, we are also preparing an investigational new drug application (IND) in the United States to conduct a future Phase 2 study for EB07 (paridiprubart) in patients with pulmonary fibrosis.

Competitive Strengths

We believe that we possess a number of competitive strengths that position us to become a leading biopharmaceutical company focused on inflammatory and immune-related diseases, including:

We believe that we possess a number of competitive strengths that position us to become a leading biopharmaceutical company focused on immuno-inflammatory diseases, including:

Validated technology and drug development capabilities.

We believe that the strength of our technologies has been validated by our favorable clinical data and progress to date, more than C$37 million in competitive government grant and funding awards, and our multiple arrangements with third parties to develop and commercialize their clinical-stage drug candidates.

We believe that the strength of our technologies and our drug development capabilities have been validated by our favorable clinical data, our multiple arrangements with third parties to develop and commercialize their clinical-stage drug candidates, more than C$37 million in competitive government grant and funding awards, and selection for a U.S.

government-funded clinical study by experts from the Biomedical Advanced Research and Development Authority (BARDA), the Centers for Disease Control and Prevention, Department of Defense, FDA and National Institutes of Health.

Innovative pipeline addressing large underserved markets.

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By initially targeting large markets that have significant unmet medical needs, we believe that we can drive adoption of new products and improve our competitive position.

For example, ARDS is associated with approximately 10% of ICU admissions globally, impacts millions of people, and costs billions of dollars annually.

For example, vitiligo affects up to 2% of the world’s population and ARDS is associated with approximately 10% of ICU admissions globally, yet both diseases have limited treatment options.

Intellectual property protection and market exclusivity.

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Our goal is to obtain regulatory approval and commercialize multiple clinical assets in our pipeline.

We seek to expedite development, in part, through the use of innovative trial designs, including adaptive design protocols, as well as by focusing on disease indications that we believe have clear regulatory pathways and interest from potential licensing or development partners.

We focus on disease indications that we believe have clear regulatory pathways and interest from potential licensing or development partners.

Given the high capital requirement for pivotal clinical studies, our preferred strategy is to seek public and private partners for Phase 3 clinical testing and scale-up.

We also plan to evaluate opportunities to apply, as applicable, for expedited regulatory review and orphan drug programs, which could potentially lead to accelerated clinical development and commercialization timelines for our product candidates.

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Our assets are designed to modulate pathways that are implicated across a number of immune and inflammatory/allergic conditions.

For example, we believe that our monoclonal antibody candidates have potential utility in additional indications, including chronic conditions like systemic sclerosis and vitiligo.

For example, we believe that our monoclonal antibody candidates have potential utility in additional indications, including chronic conditions like pulmonary fibrosis.

Maximize the commercial potential of our product candidates via direct marketing or strategic arrangements.

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Since TLR4 detects molecules found in pathogens and also binds to endogenous molecules produced as a result of injury, it is a key receptor on which both infectious and noninfectious stimuli converge to induce a proinflammatory response.

Specifically, TLR4 signaling activates leukocytes to secrete proinflammatory cytokines (i.e., CXCL10, IL-6, IFN-b, IL-1b, TNF-α), which under certain circumstances can result in a “cytokine storm” - a severe immune reaction in which the body releases too many cytokines into the blood too quickly.

Such upregulation of TLR4 and its associated cytokines has been observed in respiratory infections such as influenza and SARS-CoV-2.

In multiple third-party studies, high serum levels of alarmins, such as calprotectin (S100A8/A9) and HMGB1(high mobility group protein B1), that bind to and activate TLR4 are associated with poor outcomes and disease progression in ARDS patients.

In addition, TLR4 inhibition (antagonism) prevents cytokine production at a very early stage and has been shown to have a protective effect.

For example, in preclinical studies in mice, it was demonstrated that administration of a TLR4 antagonist blocked influenza-induced lethality and ameliorated virus-induced acute lung injury.

Antagonism of TLR4 has also been shown to modulate the secretion of proinflammatory cytokines (IL-6, CRP, IFNb, TNF-a, CXCL-10, IL8 and MIP-1b).

Based on these data as well as previous clinical results, we believe that the modulation of TLR4 provides a compelling opportunity to treat ARDS.

EB05 (paridiprubart)

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The drug has demonstrated the ability to block signaling irrespective of the presence or concentration of the various molecules that frequently bind with TLR4, known as ligands.

Based on this broad mechanism of action, we believe that paridiprubart could ameliorate TLR4-mediated inflammation cascades in ARDS patients, thereby reducing lung injury, ventilation rates and mortality.

Phase 2 Results of Phase 2/Phase 3 Study

In September 2022, we reported final results for the Phase 2 part of an international Phase 2/3 clinical study evaluating the safety and efficacy of EB05 as a therapy for adult hospitalized Covid-19 patients.

The Phase 2 part of the Phase 2/3 study was primarily exploratory and designed to refine patient stratification and statistical powering for the Phase 3 study.

The study included hospitalized Covid-19 patients, ranging from Level 3 (hospitalized, not requiring supplemental oxygen) on the nine-point WHO Covid-19 Severity Scale (WCSS) to WCSS Level 7 (hospitalized, requiring intubation plus additional organ support such as ECMO).

Enrollment in the study as well as the analysis was stratified according to baseline WCSS level into patients with mild Covid-19, defined as WCSS level ≤4, or severe Covid-19, defined as WCSS level ≥5, or critically ill, defined as WCSS level 7.

Following a single intravenous infusion of EB05 or placebo, patients were evaluated for disease progression, mortality, side effects and other critical care measurements.

Standard-of-care Covid-19 treatment was given to all patients.

In the Phase 2 study, EB05 demonstrated a statistically significant and clinically meaningful trend for 28-day mortality for all randomized subjects in the critically ill cohort (the intent to treat, or ITT, population).

Based on this broad mechanism of action and clinical results to date, we believe that paridiprubart could ameliorate TLR4-mediated inflammation cascades in ARDS patients, thereby reducing lung injury, ventilation rates and mortality.

In the signal-finding Phase 2 part of a Phase 2/3 clinical study evaluating EB05 in hospitalized Covid-19 patients at various disease severity levels, EB05 demonstrated a statistically significant and clinically meaningful trend for 28-day mortality for all randomized subjects in the critically ill cohort (the intent to treat, or ITT, population).

The 28-day death rate in the EB05 plus standard of care (SOC) arm was 7.7% versus 40% in the placebo + SOC arm in critically severe patients on ECMO therapy (extracorporeal membrane oxygenation) or Invasive Mechanical Ventilation (IMV) plus organ support with ARDS at baseline (p=0.04).

The Survival Analysis using Cox’s Proportional Hazard Model also demonstrated that patients treated with EB05 + SOC had an 84% reduction in the risk of dying when compared to placebo + SOC at 28 days.

To our knowledge, no other study has demonstrated a result of this magnitude in this population.

The 60-day mortality rate was 23.1% (3/13) in the EB05 + SOC arm versus 45% (9/20) in the placebo + SOC arm for this same population (p=0.20).

The Survival Analysis using Cox’s Proportional Hazard Model showed that the patients treated with EB05 + SOC had a 61% reduction in the risk of dying when compared to placebo + SOC at 60 days.

In addition to the critically ill population, the analysis of the full Phase 2 dataset revealed other efficacy signals.

For severe Covid-19 patients at WCSS Level 5 and 6 (99% of patients had ARDS at baseline), there were clinically meaningful differences with respect to the proportion of patients who were alive without any need for oxygen support at Day 28 (the Phase 2 study’s primary endpoint).

From the ITT analysis of this population, 45.8% in the EB05 + SOC arm versus 36.1% in the placebo + SOC arm achieved the primary endpoint (p=0.16).

Similarly positive efficacy signals were also demonstrated in this same population for the proportion of patients who achieved at least a 2-point improvement on the WCSS.

From the ITT analysis of this population, 46.7% in the EB05 + SOC arm versus 36.1% in the placebo + SOC arm achieved at least a 2-point improvement in on the WCSS (p=0.12).

For mild Covid-19 patients at WCSS Level ≤4, the study did not detect meaningful clinical differences between the arms for these endpoints, which is likely the result of the baseline severity score being too close to the endpoint (WCSS of 3 or less) on these scoring scales.

The Phase 2 study demonstrated that EB05 appears to be well-tolerated and consistent with the observed safety profile to date.

Phase 3 of a Phase 2/Phase 3 Study

In December 2022, the U.S.

Food and Drug Administration (FDA) granted Fast Track designation to EB05 as a treatment for ARDS in critically ill Covid-19 patients.

The Fast Track program provides us with the opportunity for more frequent communication with the agency to discuss the development path for EB05 as a treatment for ARDS in critically ill Covid-19 patients.

Investigational drugs that receive Fast Track designation are also eligible for rolling review of their marketing application as well as potential pathways for accelerated regulatory approval.

To receive this designation, drug candidates must both treat a serious disease and have non-clinical or clinical data that demonstrate the potential to address an unmet medical need.

The Phase 3 part of our Phase 2/3 study is designed to assess the efficacy and safety of EB05 among hospitalized patients with severe and critical disease, for whom there continues to be limited treatment options and high mortality rates.

In March 2023, we announced that the Company and the FDA agreed on the primary endpoint and population for a Phase 3 study evaluating EB05 as a therapy for hospitalized Covid-19 patients with ARDS.

Under the amended protocol design, we will evaluate a single cohort of severely ill patients on invasive mechanical ventilation, both with and without additional organ support such as ECMO.

The protocol calls for approximately 600 evaluable hospitalized subjects to be enrolled.

The primary endpoint will be the mortality rate at 28 days.

In October 2023, Canadian regulators approved an amendment that harmonized the previously approved Canadian protocol with the U.S.

Based on current hospitalization trends and our recruitment experience, we believe that Covid-19-related hospitalization patterns have become more predictable and seasonal in nature, similar to those of influenza, with increased hospitalizations and deaths anticipated in the fall/winter and among populations and geographies with low booster/vaccination rates.

As a result, we believe that the pace of future enrollment will be more closely linked to the number and location of investigational sites we activate rather than the unpredictable waves of the pandemic.

We plan to increase the number of investigational centers from 23 to up to 60 hospitals in the U.S.

We have the flexibility to adjust the timing of these and other clinical trial expenditures to manage our working capital.

In addition to Covid-19 induced ARDS, we are also exploring various approaches to evaluate our EB05 drug candidate in a general, all-cause ARDS population.

Given the broader pool of patients, we believe a general, all-cause ARDS study could increase efficiency and expedite development timelines as well as validate the broader potential utility of EB05.

Any changes we make to our clinical study protocol may impact how previously enrolled subjects are categorized and/or included in the study’s results.

As of the date of this filing, recruitment is ongoing in the U.S.

Previous Phase 1 and Phase 2 Clinical Studies

Paridiprubart has demonstrated the potential ability to regulate inflammation and resolve fever and stabilize heart and breathing rates in human subjects that were injected with lipopolysaccharide (LPS) - a potent inducer of acute systemic inflammation.

In previous Phase 1 and Phase 2 clinical studies, paridiprubart has demonstrated favorable safety and tolerability profiles.

In a previous Phase 1 study, paridiprubart was administered in healthy volunteers (HV) as a single intravenous infusion using a single ascending pharmacokinetic/pharmacodynamic dose design.

Paridiprubart was administered at different dose levels and was followed by in vivo LPS challenges.

The study demonstrated that paridiprubart inhibited the release of various pro-inflammatory cytokines (IL-6, TNF-α and CXCL10) and stabilized certain other vital signs for up to 22 days after the infusion of paridiprubart.

The study further demonstrated that cytokine response and baseline vital signs were restored at 40 days after paridiprubart infusion.

Paridiprubart demonstrated a favorable safety profile in the Phase 1 study in healthy volunteers as well as in a multiple-infusion Phase 2 study in subjects with rheumatoid arthritis (RA).

In the Phase 1 study, doses ranged from 0.001 mg/kg up to 15mg/kg.

The Phase 2 RA study was a multiple dose study where patients received one dose of paridiprubart 5 mg/kg every two weeks for 12 weeks.

In the Phase 1 study, a total of 60 subjects received paridiprubart, and in the Phase 2 RA study, 61 patients were randomized to the paridiprubart group.

There were no meaningful differences observed between the placebo and paridiprubart treatment groups with respect to the incidence of treatment emergent serious and non-serious adverse events in either of these studies.

The FDA has granted EB05 a fast-track designation for the treatment of hospitalized Covid-19 patients.

Government Funded Study

In June 2024, EB05 was selected through a competitive process by BARDA, part of the Administration for Strategic Preparedness and Response within the U.S.

Department of Health and Human Services, as one of three drug candidates for evaluation in a U.S.

government-funded Phase 2 platform study.

The randomized, double-blinded, placebo-controlled, multi-center clinical trial is investigating novel threat-agnostic host-directed therapeutics, including EB05, in hospitalized adult patients with ARDS due to a variety of causes.

The BARDA-funded study is being managed under a BARDA contract with PPD Development, LP, a clinical research business of Thermo Fisher Scientific, Inc.

For the EB05 cohort of the study, patients are being randomized one-to-one to either EB05 + SOC or to a placebo + SOC control arm.

We are providing drug products to the study as well as technical support at our own expense.

Phase 3 Study

Given the BARDA-sponsored study opportunity, we have shifted our clinical focus for EB05 to general ARDS from Covid-19 induced ARDS.

Our plan is to await the results of the BARDA-funded study before continuing with our Canadian government-supported Phase 3 study, which had exclusively recruited ARDS patients hospitalized with Covid-19.

As a result, we have discontinued enrollment in a Covid-19 focused Phase 3 study and plan to file a new study design with FDA and Health Canada based on the results of the BARDA-funded ARDS study.

We believe this strategy provides a more efficient and cost-effective path toward a commercially approved therapy for general ARDS, increases the potential commercial opportunity for EB05 and better aligns our development programs with government goals for HDTs as well as interest from potential strategic commercialization and licensing partners.

Any changes we have made and make in the future to our clinical plans and enrollment criteria may limit how data from previously enrolled subjects are utilized by the company for regulatory purposes.

Federal Funding from the Government of Canada

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The performance obligations of Edesa Biotech Research under the 2023 SIF Agreement are guaranteed by us.

As a result of the opportunity created by U.S.

government-funded study, we are in discussions with the Government of Canada to amend our 2023 SIF Agreement, including extending the project timeline and completion date.

There can be no assurance that the government will accept our proposals or, if rejected, seek the applicable remedies described above.

Our previously completed Phase 2 study of EB05 was also funded, in part, by SIF.

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All potential funding available under the 2021 SIF Agreement has been received.

As of the date of this filing, we have met all of our performance and reporting requirements under the 2021 SIF Agreement.

As of the date of this filing, we have met all of our performance and reporting requirements under our SIF Agreements.

Pulmonary Fibrosis and EB07 (Paridiprubart)

There is significant evidence that targeting TLR4 in fibrotic conditions could result in therapeutic benefit for patients.

Third party preclinical research has demonstrated that blocking TLR4 in animal models has been shown to reduce and in some cases reverse fibrosis.

Similarly, TLR4 knockout mice display attenuated fibrosis.

In addition, concentrations of agonists that bind to and activate TLR4 are often good predictors of disease severity and progression.

We are preparing an IND in the U.S.

for our EB07 (paridiprubart) product candidate to conduct a future Phase 2 proof of concept study in subjects with pulmonary fibrosis.

This project represents a potential additional use for our anti-TLR4 monoclonal antibody candidate in a chronic disease with limited treatment options and high mortality and morbidity.

Initiating recruitment in the EB07 study is subject to, among other limitations, funding, regulatory approvals, drug manufacturing and activation of clinical investigational sites.

Medical Dermatology

Vitiligo is a chronic autoimmune disease that causes the loss of skin pigmentation in patches.

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Based on the availability and limitations of current treatments, we believe there is a significant need for well targeted and systemic immunotherapies.

Overview and Status

EB06 is a monoclonal antibody candidate that binds specifically and selectively to chemokine ligand 10 (CXCL10) and inhibits the interaction of CXCL10 with its receptor(s).

We believe that there is significant scientific rationale for the potential utility of this mechanism of action to reduce disease symptoms and progression in vitiligo patients.

CXCL10 is highly expressed in vitiligo patients, and has been shown to play both a key role in the trafficking of anti-melanocytic T-cells to the epidermis as well as in inducing apoptosis (death) of melanocytes.

EB06 is a fully human monoclonal antibody candidate that binds specifically and selectively to chemokine ligand 10 (CXCL10) and inhibits the interaction of CXCL10 with its receptors, CXCR3A and CXCR3B.

CXCL10 plays an important role in both the innate and adaptive immune responses in patients with vitiligo.

EB06 is currently formulated for intravenous administration, with plans for a potential subcutaneous formulation.

We believe that there is a significant scientific rationale to target CXCL10 in order to reduce disease symptoms and progression in vitiligo patients.

CXCL10 is highly expressed in vitiligo patients and has been shown to play both a key role in the trafficking of anti-melanocytic T-cells to the epidermis (adaptive immune system response) as well as in inducing apoptosis (death) of melanocytes (innate immune response).

Furthermore, neutralization of CXCL10 has been demonstrated to both prevent and reverse depigmentation in animal models.

EB06 is currently formulated for intravenous administration, with future plans for a potential subcutaneous formulation.

We have approval from Health Canada to conduct a Phase 2 study of EB06 in moderate to severe nonsegmental vitiligo patients, and we are currently evaluating potential funding options to initiate this project, which may include both drug manufacturing and clinical activities.

Previous Clinical Experience

EB06 has demonstrated a favorable safety and tolerability profile in three previous clinical studies of 65 subjects in total.

We believe that EB06 has a number of anticipated advantages compared to other treatments available and under development for vitiligo, including:

a) EB06’s mechanism of action addresses both the adaptive and innate immune systems’ roles in disease maintenance and progression;

b) EB06 is designed to treat both lesional and non-lesional skin;

c) as a systemic therapy, EB06 can treat larger body surface areas, including patients with lesions on >10% of their body surface area;

d) EB06 is administered less frequently than topicals and oral medications;

and e) targeted immunotherapies, like EB06, are designed to provide patients a safer and more effective option than drugs with known off-target effects or even Black Box warnings.

We have approval from Health Canada to conduct a Phase 2 study of EB06 in moderate to severe nonsegmental vitiligo patients.

As planned, the double-blind, placebo-controlled trial will evaluate the safety and efficacy of EB06 in approximately 150 subjects, who will be administered intravenous infusions of either EB06 or placebo during the treatment period, followed by a follow-up period.

The primary efficacy outcome measurement will be the percentage of patients achieving ≥50% decrease (improvement) from baseline in facial Vitiligo Area Scoring Index (F-VASI50).

F-VASI is a composite measurement of the overall area of facial vitiligo patches and degree of depigmentation within patches.

To conduct the planned study at U.S.

investigational centers, we must first manufacture the drug and submit related data to the FDA as part of an IND application.

Based on feedback from the FDA and key opinion leaders, we may modify our Canadian study design and submit conforming amendments to our clinical trial application (CTA) in Canada, before proceeding with enrollment.

The manufacturing of clinical-grade drug batches and initiation of the patient enrollment is subject to funding.

We anticipate topline results for this Phase 2 study could be available within as few as 12 to 18 months following regulatory clearance in the U.S.

In three previous clinical studies of 65 healthy volunteers and non-vitiligo subjects in total, EB06 has demonstrated a favorable safety and tolerability profile.

The first Phase 1 study was a double-blind, placebo-controlled, ascending, single-dose study in 20 healthy subjects.

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As a cell-mediated response, the immune reaction primarily involves the interaction of T cells with antigens rather than an antibody response.

More specifically, ACD involves an exogenous substance binding a cell surface protein to form a hapten that is recognized as a foreign antigen by the immune system.

Haptens are known to signal through toll-like receptors, a family of receptors involved in the innate immune system, which leads to the induction of pro-inflammatory cytokines such as interleukin (IL)-1b.

EB01 has been shown in preclinical studies to inhibit the production of pro-inflammatory cytokines induced via toll-like receptor signaling (IL-1b, IL-6, IL-8, MIP-1a, and TNF-α), suggesting that EB01 may address the underlying disease mechanism of ACD.

Generally, dermatologists view chronic ACD from both a duration and recurrence perspective, considering how often and how long symptoms persist.

Chronic disease affects patients over a prolonged period, typically greater than six months or even years.

These chronic patients have either frequent intermittent exposure or continuous exposure.

Since inflammation in ACD is driven by external exposure to an allergen, the severity of ACD does not necessarily correlate with body surface area, as is often the case with other dermatological diseases.

Current treatment plans begin by attempting to identify and remove exposure to the causative allergen.

However, the causative allergen(s) is frequently not identified, and even when it is, avoiding exposure is often not possible (e.g., it is present in the workplace), according to our market research.

To our knowledge, there are no drug treatment options specifically indicated for ACD.

As such, physicians must utilize agents approved for other dermatological conditions.

Topical corticosteroids are the most commonly used therapeutic intervention for ACD but cannot be used continuously since they have well-known side-effects including skin thinning, stretch marks, acne, stinging, burning and dryness.

Other topical treatments for ACD include topical immunomodulators such as topical calcineurin inhibitors.

However, these are less efficacious than topical corticosteroids and have an FDA “black box warning” for risk of malignancies.

Systemic corticosteroids can be used for acute control of severe cases of ACD but have safety concerns including hypothalamic-pituitary-adrenal axis suppression, growth suppression and loss of bone-density, thereby limiting the utility of steroids for treating chronic disease.

Finally, patients may be treated with systemic immunomodulators, which have “black box warnings” and associated safety issues.

Systemic therapies also need to be tapered off each time the physician wants to patch test allergens to identify the source of a patient’s ACD.

EB01 (daniluromer)

Overview and Status

EB01 is a potential first-in-class, topical vanishing cream containing a novel, non-steroidal anti-inflammatory compound.

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The sPLA2 enzyme family plays a key role in initiating inflammation associated with many diseases, and we believe that targeting the sPLA2 enzyme family with enzyme inhibitors will have a superior anti-inflammatory therapeutic effect because the inflammatory process will be inhibited at its inception rather than after inflammation has occurred.

Phase 2b Clinical Results of EB01

In November 2023, we reported final results from a Phase 2b clinical study evaluating multiple concentrations of our drug candidate, EB01, as a monotherapy for chronic moderate-to-severe ACD.

Our ACD development program is at the partnering stage following completion of a Phase 2b clinical study.

In a Phase 2b clinical study of EB01 we evaluated multiple concentrations of our drug candidate, EB01, as a monotherapy for chronic moderate-to-severe ACD.

The double-blind, placebo-controlled trial evaluated the safety and efficacy of EB01 in approximately 200 subjects, who were treated for 28 days with either EB01 cream (2.0%, 1.0% or 0.2%) or a placebo/vehicle cream.

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The 2.0% and 0.2% formulations did not show significant differences compared to placebo.

We are currently evaluating potential partnerships and funding opportunities for the continued development of this drug candidate.

Previous Clinical Results of EB01

EB01 has demonstrated efficacy for the treatment of ACD in two separate clinical trials.

Both studies were double-blind, placebo/vehicle-controlled bilateral comparison studies to assess the safety, tolerability and efficacy of EB01 cream applied twice daily for the treatment of ACD of the hand and forearm as determined by the CDSI, a physician’s visual assessment.

The CDSI 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 total severity score of 15.

A diagnosis of ACD was confirmed by a positive patch test deemed to be clinically relevant by the investigator.

The first Phase 2 study (n=11) was a double-blind, placebo/vehicle-controlled clinical study to assess the safety and efficacy of topical 1% EB01 cream for the treatment of ACD.

Subjects selected for inclusion had bilateral ACD.

Prior to randomization, subjects were patch tested.

The study was bilateral in design with one lesion treated with 1% EB01 cream twice daily, while a comparable lesion was treated with placebo cream.

Disease severity was assessed before treatment (Day 0) and at Day 30 by the investigator using the CDSI.

For each individual patient, the change in disease score in the drug-treated hand was compared to that in the placebo-treated hand, thus making the latter an internal control for each patient.

The mean change from baseline for 1% EB01 cream treated lesions was 69.9%, compared to 36.5% in the placebo cream lesions (p=0.0024).

A second Phase 2 study was a larger (n=30) bilateral study was conducted to assess 2% EB01 cream applied twice daily for 21 consecutive days in connection with the treatment of ACD.

To be included in the study, patients had to have bilateral ACD with a CDSI 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 56%, compared to 24% for those treated with placebo cream (p<0.001).

Efficacy of the 2% EB01 cream was maintained through Day 42 (21-days after ending treatment) with a 49% decrease in total CDSI score for 2% EB01 cream-treated hands, compared to 15% in the placebo/vehicle-treated hands (p<0.001).

Within the total CDSI score, EB01 demonstrated statistically significant reductions for each of the individual CDSI components (dryness, scaling, redness, pruritus, and fissures).

Total clinical experience with daniluromer, including the current Phase 2b study, has involved approximately 270 subjects.

No serious adverse events have been encountered to date.

Pre-Clinical Results

Daniluromer has demonstrated anti-inflammatory activity in a variety of in vitro and in vivo preclinical pharmacology models.

Using a model for hapten signaling indicative of ACD, lipopolysaccharide-stimulated peripheral blood mononuclear cells were treated with daniluromer and shown to inhibit pro-inflammatory cytokines including IL-1b, IL-6, IL-8, MIP-1a, and TNF-α at the protein and mRNA expression levels.

Additionally, in several Good Laboratory Practice animal toxicology studies, daniluromer was well-tolerated and systemic exposure was negligible (below the limit of detection).

No genotoxicity was demonstrated in bacterial reverse mutation and micronucleus testing.

Other Future Product Candidates

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In addition, we plan to continue to identify, evaluate and potentially obtain rights to and develop additional clinical assets across various stages of development, focusing primarily on inflammatory and immune-related diseases.

Among our activities, we are preparing IND in the U.S.

for our EB07 (paridiprubart) product candidate to conduct a future study in patients with fibrotic diseases such as systemic sclerosis.

This project represents a potential additional use for our anti-TLR4 monoclonal antibody candidate in chronic diseases with limited treatment options and high mortality and morbidity.

In addition, our EB02 (daniluromer) drug candidate represents a potential extension of our sPLA2 anti-inflammatory technology.

Based on our analysis of clinical data in dermatitis, we believe that EB02, which is currently formulated as a cream, may be effective in treating the erythema, swelling and exudation associated with hemorrhoids disease (HD).

We have received approval from Health Canada for an exploratory Phase 2a clinical study of EB02 as a potential treatment for patients with grade I-III internal hemorrhoids.

In light of our focus on the development of other product candidates, we are currently evaluating the timing for the initiation of this planned study of EB02.

Initiating recruitment in the EB07 and EB02 studies is subject to, among other limitations, funding, regulatory approvals, drug manufacturing and activation of clinical investigational sites.

Intellectual Property and Key Licenses

We have an exclusive license from Yissum Research Development Company, the technology transfer company of Hebrew University of Jerusalem Ltd.

(Yissum), for patents and patent applications that cover our product candidates EB01 and EB02 in the U.S., Canada, Australia and various countries in Europe.

(Yissum), for patents and patent applications that cover EB01 in the U.S., Canada, Australia and various countries in Europe.

Method of use patents, for which we hold an inbound license from Yissum and an affiliate of Yissum, have been issued for use in dermatologic and gastrointestinal conditions and infections that will expire in 2024.

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We have also filed additional method of use patent applications which we believe, if issued, could potentially prevent biosimilar substitution until as late as 2041.

We have also filed provisional patent applications for use of these monoclonal antibody technologies in vitiligo (EB06) and systemic sclerosis (EB07).

We have also filed provisional patent applications for use of these monoclonal antibody technologies in vitiligo (EB06) and systemic sclerosis and pulmonary fibrosis (EB07).

In the event we are successful in commercializing a new drug candidate, we believe we would be eligible for data/market exclusivity, in addition to exclusivity rights granted through patent protection.

We would be eligible for up to five years of exclusivity for EB01 and EB02 and up to 12 years of exclusivity for EB05 and EB06 after approval in the U.S., and, for any of these drug products, eight years of exclusivity after approval in Canada and ten years of exclusivity after approval in the European Union (EU).

We would be eligible for up to five years of exclusivity for EB01 and up to 12 years of exclusivity for EB05/EB07 and EB06 after approval in the U.S., and, for any of these drug products, eight years of exclusivity after approval in Canada and ten years of exclusivity after approval in the European Union (EU).

We expect patents and other proprietary intellectual property rights to be an essential element of our business.

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In March 2021, through Edesa Biotech Research, we entered into a license agreement with the inventor of the same pharmaceutical product, which was subsequently amended in September 2023 (together, the Inventor License Agreement), to acquire global rights for all fields of use beyond those named under the Yissum License Agreement.

As a result of the Inventor License Agreement, we now hold exclusive global rights to the pharmaceutical product that forms the basis of our EB01 and EB02 drug candidates for all fields of use in humans and animals.

As a result of the Inventor License Agreement, we now hold exclusive global rights to the pharmaceutical product that forms the basis of EB01 for all fields of use in humans and animals.

We are required to use commercially reasonable efforts to develop and commercialize the product in accordance with the terms of a development plan established by the parties.

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We face competition from companies developing and commercializing products that will be competitive with our drug candidates, including large pharmaceutical and smaller biotechnology companies, many of which have greater financial and commercial resources than we do.

For our EB01 and EB02 product candidates, our potential competitors include, among others, Aclaris Therapeutics, Inc., Citius Pharmaceuticals Inc., Dermavant Sciences, Inc., Fresh Tracks Therapeutics, Inc.

(formerly Brickell), Incyte Corporation, Leo Pharma A/S, Pfizer Inc., Sanofi S.A., and Sun Pharmaceutical Industries Ltd.

For our EB05 product candidate, there are numerous competing therapies, including prophylactic vaccines for the SARS-Cov2 virus, experimental stem cell therapies, novel therapeutics and repurposed commercial drugs.

For our EB01 product candidate, our potential competitors include, among others, Aclaris Therapeutics, Inc., Dermavant Sciences, Inc., Incyte Corporation, Leo Pharma A/S, Pfizer Inc., Sanofi S.A., Astria Therapeutics, Inc.

and Sun Pharmaceutical Industries Ltd.

For our EB05 product candidate, there are numerous competing therapies, including prophylactic vaccines for the SARS-Cov2 and influenza viruses, experimental stem cell therapies, novel therapeutics and repurposed commercial drugs.

Our potential competitors include, among others:

Aqualung Therapeutics Corporation, Eli Lilly and Company, Enzychem Lifesciences Corp., Merck & Co, Inc., Mesoblast Limited, Pfizer Inc., Regeneron Pharmaceuticals, Inc., Roche Holding AG and Veru Inc.

Aqualung Therapeutics Corporation, Eli Lilly and Company, InflaRx N.V., Enzychem Lifesciences Corp., Merck & Co, Inc., Mesoblast Limited, Pfizer Inc., Regeneron Pharmaceuticals, Inc., Roche Holding AG and Veru Inc.

For any future product for vitiligo or fibrotic diseases, potential competitors, include, among others:

Bausch Health, Eli Lilly and Company, Galderma Laboratories, LP, Incyte Corporation, Boehringer Ingelheim AG, Chemomab Therapeutics Ltd., F.

Hoffmann-La Roche AG, GlaxoSmithKline plc., Leo Pharma A/S, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, and Sanofi S.A.

Bausch Health, Eli Lilly and Company, Incyte Corporation, Boehringer Ingelheim AG, UCB, Chemomab Therapeutics Ltd., F.

Hoffmann-La Roche AG, GlaxoSmithKline plc., Leo Pharma A/S, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Vyne Therapeutics Inc, and Sanofi S.A.

Some of the competing product development programs may be based on scientific approaches that are similar to our approach, and others may be based on entirely different approaches.

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a 4-year exclusivity period from the date of first licensure of the reference product, during which a 351(k) application referencing that product may not be submitted;

An exclusivity period for certain biological products that have been approved through the 351(k) pathway as interchangeable biosimilars.

and, an exclusivity period for certain biological products that have been approved through the 351(k) pathway as interchangeable biosimilars.

The BPCIA also establishes procedures for identifying and resolving patent disputes involving applications submitted under section 351(k) of the PHSA.

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As of the date of this filing, we have 16 full-time employees:

ten employees are primarily engaged in research and development, and six employees are engaged in management, administration, business development and finance.

nine employees are primarily engaged in research and development, and seven employees are engaged in management, administration, business development and finance.

All employees are located in Canada or the U.S.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business