Helus Pharma Investor Presentation - HELUS PHARMA INC

Financial Performance:

• No specific revenue, earnings, or cash flow figures disclosed as the company remains in clinical development; focus is on asset value and pipeline potential.
• Extensive R&D expenditures implied by the execution of Phase 3 trials (APPROACH, EMBRACE) and preparation for New Drug Application (NDA) submission.
• Intellectual property portfolio provides a competitive moat with patent protection expected through the early 2040s for lead programs HLP-003 and HLP-004.
• No mention of debt or specific cash runway; capital allocation is directed toward clinical trial execution and regulatory preparation.

Guidance and Future Outlook:

• Top-line Data: Phase 3 APPROACH study results for HLP-003 expected later in the current quarter (Q4 2026).
• Pipeline Advancement: Phase 2 monotherapy study for HLP-004 (GAD) expected to initiate in Q1 2027.
• Future Candidates: Lead candidate from the HLP-005 preclinical library anticipated to advance in H2 2027.
• Long-term Goals: Aiming to disrupt the adjunctive treatment paradigm for Major Depressive Disorder (MDD) and address the unmet need in Generalized Anxiety Disorder (GAD).
• Regulatory Path: Preparing NDA submission including non-clinical, clinical pharmacology, and CMC packages for HLP-003.

Business Segments and Product Lines:

• HLP-003 (Deuterated Psilocin): Lead program; Phase 3 for adjunctive treatment of MDD. Differentiated by deuterium substitution increasing plasma exposure (1.5x higher concentration, 2.5x higher total exposure vs. psilocybin) and rapid onset. Phase 2 showed 13-14 point MADRS improvement vs. placebo with durable remission (70%) at one year.
• HLP-004 (Deuterated DMT): Phase 2 program for Generalized Anxiety Disorder (GAD) in a monotherapy setting. Selected 30mg intramuscular dose based on correlation with "emotional breakthrough" and MEQ scores.
• HLP-005: Preclinical library targeting pipeline expansion.
• Study Designs: HLP-003 studies (APPROACH/EMBRACE) utilize a two-dose, 3-week-apart regimen; HLP-004 will use a similar two-dose monotherapy design.

Market and Competitive Landscape:

• MDD Market: 22 million US adults with MDD; 2/3 fail first-line monotherapy. Current adjunctive options are limited to 5 atypical antipsychotics with poor tolerability (weight gain, metabolic issues, tardive dyskinesia) and low adherence (<1 in 6 patients).
• GAD Market: Over 300 million globally affected; limited innovation in 20+ years with only ~6 approved first-line options compared to 25+ for MDD.
• Differentiation: Helus positions HLP-003 as the only late-stage adjunctive program for MDD, aiming to offer superior tolerability and rapid efficacy compared to atypical antipsychotics.
• Interventional Psychiatry: Expected to shift treatment "upstream," moving away from late-stage TRD (Treatment-Resistant Depression) interventions to earlier use in the patient journey, leveraging existing TMS/Ketamine infrastructure.

Risks and Challenges:

• Placebo Response: Managing placebo effects in depression trials; historical data in the psychedelic class shows lower placebo response (1-5 points) compared to general depression trials.
• Safety & Tolerability: Monitoring for adverse events of special interest (AESI), including suicidality and cardiovascular effects, though HLP-003 Phase 2 showed mild/transitory side effects.
• Regulatory Path: Reliance on successful Phase 3 readout to secure FDA approval; complex rescheduling and REMS requirements for psychedelic therapies.
• Commercial Adoption: Overcoming stigma associated with psychedelics and ensuring payer coverage/reimbursement for adjunctive therapies; potential step-edit barriers with payers.
• Trial Execution: Mitigating "professional patient" enrollment risks through independent MGH Safer interviews and duplicate registries.

Management Commentary and Tone:

• Confidence: Highly confident in the data; management emphasizes the "differentiation" of deuterated molecules over native psychedelics regarding efficiency and safety.
• Patient-Centric: Strong emphasis on patient preference for non-psychotic adjuncts and the "unmet need" in current care models (frustration with switching medications).
• Tone: Optimistic and mission-driven, framing mental health treatment as a "journey" requiring rigor and tenacity.
• Strategic Focus: Clear pivot to adjunctive MDD and monotherapy GAD to capture specific market gaps ignored by competitors focused on monotherapy MDD or TRD.

Analyst Questions and Answers:

• Approval Thresholds: Management states comparable efficacy to best-in-class antipsychotics (4-5 point MADRS improvement), combined with durability and a favorable safety profile, is required for approval and commercial success.
• Suicidality: No assumption of zero cases; suicidality is a feature of MDD. Safety monitoring committees will review all events, but no trial halts occurred during APPROACH enrollment.
• Dosing Paradigm: Acknowledges "one-and-done" is unrealistic; phase 2 data showed durability out to one year, but re-dosing may be necessary.
• Placebo Effect: Management cites controlled placebo response in recent psychedelic trials (1-5 points) vs. standard depression trials (10-12 points), attributed to rigorous trial execution and independent raters.
• Reimbursement & Infrastructure: Payor discussions will focus on durability, reduced long-term costs of chronic medication failures, and the adjunctive nature of the therapy. Clinical infrastructure is expected to utilize existing interventional psychiatry networks.
• Standard of Care: Patients are typically on SSRIs/SNRIs; atypical antipsychotics are currently used alternatives but are contraindicated with psychedelic administration due to mechanism of action overlap.

Other Key Points:

• Deuterium Technology: The key differentiator; deuterated psilocin bypasses metabolic dephosphorylation, allowing higher brain concentrations with lower drug load compared to psilocybin.
• Clinical Trial Design: APPROACH study enrolled 223 patients across 45 US sites with a baseline MADRS of ~33, indicating moderate-to-severe depression.
• Panel Consensus: KOLs (McIntyre, Jan, Koo) unanimously agreed on the failure of current adjunctive options (antipsychotics) due to tolerability and efficacy limitations, highlighting a massive opportunity for a novel class.
• Operational Readiness: Clinical sites are already being expanded and staffed specifically for the anticipated arrival of novel serotonergic agonists.
• Forward-Looking Statement: All statements reflect expectations as of October 21, 2026, with no obligation to update.