Helus Pharma Investor Presentation - HELUS PHARMA INC

Explicit Guidance:

• No financial guidance provided (revenue, EPS, capex, etc.) as the company is a pre-revenue clinical-stage biopharmaceutical.
• HLP-003 (Deuterated Psilocin): Top-line data from the Phase 3 APPROACH study expected "later this quarter" (relative to the Oct 21, 2026 presentation date).
• HLP-004 (Deuterated DMT): Next clinical study (Phase 2 for GAD) expected to initiate in the first quarter of 2027.
• HLP-005: Lead candidate expected to be advanced to clinical development in the second half of 2027.
• Patent Protection: Expected to extend into the early 2040s for HLP-003 and HLP-004.

Business-Segment Outlook:

• HLP-003 (MDD Adjunctive): Positioned as the sole late-stage program for adjunctive MDD. Phase 3 design includes two short-term pivotal studies (APPROACH, EMBRACE) and a long-term extension (EXTEND) to evaluate durability and re-dosing frequency.
• HLP-004 (GAD Monotherapy): Developing as a monotherapy for Generalized Anxiety Disorder (GAD) due to limited existing options (4 approved vs. 25+ for MDD). Selected 30mg intramuscular dose based on Phase 1/2 signal-finding.
• Pipeline Expansion: HLP-005 library offers potential for future candidates, with the lead advancing in late 2027.
• Market Entry Strategy: Plans to leverage existing "interventional psychiatry" infrastructure (TMS/Ketamine sites) to move treatment "upstream" (earlier in the disease trajectory) rather than waiting for treatment-resistant depression.

Market and Competitive Outlook:

• Competitive Landscape (MDD): Differentiation from the 5 currently approved adjunctive therapies (all atypical antipsychotics) which suffer from poor tolerability (weight gain, metabolic issues, tardive dyskinesia) and low adherence (<1 in 6 patients elect to take them).
• Efficacy Expectations: Targeting a 4–5 point placebo-adjusted improvement on MADRS (comparable to best-in-class antipsychotics) but with a superior safety/tolerability profile (transitory side effects vs. chronic metabolic risks).
• Competitive Landscape (GAD): Only ~6 FDA-approved treatments exist for GAD, with limited innovation in two decades.
• Treatment Paradigm Shift: Management anticipates a shift where patients enter the "interventional psychiatry" portal directly after failing first-line therapy, rather than undergoing a long "odyssey" of ineffective trials before accessing interventional care.
• Peer Activity: Views peer approvals (e.g., J&J/Spravato) as positive for building class infrastructure and patient awareness, positioning Helus as a "fast follower" in the adjunctive MDD space.

Macro / Industry Outlook:

• Unmet Need: Management highlights a "crippling" unmet need with 22M MDD patients in the US and 20M GAD patients, where 2/3 of MDD patients fail to remit on first-line antidepressants.
• Systemic Impact: Anticipates that effective, intermittent dosing could reduce the progression to treatment-resistant depression (TRD) and lower long-term healthcare costs associated with chronic disability.
• Regulatory Environment: Acknowledges the need for rescheduling (state/federal) for psychedelic class drugs but views the current FDA Breakthrough Therapy Designation for HLP-003 as a facilitator of the NDA process.
• Payer Dynamics: Expects payer discussions to focus on durability of effect, safety profile, and the fact that patients have already failed one prior therapy, justifying the adjunctive step.

Strategic Initiatives:

• Phase 3 Execution: Utilizing independent MGH Safer interviews and centralized blinded raters to ensure patient quality and minimize placebo response (expected 1–5 points based on recent class data).
• Operational Scaling: Interventional clinics reported hiring staff and expanding space specifically to accommodate the arrival of novel serotonergic agonists.
• Dosage Strategy: Moving toward intermittent dosing (2 doses 3 weeks apart) with potential for re-dosing in the EXTEND trial (up to 3 additional doses), challenging the need for daily maintenance therapies.
• Commercial Preparation: Focusing on medical education for community psychiatrists to drive referrals to interventional centers, leveraging the existing workforce trained in ketamine/TMS.

Risks and Headwinds to Outlook:

• Safety Signals: Potential for adverse events of suicidality (monitored by independent data monitoring committees); however, management notes these are features of MDD and not necessarily drug-induced.
• Execution Risk: Risk of "professional patients" in trials; mitigated by strict screening and duplicate registry checks.
• Placebo Response: While managed well in the class (1–5 points), variability remains a challenge in depression trials.
• Dosing Adherence: Potential for "familiarity breeding contempt" or tachyphylaxis with repeated sessions, though data suggests prior response predicts future response.
• Contraindications: Patients on atypical antipsychotics (a common adjunct) cannot be co-administered with HLP-003 due to blocking effects; these patients would need to switch off antipsychotics before treatment.
• Reimbursement: Uncertainty regarding payer step-edit rules (prior authorization) for adjunctive therapy vs. monotherapy status.

Management Tone on the Future:

• High Confidence: Management expresses strong conviction in the "differentiated" nature of deuterated compounds (higher bioavailability, lower dose load) and the "clear opportunity" in the adjunctive space.
• Urgency: Emphasizes the "desperation" of the current market and the "palpable frustration" among clinicians and patients with current antipsychotic options.
• Optimistic Outlook: Views the upcoming Phase 3 data as a critical inflection point that will validate the "game-changer" potential for interventional psychiatry.
• Strategic Clarity: Clear stance on avoiding "treatment-resistant" pathways and aiming for earlier intervention to prevent the "cancerous" progression of depression.

Miscellaneous:

• Date of Forward-Looking Statements: October 21, 2026.
• Study Designs: HLP-003 Phase 3 involves 223 participants in APPROACH (16mg dose); HLP-004 Phase 2 will enroll 144 participants (30mg dose).
• Clinical Endpoints: HLP-003 primary endpoint is MADRS change at 6 weeks; HLP-004 primary endpoint is HAM-A change at 6 weeks.
• Regulatory Path: HLP-003 holds Breakthrough Therapy Designation; HLP-004 has completed Phase 1/2 signal-finding and is moving to Phase 2.