Helus Pharma Redesigns Its Anxiety Study as Pivotal Depression Data Approach

Helus Pharma’s October 21 update changes the development strategy for its anxiety medicine, HLP004. A larger Phase 2 study will evaluate two 30 mg administrations as a standalone drug treatment, or monotherapy, against inactive placebo. The earlier study used 20 mg alongside existing medication and compared it with a low active dose. The next trial will therefore assess a different regimen in a different treatment setting.

Helus’s nearer investment catalyst remains HLP003, a separate depression medicine whose first pivotal Phase 3 results are expected in the fourth quarter of 2026. Those results will influence both the credibility of its lead asset and its position when seeking capital for the remaining development program.

Two medicines with different treatment roles

Helus Pharma, formerly Cybin and now trading on Nasdaq as HELP, develops investigational medicines derived from psychedelic compounds. HLP003 is an oral analog of psilocin for major depressive disorder, a condition involving persistent depressed mood or loss of interest that impairs daily functioning. HLP004 is an analog of dimethyltryptamine, or DMT, injected into a muscle for generalized anxiety disorder, characterized by persistent, excessive worry and associated physical symptoms.

Both compounds are deuterated: selected hydrogen atoms are replaced with a heavier form of hydrogen to modify how the body processes the medicine. They act on serotonin receptors involved in perception and mood. Helus is investigating whether a limited number of supervised administrations can produce relief that lasts beyond the acute drug experience; neither candidate has marketing approval.

Their intended roles now diverge. HLP003 is being developed as an additional treatment for people whose existing antidepressant has provided insufficient benefit. Patients continue that background medicine. HLP004’s next study will examine its ability to treat anxiety without being positioned as an add-on to another drug.

HLP004’s new comparator addresses an unresolved efficacy question

The completed anxiety study randomized only 36 participants: 25 received 20 mg HLP004 and 11 received 2 mg. Participants remained on background antidepressant or anxiety medication. In the March 2026 results presentation, Helus reported that both dose groups experienced subjective drug effects and improved on anxiety measures.

The 20 mg group’s Hamilton Anxiety Rating Scale, or HAM-A, score fell by 10.4 points from baseline at six weeks. HAM-A is a clinician-rated measure of anxiety severity, with lower scores indicating fewer symptoms. That reduction describes improvement within the treated group. Because the comparison group also received active drug, the study did not establish the benefit over an inactive placebo, including the contribution of expectations and the treatment setting. Reported adverse events were mild or moderate, with no serious events, although the higher planned dose requires further safety evaluation.

Management’s October 21 presentation explained the basis for choosing 30 mg. In Phase 1 dose-ranging work, that dose produced the highest intensity of subjective effects and questionnaire scores describing emotional insights during the drug experience. Management also cited an association between those scores and anxiety improvement in the earlier patient study. These findings informed dose selection; they do not establish that 30 mg delivers greater clinical benefit than 20 mg in patients with generalized anxiety disorder.

Monotherapy examines whether HLP004 can treat anxiety without being added to another medicine. An inactive placebo allows assessment of the selected regimen against a treatment containing no active drug, while the larger sample can improve the precision of the estimate. Recognizable psychedelic effects may still allow participants to infer their allocation and influence reported symptoms. With the dose and treatment setting also changing, the earlier 10.4-point improvement cannot be carried forward as an expected result.

Management attributes the monotherapy decision to unmet need and limitations of existing anxiety treatments. In its presentation, Helus also said the design could facilitate recruitment and detection of a clinical effect. Success could support a standalone treatment option, but the study must establish efficacy and tolerability for that use. Initiation is planned for the first quarter of 2027; the announcement gives no date for results.

HLP003 supplies the nearer clinical catalyst

HLP003 is further advanced. APPROACH has enrolled 223 participants with depression who responded inadequately to an antidepressant. It compares two 16 mg doses, three weeks apart, with inactive placebo while patients continue their antidepressant. The primary assessment is the difference between groups in change in Montgomery–Åsberg Depression Rating Scale, or MADRS, score at six weeks; a 12-week assessment examines persistence of benefit. MADRS is a clinician-rated depression scale on which lower scores indicate less severe symptoms.

Earlier results explain the interest, but their scale requires care. The original Phase 1/2a poster reports a roughly 13-point advantage over placebo at day 21 after one 16 mg dose, comparing nine recipients with nine placebo participants pooled across study cohorts. Separately, the much-publicized 71% remission rate at 12 months represented five of seven participants who received two 16 mg doses and completed that follow-up, according to the original November 2024 disclosure. That long-term observation had no concurrent untreated comparison.

APPROACH therefore offers a much larger controlled assessment of whether the early signal persists across more patients and sites. The size and precision of the placebo-adjusted benefit, persistence at 12 weeks and adverse-event profile will carry more weight than reproducing an unusually high percentage from seven people.

A positive APPROACH result would still leave the second pivotal study, EMBRACE, and longer-term work in EXTEND. The latter examines durability and additional dosing when needed, which will help determine how often patients must return for treatment. Helus continues to target an FDA application in 2028. Its Breakthrough Therapy designation supports development discussions with the regulator; it does not provide marketing authorization.

The treatment setting is part of the commercial proposition

HLP003 would enter a treatment setting already served by oral add-on medicines, including atypical antipsychotics. In its October 21 presentation, management positioned HLP003 as a potential alternative offering lasting additional benefit from infrequent administrations. This approach would retain the patient’s background antidepressant while seeking to improve symptoms without adding a second daily medicine. It would also require supervised clinic visits, making the duration of relief and retreatment frequency central to the commercial proposition.

These programs involve more than supplying a prescription. Helus uses its EMBARK psychological-support framework around supervised administration. Monotherapy describes HLP004’s pharmaceutical role; it does not imply an unsupervised injection or absence of supportive care.

Treatment duration affects the number of patients a clinic can accommodate, staff requirements and the burden on patients. Helus reported acute HLP004 effects lasting approximately 90 minutes and discharge readiness within about three hours in a Phase 1 study at 30 mg. Those observations, identified in its regulatory filing, support the proposed delivery model but do not establish the full care requirement for patients with anxiety.

Safety monitoring also occupies time. A September HLP003 safety poster, covering a small earlier-study cohort, reported temporary increases in blood pressure and pulse. Larger studies must characterize that profile alongside psychiatric adverse events.

If benefits last for months, infrequent dosing could make a resource-intensive visit worthwhile. More frequent retreatment would increase service costs and capacity requirements. Commercial uptake would also depend on access to clinics and reimbursement for both the medicine and accompanying care. Drug pricing and those care arrangements have not been established.

Cash grew through financing as clinical spending increased

Helus reported $166.4 million of cash at June 30, 2026, up from $157.3 million at March 31. Its cash-flow statement records $46.5 million of net common-share issuance proceeds, which more than offset cash consumed by operations and smaller investing and currency outflows.

Operating cash use rose from $29.5 million in the comparable prior-year quarter to $37.1 million. Helus’s August results presentation linked higher spending to progress across APPROACH, EMBRACE and EXTEND.

The June-quarter management discussion estimated $14.1 million of remaining APPROACH spending from June 30 to its readout. That amount covered the first pivotal study’s milestone, while EMBRACE, EXTEND, the new HLP004 study and corporate operations require further expenditure. Helus has not disclosed a complete budget for the new anxiety trial or committed funding through the planned 2028 depression application.

June’s $50 million gross offering issued 10.3 million shares and was already reflected in the closing cash balance. Separately, the subsequent-events disclosure records 7.9 million shares issued upon vesting of restricted share units on July 1, without raising cash. AER calculates that the July issuance equalled approximately 13% of the 62.0 million common shares outstanding at June 30, as reported in the share-capital disclosure.

HLP004’s next study can establish whether its selected 30 mg regimen provides an anxiety benefit beyond inactive placebo in the standalone setting. The nearer shareholder outcome depends on HLP003’s Q4 readout. A clinically meaningful depression benefit that persists to 12 weeks with manageable adverse events would strengthen the case for supervised treatment and further investment in the program. A weak or short-lived benefit would reduce that commercial proposition while the remaining trials continue to consume cash.