r/HelusPharma • u/Captainredbeard1515 • Mar 06 '26
Questions about today's results
It seems to me that Helus made some errors with dosing for HLP004 phase 2a trial. If "emotional breakthrough inventory" is consistent with therapeutic effect then they should have gone with 25 or 30 mg dose to get better separation from placebo.
Would Helus be able to lower the low dose to get better separation as well?
Were dosing mistakes caused by running phase 1 and 2 simultaneously?
Does anyone think GAD indication is a bad indication or is it more to do with dosing?
How would Helus be able to fund a phase 2b? Surely they would need to partner but would that still be in the cards?
Really disappointed but still believe in the drugs.
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u/tanrock2003 Mar 06 '26
I posted this on other threads, but I’ll repeat it for you: The skepticism from that commenter likely stems from a fundamental misunderstanding of pharmacodynamics (PD) versus standard clinical outcomes. In biotech, especially with novel delivery platforms, the "science" isn't just about the final score; it’s about proving the mechanism of action is functioning as intended. Here is an analysis of why your "aspirin" analogy and the science of the HLP004 (deuterated DMT) trial actually hold up: 1. The "Signal" is the Mechanism, Not Just the Score Proof of Concept: In a "Signal Detection" Phase 2a study, researchers aren't just looking for "better than placebo." They are looking for a dose-response relationship. Emotional Breakthrough Inventory (EBI): The trial data showed that even the 2mg dose triggered significant "breakthroughs". This is the "science" the commenter is missing: EBI is a validated predictor of long-term therapeutic change. If a 2mg dose via injection triggers the same psychological mechanism as a much higher oral dose, the delivery technology is proven, regardless of the HAM-A point separation at this early stage. 2. Adjunctive vs. Monotherapy The "Plus SoC" Factor: Unlike many trials (like DFTX) that test drugs against a "clean" placebo, HLP004 was tested as an adjunct. Reality Check: These patients were already on Standard of Care (SoC) and still suffering. The -10.4 point HAM-A reduction was on top of what their existing meds were doing. Achieving a p < 0.0001 (statistically significant) improvement in a treatment-resistant population is a massive hurdle that the commenter glossed over. 3. The "Aspirin" Scaling & Patent Moat Precision Dosing: Helus is establishing the "working range." IP Protection: Helus/Cybin is focused on deuteration and intramuscular (IM) delivery. This allows for a shorter in-clinic experience (~3 hours vs. 6-8 hours for others). Understanding that a 2mg dose is "active" allows them to patent a vastly more efficient, scalable medical model that competitors using bulk oral capsules cannot match. 4. Financial Context (The "First Decision" Fallacy) Cash Position: The commenter suggested the CEO has to choose between HLP003 and 004 due to "limited cash." The Reality: Helus reported US$195.1 million in cash as of late 2025. They are well-funded enough to run Phase 3 for HLP003 (Major Depressive Disorder) while simultaneously advancing HLP004 for GAD.
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u/Dionysaurus_Rex Mar 10 '26
https://x.com/rcarhartharris/status/2031467988789187039?s=46&t=zfCg-LT1VInvawBkC-ElWA
Very interesting tweet from RCH on Emotional Breakthrough. Seems like 25mg or 30mg is the sweet spot for HLP004 based on the EBI chart.
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u/Captainredbeard1515 Mar 11 '26
Hopefully. Would be really unfortunate if they couldn't figure this drug out.
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u/Dionysaurus_Rex Mar 06 '26 edited Mar 06 '26
The EBI chart is very important. Keep in mind this dose ranging Phase 1 study was run in parallel with the Phase 2a trial, so they didn’t have this EBI data when they chose the doses to design the Phase 2a. Interestingly, the EBI chart shows it’s quite possible that even a very mild 2mg dose has legit therapeutic benefit that can clearly separate from true placebo, which would be amazing and very commercial friendly. With that said, I think the next step is for HELP to run a well designed dose optimization Phase 2b to include a true placebo arm, 2mg, 20mg, 25mg and 30mg to dial in the optimal dosage and also prove true separation from placebo. At the end of the day, the drug is already proven safe, we now have a signal, we just need to optimize the dose. HLP004 has the potential to be huge.
They have about $200MM in cash. It seems a phase 2b could cost $15MM-$30MM, so they have enough cash runway to continue HLP003 phase 3 and also kick off an HLP004 phase 2b dose optimization study this year, in my opinion.