On 22 June, Definium Therapeutics, the company that was MindMed until it rebranded in January, reported positive topline results from Emerge, a Phase 3 trial of DT120, a 100µg orally disintegrating tablet of lysergide (LSD) tartrate, in major depressive disorder. The headline is enormous: an 8.1-point placebo-adjusted reduction on the MADRS at Week 6 (p<0.0001), with a 14.2-point separation as early as Week 1 and 7.3 points still standing at Week 12. For scale, the two Compass COMP360 psilocybin pivotals we covered last week hit the same Week-6 MADRS endpoint at −3.6 and −3.8, the numbers the field has been calling a clinically modest win. Emerge is roughly double that: the largest placebo-adjusted MADRS effect any psychedelic Phase 3 has reported so far, with COMP360 in TRD as the benchmark it's measured against.

Before anyone in Europe reads it as LSD lapping psilocybin, two things: first, the populations differ: Emerge enrolled MDD, a broader and less refractory group than Compass's treatment-resistant depression, where effect sizes run structurally smaller. You cannot net the two numbers across populations, and we won't. Second, and this is the part that matters for a franchise built on last week's EPIsoDE post, Emerge was a two-arm trial: 100µg versus an inert placebo ODT, 149 patients across 20 US sites, no low-dose comparator. (Emerge is US-only; the European stakes here run entirely through Panorama, below.) EPIsoDE missed precisely because an active placebo and tight blinding stripped out the expectancy effect. Emerge did the opposite. And the number's shape, 14.2 at Week 1 decaying to 8.1 by Week 6 to 7.3 by Week 12, is the functional-unblinding signature you'd flag in anyone else's data: biggest when patients most know what they took, fading as the acute experience recedes.

The tell is in Definium's own protocols. Its GAD Phase 3 program and its second MDD pivotal, Ascend, both add a 50µg low-dose arm built, in the company's words, to confound participants' ability to guess their assignment. Emerge, the one that just read out, did not. So the European question isn't whether LSD "works." It's whether this effect survives the blinding the sponsor itself thinks is necessary. That test arrives later this year, when the GAD trials read out. One of them, Panorama, carries European sites and the 50µg arm built in.

Definium Therapeutics is MindMed. Mind Medicine (MindMed) Inc. changed its corporate name to Definium Therapeutics, Inc. on 9 January 2026, in an 8-K dated 12 January. It kept the same SEC registrant (CIK 1813814), and its shares have traded as DFTX since mid-January. The lead asset is one molecule under two names: ClinicalTrials.gov still lists it as MM120, while the company's IR materials now call it DT120 ODT. Same lysergide d-tartrate, same single-dose-with-monitoring model, new wrapper. The late-stage pipeline is now an LSD armada: Emerge and Ascend in MDD, Voyage and Panorama in GAD, all Phase 3. Of those, Panorama is the one this newsletter watches most closely: it is the only one carrying European trial sites, and it adds the 50µg low-dose arm.

Basel completes a Phase 1 co-administering MDMA with psilocybin. University Hospital Basel's Liechti group has marked complete a Phase 1 study on the acute effects of giving MDMA alongside psilocybin in healthy subjects. No results yet, but the question, whether co-dosing softens psilocybin's harder edges without dulling the antidepressant mechanism, is exactly the kind of pharmacology the commercial programs are too busy running pivotals to ask. Swiss academic groups keep doing the field's mechanistic homework.

Norway opens a trial of ketamine for depression that travels with alcohol use disorder. The University Hospital of North Norway is recruiting a 34-patient Phase 1/2 study testing ketamine on top of standard inpatient addiction therapy in adults who have both major depression and alcohol use disorder. Comorbid depression and AUD is one of the harder populations to treat, and one the registries rarely target head-on. Running it inside an addiction ward, where these patients actually present, is the useful part.

AtaiBeckley's BPL-003 still has no Phase 3 on the registry as Q2 closes. With this issue publishing on the last day of Q2, ClinicalTrials.gov carries no Phase 3 record for BPL-003 in TRD, only Phase 1 and Phase 2, and AtaiBeckley's guidance still reads "initiation on track for Q2 2026." Initiation language to the wire, dosing not yet in evidence (see The Call).

149. The patients randomized in Emerge, the Phase 3 behind the largest placebo-adjusted MADRS effect a psychedelic trial has reported so far: 75 to DT120, 74 to placebo, across 20 sites. What it reveals: that headline rests on about 75 dosed patients in a single two-arm, inert-placebo comparison, a fraction of the roughly 250 to 570 in Compass's TRD pivotals. A genuinely large effect needs fewer patients to clear significance, so a lean trial isn't damning on its own. But lean and singly-controlled is also where expectancy effects are least constrained, which is the whole question hanging over the readout.

EU CTR / EMA. A positive LSD Phase 3 in MDD raises the obvious question of the European filing path. But Definium has disclosed no EMA scientific advice or EU submission for DT120. Its European exposure so far is trial sites (Panorama), not a regulatory dossier. Reported as "nothing disclosed," not "nothing happening": we still have no working EMA feed.

Germany / BfArM. The psilocybin compassionate-use pathway is still pending a primary source beyond secondary reporting. Carried from Issue 3, not yet confirmed.

UK / MHRA. No new motion this week. Compass's COMP360 ILAP designation stands (context, not news).

One falsifiable prediction per issue. Scored in the next one.

Scoring Issue 2. Last issue I called it: AtaiBeckley will not announce its first BPL-003 Phase 3 patient dosed before 30 June 2026, and I said in print I'd mark myself wrong if a dosed-patient release landed. It didn't. There is no BPL-003 Phase 3 first-patient-dosed announcement, and still no Phase 3 record on ClinicalTrials.gov. Guidance remains "initiation on track for Q2 2026": initiation, not dosing. One trap to disarm, because a careful reader will hit it: AtaiBeckley has talked about a "first patient dosed," but that's the Phase 2a Part 4 cohort testing a two-dose induction regimen, not Phase 3. Phase 2a Part 4 is not Phase 3 initiation, and neither is on the registry as a Phase 3 trial. Checked again the morning this publishes (30 June): no dosed-patient release, and ClinicalTrials.gov still carries only Phase 1 and Phase 2 BPL-003 records, no Phase 3. Scored: hit.

This week's call. Panorama will show a smaller placebo-adjusted effect than its sister trial Voyage. Both are Definium's Phase 3 GAD studies, both DT120 100µg, both scored on the same scale (HAM-A at Week 12). Both are already fully enrolled and dosing: the registry lists each as active and no longer recruiting, with topline guided for 2026 (Voyage first, Panorama behind it). The only structural difference: Panorama adds a 50µg low-dose arm built to stop patients guessing their assignment, and Voyage doesn't. My thesis says that arm will visibly compress the signal. If the trial with the unblinding control posts the bigger effect, I'm wrong, and these numbers are more drug than expectancy than I've been giving them credit for. Resolve: once both the Voyage and Panorama toplines are public. Both are fully enrolled with readouts guided for 2026, so I expect to score this by year-end. If a readout slips into 2027, the call stays open until it reports. Falsifiable and a direct test of the lead.

If something here is wrong, tell me and I'll correct it openly.

Thank you so much for reading.

Dhruv

Sources

Definium Therapeutics, positive topline Phase 3 Emerge results for DT120 ODT in MDD, 22 June 2026: https://www.businesswire.com/news/home/20260622572802/en/
Emerge registry record (NCT06941844): https://clinicaltrials.gov/study/NCT06941844
Definium Therapeutics, Inc., formerly Mind Medicine (MindMed) Inc., renamed 9 January 2026, SEC EDGAR registrant CIK 1813814: https://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=1813814&type=8-K
Voyage, Phase 3 GAD (NCT06741228): https://clinicaltrials.gov/study/NCT06741228
Panorama, Phase 3 GAD (NCT06809595): https://clinicaltrials.gov/study/NCT06809595
Compass Pathways, COMP360 psilocybin Phase 3 in TRD, COMP005 −3.6 and COMP006 −3.8 MADRS at Week 6: https://ir.compasspathways.com/News--Events-/news/news-details/2026/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-Second-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx
University Hospital Basel, Phase 1 MDMA with psilocybin (NCT06884514): https://clinicaltrials.gov/study/NCT06884514
University Hospital of North Norway, ketamine for comorbid depression and AUD, Phase 1/2 (NCT06090422): https://clinicaltrials.gov/study/NCT06090422
AtaiBeckley Inc., news releases, no BPL-003 Phase 3 record: https://ir.ataibeckley.com/news-releases