Definium Therapeutics, Inc. Q2 FY2024 earnings call

• Successfully completed an End-of-Phase 2 meeting with the FDA for MM120 in GAD, on track to initiate Phase 3 in GAD in 2024.
• Plan to expand MM120 R&D to MDD with initiation of Emerge Study (Phase 3 registrational trial) in first half of 2025 and a second MDD study informed by Emerge.
• Completed a $75M underwritten public offering, extending cash runway into 2027.
• Phase 2b trial for MM120 in GAD showed significant efficacy, including over double the effect size of standard care and 48% remission rate at 12 weeks.
• MM120 has potential in large unmet markets for GAD and MDD in the US.
• Phase 3 trials for MM120 in GAD (Voyage, Panorama) and MDD (Emerge) designed with specific parts A and B for efficacy, safety, and long-term data collection.

As of June 30, 2024, MindMed had cash and cash equivalents totaling $243.1 million. For the quarter ended June 30, 2024, research and development expenses were $14.7 million, general and administrative expenses were $9.8 million, and the net loss was $5.9 million. The company's R&D expenses showed a decrease in MM120 GAD program and preclinical activities but an increase in MM402 program and internal personnel costs. Revenue contribution details were not applicable as the focus was on clinical programs rather than product segment revenue breakdown.

• Anticipate initiating Phase 3 trial for MM120 in GAD in second half of 2024 and Phase 3 in MDD (Emerge) in first half of 2025.
• Project top line Part A readouts for pivotal trials starting with Voyage in first half of 2026, followed by Panorama and Emerge in second half of 2026.
• Cash runway expected to support operations at least 12 months beyond first Phase 3 readout in GAD, extending into 2027.

• Changes in market conditions that could impact commercialization.
• Difficulties associated with research and development, including uncertainties in clinical trial outcomes.
• Regulatory approval processes challenges that could delay or prevent product launch.
• Uncertainties related to the interpretation of data and potential regulatory scrutiny on issues like expectancy bias and functional unblinding in clinical trials.

Q: Is the open label 100 microgram dose to help maintain response or remission rates versus having patients continue the 50 microgram dose in the 40 week follow-up? And for reduction of the treatment session duration to 8 hours from 12 hours, what information enabled this decision to be agreed by the FDA and what requirements for patient care following the 8 hour treatment session, what requirements will be implemented?

A: Daniel Karlin responded that the selection of 100 micrograms is due to it being the clinical dose of interest based on Phase 2b results. The 50 microgram control is for functional masking. For the treatment session duration, data was presented showing a time course of assessments to characterize when patients could be released, leading to the decision to reduce monitoring to 8 hours with structured criteria for readiness to depart as early as hour 5.

Q: Can you elaborate on the degree of follow-up and retreatment data that is going to be required prior to filing and potential approval in GAD. Is there a bar for the durability that you need to demonstrate beyond 12 weeks and/or a certain proportion of patients who will need to be retreated?

A: Robert Barrow stated that the expectation is that a 12 week duration is sufficient to demonstrate durability as per FDA guidance, and the extension phase will inform retreatment dynamics but the primary endpoint is the 12 week change from baseline.

Q: How much dose dependence will you need to demonstrate between 50 and 100 micrograms in order to address the potential regulatory questions about functional unblinding, do you need to show a statistical separation between those two arms or just a trend?

A: Robert Barrow explained that the 50 microgram dose is included as a functional mask to address expectancy bias, not for statistical comparison of efficacy. The 100 microgram dose is the go-forward dose based on Phase 2 results, and the 50 microgram arm is not intended for clinical use but as a control.

Q: Regarding the End-of-Phase 2 meeting, especially considering the Lykos AdCom, whether there were any issues or concerns that were raised during the meeting? And was there any surprises during the meeting?

A: Robert Barrow said the meeting was constructive with no surprises, and they were able to integrate feedback from the Lykos AdCom into discussions with the FDA, leading to a clear path forward.

Q: In terms of MM120, have you started at all analyzing ex-U.S. opportunities? And if so, how would you characterize that analysis?

A: Robert Barrow stated that they have started analyzing ex-U.S. markets but currently focus on the US, with openness to collaborations for commercialization in ex-U.S. markets but lower priority compared to the US.

Q: Do you have any specific targets for prior use of LSD or other psychedelic inclusion criteria in your Phase 3 trials? And in the open-label portions of your studies, how do you ensure integrity is maintained to make sure that any potential durability of effect is more purely attributable to MM120 versus other treatments or therapy?

A: Daniel Karlin responded that there are explicit exclusion criteria for recent or heavy psychedelic use. For data integrity, the extension phase is run similarly to the blinded phase, with restrictions on outside therapy and ensuring that the only pharmacological treatment in the extension phase is MM120.