Q1 EPS: Novel Muscarinic with De-Risking Schizophrenia Data by Early Q3

Research evidence excerpt

Q1 EPS: Novel Muscarinic with De-Risking Schizophrenia Data by Early Q3

mg QD or pbo, evaluating Week

5 PANSS (primary endpoint). (2) Each arm is conservatively >90% powered to detect an effect size

(over pbo) at a discount to BMY's xanomeline (M1/M4)+trospium (approved as Cobenfy in 2024),

which showed absolute PANSS benefits of -20-21 (vs -11-12 pbo) in Phase III (EMERGENT-2/3), or a

-8-10 pbo-adj delta. (3) MPLT's base case is to show (a) competitive efficacy plus, (b) better safety/

tolerability (at least for BID dosing) and (c) better ease-of-use. We think QD dosing with similar

efficacy/safety to Cobenfy (BID) is upside. Arguably, each of the 3 attributes is interconnected,

since improving tolerability/compliance can lead to fewer discontinuations, enhancing efficacy (a

positive feedback loop). (4) On efficacy, MPLT's stronger M1/M4 agonism could benefit all SCZ

domains, including negative symptoms. That said, Cobenfy's prior Phase II/IIIs may have benefited

from functional unblinding (due to high rates of vomiting/nausea/GI AEs) and expectation bias (M1/

M4 MOA was quite novel at the time), widening its pbo-adj efficacy.

Also by mid-Aug, ML-004 (oral 5-HT1B/1D) has 12-week Phase II ASD data (IRIS; N=161).

(1) Roughly N=60 adults and N=100 adolescents are taking flexible doses (48-72mg target)

or pbo, assessing the ABI-SC social communication scale (licensed from JNJ). Secondary

endpoints include ABC-I irritability, which was the approval basis for antipsychotics. (2) Social

communication deficits are a larger market (though the regulatory pathway is higher risk), whereas

irritability is a smaller market (but still meaningful), but the pathway is established. Mgmt has

optionality. (3) The last patient visit completed in May. Andrew Tsai * | Equity Analyst