Slides
Page 1
Corporate Presentation January 09, 2026
Page 2
This presentation and any accompanying oral commentary have been prepared by MapLight Therapeutics, Inc. (“MapLight”, “we,” “us,” “our,” the “Company”, or similar terms) for informational purposes only and not for any other purpose. This presentation contains trademarks, service marks, trade names and copyrights of MapLight and other companies which are the property of their respective owners. This presentation discusses product candidates that are under pre-clinical and clinical study, and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or efficacy of these product candidates for the uses for which they are being studied. Statements contained in this presentation and the accompanying oral commentary, other than statements of historical facts, may be forward-looking statements, including, but not limited to: statements about our expectations regarding the potential benefits, efficacy and safety of our product candidates and platform; our expectations with regard to the design and results of our research and development programs, preclinical studies, and clinical trials; our preclinical, clinical, and regulatory development plans for our product candidates; our expectations with regard to our ability to discover, develop, license, or acquire additional product candidates and advance such product candidates into, and successfully complete, preclinical studies and clinical trials; the potential patient populations for our product candidates and any future product candidates; our cash runway; and our business strategy. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “targets,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These statements involve substantial known and unknown risks, uncertainties and other factors that may cause our actual results, timing of results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include risks and uncertainties that are described in the “Risk Factors” section of our Quarterly Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (“SEC”) on December 4, 2025 and other filings we make with the SEC from time to time. These documents are available under the “SEC Filings” page of the “Investors” section of our website at www.maplightrx.com. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially and adversely from those anticipated or implied in the forward-looking statements. We may not actually achieve the plans, intentions, or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements in this presentation represent our views as of the date of this presentation. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. Except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements in this presentation and the accompanying oral commentary. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2 Safe Harbor and Forward-Looking Statements
Page 3
3 MapLight Therapeutics Working to Improve the Lives of Patients Suffering From Debilitating CNS Disorders ADP = Alzheimer’s disease psychosis; ASD = autism spectrum disorder; CNS = central nervous system. (1) Unaudited estimated cash and cash equivalents (including investments and accrued interest) as of December 31, 2025. • Novel M1/M4 muscarinic agonist in combination with a peripheral antagonist • Data supports potential differentiation on safety/tolerability, ease of use, and broad symptom improvement • Ongoing Phase 2 trials in schizophrenia and ADP - designed to be adequate and well-controlled Potential Best-in-Class Muscarinic Agonist • Founded by globally recognized leaders in neuropsychiatry to address lack of circuit- specific therapies • Discovery platform to identify and validate novel drug targets causally linked to disease symptoms • Diversified product pipeline with potential across several CNS disorders Circuit-Driven Discovery Engine • Phase 2 topline results for ML-007C-MA in schizophrenia and ML-004 in ASD expected in Q3 2026 • Strong financial position with ~$450M in cash and runway through 2027 (1) • Led by a team with CNS drug discovery and development expertise Positioned to Deliver on Key Milestones
Page 4
Advancing a Broad and Diversified Pipeline GPR = G-protein-coupled receptor. PAC = peripherally acting anti-cholinergic. PAM = positive allosteric modulator. 4 Leveraging our versatile circuit-based discovery platform for ongoing pipeline expansion Program Circuit Indications Preclinical Phase 1 Phase 2 Phase 3 Anticipated Milestones ML-007C-MA M1/M4 agonist co-formulated with PAC Direct and Indirect Pathways Schizophrenia Topline results in Q3 2026 Alzheimer’s Disease Psychosis Topline results in 2H 2027 ML-004 5-HT1B/1D agonist Dorsal Raphe to Nucleus Accumbens Autism Spectrum Disorder Topline results in Q3 2026 ML-021 M4 antagonist Direct Pathway Parkinson’s Disease Complete IND-enabling studies in 2H 2026 ML-009 GPR52 PAM Indirect Pathway Hyperactivity/Impulsivity Nominated preclinical candidate ZEPHYR VISTA IRIS Potential in other indications being explored
Page 5
ML-007C-MA Lead Asset in Development for Schizophrenia and ADP
Page 6
6 Muscarinic Receptor Agonism is the First Novel MoA Approved for Treatment of Schizophrenia in Decades AD = Alzheimer’s disease; EPS = extrapyramidal symptoms; DRP = dementia -related psychosis. (1) Siskind et al., Br J Psychiatry (2022); treatment resistant ≥2 treatments. Samara et al., Schizophrenia Bulletin (2019); response as measured within 4-6 weeks. (2) National Institute of Mental Health (NIMH). (3) Lieberman et al., NEJM (2005). CATIE trial; all-cause discontinuation. (4) Represents global sales estimates based on third -party market research sources, accessed November 2025. SOC Antipsychotics (Primarily D2 Receptor Blockade) Global sales for antipsychotics and muscarinic classes projected to exceed $20B by 2032 (4) Risk of serious long-term side effects × EPS, metabolic issues, weight gain, sedation × Boxed warning for increased mortality risk in elderly patients with DRP Avoids serious long-term side effects associated with D2-antipsychotics No warnings for EPS, metabolic issues, sedation No boxed warning in elderly patients with DRP Primarily treat only positive symptoms × Do not address negative or cognitive symptoms × ~30% of patients are treatment resistant and ~40-50% have inadequate response (1) Potential for comprehensive symptom improvement Demonstrated improvements in positive and negative symptoms and signal in cognitive symptoms Potential across multiple indications, including ADP, AD dementia, bipolar disorder, etc. Novel Muscarinic Class (Modulate Acetylcholine) Significant Unmet Need • ~1.6M treated for schizophrenia in US (2) • ~70% discontinue treatment within 18 months (3)
Page 7
Broad peripheral expression of M₁ and M₄ receptors drives dose-limiting pro-cholinergic AEs 7 Prior Clinical Development Efforts Within Muscarinic Class Have Been Limited by Cholinergic AEs Structural and Biological Constraints Historical Development Approaches and Challenges Emraclidine • Phase 1 • Healthy volunteers • Moderate cardiovascular AEs at highest dose in SAD study (2) M1 Selective PAMs • Cholinergic toxicity constraining dose escalation (3) Xanomeline • Phase 2 • Alzheimer’s disease • High discontinuation rates (48-59%) despite TID dosing (1) KarXT (Cobenfy)(4) • Phase 1 (KAR-003) • Healthy adults • Elevated rates of cholinergic AEs across dose cohorts • Tolerability issues at highest dose KarXT (Cobenfy)(5) • Phase 1 (KAR-030) • Healthy elderly • Higher rate of AEs than previously reported despite TID dosing Dual M1/M4 Agonist without Peripheral Antagonist Dual M1/M4 Agonist in Combination with Peripheral Antagonist High conservation of orthosteric binding sites limits receptor subtype selectivity approaches Cholinergic neuron loss in neurodegenerative disorders presents challenges for allosteric approaches Ach = acetylcholine; AE = adverse events; SAD = single ascending dose; TID = three times daily. (1) Bodick et al, 1997: Effects of Xanomeline, a Selective Muscarinic Receptor Agonist, on Cognitive Function and Behavioral Symp toms in Alzheimer Disease. (2) Cerevel presentation at SIRS 2021 conference. (3) Alt et al, 2016: Evidence for Classical Cholinergic Toxicity Associated with Selective Activation of M1 Muscarinic Receptors. (4) ASCP Annual Meeting, 2019 poster: Xanomeline plus trospium: A novel strategy to enhance pro -muscarinic efficacy and mitigate peripheral side effects. (5) Cobenfy’s FDA NDA review materials and USPTO IP filings. Receptor Sub-Type Selective Approaches (M1- or M4 Agonist or PAM)
Page 8
Cobenfy’s Approach is Challenged by Mismatched Peripheral Exposures of Agonist & Antagonist BID = twice daily; PK = pharmacokinetic. (1) Cobenfy’s FDA integrated review. (2) KarXT USPTO IP filings; based on Day 7 of dosing at 100/20 BID and 125/40 BID in the Phase 1 MAD study in healthy volunteers (KAR-003). (3) Based on publicly disclosed study designs for EMERGENT -1/2/3 trials in schizophrenia. Based on publicly disclosed study designs for ADEPT -1/2/4 trials in ADP. Parameter(1)(2) Xanomeline M1/M4 Agonist Trospium Peripheral Antagonist Oral Bioavailability ~1% ~15% Plasma Protein Binding 95% 80% Tmax ~2.0 hours ~0.7 hours Coefficient of Variation ~94-107% ~88-94% Fed vs. Fasted (Cmax) 0-30% higher 70-90% lower High rates of both pro- and anti-cholinergic AEs Safety and Tolerability Challenges BID in schizophrenia TID in ADP Inconvenient Dosing Frequency (3) Likely contributes to the tolerability challenges reported in real-world settings Fasting Requirements 3-8 days in schizophrenia – longer in real world usage 5 weeks in ADP Titration Requirements (3) × Excess agonist pro-cholinergic AEs (vomiting, nausea, diarrhea, etc.) × Excess antagonist anti-cholinergic AEs (urinary retention, constipation, etc.) Significant Intra- and Inter-patient Variability Results in PK Mismatch 8
Page 9
Safety and Tolerability • Mostly mild and transient TEAEs • Limited episodes of vomiting • Low rates of anti-cholinergic TEAEs Improved Ease of Use • QD / BID dosing • No fasting requirements • Minimal titration required Broad Symptom Improvement • Robust M1/M4 agonism in vitro • In vivo studies support potential for improvement across positive, negative and cognitive symptoms 9 ML-007C-MA: Our Novel M1/M4 Muscarinic Agonist Potential Areas of Differentiation Strong Activation of Both M1 & M4 Receptors Rational and Deliberate Clinical Strategy Significant Need for a Safer and More Convenient Treatment Option With Robust M 1/M4 Activation Synchronized Agonist / Antagonist Exposure QD = once daily; TEAE = treatment -emergent adverse event.
Page 10
10 Extensive preclinical and clinical development efforts to support dose optimization and selection Broad IP coverage into 2040s (3) Robust M1 and M4 agonism CNS penetrant High oral bioavailability Favorable physical/chemical properties Low DDI risk ML-007C-MA Well characterized (1) Primarily peripherally restricted (2) High oral bioavailability Favorable physical/chemical properties Low DDI risk ML-007 Novel M1/M4 Muscarinic Agonist Fesoterodine Peripherally-Acting Muscarinic Antagonist Deliberate Approach to Selection of Components Well Suited for a Fixed Dose Combination DDI = drug-drug interaction. (1) Fesoterodine is indicated for the treatment of overactive bladder in adult patients with symptoms of urge urinary incontinenc e, urgency, and frequency. (2) Minimal CNS penetration observed in preclinical studies, with low or undetectable CSF exposure across species, and no evidenc e of clinically relevant cognitive effects in humans. (3) Intellectual property portfolio coverage based on latest -to-expire issued patents and provisional applications.
Page 11
11 Frontal cortex Ventral striatum Hippocampus Laterodorsal tegmental nucleus Dorsal striatum M1 and M4 Muscarinic Receptors’ Complementary Role Dual M1 / M4 Muscarinic Agonism Offers the Potential for Comprehensive Symptom Improvement Relative Peak Intrinsic Activity (1) M4 Frontal cortex Ventral striatum Hippocampus Laterodorsal tegmental nucleus Dorsal striatum • Expressed in striatum, cortex, hippocampus and basal ganglia • Modulate psychomotor activation via “indirect pathway” • Central role in synaptic plasticity, learning and memory • Highest expression in striatum • Regulate psychomotor activation via “direct pathway” >2x >2x Symptom Domains Symptom Domains M1 Source: Yohn SE et al (2022): Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic. (1) Represents data normalized to responses of control agonist, oxotremorine , in human GTPγS M1 and M4 in vitro assays.
Page 12
12 Agonism at Both M1 and M4 Receptors Required to Drive Robust Efficacy at Clinically Relevant Doses ML-007 Demonstrated >8x Greater Activity vs. Xanomeline Across M1KO, M4KO and WT Models (2) Head-to-Head Pharmacodynamic Effects in AIH Models (1) AIH = Amphetamine-induced hyperlocomotion; ED50 = median effective dose; M1KO = M 1 knock-out; M4KO = M4 knock-out; WT = wild type. (1) Based on pharmacodynamic activity observed during 5 -15 mins post-dosing. (2) Represents ratios of ED50 dose for ML-007 vs. xanomeline in head-to-head preclinical models. Dose (mg/kg) Dose (mg/kg) % Reduction in Locomotor Activity % Reduction in Locomotor Activity ML-007 Dose Response Xanomeline Dose Response
Page 13
Head-to-Head Pharmacodynamic Effects in AIH Models(1) Consistent Effects Demonstrated Across In Vivo Models CSF = cerebrospinal fluid; LID = L-DOPA–induced dyskinesia; NHP = non -human primates; PCP = phencyclidine; PK/PD = pharmacokinetics/pharmacodynamics; TD = tardive dyskinesia. (1) Based on pharmacodynamic activity observed during 5 -15 mins post-dosing. (2) Represents ratios of ED50 dose for ML-007 vs. comparator in head-to-head preclinical models. PK/PD correlation informed selection of a “conservative” CSF target exposure range PCP-Induced Hyperlocomotion Conditioned Avoidance Response Resident Intruder Chronic Haloperidol Model of TD Spatial & Social Memory in AD Model Dyskinesia in MPTP-Treated NHPs Dose (mg/kg) % Reduction in Locomotor Activity >10x vs. xanomeline >20x vs. emraclidine >35x vs. direclidine Potency by Dose (2) ML-007 Demonstrated Robust, Dose-Dependent Activity Across Behavioral Models ML-007 13
Page 14
14 In Vitro Assays (2) • M1 EC50 ~16 ng/mL • M4 EC50 ~27 ng/ml ML-007 CSF Concentration (ng/mL) Time (hours) Time (hours) Reference Concentrations In Vivo Models (3) • AIH ED50 ~14 ng/mL • PCP ED50 ~27 ng/mL 210/3 mg BID Dose 330/6 mg QD Dose CSF Exposures Achieved in Study 013 at the Doses Selected for Phase 2 Exceeded Conservative Targets ML-007 Target range Xanomeline Equivalent (4) Cavg ~140 ng/mL Cavg ~120 ng/mL Cavg ~6 ng/mL Dose notation refers to the co-formulated combination of ML-007 and PAC (fesoterodine). For example, 210/3 mg indicates 210 mg of ML-007 and 3 mg of fesoterodine . Cavg = average concentration; Cmax = maximum concentration; EC50 = median effective concentration. (1) ML-007 lines represents modeled estimates for CSF exposures based on LP sampling conducted during Study 013. (2) EC50 estimates for M1 based on IP1 levels measured using an IPOne assay and M4 based on cAMP levels measured using a GloSensor assay. (3) CSF exposure-response was conducted across multiple preclinical animal models which defined a target efficacious range of 14 –27 ng/mL (AIH and PCP models, respectively). (4) Represents the ML-007 equivalent CSF concentration estimate of xanomeline (Cobenfy) based on reported median Cavg and Cmax human plasma concentrations at steady state of ~5 ng/mL and ~9 ng/mL, respectively, and 1% CSF:plasma ratio based on NHPs. These estimates rely on Company’s extrapolations as xanomeline’s CSF concentrations have not been direct ly reported. Modeled Steady State CSF Concentrations Based on Phase 1 Sampling (1)
Page 15
15 100 600 0 1 10 100 1,000 0 4 8 12 16 20 24 100 600 0 1 10 100 1,000 0 4 8 12 16 20 24 Concentration Ratio Concentration Ratio Steady State Plasma Concentrations From Study 013 (1) 210/3 mg BID Dose (2) 330/6 mg QD Dose (2) ML-007 or PAC Plasma Concentration (ng/mL) ML-007 or PAC Plasma Concentration (ng/mL) Time (hours) Time (hours) ML-007 PAC Ratio Close Matching of Plasma Exposures for ML-007 & PAC to Offset Peripheral Cholinergic Activity Low PK Variability Observed at Target Doses – CV of ~30% (3) CV = coefficient of variation. (1) Data points show geometric mean observed data from Study 013; lines represent modeled values. (2) Observations after 7 days of maintenance dosing. PAC concentration of active metabolite 5 -HMT. (3) Calculated using last maintenance Day 7 dose data.
Page 16
Significant opportunity for a safer and more convenient treatment option with robust M 1/M4 activation RCT = randomized controlled trials. Note: Assessments reflect management’s current views based on publicly available information and internal analyses; comparisons are qualitative and subject to uncertainty around interpretation. Differences exist among study designs, and caution should be exercised when comparing data across tria ls. (1) Based on FDA prescribing information. (2) Based on results from the Phase 2 EMPOWER-1 and EMPOWER-2 clinical trials, which failed to demonstrate a statistically significa nt improvement. (3) Based on results from the Phase 2 clinical trial, which showed statistically significant improvement only at the lowest dose of the four active drug arms evaluated. ML-007C-MA is Well Positioned to be Differentiated Across Multiple Dimensions 16 Program Mechanism of Action Tolerability Demonstrated in Phase 1 Dosing Convenience Demonstrated in Phase 1 Efficacy in RCTs Ongoing Phase 2 Cognitive Improvement Robust M1 agonism No mechanistic rationale Direclidine (3) M4 Agonist Emraclidine (2) M4 PAM Cobenfy (KarXT) (1) M1/M4 Agonist + Peripheral Antagonist ML-007C-MA M1/M4 Agonist + Peripheral Antagonist
Page 17
17 Establish Efficacy & Safety in Key Indications Explore and Pursue Additional Indications • Parallel development in schizophrenia and ADP • Ongoing Phase 2 studies (ZEPHYR and VISTA) designed to be adequate and well controlled • Data-driven clinical design and execution strategy designed to mitigate placebo response • Prioritization of key registration-enabling activities • Broad potential in multiple indications, including: – Cognition in Alzheimer’s disease – Parkinson’s disease psychosis / Lewy Body – Bipolar disorder – AD agitation – Autism spectrum disorder Our Development Strategy for ML-007C-MA
Page 18
ML-007C-MA Phase 1 Studies
Page 19
Four Phase 1 Studies Completed 270 Subjects Enrolled – Healthy Adults and Elderly 1,500+ Doses of ‘007 Administered 19 N = 58 • Dose-dependent target engagement with ML-007 • Achieved single agent MTD • Pairing with fesoterodine blocked peripheral cholinergic effects N = 106 • Wide range of ML-007 to fesoterodine ratios evaluated across 13 cohorts • Identified optimal ratios to balance pro- and anti-cholinergic peripheral effects N = 24 • Close matching of ML-007 and fesoterodine peripheral exposures • Low rates of TEAEs observed that were mild and transient in nature • Exposure profile supported potential BID / QD dosing N = 82 • First study that evaluated co- formulated bi-layer tablet • Four cohort design, included two cohorts with multi-day dosing paradigm • Evaluated food effects, titration and dosing in healthy adults and healthy elderly • Finalized study design of Phase 2 trials in schizophrenia & ADP Co-Administered Extended Release Co-Formulated Extended Release Immediate Release Immediate Release Study 001 Study 011 Study 012 Study 013 MTD = maximum tolerated dose. Rational and Deliberate Clinical Development Strategy to Establish a Differentiated Profile
Page 20
Placebo Combined (N=8) 165/3 mg BID (N=6) 210/3 mg BID (N=6) 270/6 mg QD (N=6) 330/6 mg QD (N=6) Subjects With Any TEAE (1) 2 (25%) 6 (100%) 3 (50%) 3 (50%) 4 (67%) Cholinergic Classification – Subjects (%) Procholinergic 0 (0%) 4 (67%) 3 (50%) 2 (33%) 4 (67%) Anticholinergic 1 (13%) 3 (50%) 0 (0%) 1 (17%) 0 (0%) Other 1 (13%) 5 (83%) 3 (50%) 3 (50%) 3 (50%) % of TEAEs by Severity Mild 100% 100% 95% 93% 86% Moderate 0% 0% 5% 7% 14% Severe 0% 0% 0% 0% 0% Study 013: Safety and Tolerability in Healthy Adults 1-4 Dose Titration + 7 Days at Target Dose Phase 2 Target Doses for Schizophrenia • Generally favorable safety and tolerability • Consistent with profile previously observed at similar doses • Mostly mild and transient TEAEs • Low rates of moderate TEAEs • Low rates of anticholinergic TEAEs at target doses • No clinically meaningful changes in mean blood pressure or ECG parameters • No liver-related findings 20 ECG = electrocardiogram. (1) AEs include events occurring after administration of target dose until 24 hours after last dose. Procedural AEs are excluded. Reported as N (%).
Page 21
Study 013: Safety and Tolerability in Healthy Adults Target Doses Selected for Phase 2 Schizophrenia Clinical Trial 21 • Most TEAEs (~91%) were mild and transient • Low rates of moderate TEAEs – nausea (n=1), dyspepsia (n=2) • No severe or serious TEAEs • Nausea AEs were mostly mild and self- limited with no episodes of vomiting • No episodes of constipation • Dizziness AEs were mild and not associated with orthostatic changes Placebo Combined (N = 8) (2) 210/3 mg BID (N = 6) 330/6 mg QD (N = 6) (3) Subjects With Any TEAE (1) 2 (25%) 3 (50%) 4 (67%) Mild 2 (25%) 3 (50%) 4 (67%) Moderate (3) 0 (0%) 1 (17%) 2 (33%) Severe 0 0 0 Most Common TEAEs (>1 Subject in any Dose Group) Chills 0 0 2 (33%) Hyperhidrosis 0 1 (17%) 2 (33%) Nausea 0 3 (50%) 3 (50%) Dizziness 0 3 (50%) 2 (33%) Dyspepsia 0 0 2 (33%) • KarXT Phase 1 study in healthy adults (KAR-003) reported high rates of pro- and anti-cholinergic AEs across dosing cohorts • In the 100/20 mg cohort (lower approved dose), AEs were reported in 67% of subjects which included 28% vomiting (1) AEs include events occurring after administration of target dose until 24 hours after last dose. Procedural AEs are excluded. Reported as N (%). (2) Placebo arm reported three AEs, including two episodes of headache. (3) One 330/6 mg participant discontinued; after mild AEs and one moderate AE (dyspepsia), the investigator supported continuatio n, but the participant withdrew consent.
Page 22
Study 013: Safety and Tolerability in Healthy Elderly 2-7 Day Titration + 7 Days at Target Dose Placebo Combined (N=7) (2) 165/3 mg BID (with 2d titration) (N=6) 210/3 mg BID (with 2-7d titration) (N=11) (3) 330/6 mg QD (with 7d titration) (N=6) (4) Subjects with Any TEAE (1) 5 (71%) 4 (67%) 8 (73%) 6 (100%) Cholinergic Classification – Subjects (%) Procholinergic 1 (14%) 2 (33%) 6 (55%) 6 (100%) Anticholinergic 1 (14%) 1 (17%) 4 (36%) 0 Other 3 (43%) 3 (50%) 8 (73%) 6 (100%) % of TEAEs by Severity Mild 100% 100% 93% 72% Moderate (3) 0% 0% 7% 28% Severe 0% 0% 0% 0% Phase 2 Target Dose for ADP • Generally favorable safety and tolerability with BID dosing • Highest dose given QD was not well tolerated – potential to explore lower doses in future • Mostly mild and transient TEAEs • Low rates of anticholinergic TEAEs • No clinically meaningful changes in mean blood pressure or ECG parameters • No liver-related findings 22 (1) AEs include events occurring after administration of target dose until 24 hours after last dose. Procedural AEs are excluded. Reported as N (%). (2) One participant (placebo) discontinued from the study due to an AE during titration; one participant (placebo) had an AE du ring maintenance dosing that led to study drug withdrawal. (3) Two participants had their dose reduced to 165/3 mg BID after experiencing AEs; one additional participant was discontinued f rom the study for non-compliance with clinic rules. (4) Four participants had AEs that led to withdrawal of study drug and one additional participant had their dose reduced to 270/6 mg QD due to AEs.
Page 23
Study 013: Safety and Tolerability in Healthy Elderly Target Dose Selected for Phase 2 ADP Clinical Trial 23 • Most TEAEs (~93%) were mild and transient • Low rates of moderate TEAEs • No serious or severe TEAEs • Limited episodes of vomiting (n=1) or constipation (n=1) • No episodes of urinary retention Placebo Combined N = 7 (2) 210/3 mg BID (with 2-7d titration) N = 11 (2) Subjects with Any TEAE (1) 5 (71%) 8 (73%) Mild 5 (71%) 8 (73%) Moderate 0 2 (18%) Severe 0 0 Most Common TEAEs (>2 Subjects) Hyperhidrosis 0 3 (27%) Nausea 0 3 (27%) Dizziness 1 (14%) 3 (27%) Headache 0 4 (36%) Tremor 0 3 (27%) KarXT Phase 1 study in healthy elderly volunteers (KAR-030) reported 47% of participants had >=1 moderate AEs related to study drug (vs. 8% pbo), with higher rates of cholinergic AEs than previously reported in non-elderly (1) AEs include events occurring after administration of target dose until 24 hours after last dose. Procedural AEs are excluded. Reported as N (%). (2) Two participants discontinued study drug (placebo) due to AEs. Two participants on 210/3 mg BID dose reduced to 165/3 mg BID after experiencing AEs.
Page 24
ML-007C-MA Phase 2 Studies
Page 25
Screening Period (Day -7 to -1) Blinded Treatment Period (Day 1 to 35) Follow-up Period (Day 36 to 42) Week 1 Week 2 Week 3 Week 4 Week 5 25 • N = 300 • Randomized 1:1:1 • Sites: 25 (US only) Placebo BID (n=100) ML-007C-MA 210/3mg BID (1) (n=100) ML-007C-MA 330/6mg QD (1) (n=100) Primary Endpoint Phase 2 Study Design Topline results expected in Q3 2026 Study Population • 18 to 64 years of age with diagnosis of schizophrenia with MINI • PANSS 80-120 at screening and baseline • Score ≥4 for two or more positive symptom items • CGI-S score ≥4 • Untreated or recent wash-out of antipsychotics Primary Endpoint • CFB PANSS at Week 5 Key Secondary Endpoints • CFB CGI-S at Week 5 • CFB PANSS positive Marder factor at Week 5 • CFB PANSS negative Marder factor at Week 5 CFB = Change from baseline, CGI-S = Clinical Global Impression of Severity; MINI = Mini-International Neuropsychiatric Interview ; PANSS = Positive and Negative Syndrome Scale. (1) Single dose titration; flexibly dosed with down -titration permitted once between Week 1 to 3 to 270/6mg QD or 165/3mg BID.
Page 26
Phase 2 Study Design 26 Screening Period (Day -35 to -1) Blinded Treatment Period (Day 1 to 49) Follow-up Period (7 + 2 days after last dose)Week 1 Week 2 Week 3 Week 5 Week 7 ML-007C-MA 210/3mg BID (n=150) Primary Endpoint Week 1 105/1.5mg BID Weeks 2-7 210/3mg BID (1) Placebo BID (n=150)• N = 300 • Randomized 1:1 • Sites: 100 (global) Topline results expected in 2H 2027 NPI-C A+A = Neuropsychiatric Inventory Clinician, Agitation and Aggression; NPI-C H+D = Neuropsychiatric Inventory Clinician, Hallucinations and Delusions. (1) Increase to the target dose of 210/3 mg BID at Week 1, unless the participant is experiencing tolerability issues that, in th e investigator’s opinion, would preclude a higher dose. Every effort should be made to increase to the target dose as soon as possible up until Week 3. One -time dose reduction to 105/1 .5 mg allowed for tolerability. Study Population • 55 to 90 years of age • Possible or probable Alzheimer’s disease • Psychotic symptoms for >2 months • NPI-C H+D score of ≥6; and ≥2 on at least two items of either the H or D domain scores • CGI-S score ≥4 Primary Endpoint • CFB to Week 7 on the NPI-C H+D domain scores Key Secondary Endpoints • CFB to Week 7 on CGI-S score • CFB to Week 7 on NPI-C A+A domain score in participants with moderate agitation at Baseline
Page 27
27 Strategies to Mitigate Placebo Response in Ongoing Phase 2 Schizophrenia Study • Limited # of US-only sites • Limited # of participants • Conservative enrollment targets • Moderate-to-severe baseline symptom requirements Trial Design • Rigorous site and investigator selection • Robust eligibility and duplicate patient controls • Regular placebo response training of site, staff, and patients Trial Execution • In-house site relationships, monitoring, and data quality oversight • Independent central review and regular blinded data analyses • CRO selection Trial Oversight Similar Strategies Employed in the Ongoing Phase 2 VISTA Study for ADP CRO = contract research organization.
Page 28
Designed to achieve robust M1/M4 activation in combination with a synchronized peripheral antagonist Potentially favorable tolerability profile with convenient dosing, no fasting requirements, and minimal titration Strong agonism at both M1 and M4 offers the potential for improvement across key symptom domains Parallel development in schizophrenia and ADP, with Phase 2 studies designed to be adequate and well-controlled Near-term clinical readouts supported by a strong balance sheet and execution track record 28 ML-007C-MA: Potential Best-in-Class Muscarinic Agonist Rational Development Approach Simplified Patient Experience Potential Symptom Improvement Focused Development Strategy Positioned to Deliver on Key Milestones
Page 29
ML-004 Autism Spectrum Disorder (ASD)
Page 30
30 • Core symptoms: – Impaired social communication – Restricted, repetitive thoughts and behaviors • Comorbid neurobehavioral symptoms include: – Irritability and aggression (in 25% of ASD patients) – Hyperactivity, mood lability • Affects ~1.8M children & adolescents and >5M adults in US • No FDA approved treatments for core symptoms of ASD • Only widely accepted intervention is long-term behavioral therapy • Off label usage of ADHD medications, SSRIs, SNRIs, and supplements • Two atypical antipsychotics approved for ASD-associated irritability – Risk of serious side effects – Ineffective in treating core social features • Dysregulated serotonin signaling implicated in ASD pathology • ML-004 – novel IR/ER oral formulation of zolmitriptan (5-HT 1B/1D agonist)(1) • Safety, tolerability and pharmacokinetics evaluated in Phase 1 trials • Ongoing Phase 2 IRIS trial to evaluate efficacy and safety – Topline results expected in Q3’26 ASD Overview Unmet Medical Need ML-004 Potential ADHD = attention-deficit/hyperactivity disorder; SNRI = serotonin -norepinephrine reuptake inhibitors; SSRI = selective serotonin reuptake inhibitors. Source: US CDC prevalence estimates. (1) Zolmitriptan approved for acute treatment of migraines. ML-004: Potential Treatment of Social Communication Deficits and Irritability in ASD Patients
Page 31
• Multi-center, randomized, double-blind, placebo-controlled trial • Randomized approximately 160 subjects with ASD – Adolescent (age 12-17) and adult (age 18-45) • Flexible dosing paradigm, with target maintenance dose of 48mg and 72mg • Primary Endpoint: – ABI, Social Communication Domain Score – Change vs. baseline assessed after 12 weeks of maintenance dosing • Secondary Endpoint: – Change in ABC-I score vs. baseline for patients with moderate or greater irritability score at baseline – Other secondary and exploratory endpoints • Topline results expected in Q3 2026 31 Phase 2 Study Design ABI - Autism Behavior Inventory, ABC-I - Aberrant Behavior Checklist-Irritability.
Page 32
• Potential for a well-tolerated and convenient option without sacrificing strong M1/M4 activation • Broad development strategy, including parallel advancement in schizophrenia and ADP • Versatile and reproducible discovery platform leveraging our deep understanding of circuit biology • Extensive medicinal chemistry and formulation expertise • ML-004 in Phase 2 trial for treatment of sociability and / or irritability symptoms of ASD • Expect to continue advancing early- stage pipeline • Seasoned team with experience in drug development and commercialization • Strong financial position with cash runway through key milestones Differentiated M1/M4 Muscarinic Agonist Broad and Diversified Product Pipeline 32 Circuit-Specific Discovery Strategy Established Track Record of Execution Corporate Summary
Page 33
Appendix
Page 34
34 KarXT: Translation of Tolerability Profile From Healthy Volunteers to Schizophrenia Patients % of Subjects with TEAEs – Represents Highest Severity Phase 1 in HV (1) Phase 2/3 in Schizophrenia (2) HV = healthy volunteers; RWE = real -world evidence. OLE = open -label extension. (1) “Xanomeline plus trospium: A novel strategy to enhance pro -muscarinic efficacy and mitigate peripheral side effects” poster pres ented at ASCP 2019. (2) Cobenfy’s FDA NDA Review. (3) Cobenfy’s FDA integrated review (KAR-011 and KAR-008, respectively). (4) Kutz et al, 2025 poster presented at Psych Congress – Retrospective Analysis of Real-World Transition Strategies for Xanomeline and Trospium Chloride in Adult Patients with Schizophrenia. Generally consistent or better tolerability profile in clinical trials with schizophrenia patients compared to healthy volunteers • Similar or lower overall severity observed in Phase 2/3 vs. Phase 1 HV • Types of AEs and % of moderate AEs show high translatability from healthy subjects to schizophrenia patients • Discontinuation rate of ~47–72% reported in 52-week OLE studies (3) RWE suggests a more challenging tolerability profile despite longer titration, lower doses, and pharmacological intervention (4) • ~18% of patients at 125/30 mg dose; majority at 100/20 mg dose • 64% and 37% of patients experienced nausea and vomiting, respectively • Prophylactic or as needed antiemetic usage in ~65% of patients Severe Moderate Mild