Slide 1: Topline Data from Phase 2 IRIS Trial Evaluating ML-004 in Autism Spectrum Disorder
Topline Data from Phase 2 IRIS Trial Evaluating ML-004 in Autism Spectrum Disorder June 22, 2026 Exhibit 99.1
Slide 2: Forward-looking statements disclaimer
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 a
Slide 3: Agenda
Executive Summary and Key Takeaways for ML-004 Chris Kroeger, M.D. Co-Founder and Chief Executive Officer Phase 2 IRIS Study Results Erin Foff, M.D., Ph.D. Chief Medical Officer Unmet Medical Need in ASD Irritability Chris Kroeger, M.D. Co-Founder and Chief Executive Officer Closing Remarks Chris Kr
Slide 4: Summary of IRIS Phase 2 Topline Results
Summary of IRIS Phase 2 Topline Results ML-004 is an IR/ER reformulation of the 5-HT1B/1D agonist zolmitriptan Zolmitriptan demonstrates activity in both sociability and irritability/aggression animal models Activation of 5-HT₁B receptors in the nucleus accumbens recapitulates the prosocial effects
Slide 5: Potential Future Development Considerations
Potential Future Development Considerations Effect sizes observed in adolescents with moderate irritability are at/above those observed in clinical trials with antipsychotics currently approved for the treatment of irritability in ASD Tolerability findings suggest potential differentiation from D2-b
Slide 6: Translational Rationale
Translational Rationale Resident Intruder Aggression Assay Decreased serotonin or loss of 5-HT1B receptor function is linked to aggression in mice and humans (1)(2)(3)(4) Increased serotonin or activation of 5-HT1B receptors inhibits brain circuits associated with aggression (2) At clinically-releva
Slide 7: Phase 2 Results
Phase 2 Results Erin Foff, M.D. | Chief Medical Officer
Slide 8: Phase 2 Study Background and Design
Multi-center, randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of ML-004 161 participants randomized 1:1 to ML-004 or placebo 102 adolescents ages 12-17; 59 adults ages 18-45 Once-daily oral bilayer IR/ER tablet formulation with flexible dosing par
Slide 9: Primary and Key Secondary Endpoints Results
Primary Endpoint Other (1) Key Secondary Endpoints Scale ABI-SC CGI-I ABI-C ABC-I CGI-I Irritability Rater Care-partner reported Clinician-rated Clinician-rated Care-partner reported Clinician-rated Domain Assessed Social Communication Global Autism Global Autism Irritability (with baseline ABC-I>16
Slide 10: ABC-I: Prespecified Adolescent Subgroup
ABC-I: Prespecified Adolescent Subgroup Includes Subjects with ABC-I >16 at Baseline Numerical separation from PBO emerged early and increased through the end of maintenance dosing Large treatment effect at EOMD with a 9.6-point PBO-adjusted improvement N=20 * p < 0.05 LS = least squares. Note: Nega
Slide 11: Irritability Outcomes
Irritability Outcomes Includes Subjects with ABC-I >16 at Baseline ABC-I Subscale (1) Care partner-reported CGI-I Irritability Domain (2) Clinican-reported Two measures of irritability assessed by different raters LS Mean Difference vs. Placebo (95% CI), by Scale and Age Group Total N = 26 Adolescen
Slide 12: Adolescent Subgroup Analysis by Irritability Score at Baseline
Change From Baseline to End of Maintenance Dose Adolescent Subgroup Analysis by Irritability Score at Baseline CGI-I Irritability Domain ABC-I Subscale Subgroup N=active/PBO LS Mean Diff [95% CI] Effect Size P-value (* p < 0.05) All adolescents N = 49/51 0.34 0.107 ABC-I > 0 N = 43/48 0.43 0.054 ABC
Slide 13: ML-004 Was Generally Well Tolerated Across All Doses and Age Groups
ML-004 Was Generally Well Tolerated Across All Doses and Age Groups Majority of TEAEs were mild, transient, and resolved without the need for dose reduction No severe or serious TEAEs occurred with ML-004 (all in PBO arm) No deaths or life-threatening events occurred Most frequent TEAEs (>5% and >PB
Slide 14: Unmet Medical Need
Unmet Medical Need Chris Kroeger, M.D. | Co-Founder and Chief Executive Officer
Slide 15: Unmet Need in ASD Irritability Remains High
Unmet Need in ASD Irritability Remains High ~830K adolescents diagnosed with ASD (U.S., 2039E) (1) ~20-35%+ experience clinically significant irritability or aggression (2) 1 in 6 young people with ASD receive antipsychotics (3) Only 2 approved therapies both with warnings and precautions relevant t
Slide 16: Current Standard of Care in ASD Irritability
Current Standard of Care in ASD Irritability Risperidone Aripiprazole Effect Size (ABC-I) 0.92 - 1.2 0.43 - 0.87 Weight Gain Adverse events Weight increased 6% (1) Increased appetite 29% (1) Weight change 1.4 kg more weight gain (2) 26% more subjects gained >7% weight (2) Adverse events Decreased ap
Slide 17: ML-004 Has the Potential to Address Unmet Needs Through Established Development Path
ML-004 Has the Potential to Address Unmet Needs Through Established Development Path Initial efficacy signal from IRIS appears in line with approved therapies (1) Clinically meaningful improvement observed across ABC-I and CGI-I in adolescents with elevated irritability Magnitude of effect appears c
Slide 18: Closing Remarks
Closing Remarks Chris Kroeger, M.D. | Co-Founder and Chief Executive Officer
Slide 19: Closing Remarks
Closing Remarks ML-004 demonstrated clinically meaningful improvements in irritability in adolescents with moderate or greater baseline irritability across both caregiver- and clinician-rated scales ABC-I (effect size of 1.33, nominal p-value of 0.013) CGI-I irritability (effect size of 1.08, nomina
Slide 20: Pipeline and anticipated milestones
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 by mid-August 2026 Alzheimer’s Disease Psychosis Topline results in 2H 2027 ML-004 5-HT1B/1D agonist Dorsa
Slide 21: MapLight Q&A
“& MapLight Q&A 21