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There remains a significant unmet need in both schizophrenia and ADP for medicines that can effectively treat the breadth of symptoms while reducing the significant safety and tolerability risks for patients. Schizophrenia is a complex psychiatric disorder characterized by a range of symptoms that include positive symptoms of hallucinations, delusions, and disorganized thinking; negative symptoms of social withdrawal, decreased emotional expression, anhedonia, and apathy; and cognitive impairment. Schizophrenia is one of the most common psychotic disorders and affects over 20 million people globally, including more than 3 million people in the United States. Schizophrenia remains one of the leading causes of disability and is associated with an increased risk for premature mortality. Atypical antipsychotics represent the current standard of care and primarily exert their therapeutic effects by binding to and inhibiting the activity of dopamine D2 receptors in the brain. These dopaminergic antipsychotics are associated with risk of highly morbid side effects of extra pyramidal symptoms, or EPS, (e.g., dystonia, akathisia, tardive dyskinesia), metabolic abnormalities (e.g., weight gain, dyslipidemia, hyperglycemia), hyperprolactinemia, QTc prolongation and sedation. Furthermore, these medications are approved by the FDA only for the treatment of the positive symptoms of schizophrenia and do not address the negative or cognitive symptoms. Meta-analyses of real-world usage of dopaminergic antipsychotics have shown poor treatment adherence and high discontinuation rates due to lack of efficacy and/or undesirable side effects.

ADP represents another significant unmet need, as approximately 40% of the approximately 7 million people in the United States living with Alzheimer's disease also experience symptoms of psychosis. These symptoms are associated with a worsened prognosis and are predictive of earlier progression to nursing home care, severe dementia and death. There are currently no therapies approved for the treatment of ADP, although there is widespread use of off-label dopaminergic antipsychotics. However, based on a meta-analysis, the efficacy of these medications for ADP was shown to be modest at best. Furthermore, dopaminergic antipsychotics are associated with significant side effects, including EPS, metabolic syndrome, cerebrovascular accidents, falls and increased mortality risk in elderly patients with dementia-related psychosis.

We believe targeting muscarinic receptors represents a compelling therapeutic alternative to dopaminergic antipsychotics for the treatment of schizophrenia and ADP. Muscarinic receptors are localized to brain circuits known to be critical for psychosis and cognition, and alterations in muscarinic receptor binding have been observed in post-mortem brain tissue from schizophrenia and Alzheimer's disease patients. The FDA approval of Cobenfy, an M1/M4 muscarinic agonist, represents the first product with a novel mechanism approved for the treatment of schizophrenia in decades. Muscarinic receptor-targeted approaches have shown improvements in both positive and negative symptoms of schizophrenia, as demonstrated in multiple randomized controlled clinical trials conducted by third parties. Additionally, in these trials and other open-label extension trials, muscarinic agonists were shown not to cause the serious side effects of EPS and metabolic disturbance associated with dopaminergic antipsychotics.

However, some of these same clinical trials have also demonstrated a high rate of both pro- and anticholinergic side effects, which we believe are caused by a mismatch of agonist and antagonist exposures in the periphery. To mitigate these cholinergic side effects, certain muscarinic agonists have required inconvenient dosing regimens (frequency, titration and fasting requirements) that are likely to result in patient compliance and adherence challenges. Furthermore, although exploratory analyses in these trials suggested a positive effect on cognition symptoms in patients with baseline cognitive impairment, these analyses were not adequately powered to assess statistical significance. These findings suggest that despite the approval of a first agent within the new muscarinic class, there remains a significant opportunity for improvement across efficacy, safety and tolerability, and ease of use.

Based on the results of our Phase 1 Study 013, we believe ML-007C-MA has demonstrated the potential to be a well-tolerated treatment option with convenient dosing, while achieving or exceeding CSF exposures expected to result in improvement across key symptom domains. Study 013 evaluated the safety, tolerability and pharmacokinetics, or PK, of ML-007C-MA in healthy adult and elderly participants that were dosed for up to 14 days. ML-007C-MA was generally well tolerated at the doses being evaluated in our ongoing Phase 2 trials. Most treatment-emergent adverse events, or TEAEs, were mild, self-limited and transient in nature. The mean plasma concentration ratio of ML-007 and PAC remained within the target range established to minimize adverse events over the majority of the dosing interval. ML-007C-MA also achieved and maintained CSF exposures above the anticipated clinically relevant levels with both once- and twice-daily dosing regimens. Based on the PK parameters observed in fasted and fed states, ML-007C-MA will not require administration in a fasted state. Together, the safety and PK observations supported advancing ML-007C-MA to Phase 2 trials in both adult and elderly participants.

Our second product candidate, ML-004, is a 5-HT1B/1D agonist that we are developing for the treatment of social communication deficit and/or irritability in autism spectrum disorder, or ASD. Historical clinical development efforts for ASD have been challenging given the biological heterogeneity of symptoms across age, developmental level and sex, and the lack of validated outcome measures. There are currently no FDA-approved therapies for the core symptoms of ASD, social communication deficit and repetitive/restricted behavior. The only two therapies approved for ASD-associated irritability are atypical antipsychotics, which are associated with serious side effects. ML-004 is an immediate-release, or IR, and extended-release, or ER, formulation of zolmitriptan. We are currently conducting IRIS, a Phase 2 trial to evaluate the efficacy of ML-004 for the improvement of social communication deficits in patients with ASD. Change from baseline in irritability symptoms is a secondary endpoint. We have completed enrollment in this trial and expect to report topline results in the third quarter of 2026. Based on the results from the IRIS trial, we intend to explore potential strategies for further development of ML-004.

In addition, we are advancing multiple preclinical programs, including ML-009, ML-055 and ML-021.

ML-009 is our G-protein-coupled receptor 52 positive allosteric modulator, or GPR52 PAM, program for the treatment of hyperactivity, impulsivity and agitation-related disorders. We have nominated a preclinical candidate for further advancement and expect to complete investigational new drug application, or IND, -enabling studies in 2027.

ML-055 is our next-generation, novel M1/M4 muscarinic agonist program, which we are developing for the treatment of neuropsychiatric conditions. Preclinical in vitro and in vivo studies evaluating multiple potential candidates have demonstrated significantly greater potency relative to ML-007 and the potential for once-daily dosing and long-acting injectable formulation. We expect to nominate a preclinical candidate to advance to IND-enabling studies in 2026.

ML-021 is our M4 antagonist program for the treatment of motor deficits in Parkinson's disease. We have conducted preclinical studies using multiple potential candidates, including our lead preclinical candidate, and expect to finalize a preclinical candidate to advance to IND-enabling studies in 2027.

Our current and future pipeline is supported by our platform, which is built on our deep understanding of neural circuits that perform specific functions in the brain. We leverage our platform technologies to define how the activity of specific neural circuits is causally linked to disease symptoms and then identify druggable targets within those circuits that correct aberrant circuit activity. Utilizing this approach, we are advancing a robust pipeline of product candidates for the treatment of highly prevalent CNS conditions that collectively afflict millions of people and impose substantial disease burden and costs on patients, families, caregivers and society.

Our Pipeline of Product Candidates

Our pipeline of product candidates is diversified by mechanism and neural circuit to address a breadth of debilitating CNS disorders, and we currently retain global development and commercial rights to all programs.

Figure 1. MapLight Therapeutics Pipeline

Our Approach and Platform

We were founded by globally recognized leaders in psychiatry and neuroscience research to fill a void in CNS drug discovery by building a platform to identify disease-related neural circuits and target them for therapeutic modulation. Our differentiated approach is based on our deep understanding of the causal links between the modulation of defined neural circuits and the resulting changes in disease-specific behaviors. Our platform consists of three key technologies: optogenetics, a technique that uses light to probe the function of specific neural circuits in the living brain; single cell transcriptomics, a high-throughput technology that isolates single cells from a tissue and then reads out gene expression levels in different cell types; and STARmap, a spatial transcriptomics technology that allows for the visualization of gene expression in neural circuits within preserved slices of brain tissue. We use optogenetics to identify how aberrant activity in a defined neural circuit can cause disease symptoms. Once we have identified a circuit of interest, we employ single-cell transcriptomics and STARmap to identify and spatially localize druggable targets that are selectively expressed within those circuits. We then apply our expertise in medicinal chemistry and drug formulation to identify product candidates that engage the identified targets to ameliorate dysfunctional circuit activity.

We believe this approach holds the potential to generate compelling pipeline opportunities by validating promising targets earlier in the discovery and development process. The multiple, synergistic technologies comprising our platform facilitate our efforts to discover potential product candidates with the optimal combination

of specificity, activity and safety. We believe that our circuit-based discovery strategy will enable us to deliver additional novel and differentiated pipeline programs.

Figure 2. MapLight Therapeutics Discovery Platform

Our Programs

ML-007C-MA for the Treatment of Schizophrenia and Alzheimer's Disease Psychosis

Our lead product candidate, ML-007C-MA, is a fixed-dose combination of an M1/M4 muscarinic agonist, ML-007, co-formulated with a PAC, which we are initially developing for the treatment of schizophrenia and ADP. ML-007C-MA is designed to activate both M1 and M4 muscarinic receptors centrally to drive efficacy, while synchronizing the pharmacokinetics of the agonist and antagonist components to mitigate peripheral cholinergic side effects. ML-007 alone, co-administered, or co-formulated with PAC has been evaluated in four Phase 1 trials, with a total of 270 healthy participants enrolled and more than 1,500 doses of ML-007 administered. Based on our clinical and preclinical data, we believe that ML-007C-MA has demonstrated the potential to be a well-tolerated treatment option with convenient dosing, while achieving or exceeding CSF exposures expected to result in improvements across key symptom domains. We are conducting ZEPHYR, a Phase 2 trial evaluating ML-007C-MA for the treatment of schizophrenia, and we expect the trial to reach the target enrollment of 300 participants in April 2026 and report topline results in the third quarter of 2026. We are also conducting VISTA, a Phase 2 trial evaluating ML-007C-MA for the treatment of ADP, and expect to report topline results in the second half of 2027. In December 2025, ML-007C-MA was granted Fast Track designation by the FDA for the treatment of hallucinations and delusions associated with ADP.

Overview of Schizophrenia

Schizophrenia is a complex psychiatric disorder characterized by a range of symptoms that include positive symptoms of hallucinations, delusions and disorganized thinking; negative symptoms of social withdrawal, decreased emotional expression, anhedonia and apathy; and cognitive impairment, including attention, memory and executive function deficits. Schizophrenia has a highly variable clinical course characterized by continuous or relapsing episodes of psychosis and hospitalizations, and outcomes range from complete recovery to long-term severe disability. The underlying causes of schizophrenia remain elusive, but the disorder is believed to arise from a combination of genetic, environmental and neurobiological factors. Psychotic features of schizophrenia typically emerge in adolescence or early adulthood, and life expectancy following diagnosis is substantially reduced relative to the general population. Schizophrenia is one of the most common psychotic disorders and affects over 20 million people globally, including more than 3 million people in the United States.

Atypical antipsychotics represent the current standard of care and primarily exert their therapeutic effects by inhibiting the activity of dopamine D2 receptors in the brain, though most also interact with other receptors (e.g., serotonin, histamine and adrenergic receptors). These dopaminergic antipsychotics are associated with significant side effects, including the risk of serious movement disorders (e.g., tardive dyskinesia, akathisia, dystonia), metabolic abnormalities (e.g., weight gain, dyslipidemia, hyperglycemia), hyperprolactinemia, QTc prolongation and sedation. Furthermore, these medications are approved by the FDA only for the treatment of the positive symptoms of schizophrenia and do not address the negative symptoms nor cognitive impairment. It is estimated that approximately 30% of patients have no response to treatment and an estimated 30 to 60% of patients only have a partial or inadequate response to dopaminergic antipsychotics. A large meta-analysis of real-world usage of commonly prescribed dopaminergic antipsychotics showed that approximately 74% of patients discontinued treatment within 18 months due to undesirable side effects or lack of efficacy. There is an urgent unmet medical need for safe and effective new treatments that address the entire spectrum of symptoms associated with schizophrenia.

Overview of Alzheimer's Disease Psychosis

Alzheimer's disease, or AD, is a progressive and chronic neurodegenerative disease defined by memory and cognitive deterioration beyond normal aging that becomes severe enough to interfere with daily tasks. It is characterized by the loss of neurons and synapses in the cerebral cortex and certain subcortical regions. Neuropsychiatric symptoms and disorders are frequently observed with most patients living with AD. Psychotic symptoms, which are characterized by the presence of delusions and/or hallucinations, occur in approximately 40% of people with Alzheimer's disease at some point during their illness and their likelihood increases as the disease progresses. Psychotic symptoms are associated with poorer disease outcomes, including high rates of institutionalization, more rapid cognitive and functional decline, and increased mortality rates.

There are currently no therapies approved for the treatment of ADP, although there is widespread use of off-label antipsychotics. A large meta-analysis showed that antipsychotics carry a risk of increased mortality in elderly patients with dementia-related psychosis, or DRP, including those with ADP (a subset of DRP). This meta-analysis resulted in the FDA issuance of a boxed warning in the labeling of another product for increased risk of mortality in elderly patients with DRP with antipsychotic usage. Furthermore, dopaminergic antipsychotics are also associated with the risk of serious side effects, including EPS, metabolic syndrome, cerebrovascular accidents, and falls. There is a significant unmet need for effective, safe, and well-tolerated treatments for ADP.

Muscarinic Receptors – Overview and Therapeutic Potential

Muscarinic receptors have emerged as potentially compelling therapeutic targets in recent years for treatment of psychosis and cognitive impairment in several neuropsychiatric disorders, including schizophrenia and ADP. Muscarinic receptors are a family of G protein-coupled receptors that are activated by the neurotransmitter acetylcholine. Muscarinic receptors serve several key physiological roles in cognitive, behavioral, sensory, motor and autonomic processes. There are five subtypes of muscarinic receptors (M1-M5), each with distinct regional distributions and functional roles. M1 and M4 receptor subtypes show the highest expression in brain where they localize to regions implicated in psychosis and cognitive impairment. Alterations in muscarinic receptors have been observed in post-mortem brain tissue from schizophrenia and Alzheimer's patients.

The therapeutic effect of muscarinic receptor agonism in psychosis is thought to be mediated by M1 and M4 receptors in the basal ganglia, prefrontal cortex and hippocampus. In the basal ganglia, the activation of M1 and M4 receptors is thought to counterbalance dopamine activity through the direct and indirect pathways, leading to a stronger reliance on external cues to shape reality, thereby reducing delusions, hallucinations and other symptoms of psychosis. In the prefrontal cortex and hippocampus, activation of M1 receptors is thought to enhance the formation of a coherent and linear set of short- and long-term memories that underpins the perception of a stable reality.

Although activation of M1 or M4 alone has shown efficacy in animal models of psychosis at high doses, targeting both M1 and M4 is considered to be important for achieving meaningful efficacy in these models at clinically relevant doses. Targeting both M1 and M4 receptors is predicted to regulate basal ganglia circuitry synergistically and more effectively than either receptor alone. Together, these multifaceted actions of muscarinic agonists offer the potential of treating psychosis without relying on direct dopamine receptor blockade, the mechanism theorized to drive many of the serious side effects of dopaminergic antipsychotics.

However, muscarinic receptors are also present in various peripheral tissues where acetylcholine plays a role in mediating involuntary muscle movements and glandular secretions. Agonism of peripheral muscarinic receptors could lead to procholinergic side effects, including vomiting, diarrhea, increased salivation and sweating. Despite the promising therapeutic benefit of targeting muscarinic receptors to treat psychosis and related behavioral symptoms in patients with schizophrenia and AD, historical efforts to develop muscarinic agonists have been challenged by the inability to achieve sufficient CNS exposures for efficacy without accompanying peripheral cholinergic side effects.

Two different strategies have emerged to reduce the peripheral side effects of muscarinic agonism: (1) combination of the muscarinic agonist with a peripheral antagonist and (2) receptor selectivity without pairing with a peripheral antagonist, each as described below.

M1/M4 Muscarinic Agonist Paired with Peripheral Antagonist:

The rationale for combining a M1/M4 muscarinic agonist with a peripherally acting muscarinic antagonist is to enable sufficient agonist activity centrally to achieve efficacy while using an antagonist to mitigate peripheral procholinergic side effects.

Cobenfy, also known as KarXT, currently being developed and marketed by Bristol Myers Squibb, is a combination product consisting of xanomeline, an M1/M4 muscarinic agonist, co-formulated with the peripherally acting muscarinic antagonist, trospium. Cobenfy represents the first drug with a novel mechanism of action that has been approved by the FDA for the treatment of schizophrenia in decades. Multiple Phase 3 trials for Cobenfy are ongoing or planned for the treatment of ADP, Alzheimer's disease cognition, Alzheimer's disease agitation and bipolar disorder.

In Phase 2 and Phase 3 schizophrenia trials, patients treated with Cobenfy showed a statistically significant and clinically meaningful placebo-adjusted reduction in total PANSS score (both positive and negative symptoms independently) and clinician-rated improvements in symptoms. Furthermore, although exploratory analyses suggested a positive effect on cognition symptoms in patients with baseline cognitive impairment, these analyses were not adequately powered to fully assess statistical effect in these trials. Additionally, in these trials and other open-label extension, or OLE, trials, treatment with Cobenfy did not cause the serious side effects of EPS and metabolic disturbance traditionally associated with dopaminergic antipsychotics.

However, treatment with Cobenfy has been associated with both procholinergic (e.g., diarrhea, vomiting, nausea, hypersalivation, sweating) and anticholinergic (e.g., constipation, dry mouth, tachycardia, urinary retention) side effects. In Phase 1 trials in healthy adult and elderly participants, Cobenfy was associated with high rates of cholinergic adverse events, a meaningful portion of which were moderate adverse events. Similar rates and types of cholinergic adverse events were also reported in Phase 2, Phase 3 and OLE studies for Cobenfy in schizophrenia patients.

Based on Cobenfy's dosing frequency, fasting requirements (taken at least 1 hour before or 2 hours after a meal), and extended titration period, we believe there is significant room for improvement for more convenient treatment options. According to the FDA prescribing label for schizophrenia, Cobenfy is dosed twice daily and requires a 3-8 day titration period. In the currently ongoing Phase 3 ADEPT-2/3/4 studies for ADP, Cobenfy is dosed three times a day and requires a 5-week titration period. Finally, Cobenfy is also contraindicated or not recommended in certain patients with hepatic and renal impairment.

Together, these findings suggest that further optimization is possible to address side effects and improve the therapeutic profile of the muscarinic class. We believe that synchronization of the PK of the agonist and antagonist components of ML-007C-MA could result in mitigation of pro- and anticholinergic side effects, enabling enhanced tolerability and more convenient dosing, while achieving or exceeding CSF exposures expected to result in improvement across key symptom domains.

Receptor Selectivity Approach Without Pairing with Peripheral Antagonist (e.g., M4-only agonists):

Receptor selective approaches such as those employed by M4-selective agonists rely on sacrificing efficacy at the M1 receptors with the goal of reducing some of the peripheral procholinergic side effects. While product

candidates relying on these approaches have demonstrated favorable safety, tolerability and dosing convenience, the efficacy of these programs in large randomized controlled trials has been negative, mixed or remains unknown. In addition, the lack of M1 activity with these approaches suggests that they would not be expected to address the cognitive symptoms in either schizophrenia or Alzheimer's disease.

Overview of Our Approach

We believe that the combination approach of activating both M1 and M4 muscarinic receptors in the CNS, paired with precision-matched antagonism of muscarinic receptors in the periphery, is the key to achieving the optimal therapeutic profile for the muscarinic agonist class. ML-007C-MA is designed to activate both M1 and M4 muscarinic receptors centrally to drive efficacy, while synchronizing the pharmacokinetics of the agonist and antagonist components to mitigate peripheral cholinergic side effects.

ML-007 Has Robust Activity at Both M1 and M4 Receptors

ML-007 is a brain-penetrant muscarinic M1/M4 agonist that has demonstrated strong activation of both M1 and M4 receptors across in vitro and in vivo preclinical studies.

In the GTPgS assay, which measures one of the signaling events proximal to receptor activation, ML-007 was a strong partial agonist at both the M1 and M4 receptors. In a head-to-head comparison, ML-007 demonstrated a greater than two-fold higher peak intrinsic activity relative to xanomeline in this assay (see Figure 3). Stronger agonism of ML-007 supports the potential for a wider range of agonist activity, requiring fewer ligand-receptor binding events, lower likelihood of acting as a functional antagonist at high concentrations, and a potential to improve specific symptoms that may require a higher level of activity for physiological response.

Figure 3: Relative Peak Intrinsic Activity at M1 and M4 Receptors for ML-007 and Xanomeline

ML-007 has been evaluated in dose-response assays in multiple species and animal models that are predictive of muscarinic receptor activation, including hyperlocomotion, conditioned avoidance response, resident intruder, cognition and dyskinesia models. The pharmacodynamic activity of ML-007 in these animal studies was correlated with CSF exposures to define our target efficacious CSF concentration range of 14 to 27 ng/mL. To validate our target CSF concentration range, we benchmarked the in vivo pharmacodynamic activity and CSF exposures of ML-007 and xanomeline in these preclinical models. ML-007 has demonstrated approximately 10-fold greater potency by dose compared to xanomeline, as shown in head-to-head studies across multiple in vivo models, including amphetamine-induced hyperlocomotion, phencyclidine-induced hyperlocomotion, and conditioned avoidance response.

The relevance of activity at M1 and M4 muscarinic receptors in reducing hyperlocomotion was also established with knockout, or KO, mice in the amphetamine induced hyperlocomotion, or AIH, model for both ML-007 and xanomeline. These studies demonstrated that at clinically relevant doses, greater pharmacodynamic effects are observed with activation of both M1 and M4 receptors (wild type) compared to either receptor alone (M1 or M4 KO) for both ML-007 and xanomeline. These studies also demonstrated ML-007's robust activity at both M1 and M4 receptors. Consistent with its stronger M1 activity, ML-007 (but not xanomeline) improved both spatial and social memory in a mouse model of Alzheimer's disease.

Favorable Physical / Chemical Properties for Combination Product

ML-007 is highly soluble, is quickly absorbed and distributed throughout the body and has low protein binding. In addition, it has demonstrated high oral bioavailability in animals and is not subject to substantial first-pass metabolism by the liver following absorption in the gastrointestinal tract. These physical and chemical properties have resulted in low inter-patient variability in exposure in clinical trials to date, which has allowed us to optimize the PK synchronization of the two components in the development and formulation of ML-007C-MA.

ML-007 activates muscarinic receptors in the brain, and like other muscarinic agonists, also engages muscarinic receptors in peripheral tissues. Activation of these peripheral receptors produces unwanted procholinergic effects, including nausea, vomiting, diarrhea, hypersalivation and increased sweating. Combining ML-007 with a precision-matched PAC is intended to mitigate these effects, while preserving the desired activity in the brain. To reliably block the peripheral activation of muscarinic receptors, the antagonist must have predictable PK, and its peripheral exposure should match the exposure of the agonist both temporally and quantitatively. Insufficient antagonist activity to neutralize agonist activity results in procholinergic side effects, whereas excessive antagonist activity results in anticholinergic side effects.

We have selected fesoterodine as the PAC component based on its attractive physical and chemical properties (similar to ML-007) and predictable exposures. Fesoterodine is an FDA-approved PAC for the treatment of overactive bladder with symptoms of urinary incontinence, urgency and frequency. The PAC has high solubility (> 50 mg/mL in water), high oral bioavailability, low protein binding, and minimal drug-drug interaction liability. The favorable physical chemical properties of the PAC make it ideal for a combination product to enable precision matching of the PK profiles. In addition, the PAC has demonstrated low CNS permeability compared to other anticholinergics across in vitro and in vivo studies, which is further confirmed by the low rates of CNS-related AEs relative to placebo reported in prior clinical trials conducted by third parties. The low CNS penetration of the PAC was also confirmed in our dose-escalating animal studies, which demonstrated that plasma ratios of ML-007 to PAC greater than 10:1 resulted in no meaningful inhibition of ML-007's central effects.

Synchronized Agonist / Antagonist Exposures

ML-007 alone, co-administered or co-formulated with PAC has been studied in four completed Phase 1 clinical trials, with 270 healthy participants enrolled and more than 1,500 doses of ML-007 administered. Our deliberate and methodical approach to the Phase 1 clinical development has allowed us to evaluate a broad range of doses and dose ratios of the combination to characterize the impact on safety and tolerability. The fixed dose combination of ML-007C-MA is denoted as dose of ML-007 (in mg) in combination with dose of PAC (in mg) in subsequent sections.

Study 011, which enrolled 13 cohorts and evaluated 22 different dosing paradigms of immediate-release oral solution ML-007 alone and co-administered with oral solution PAC, explored a wide range of dosing ratios to attempt to optimize the peripheral side effect profile of the combination. Pharmacodynamic measures of peripheral muscarinic activity, and in particular salivary volume changes, functioned as real-time markers in the refinement of ratios of ML-007 to PAC. Anticholinergic events (e.g., dry mouth, tachycardia, feeling hot, and dry eye) were most frequently observed at ML-007:PAC plasma exposure ratios less than 100:1, and procholinergic events (e.g., nausea, vomiting, diarrhea, hyperhidrosis, and hypersalivation) were more common at plasma ratios greater than 600:1. Together with an evaluation of tolerability, including cholinergic side effects and objective safety measures (e.g., heart rate, blood pressure and ECG findings), the analyses allowed for establishment of a target plasma ratio of ML-007:PAC of 100:1 to 600:1.

Study 012 evaluated escalating once-daily and twice-daily doses of extended-release ML-007, or ML-007 ER, co-administered with PAC ER at doses and ratios informed by the prior clinical trials. Although the release profiles of the two components were not fully optimized, the study demonstrated close PK synchronization of the two components. The observed and modeled ratio of the plasma concentrations of the two components was tightly matched and remained within the target range throughout the duration of the dosing cycle.

Study 013 evaluated doses up to 210/3 mg twice daily, or BID, and 330/6 mg once daily, or QD, in single and multiple-dose paradigms. This was the first study to utilize the bi-layer, co-formulated tablet of ML-007C-MA, the same formulation that is currently under evaluation in our ongoing Phase 2 trials. The study demonstrated that ML-007C-MA BID and QD target doses at steady state achieved and maintained ML-007 CSF concentrations that exceeded our target range over the majority of the dosing period in both healthy adults and healthy elderly participants. In addition, ML-007:PAC plasma concentration ratios were generally maintained within the target range at steady state (see Figure 4 below) during the dosing period. The PK exposures at the target doses at steady state (Day 7) demonstrated low variability, with a coefficient of variation (CV) of approximately 30%.

For a further description of the design of our Phase 1 clinical trials, see "—ML-007C-MA Clinical Development History" below.

Figure 4: Matching of ML-007 and PAC Plasma Concentrations Demonstrated in Study 013

Potential Advantages of Our Lead Product Candidate, ML-007C-MA

Based on the results of our preclinical and clinical studies to date, we believe that ML-007C-MA has demonstrated the potential to be differentiated across the following key domains:

Safety and Tolerability Profile: Precision matching of the peripheral exposures of the muscarinic agonist, ML-007, and PAC is designed to limit the pro- and anticholinergic side effects. ML-007C-MA was generally well tolerated in healthy adult and elderly participants at the doses being evaluated in the ongoing Phase 2 studies.

Ease of Use: In Study 013, ML-007C-MA was well tolerated with minimal titration and achieved CSF exposures above anticipated clinically relevant levels with once- or twice- daily dosing. The PK parameters in different food states showed that ML-007C-MA administration will not require a fasted state. Our Phase 2 ZEPHYR trial for schizophrenia employs a single titration dose and our Phase 2 VISTA trial for ADP employs a 1-week titration to reach the target maintenance dose.

Therapeutic Benefit Across Key Symptom Domains: We believe that strong activation of both M1 and M4 receptors by ML-007C-MA has the potential to improve both positive and negative symptoms of schizophrenia. ML-007C-MA also offers the potential to improve cognitive symptoms based on ML-007's strong M1 agonism shown in preclinical studies and provide cognitive benefit previously demonstrated by other muscarinic agonists in clinical trials.

Safety and Tolerability Profile

We have performed clinical PK / PD trials of ML-007 and the PAC along with formulation optimization to attempt to precisely match the peripheral exposures of the agonist and antagonist components of ML-007C-MA, which has shown favorable tolerability in healthy adult and elderly participants.

In Study 013, at steady state after multiple BID and QD doses of ML-007C-MA were administered in healthy adults and elderly participants, the plasma ML-007:PAC concentration ratios were generally maintained within the desired range over the dosing interval. In addition, the PK exposures at steady state demonstrated low inter- and intra-subject variability.

ML-007C-MA was generally well tolerated in healthy volunteers at the doses currently being evaluated in the ongoing Phase 2 trials. At these doses:

Most of the TEAEs observed were mild, transient and self-limiting in nature.

Low rates of moderate TEAEs were observed, and there were no serious or severe adverse events.

Most TEAEs were cholinergic in nature, and procholinergic events were reported more frequently than anticholinergic events.

No clinically meaningful changes in mean blood pressure were observed.

No clinically meaningful mean changes across any laboratory values, including liver enzyme levels, were observed.

The safety and tolerability profile observed in this trial supported advancing doses up to 210/3 mg BID and 330/6 mg QD for the Phase 2 ZEPHYR trial in schizophrenia and doses up to 210/3 mg BID for the Phase 2 VISTA trial in ADP.

Ease of Use

Once- and Twice-Daily Dosing Expected

Bioanalysis of plasma and CSF samples that were collected throughout our Phase 1 development has allowed us to reliably model the CSF exposures for ML-007 based on plasma PK exposures. PK modeling of the observed plasma and CSF data in Study 013 was used to predict ML-007 CSF concentration profile at steady state for our target doses over the dosing interval. The target doses of 210/3 mg BID and 330/6 mg QD doses resulted in predicted CSF exposures at or above the target range for all or most of the dosing period, as shown in Figure 5.

Figure 5: Modeled CSF Exposures for ML-007 at the Phase 2 Target Doses

Minimal Titration Requirements Expected

We have evaluated a number of titration regimens through our Phase 1 development. In Study 013, the target doses in healthy adults were better tolerated when preceded by a single lower titration dose. In this trial, we also evaluated both a 2- and 7-day titration period in healthy elderly participants, demonstrating that both were tolerable. Our Phase 2 ZEPHYR trial for schizophrenia employs a single titration dose to reach the target maintenance dose for both BID and QD dosing regimens. Our Phase 2 VISTA trial for ADP employs a 1-week titration to reach the target maintenance dose.

No Fasting Requirements Expected

In Study 013, we explored dosing in healthy participants under fasted and fed conditions. ML-007C-MA was well tolerated in fed and fasted conditions, but tolerability was improved when administered in the fed conditions. ML-007 PK exposures were higher in the fed conditions compared with the fasted condition while there was no food effect on the PAC PK. Between low-calorie/low-fat and high-calorie/high-fat conditions, the PK exposures for both ML-007 and PAC were comparable. In the ongoing Phase 2 trials, ML-007C-MA will be dosed proximal to a meal.

Therapeutic Benefit Across Key Symptom Domains

Both M1 and M4 Receptors Played Significant Roles in the Reduction of Symptoms in the Amphetamine-Induced Hyperlocomotion Model

Activation of both M1 and M4 receptors has been proposed to alleviate psychotic behaviors. To test which receptors contribute to the therapeutic effects of ML-007 and xanomeline in the AIH model, both drugs were evaluated in wild-type M1 knockout, or M1KO, and M4 knockout, or M4KO, mice. This study demonstrated that activation of both M1 and M4 receptors is required for antipsychotic activity of ML-007 and xanomeline at clinically relevant doses in the AIH model. At high doses, M1 or M4 activation by ML-007 was sufficient to reverse hyperlocomotion in the AIH model (see Figure 6). Xanomeline did not reach full activity with M1 activation alone. Importantly, ML-007 showed a slight M1 bias whereas xanomeline showed a slight M4 bias, suggesting that in addition to having strong antipsychotic activity, ML-007 may have additional potential to treat M1-dependent deficits such as cognition.

Figure 6: Pharmacodynamic Effects of ML-007 and Xanomeline in WT, M1KO and M4KO AIH Models

ML-007 Improved Memory in a Mouse Model of Alzheimer's Disease

To evaluate the pro-cognitive effects of ML-007 and to compare its activity with xanomeline in a head-to-head study, mice with impaired memory (in a model of Alzheimer's disease) were given each drug separately and assessed in one of two tasks: a Y-maze spatial reference memory assay (see Figure 7, left) or a social memory assay (see Figure 7, right). Equipotent doses of ML-007 and xanomeline were chosen based on their similar effects on locomotion. Treatment with ML-007 significantly improved spatial memory in the Y-maze, improving discrimination between familiar and novel spaces, whereas xanomeline did not improve memory performance. In the social memory test, ML-007, unlike xanomeline, enhanced the memory of a familiar mouse, relative to a novel mouse and the test mouse spent more time with the novel mouse. Taken together, these data support the conclusion that ML-007 exerted pro-cognitive effects in an animal model with memory impairment.

Figure 7: Observed Improved Spatial Memory and Social Memory Following ML-007 Administration

ML-007C-MA Clinical Development History

We have completed four Phase 1 clinical trials with ML-007 alone, co-administered or co-formulated with PAC, with 270 healthy participants enrolled and more than 1,500 doses administered. These trials allowed for the establishment of well-tolerated dosing regimens expected to provide adequate CNS exposure of ML-007 while mitigating the peripheral cholinergic AEs. See Figure 8 below for the Phase 1 development history.

Figure 8: Summary of Phase 1 Clinical Trials

Study 013

Our most-recent Study ML-007C-MA-013, or Study 013, was a single-center Phase 1, 4-cohort study to evaluate the safety, tolerability, and PK of ML-007C-MA under fasted versus fed conditions, with single and multiple doses of ML-007C-MA in healthy adult participants and multiple doses of ML-007C-MA in healthy elderly participants. In addition, this study explored the safety and tolerability of higher doses of ML-007 than previously tested, and whether titration had an impact on safety and tolerability.

Cohort 1 evaluated a single ML-007C-MA dose of 165/3 mg in 10 healthy adult participants under fasted and fed conditions.

Cohort 2 evaluated escalating doses of ML-007C-MA up to 210/3 mg BID and 330/6 mg QD in 8 healthy adult participants.

Cohorts 3 and 4 evaluated ML-007C-MA and placebo in healthy adult (Cohort 3) and healthy elderly (Cohort 4) participants in a multi-dose paradigm with a 7-day treatment at target maintenance doses. In each cohort, 32 participants were enrolled with 8 participants in each dosing group, 2 of whom were randomized to receive placebo.

In Cohort 1, ML-007 PK exposures were higher in the fed conditions compared with that in the fasted condition, while there was no food effect on the PAC PK. Between low-calorie/low-fat and high-calorie/high-fat conditions, the PK exposures for both ML-007 and PAC were comparable. ML-007C-MA was well tolerated in fed and fasted conditions, but tolerability was improved when administered in the fed conditions.

In Cohort 2, ascending doses of up to 210/3 mg BID and 330/6 mg QD were considered safe and well tolerated. Tolerability of 210/3 mg was improved when a single lower titration dose was administered 12 hours prior.

In Cohort 3, maintenance doses of 165/3 mg BID, 210/3 mg BID, 270/6 mg QD, and 330/6 mg QD were evaluated in healthy adult participants. Titration regimens of one dose to four days of dosing were assessed. All four dosing regimens of ML-007C-MA were well tolerated during titration and for the full 7-day maintenance dosing duration. Most TEAEs were mild and no severe or serious TEAEs were observed. Most TEAEs were cholinergic in nature, and procholinergic events were reported more frequently than anticholinergic events. The types of TEAEs,

their incidence and intensity did not worsen with multiple days of dosing. At these doses, the most common non-procedural TEAEs (occurring in more than one participant in any ML-007C-MA group and at a greater incidence than placebo) during maintenance dosing were chills, constipation, dizziness, dyspepsia, headache, hyperhidrosis, nausea, salivary hypersecretion, and vomiting.

At the target doses selected for the ongoing Phase 2 ZEPHYR trial in schizophrenia, the most common non-procedural TEAEs (occurring in more than 1 participant in any ML-007C-MA group and at a greater incidence than placebo) during maintenance dosing are shown in Figure 9. At these target doses during the maintenance dosing period, no episodes of vomiting or constipation were reported. In addition, there were no episodes of anticholinergic TEAEs.

Figure 9: Summary of TEAEs Observed in >1 Participant During the 7-Day Maintenance Dose Period at Target Doses Selected for Ongoing Phase 2 ZEPHYR Trial in Schizophrenia

In Cohort 4, maintenance doses of 165/3 mg BID, 210/3 mg BID and 330/6 mg QD were evaluated in healthy elderly participants. Titration regimens of 2 days and 7 days were assessed. The titration dose of 105/1.5 mg BID and maintenance doses of 165/3 mg BID and 210/3 mg BID were well tolerated. However, the maintenance dose of 330/6 mg QD was not well tolerated. Most TEAEs across the cohort were mild and there were no severe or serious TEAEs. Most TEAEs were cholinergic in nature, and procholinergic events were reported more frequently than anticholinergic events.

In healthy elderly participants who received BID dosing regimens up to 210/3 mg, the most frequently reported non-procedural TEAEs (occurring in more than one participant in any ML-007C-MA BID group and at a greater incidence than placebo) during maintenance dosing were abnormal feces, hyperhidrosis, nausea, feeling hot, upper abdominal pain, dizziness, headache, penile burning sensation, and tremor. In elderly adults who received QD 330/6 mg, which was not considered well tolerated, the most frequently reported non-procedural TEAEs during maintenance dosing were nausea, dizziness, headache, tremor, hyperhidrosis, salivary hypersecretion, vomiting, chills, fatigue, malaise, increased blood pressure and decreased appetite.

At the target dose selected for the ongoing Phase 2 trial in ADP, the most common non-procedural TEAEs (occurring in more than one participant in any ML-007C-MA group and at a greater incidence than placebo) during maintenance dosing are shown in Figure 10. At the target dose during the maintenance dosing period, only one episode of vomiting and one episode of constipation were reported. In addition, there were low rates of anticholinergic TEAEs, including no episodes of urinary retention.

Figure 10: Summary of TEAEs Observed in >2 Participants During the 7-Day Maintenance Dose Period at Target Dose Selected for Ongoing Phase 2 VISTA Trial in ADP

Transient dose-dependent mean increases in heart rate, or HR, were observed with ML 007C-MA. However, the magnitude of the increase was generally smaller in elderly adults relative to non-elderly adults. Increased HR has been previously reported for the PAC as a single agent or in other muscarinic agonist programs. There were no clinically meaningful mean changes across any laboratory values. There were no other clinically meaningful changes in vital signs and physical examination findings.

Across all cohorts, the PK of ML-007 and PAC were approximately linear and the PK exposure was not affected by different dose combinations. The steady-state ML-007:PAC concentration ratios after multiple repeated BID or QD dosing generally remained within the desired range of 100:1 to 600:1 over the majority of the dosing interval. In addition, the ML-007 CSF concentration was maintained at or above the predicted efficacious CSF levels as defined by preclinical studies. As a result, we determined the safety and PK observations in ML-007C-MA supported advancing target doses in Phase 2 studies of up to 210/3 mg BID and 330/6 mg QD in non-elderly adult participants and target doses of up to 210/3 mg BID in elderly participants.

Additional Previous Phase 1 Trials

Study 001

Study ML-007-001, or Study 001, was a randomized, placebo-controlled Phase 1 first-in-human, single-ascending dose, or SAD, trial that evaluated the PK, safety and tolerability of ML-007 oral solution in 58 healthy adult participants across two groups.

Group 1 received ML-007 only, with cohorts receiving escalating single doses (0.8 mg, 2.5 mg, 8.2 mg, 16 mg, 32 mg and 49 mg) until a maximum tolerated dose, or MTD, was reached.

Group 2 received 6 mg PAC ER or matched placebo administered 4 hours before 32 mg ML-007 (in an effort to match the Tmax of the two drugs).

The resulting data indicated that ML-007 was generally well tolerated when administered alone up to the MTD of 32 mg. At the ML-007 dose of 32 mg, a CSF concentration of 50 ng/mL was reached around the time of Cmax, which exceeded the target-estimated, minimum-efficacious CSF level of 20 ng/mL based on animal studies. Data from Group 2 indicated that predosing with 6 mg of PAC reduced procholinergic effects and improved the tolerability of a single dose of ML-007.

Study 011

Study ML-007-011, or Study 011, was a Phase 1 randomized, three-part SAD/multiple ascending dose, or MAD, trial evaluating the safety, tolerability and PK of ML-007 (oral solution) with and without PAC (oral solution) in 106 healthy adults and elderly adult participants.

The three-part trial was designed to evaluate the relative dose and timing of PAC co-treatment required to ameliorate ML-007-associated cholinergic effects in healthy adult participants (Part 1); to evaluate the multiple-dose safety and tolerability of ML-007 oral solution in combination with PAC oral solution in healthy adult participants (Part 2); and to evaluate the multiple-dose safety and tolerability of ML-007 oral solution in combination with PAC oral solution in healthy elderly participants (Part 3).

In this trial, we found that single doses of ML-007 oral solution up to and including 164 mg (which is approximately five times the single agent MTD) were well tolerated with the co-administration of PAC oral solution. An intolerable dose was not reached when ML-007 was co-administered with the PAC. Multiple doses of ML-007 up to and including 111 mg co-administered with PAC were well tolerated in a multiple-dosing regimen of five days to seven days in healthy adult and elderly participants, respectively.

Most TEAEs were mild and self-limited in nature and there were no serious adverse events, or SAEs. At fixed single doses of ML-007, TEAE rates declined when the PAC dose was reduced, and a more optimal ratio of pro- and anticholinergic components was achieved. The type, severity, and duration of TEAEs experienced by the healthy elderly participants were similar to those experienced by non-elderly adults.

Study 012

Study ML-007-012, or Study 012, was the first trial to assess the ER ML-007 formulation. It was a two-part, single-center, non-randomized, open-label Phase 1 trial of ML-007 ER administered with or without PAC ER in 24 healthy adult participants. The two-part trial was designed to evaluate the safety, tolerability and PK of single escalating doses of ML-007 ER (with and without PAC ER) and to compare ML-007 solution with ML-007 ER under fed or fasted conditions (Part 1); to evaluate the safety, tolerability and PK of escalating doses of ML-007 ER administered BID with PAC ER (Part 2); and to assess the intended relevant clinical dosing strategy for future trials.

The two-part trial design included:

Part 1, comprised of two cohorts with eight non-elderly adult participants per cohort (total n=16), with escalation of QD doses up to 250 mg ML-007 ER with PAC ER.

Part 2, comprised of one cohort with eight non-elderly adult participants (n=8), with escalation of BID doses up to 165 mg ML-007 ER with PAC ER.

The results of Study 012 demonstrated that ML-007 ER administered with or without PAC ER was generally well tolerated. AEs were infrequent, and AE rates were lower than those observed with ML-007 oral solution. All TEAEs observed were mild in severity. There were no moderate or severe AEs with the ER formulation, and no SAEs or deaths. BID dosing did not result in higher rates of TEAEs than once-daily dosing and there were no new TEAEs observed, when compared with previous TEAE profiles associated with ML-007 oral solution administration.

This trial also assessed the safety, tolerability and PK of a novel, orally dissolving tablet, or ODT, formulation of ML-007. The observed data with the ODT formulation was similar to that with oral solution, consistent with its similar PK.

Our Ongoing Clinical Development

Phase 2 ZEPHYR Study for Schizophrenia

We are currently conducting a double-blind, placebo-controlled Phase 2 clinical trial of ML-007C-MA in hospitalized adult patients with a schizophrenia diagnosis who are experiencing an acute exacerbation of psychotic

symptoms. We expect to enroll approximately 300 participants in this trial across multiple sites throughout the United States. Patients are randomized 1:1:1 to receive either placebo, ML-007C-MA 210/3mg BID, or ML-007C-MA 330/6mg QD.

Ongoing antipsychotics, if applicable, are discontinued during the screening period. After the wash-out period, participants receive a single titration dose of ML-007C-MA 105/3mg (or placebo) before receiving the maintenance dose (or placebo). Participants are permitted a one-time dose reduction from their target dose, if needed, to address tolerability issues. Participants requiring a dose reduction will remain on the reduced dose for the remainder of the study.

The primary efficacy endpoint is change in total PANSS score from baseline to week 5. Additional key secondary endpoints include changes in the clinical global impression scores and PANSS Marder factor scores. Our multi-pronged approach to study design and conduct to mitigate potential placebo response in the study includes strategic site selection, rigorous patient eligibility review, in-house data monitoring and quality oversight directed by our team.

We expect the trial to reach the target enrollment of 300 participants in April 2026 and report topline results in the third quarter of 2026.

Figure 11: Phase 2 ZEPHYR Trial Design

Phase 2 VISTA Trial for ADP

We are conducting a double-blind, placebo-controlled Phase 2 clinical trial of ML-007C-MA for the treatment of hallucinations and delusions associated with ADP. We expect to enroll approximately 300 participants in this trial globally. Participants are randomized 1:1 to receive either placebo or ML-007C-MA 210/3 mg BID.

Eligible participants begin dosing with titration dose of ML-007C-MA 105/1.5mg (or placebo) for one week before receiving the maintenance dose (or placebo). Participants are permitted a one-time dose reduction to the reduced dose, if needed, to address tolerability issues. Participants requiring a dose reduction will remain on the reduced dose for the remainder of the study.

The primary efficacy endpoint is change in NPI-C H+D score from baseline to week 7. Additional secondary endpoints include changes in the clinical global impression scores and NPI-C agitation and aggression scores.

We expect to report topline results from this study in the second half of 2027. In December 2025, ML-007C-MA was granted Fast Track designation by the FDA for the treatment of hallucinations and delusions associated with ADP.

Figure 12: Phase 2 VISTA Trial Design

ML-004 for the Treatment of Autism Spectrum Disorder

Our second product candidate, ML-004, is a 5-HT1B/1D agonist that we are developing for the treatment of social communication deficit and/or irritability in ASD. Historical clinical development efforts for ASD have been challenging given the biological heterogeneity of symptoms across age, developmental level and sex, and the lack of validated outcome measures. There are currently no FDA-approved therapies for the core symptoms of ASD, social communication deficit and repetitive/restricted behavior. The only two therapies approved for ASD-associated irritability are atypical antipsychotics, which are associated with serious side effects. ML-004 is an IR/ER formulation of zolmitriptan. We are currently conducting IRIS, a Phase 2 trial to evaluate the efficacy of ML-004 for the improvement of social communication deficits in patients with ASD. Change from baseline in irritability symptoms is a secondary endpoint. We have completed enrollment in this trial and expect to report topline results in the third quarter of 2026. Based on the results from the IRIS trial, we intend to explore potential strategies for further development of ML-004.

Overview of Autism Spectrum Disorder

ASD is a neurodevelopmental condition characterized by the core features of impaired social communication and restricted / repetitive thoughts and behaviors. In addition to the core symptoms of the disorder, many individuals with ASD experience high rates of comorbid neurobehavioral symptoms, including irritability and aggression (in approximately 25% of ASD patients), hyperactivity and mood lability. Greater impairments in social communication are associated with higher rates of these maladaptive behaviors and decreased social functioning. The prevalence of ASD has been steadily increasing, and approximately 1.8 million U.S. children and adolescents ages 3-17 and over five million adults in the United States are living with ASD. ASD is associated with higher health care and school costs, increased caregiver burden and loss of caregiver income and substantial functional, occupational and quality-of-life impacts to patients and families affected by the condition.

There are no FDA-approved pharmaceutical treatments for the core symptoms of ASD. The only widely accepted intervention with supportive clinical evidence is long-term behavioral therapy, for up to 30-40 hours per week, which can place substantial burdens on families and reduce the amount of school time available to children. The atypical antipsychotics, risperidone and aripiprazole, are approved by the FDA to treat irritability symptoms

associated with ASD. However, both have potentially serious side effects, including increased appetite, weight gain, fatigue, EPS, metabolic changes (hyperglycemia, diabetes mellitus and dyslipidemia), hyperprolactinemia, somnolence and sedation. Additionally, both drugs are ineffective in treating the core social features of the disorder and symptoms often return when the drug is discontinued. The need to find effective treatments to address ASD's core and associated symptoms, therefore, remains significant.

Our Product Candidate, ML-004

ML-004 is an IR/ER oral tablet formulation of the 5-HT1B/1D agonist, zolmitriptan, intended for once-daily dosing for the chronic treatment of social communication deficits and behaviors associated with ASD. Zolmitriptan has been commercially available since 1997 for the acute treatment of migraine headaches in adults. More than 25 million prescriptions have been filled for zolmitriptan in the United States since its launch.

Rationale for 5-HT1B Receptor Agonism for the Treatment of Sociability and Irritability in ASD

Our rationale for this program is built upon the historical association between dysregulated serotonin and ASD pathology. More recent evidence establishing the role of 5-HT1B receptor activation in sociability was generated through experiments in which blocking 5-HT1B receptors disrupted social reward. These findings were further supported by our preclinical work demonstrating that 5-HT1B agonists increased sociability in ASD models and decreased aggression.

Optogenetic experiments have demonstrated that activating the serotonin circuit from the dorsal raphe nucleus, or DRN, to the nucleus accumbens, or NAc, could increase sociability. Conversely, suppressing this serotonin circuit using an inhibitory opsin decreased sociability. In mouse models of ASD, including the 16p11 syntenic deletion model, that show baseline decreases in social behavior, activation of the DRN to NAc circuit significantly increased social interaction, an effect that was blocked by a 5-HT1B antagonist.

An additional set of findings independently established that 5-HT1B activation can increase sociability. This finding emerged from work aimed at identifying circuit biology responsible for the known pro-social effects of methylamphetamine, or MDMA. MDMA is an illicit drug known to cause profound feelings of social connectedness and empathy in humans. In animal models, it was shown that mice treated with MDMA demonstrated dose-dependent increases in social behavior. This increase in sociability was blocked by infusing a 5-HT1B blocker into the NAc, indicating that 5-HT1B receptors located in the NAc are necessary for the pro-social benefits of MDMA.

Our Preclinical Studies

Based on these findings, we hypothesized that a selective 5-HT1B agonist could increase sociability, replicating the pro-social effects of MDMA without the addictive liability. We chose the approved brain-penetrant 5-HT1B/1D agonist zolmitriptan and demonstrated that it could reproduce the pro-social effects of both MDMA and the optogenetic activation of the DRN to NAc circuit in animal models. Zolmitriptan (marketed as ZOMIG) is commonly used in low doses as an acute treatment for migraine headaches, and as such, its IR safety profile has been well established. However, for chronic treatment of social communication deficits and irritability, a different formulation is required. ML-004 is an IR/ER oral tablet designed for chronic use at higher doses than those previously approved, prompting additional studies to establish safety, tolerability and PK prior to Phase 2 efficacy trials.

To evaluate zolmitriptan's potential therapeutic impact in treating sociability and irritability in ASD, we have conducted several in vivo animal studies, including mouse models for valproic acid, or VPA, and CNTNAP2 knock out. These studies demonstrated consistent, statistically significant improvements in sociability and aggression. In both animals and humans, prenatal VPA is known to increase the risk for ASD in offspring. Mice born to mothers treated prenatally with VPA show a higher rate of social deficit. Administration of zolmitriptan at a dose of 10 mg/kg significantly reversed the social deficit in these mice. Neurobiological, genetic and imaging data provide evidence for the CNTNAP2 gene as a risk factor for ASD and related neurodevelopmental disorders. As with the VPA-treated mouse model, treatment with zolmitriptan 10 mg/kg significantly improved the social deficit phenotype in CNTNAP2 KO mice. Our preclinical studies utilized commercially available zolmitriptan.

Our Clinical Trials of ML-004

We have formulated ML-004 for chronic use at higher doses than approved doses for zolmitriptan and have conducted two Phase 1 trials for our ML-004 program to evaluate safety, tolerability and PK. Based on the results of the Phase 1 trials, we are currently conducting a Phase 2 trial in ASD patients to evaluate the safety and efficacy of ML-004 compared with placebo in the improvement of social communication deficits and expect to report results in the third quarter of 2026.

Phase 1 Trial MAP-ZOL-HV-001

We completed a randomized, double-blind, placebo-controlled MAD PK Phase 1 trial that evaluated high-dose IR zolmitriptan oral formulation in a total of 40 healthy adult volunteer participants randomized into five ascending dose study drug cohorts of 5 mg, 10 mg, 20 mg, 30 mg and 40 mg, or placebo dosed three times a day, or TID. The dosing regimen included a two-day to four-day 'up-titration period' followed by a seven-day 'treatment period' at the targeted treatment dose, followed by a two-day to five-day 'down-titration' period.

In this Phase 1 trial, the most common AEs in participants on zolmitriptan were headache, dizziness, nausea and hiccups. These AEs occurred at a higher frequency at the 40 mg TID dose. Most AEs were mild in nature and there were no SAEs. In addition, there were no clinically significant or dose-responsive changes in mean QTc.

Phase 1 Trial ML-004-ER-001

We completed an open-label bioavailability and PK Phase 1 trial that evaluated ML-004 as a zolmitriptan bi-layer IR/ER gastroretentive 24 mg oral tablet formulation (6 mg IR/18 mg ER) in a total of 12 healthy adult participants under fasted and fed conditions. The dosing regimen included 20 mg of zolmitriptan IR on Day 1, 24 mg of ML-004 under fasted conditions on Day 2 and 24 mg of ML-004 under fed conditions on Day 4.

In the trial, a single dose of ML-004 24 mg in healthy adult participants resulted in a prolonged absorption phase and reduced Cmax compared to IR zolmitriptan. Based on these results, modeled data suggested that ML-004 48 mg and 72 mg would result in target plasma exposure based on preclinical efficacy models for approximately 12-15 hours, respectively.

In the trial, zolmitriptan IR and ML-004 24 mg were generally well tolerated, and AEs were less common with ML-004 dosing than with IR zolmitriptan dosing. All TEAEs were non-serious and mild to moderate. All participants completed the trial, and no participants discontinued or interrupted trial treatment due to AEs.

Ongoing Phase 2 Trial

Our Phase 2 IRIS trial is an ongoing multicenter, randomized, double-blind, placebo-controlled trial that enrolled approximately 160 adolescent (age 12-17) and adult (age 18-45) participants with ASD to evaluate the efficacy of ML-004 compared with placebo in the improvement of core social communication deficits. The trial employs a flexible dosing paradigm (target maintenance doses of ML-004 include 24 mg, 48 mg and 72 mg), and the primary endpoint (change from baseline to the end of the maintenance dosing on the Autism Behavior Inventory, Social Communication Domain Score) is assessed after 12 weeks of maintenance dosing. A key secondary endpoint includes the change from baseline on the Aberrant Behavior Checklist-Irritability, or ABC-I, for patients whose ABC-I score at baseline represented moderate or greater irritability.

Following completion of the antecedent IRIS trial, patients are eligible to participate in an active 52-week open-label extension trial designed to assess the long-term safety of ML-004 administration.

We have completed enrollment in this trial and expect to report topline results in the third quarter of 2026. Based on the results from the IRIS trial, we intend to explore potential strategies for further development of ML-004.

Preclinical Programs

ML-009

ML-009 is our GPR52 PAM program, which we are developing for the treatment of hyperactivity, impulsivity and agitation-related disorders. GPR52 is an orphan receptor that is selectively expressed in the indirect pathway neurons of the striatum, where it regulates neuronal function through activation of cAMP-dependent pathways. GPR52 is co-localized with dopamine D2 receptors, which are the primary target of antipsychotics. Activation of GPR52 opposes the actions of D2 receptors and increases the activity of indirect pathway striatal neurons.

In preclinical studies, GPR52 activation reduced stimulant-induced hyperactivity, impulsivity and aggression, without causing catalepsy. Using our internal medicinal chemistry, we have identified multiple novel potential product candidates that are selective, orally bioavailable positive modulators of GPR52. We have nominated a preclinical product candidate for further advancement and expect to complete IND-enabling studies in 2027.

ML-055

ML-055 is our next-generation, novel M1/M4 muscarinic agonist program, which we are developing for the treatment of neuropsychiatric conditions. Leveraging our experience with ML-007, we have continued to discover and develop multiple novel chemical series of M1/M4 agonists with varying potency, pharmacology and chemical properties. Preclinical in vitro and in vivo studies evaluating multiple potential candidates have demonstrated significantly greater potency relative to ML-007 and the potential for once-daily dosing and long-acting injectable formulation. We expect to nominate a preclinical candidate to advance to IND-enabling studies in 2026.

ML-021

ML-021 is our M4 antagonist program for the treatment of motor deficits in Parkinson's disease. ML-021 is designed to selectively target the muscarinic M4 receptors, which are highly expressed in direct pathway neurons of the striatum. Loss of striatal dopamine in Parkinson's disease results in an increase in striatal acetylcholine, which activates M4 receptors on direct pathway neurons and is predicted to reduce their activity and contribute to motor deficits in Parkinson's disease. Anticholinergic agents have been used for decades to treat Parkinson's disease, but their utility is limited by antagonist activity at M1 receptors that is linked to adverse effects including cognitive impairment, psychosis, and constipation. Selective antagonism of the M4 receptor is predicted to increase the activity of the direct pathway and improve motor symptoms in Parkinson's disease without the unwanted side effects associated with M1 antagonism. This mechanism is supported by optogenetic experiments in which activation of the direct pathway enhanced movement and rescued motor deficits in Parkinson's disease.

We have shown significant improvements in motor deficits in animal models of Parkinson's disease using multiple potential candidates and tool compounds. We have conducted preclinical studies using multiple potential candidates, including our lead preclinical candidate, and expect to finalize a preclinical candidate to advance to IND-enabling studies in 2027.

Intellectual Property

Overview of our Intellectual Property

Our success depends in part on our ability to obtain and maintain protection of intellectual property, particularly patents, in the United States and other countries with respect to product candidates and technology that are important to our business. We are actively building our intellectual property portfolio around our product candidates and discovery programs and have developed numerous patents and patent applications and possess substantial know-how and trade secrets relating to the development and commercialization of our neuropsychiatric product candidates. In addition to patent protection, we also rely on trade secrets to protect aspects of our business for which we do not consider patent protection appropriate. For information regarding risks related to our intellectual property, see the section titled "Risk Factors—Risks Related to Our Intellectual Property."

As of December 31, 2025, our patent estate contains approximately 86 issued patents and pending patent applications directed to our product candidates and certain of our proprietary technology, inventions, and improvements. In the United States, we own four issued patents, four pending non-provisional patent applications, and three pending provisional patent applications. We also own two pending Patent Cooperation Treaty, or PCT, applications. In jurisdictions outside of the United States, we own approximately 73 issued patents and pending patent applications that, in some cases, are counterparts to the foregoing U.S. patents and patent applications.

Our patent estate, which includes protection for our clinical and preclinical product candidates, as of December 31, 2025, is summarized below.

ML-007C-MA

As of December 31, 2025, we own three issued U.S. patents covering the composition of matter of ML-007 and one issued U.S. patent covering the use of ML-007 to treat, among other things, schizophrenia and ADP. The issued patents covering the composition of matter of ML-007 are expected to expire between 2031 and 2032, exclusive of possible patent term adjustments or extensions or other forms of exclusivity, and the issued patent covering the use of ML-007 to treat schizophrenia and ADP is expected to expire in 2031, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. We also own one pending U.S. application and 16 pending foreign applications (in Australia, Bahrain, Canada, China, the EPO, Eurasia, Hong Kong, Israel, Japan, the Republic of Korea, Kuwait, Mexico, New Zealand, Oman, Singapore and the United Arab Emirates) and two U.S. provisional applications directed to the combination of ML-007 and a PAC to treat, among other things, schizophrenia and ADP. Any patents issuing from these applications, if granted, will be expected to expire in 2042, exclusive of possible patent term adjustments or extensions or other forms of exclusivity and any patents issuing from patent applications that claim priority to these provisional applications, if granted, will be expected to expire in 2046, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. We also own one U.S. application and 18 pending foreign applications (in Australia, Bahrain, Brazil, Canada, China, Europe, Israel, India, Japan, Korea, Kuwait, Mexico, New Zealand, Oman, Russia, Saudi Arabia, Singapore, and the United Arab Emirates) directed to pharmaceutical compositions containing ML-007 and a PAC, and the use of such pharmaceutical compositions, to treat, among other things, schizophrenia and ADP. Any patents issuing from these applications, if granted, will be expected to expire in 2044, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Additionally, we own one pending PCT application covering salts and crystalline polymorphs of ML-007. Any patents issuing from this PCT application, if granted, will be expected to expire in 2045, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

ML-004

As of December 31, 2025, we own five issued foreign patents (in the EPO, Japan, Singapore, the Russian Federation, and Mexico), one pending U.S. application and 13 pending foreign applications (in Australia, Canada, China, the EPO, Hong Kong, Israel, Japan, the Republic of Korea, Mexico, New Zealand, the Russian Federation, Singapore and South Africa) directed to the use of ML-004 to treat, among other things, the symptoms of ASD. Any patents issuing from these pending patent applications, if granted, will be expected to expire in 2040, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. We also own one pending U.S. application and 21 pending foreign applications (in Australia, Bahrain, Brazil, Canada, China, the EPO, Hong Kong, Israel, India, Japan, the Republic of Korea, Kuwait, Mexico, New Zealand, Oman, Qatar, the Russian Federation, Saudi Arabia, Singapore, South Africa and the United Arab Emirates) directed to our IR/ER oral ML-004 compositions and their use to treat the symptoms of ASD. Any patents issuing from these pending patent applications, if granted, will be expected to expire in 2042, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

ML-009

As of December 31, 2025, we own one pending PCT application directed to small molecule GPR52 agonists. Any patents issuing from this PCT application will be expected to expire in 2044, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

ML-055

As of December 31, 2025, we own one pending U.S. provisional application directed to small molecule M1/M4 muscarinic agonists. Any patents issuing from patent applications that claim priority to this provisional application, if granted, will be expected to expire in 2046, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

ML-021

As of December 31, 2025, we own one pending U.S. provisional application directed to small molecule M4 antagonists. Any patents issuing from patent applications that claim priority to this provisional application, if granted, will be expected to expire in 2046, exclusive of possible patent term adjustments or extensions or other forms of exclusivity.

Patents

Individual patents have terms for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained. Generally, utility patents issued for applications filed in the United States are granted a term of 20 years from the earliest effective filing date of a non-provisional patent application. The duration of foreign patents varies in accordance with provisions of applicable local law, but typically is also 20 years from the earliest effective filing date. With regard to our U.S. provisional patent applications, if we do not file any corresponding non-provisional patent applications within 12 months of the provisional patent application filing date, we may lose our priority date with respect to our provisional patent applications and any patent protection on the inventions disclosed in our provisional patent applications. All taxes, annuities or maintenance fees for a patent, as required by the U.S. Patent and Trademark Office and certain foreign jurisdictions, must be timely paid in order for the patent to remain in force during this period of time.

The actual protection afforded by a patent may vary on a product-by-product basis, from country to country and can depend upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions and the availability of legal remedies in a particular country and the validity and enforceability of the patent. Our patents and patent applications may be subject to procedural or legal challenges by others. We may be unable to obtain, maintain and protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business. For more information, see the section titled "Risk Factors—Risks Related to Our Intellectual Property."

Trademarks, Trade Secrets and Proprietary Information

In addition to patents, we rely on trademarks, trade secrets, and know-how relating to our proprietary technology and programs, continuing innovation, and in-licensing opportunities to develop, strengthen and maintain our proprietary position in the field of neuropsychiatric medicine. As of February 25, 2026, our trademark portfolio currently contains seven trademark registrations in the United States, European Union, United Kingdom, China, Japan and South Korea for the mark "MAPLIGHT THERAPEUTICS."

We rely upon unpatented trade secrets and know-how and continuing technological innovation to develop and maintain our competitive position. However, trade secrets and know-how can be difficult to protect. We seek to protect our proprietary information, in part, by executing confidentiality agreements with our collaborators and scientific advisors and non-competition, non-solicitation, confidentiality and invention assignment agreements with our employees, consultants and independent contractors. We have also executed agreements requiring assignment of inventions with selected scientific advisors and collaborators. The confidentiality agreements we enter into are designed to protect our proprietary information, and the agreements or clauses requiring assignment of inventions to us are designed to grant us ownership of technologies that are developed through our relationship with the respective counterparty. We cannot guarantee, however, that we have executed such agreements with all applicable counterparties, such agreements will not be breached, or that these agreements will afford us adequate protection of

our intellectual property and proprietary rights. See the section titled "Risk Factors—Risks Related to our Intellectual Property."

NeuroSolis Asset Purchase Agreement

On June 18, 2020, we entered into an Asset Purchase Agreement with NeuroSolis, Inc., or NeuroSolis, to acquire its proprietary M1/M4 agonist molecules and associated intellectual property.

Pursuant to that agreement, NeuroSolis sold us its assets related to both its proprietary M1/M4 agonist molecules, and its program for the identification of molecules that modulate the activity of the muscarinic M1 receptor or the muscarinic M4 receptor. We did not assume any liabilities of NeuroSolis in connection with our purchase of these assets. We are obligated to use commercially reasonable efforts to achieve specified development and regulatory milestones by certain achievement dates by developing a product covered by a transferred patent, including ML-007C-MA. In May 2024, we and NeuroSolis entered into a Waiver of Milestone Deadline pursuant to which NeuroSolis agreed to waive the milestone achievement date for one of the specified development milestones, which we subsequently achieved in June 2025.

We have made upfront and development milestone payments of $150,000 in the aggregate to NeuroSolis. In addition, we agreed to issue NeuroSolis up to an aggregate of 62,083 shares of our common stock, contingent upon the occurrence of specified development and regulatory milestones, of which we issued 26,607 shares in June 2025 upon the achievement of a specified milestone.

Manufacturing

We do not own or operate and currently have no plans to purchase or establish any manufacturing facilities. We have engaged and expect to continue to rely on well-established third-party contract manufacturing organizations, or CMOs, to supply our product candidates for use in our preclinical studies and clinical trials. We intend to continue to rely on CMOs for later-stage development and commercialization of our product candidates, including any additional product candidates that we may identify. Because we rely on contract manufacturers, we employ personnel with extensive technical, manufacturing, analytical and quality experience to oversee contract manufacturing and testing activities and to compile manufacturing and quality information for our regulatory submissions. We believe our current manufacturers have the scale, systems and experience to supply our currently planned clinical trials.

Sales and Marketing

We do not currently have a commercial organization for the marketing, sales and distribution of products. We intend to build our global commercialization capabilities internally over time, such that we are able to commercialize any product candidate for which we may obtain regulatory approval. We expect to manage sales, marketing and distribution through internal resources and third-party relationships. In addition, we will opportunistically explore commercialization partnerships, particularly with entities that have strong capabilities in geographies outside the United States. As our current and future product candidates progress through clinical development, our commercial plans may change. Clinical data, the size of the development programs, the size of our target markets, the size of the requisite commercial infrastructure and manufacturing needs may all influence our commercialization strategies.

Competition

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property. While we believe our product candidates, approach, knowledge, experience and scientific resources provide us with competitive advantages, we face potential competition from many different sources, including pharmaceutical and biotechnology companies, academic institutions and governmental agencies, as well as public and private research institutions. Any product candidates that we successfully develop and commercialize will compete with approved treatment options, off-label therapies and new therapies that may become available in the future.

Our competitors may have significantly greater financial resources, established presence in the market and expertise in research and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and reimbursement and marketing approved products than we do. Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated among a smaller number of competitors. These competitors also compete with us in recruiting and retaining qualified scientific, sales, marketing and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to or necessary for our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Our commercial opportunity could be reduced or eliminated if competitors develop and commercialize products that are safer and more effective, have fewer or less severe side effects, are more convenient or are less expensive than any products that we may develop. Competitors also may obtain FDA or other regulatory approval for their products more rapidly or earlier than us, which could result in our competitors establishing a strong market position before we are able to enter the market. Additionally, technologies developed by our competitors may render our potential product candidates uneconomical or obsolete, and we may not be successful in marketing our product candidates against competitors.

Schizophrenia

We are developing ML-007C-MA for the treatment of schizophrenia. While there remains significant unmet need in schizophrenia, we may face competition from typical and atypical antipsychotic treatments that work primarily by inhibiting dopamine receptors.

We are aware of several product and product candidates in clinical development that modulate muscarinic receptors, such as Cobenfy (also known as KarXT), which is currently marketed by Bristol Myers Squibb Company for the treatment of schizophrenia; emraclidine, which is being developed by AbbVie Inc.; and direclidine, NBI-'570 and NBI-'567, which are being developed by Neurocrine Biosciences, Inc. In addition, we are aware of other companies that are in earlier stages of developing muscarinic agents for schizophrenia, as well as other CNS indications, including Neumora Therapeutics, Inc. and Syremis Therapeutics Ltd.

We may also face competition from other companies developing product candidates that modulate other receptors for the treatment of schizophrenia.

Alzheimer's Disease Psychosis

We are also developing ML-007C-MA for the treatment of ADP. Despite the severity of the condition, there are no FDA-approved medicines indicated for the treatment of patients with ADP. In the absence of approved treatments and reflecting significant unmet medical need, atypical and even some typical antipsychotics are used as off-label treatments. We are aware of several product candidates in clinical development that are designed to modulate muscarinic receptors, including Cobenfy, which is being developed by Bristol Myers Squibb Company.

We may also face competition from other companies developing product candidates to address ADP that modulate other receptors, including ACP-204, which is being developed by Acadia Pharmaceuticals, Inc. We may also face competition from other companies developing product candidates to address agitation or other behavioral symptoms associated with Alzheimer's disease.

Autism Spectrum Disorder

We are developing ML-004 for the treatment of ASD. Given the lack of approved, effective and safe treatment options, there is a significant unmet need for an effective therapeutic option for the treatment of social communication deficits in ASD. In the treatment of the irritability symptoms associated with ASD, we may face competition from ABILIFY, marketed by Otsuka Pharmaceutical Co., Ltd., and RISPERDAL, marketed by Johnson & Johnson, as well as from generic forms of those drugs that are being marketed and sold.

Government Regulation

Government authorities in the United States, at the federal, state and local level and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of products such as those we are developing. A new drug must be approved by the FDA through the New Drug Application, or NDA, process before it may be legally marketed in the United States.

U.S. Drug Development Process

In the United States, the FDA regulates drugs under the federal Food, Drug and Cosmetic Act, or FDCA, and its implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state and local statutes and regulations require the expenditure of substantial time and financial resources. The process required by the FDA before a drug may be marketed in the United States generally involves the following:

completion of preclinical laboratory tests, animal studies and formulation studies in accordance with Good Laboratory Practice regulations and other applicable regulations;

submission to the FDA of an IND, which must become effective before human clinical trials may begin;

approval by an IRB or ethics committee at each clinical site before each trial may be initiated;

performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice, or GCP, regulations to evaluate the safety and efficacy of the product candidate for its intended use;

submission to the FDA of an NDA after completion of all pivotal trials;

satisfactory completion of an FDA advisory committee review, if applicable;

satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is produced to assess compliance with current Good Manufacturing Practice, or cGMP, regulations to assure that the facilities, methods and controls are adequate to preserve the drug's identity, strength, quality and purity;

satisfactory completion of potential inspection of selected clinical investigation sites to assess compliance with GCP regulations; and

FDA review and approval of the NDA to permit commercial marketing of the product for particular indications for use in the United States.

Once a product candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information and analytical data, to the FDA as part of an IND. An IND is a request for allowance from the FDA to administer an investigational drug product to humans. An IND will also include a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated, if the trial includes an efficacy evaluation. Some preclinical testing may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns about ongoing or proposed clinical trials or non-compliance with specific FDA requirements, and in such case, the trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted.

All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP regulations, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials must be conducted under protocols detailing the objectives of the trial, dosing procedures, subject selection and exclusion criteria and the safety and

effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND, and a separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected AEs, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.

Furthermore, an IRB at each institution participating in the clinical trial must review and approve each protocol before a clinical trial commences at that institution and must also approve the information regarding the trial and the consent form that must be provided to each trial subject or his or her legal representative, monitor the trial until completed and otherwise comply with IRB regulations. The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB's requirements or if the drug has been associated with unexpected serious harm to patients. In addition, some clinical trials are overseen by an independent group of qualified experts organized by the sponsor, known as a data safety monitoring board or committee. Depending on its charter, this group may determine whether a trial may move forward at designated check points based on access to certain data from the trial. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries, including clinicaltrials.gov.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

Phase 1: The product candidate is initially introduced into healthy human subjects or patients with the target disease or condition, and tested for safety, dosage tolerance, absorption, metabolism, distribution and excretion and, if possible, to gain an early indication of its effectiveness.

Phase 2: The product candidate is administered to a limited patient population with a specified disease or condition to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product candidate for specific targeted diseases and to determine dosage tolerance and appropriate dosage.

Phase 3: The product candidate is administered to an expanded patient population to further evaluate dosage, to provide substantial evidence of efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk-benefit ratio of the product candidate and provide an adequate basis for product labeling.

Post-approval trials, sometimes referred to as Phase 4 trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

Concurrent with clinical trials, companies usually complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP regulations. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug. In addition, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

FDA Regulatory Framework for Fixed-Combination Prescription Drugs for Humans

The FDA's regulation at 21 CFR § 300.50 governing fixed-combination drug products provides, among other things, that two or more drugs may be combined in a single dosage form when each component contributes to the claimed effects and the dosage of each component (amount, frequency, duration) is such that the combination is safe and effective for a significant patient population requiring such concurrent therapy as defined in the labeling for the

drug. This rule is meant to ensure that any fixed-dose combination drug provides an advantage to the patient over and above that obtained when one of the individual ingredients is used in the usual safe and effective dose.

U.S. Review and Approval Process

The results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.

Once an NDA has been submitted, the FDA conducts a preliminary review of the application within the first 60 days after submission, before accepting it for filing, to determine whether it is sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product's identity, strength, quality and purity. Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of "filing" of a standard NDA for a new molecular entity to review and act on the submission. This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a "filing" decision after the application is submitted.

The FDA may refer an application for a novel drug to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the FDA will typically inspect the facility or facilities where the product is manufactured. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP regulations.

After the FDA evaluates an NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter, or CRL. An approval letter authorizes commercial marketing of the drug with prescribing information for specific indications. A CRL indicates that the review cycle of the application is complete, and the application will not be approved in its present form. A CRL usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, such as additional clinical trials or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing. If a CRL is issued, the sponsor must resubmit the NDA addressing all of the deficiencies identified in the letter or withdraw the application. Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product. In addition, the FDA may require a sponsor to conduct "Phase 4" testing, which involves clinical trials designed to further assess a drug's safety and/or effectiveness following NDA approval, and may require additional testing and surveillance programs to monitor the safety of approved products that have been commercialized. The FDA may also place other conditions on approval including the requirement for a risk evaluation and mitigation strategy, or REMS, to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without an approved REMS, if required. A REMS could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

In addition, the Pediatric Research Equity Act, or PREA, requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration. Under PREA, original NDAs and certain supplements must contain a pediatric assessment unless the

sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is deemed safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Expedited Development and Review Programs

The FDA has a number of programs intended to expedite the development or review of a marketing application for an investigational drug. For example, the Fast Track designation program is intended to expedite or facilitate the process for developing and reviewing product candidates that meet certain criteria. Specifically, investigational drugs are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. The sponsor of a Fast Track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the application may be eligible for priority review. With regard to a Fast Track product candidate, the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable and the sponsor pays any required user fees upon submission of the first section of the NDA.

A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review. A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the Fast Track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.

Any product candidate submitted to the FDA for approval, including a product candidate with a Fast Track designation or breakthrough designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. An NDA is eligible for priority review if the product candidate is designed to treat a serious condition and, if approved, would provide a significant improvement in safety or efficacy compared to available therapies. The FDA will attempt to direct additional resources to the evaluation of an NDA designated for priority review in an effort to facilitate the review. The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for review of new molecular entity NDAs under its current PDUFA review goals.

In addition, a product candidate may be eligible for accelerated approval. Drugs intended to treat serious or life-threatening diseases or conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA generally requires that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials, and may require that such confirmatory trials be underway prior to granting accelerated approval. Drugs receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required confirmatory trials in a timely manner or if such trials fail to verify the predicted clinical benefit. In addition, the FDA currently requires as a condition of accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Fast Track designation, breakthrough therapy designation, priority review, and accelerated approval do not change the standards for approval but may expedite the development or approval process. Even if a product

candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Post-Approval Requirements

Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications, certain manufacturing changes and additional labeling claims, are subject to further FDA review and approval. Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP regulations and other laws and regulations. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP regulations and other aspects of regulatory compliance.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with manufacturing processes or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of requirements for post-market trials or clinical trials to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include:

restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

fines, warning letters or untitled letters;

clinical holds on ongoing or planned clinical trials;

refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of approvals;

product seizure or detention, or refusal to permit the import or export of products;

consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

mandated modification of promotional materials and labeling and the issuance of corrective information;

the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

injunctions or the imposition of civil or criminal penalties.

In addition, the FDA closely regulates the marketing, labeling, advertising and promotion of drug products. A company can make only those claims relating to safety and efficacy that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the product's labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer's communications on the subject of off-label use of their products.

Hatch-Waxman Act

Section 505 of the FDCA describes three types of marketing applications that may be submitted to the FDA to request marketing authorization for a new drug. A Section 505(b)(1) NDA is an application that contains full reports of investigations of safety and efficacy. A 505(b)(2) NDA is an application that contains full reports of investigations of safety and efficacy but where at least some of the information required for approval comes from investigations that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted. This regulatory pathway enables the applicant to rely, in part, on the FDA's prior findings of safety and efficacy for an existing product, or published literature, in support of its application. Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an Abbreviated New Drug Application, or ANDA. An ANDA provides for marketing of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and intended use, among other things, to a previously approved product. ANDAs are termed "abbreviated" because they are generally not required to include preclinical (animal) and clinical (human) data to establish safety and efficacy. Instead, generic applicants must scientifically demonstrate that their product is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo, or other testing. The generic version must deliver the same amount of active ingredients into a subject's bloodstream in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug. In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant's drug or a method of using the drug. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, or the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an ANDA or 505(b)(2) NDA.

Upon submission of an ANDA or a 505(b)(2) NDA, an applicant must certify to the FDA that (1) no patent information on the drug product that is the subject of the application has been submitted to the FDA; (2) such patent has expired; (3) the date on which such patent expires; or (4) such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application is submitted. Generally, the ANDA or 505(b)(2) NDA cannot be approved until all listed patents have expired, except where the ANDA or 505(b)(2) NDA applicant challenges a listed patent through the last type of certification, also known as a paragraph IV certification. If the applicant does not challenge the listed patents or indicates that it is not seeking approval of a patented method of use, the ANDA or 505(b)(2) NDA application will not be approved until all of the listed patents claiming the referenced product have expired. If the ANDA or 505(b)(2) NDA applicant has provided a Paragraph IV certification to the FDA, the applicant must send notice of the Paragraph IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. If the Paragraph IV certification is challenged by an NDA holder or the patent owner(s) asserts a patent challenge to the Paragraph IV certification, the FDA may not approve that application until the earlier of 30 months from the receipt of the notice of the Paragraph IV certification, the expiration of the patent, when the infringement case concerning each such patent was favorably decided in the applicant's favor or settled or such shorter or longer period as may be ordered by a court. This prohibition is generally referred to as the 30-month stay. In instances where an ANDA or 505(b)(2) NDA applicant files a Paragraph IV certification, the NDA holder or patent owner(s) regularly take action to trigger the 30-month stay, recognizing that the related patent litigation may take many months or years to resolve. Thus, approval of an ANDA or 505(b)(2) NDA could be delayed for a significant period of time depending on the patent certification the applicant makes and the reference drug sponsor's decision to initiate patent litigation.

Marketing Exclusivity

Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a five-year period of non-patent data exclusivity within the United States to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an ANDA or 505(b)(2) NDA submitted by another company for another drug based on the same active moiety, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all the data required for approval.

However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The FDCA alternatively provides three years of non-patent exclusivity for an NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the active agent for the original indication or condition of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct, or obtain a right of reference to, all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of marketing exclusivity available in the United States. Pediatric exclusivity provides for an additional six months of marketing exclusivity attached to another period of existing exclusivity or an available patent term if a sponsor conducts clinical trials in children in response to a "written request" from the FDA. The issuance of a written request does not require the sponsor to undertake the described clinical trials, and the FDA's grant of pediatric exclusivity does not require the FDA to approve labeling containing information on pediatric use based on the studies conducted.

Healthcare Laws and Regulations

We are subject to healthcare regulation and enforcement by the federal government and the states and foreign governments in which that may constrain the business or financial arrangements and relationships through which we research, market, sell and distribute our drugs, if we obtain marketing approval. The healthcare laws and regulations that may affect our ability to operate include the following:

The federal Anti-Kickback Statute makes it illegal for any person or entity to knowingly and willfully, directly or indirectly, solicit, receive, offer or pay any remuneration that is in exchange for or to induce the referral of business, including the purchase, order, lease of any good, facility, item or service for which payment may be made under a federal healthcare program, such as Medicare or Medicaid. The term "remuneration" has been broadly interpreted to include anything of value.

Federal false claims and false statement laws, including the federal civil False Claims Act and civil monetary penalties laws, prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, for payment to, or approval by, federal programs, including Medicare and Medicaid, claims for items or services, including drugs, that are false or fraudulent.

The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors or making any false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, and their implementing regulations, imposes obligations on covered entities, including certain healthcare providers, health plans, and healthcare clearinghouses and their respective business associates and covered subcontractors that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children's Health Insurance Program, with specific exceptions, to report annually to CMS information related to payments or other transfers of value made to physicians (as defined to include doctors of medicine, dentists, optometrists, podiatrists and chiropractors by such law), other healthcare professionals (such as physician assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

Also, many states have similar laws and regulations, such as anti-kickback and false claims laws that may be broader in scope and may apply regardless of payor, in addition to items and services reimbursed under Medicaid and other state programs. Additionally, we may be subject to state laws that require certain regulatory licenses to manufacture or distribute our products commercially and/or the registration of pharmaceutical sales representatives in the jurisdiction, state laws that require pharmaceutical companies to comply with the federal government's and/or pharmaceutical industry's voluntary compliance guidelines, state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures, state laws that require drug manufacturers to report information on the pricing of certain drugs, state and local laws that require the registration of pharmaceutical sales representatives, as well as state and foreign laws governing the privacy and security of personal information, including health information, many of which differ from each other in significant ways and often are not preempted by HIPAA.

Ensuring that our business operations and arrangements with third parties comply with applicable healthcare laws and regulations will likely be costly. If our operations were found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, possible exclusion from government funded healthcare programs, such as Medicare and Medicaid, ongoing governmental oversight, contractual damages, reputational harm, diminished profits and future earnings and curtailment of our operations.

Additionally, to the extent that our products are sold in a foreign country, we may be subject to similar foreign laws.

Coverage and Reimbursement

Successful sales of our products in the U.S. market, if approved, will depend, in part, on the extent to which our products will be covered by third-party payors, such as government health programs like Medicaid and Medicare, or private health insurance (including managed care plans). Patients generally rely on such third-party payors to cover all or part of the costs associated with their health care, and therefore obtaining formulary status and adequate coverage from third-party payors is critical to new and ongoing product acceptance. Although antipsychotics are currently a protected class, formulary status and coverage for drug products can differ significantly from payor to payor as there is no uniform policy of coverage and reimbursement for drug products among third-party payors in the United States. There may be significant delays in obtaining formulary status and coverage, as the process of determining coverage is often time consuming and costly. A third-party payor's decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be approved. Further, one payor's determination to provide coverage for a drug product does not ensure that other payors will also provide coverage for the drug product. Third-party payors are increasingly reducing coverage for medical drugs and services and implementing measures to control utilization of drugs (such as requiring prior authorization for coverage). Patient copays can be significant and may vary among products within a class depending upon the formulary status of an agent with a particular payor. Inconsistencies in formulary status across state Medicaid plans and commercial payors may result in coverage gaps in some geographical areas.

Additionally, the containment of healthcare costs has become a priority of federal and state governments, and the prices of drugs have been a focus in this effort. The U.S. government, state legislatures, and foreign governments have shown significant interest in implementing cost-containment programs, including price controls, restrictions on coverage and requirements for substitution of generic drugs. For example, the U.S. Department of Health and Human Services, or HHS, imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis. HHS has also been empowered to negotiate the price of certain single-source drugs that have been on the market for at least seven (7) years under Medicare as part of the Medicare Drug Price Negotiation Program. Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program. Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Adoption or expansion of price controls and cost-containment measures could further limit our net revenue and results. Decreases in third-party coverage for our product candidates, if approved, or a decision by a third-party payor to not cover our product candidates could have a material adverse effect on our sales, results of operations, and financial condition.

General legislative cost control measures may also affect reimbursement for our products. If we obtain approval to market a product candidate in the United States, we may be subject to spending reductions affecting Medicare, Medicaid or other publicly funded or subsidized health programs and/or any significant taxes or fees.

U.S. Healthcare Reform

The U.S. government, state legislatures, and foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price-controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs.

For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, was enacted in the United States in 2010 and substantially changed the way healthcare is financed by both the government and private insurers. Since its enactment, there have been executive, judicial and Congressional challenges to certain aspects of the ACA. For example, on July 4, 2025, the One Big Beautiful Bill Act, or OBBBA, was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance. The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program. Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies. We expect that additional U.S. federal healthcare reform measures will be adopted in the future. We are unable to predict the future course of federal or state healthcare legislation in the U.S. directed at broadening the availability of healthcare and containing or lowering the cost of healthcare, particularly in light of the recent U.S. Presidential and Congressional elections. The current Trump administration is pursuing policies to reduce regulations and expenditures across government, including at HHS, the FDA, CMS, and related agencies. These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business. For example, the current administration has announced agreements with pharmaceutical companies that require the drug manufacturers to offer, through a direct-to-consumer platform (TrumpRx), U.S. patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues. Other recent actions and proposals include, for example (1) reducing agency workforce and cut programs; (2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives; (3) imposing tariffs on imported pharmaceutical products; and (4) as part of the Make America Healthy Again Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising. Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager payment methodologies, among other things. These actions and policies may significantly reduce U.S. drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks. In June 2024, in Loper Bright Enterprises v. Raimondo, the U.S. Supreme Court greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations. Congress may introduce and ultimately pass health care related legislation that could, among other things, impact the drug approval process and make changes to modify the Medicare Drug Price Negotiation Program.

At the state level, legislatures and state agencies have increasingly passed legislation and implemented regulations that are designed to control pharmaceutical and biological product pricing, including price or reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, that are designed to encourage importation from other countries and bulk purchasing. Some states have enacted legislation creating so-called prescription drug affordability boards, which ultimately may attempt to impose price limits on certain drugs in these states, while some states are also seeking to implement general, across-the-board price caps for pharmaceuticals, or are seeking to regulate drug distribution. Legally mandated price controls on payment amounts by third-party payors or other restrictions could materially and adversely impact our business, financial condition, results of operations and prospects. In addition, regional

healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

Existing healthcare reform measures, as well as the implementation of additional cost containment measures or other reforms, may prevent us from being able to generate revenue, attain profitability or commercialize our product candidates, if approved.

Data Privacy and Security

Numerous state, federal, and foreign laws, regulations, standards, and other obligations govern the collection, use, dissemination, access to, confidentiality, and security of health-related and other personal data, including clinical trial data. In the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws, including HIPAA, and consumer protection laws and regulations, including Section 5 of the Federal Trade Commission Act, govern the collection, use, disclosure and protection of health-related and other personal data. Outside of the United States, many jurisdictions also have laws governing the privacy and security of personal data, including health-related data, such as the European Union's General Data Protection Regulation, and impose stringent obligations on covered entities. In addition, use of artificial intelligence or machine learning technology is subject to evolving laws and regulations, including obligations to mitigate risks of bias and anti-discrimination. We and certain of the third parties with whom we work face cybersecurity risks that threaten the confidentiality, integrity and availability of our IT systems and personal data, including health-related data.

Privacy and security laws, regulations and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and in the event of a security incident or our actual or perceived failure to comply with such laws, regulations and obligations can result in investigations, proceedings or actions that lead to significant civil and/or criminal penalties, private litigation and restrictions on data processing, disgorgement of software algorithms trained on health-related data, or other material adverse consequences.

Additional Regulation

In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act and the Toxic Substances Control Act, may affect our business. These and other laws govern the use, handling and disposal of various biologic, chemical and radioactive substances used in, and wastes generated by, operations. If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines. Equivalent laws have been adopted in other countries that impose similar obligations.

Foreign Corrupt Practices Act

The U.S. Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying, offering or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the companies to maintain books and records that accurately and fairly reflect all transactions of the companies, including international subsidiaries and to devise and maintain an adequate system of internal accounting controls for international operations.

Employees and Human Capital Resources

As of December 31, 2025, we had 133 full-time employees and no part-time employees. Our employees are not represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our employees. We believe our success depends on our ability to attract, retain, develop and motivate diverse, highly skilled personnel. In particular, we depend upon the personal efforts and abilities of the principal members of our senior management to partner effectively as a team and to provide strategic direction, develop our business, manage our operations and maintain a cohesive and stable work environment. We also rely on qualified managers and skilled employees, such as scientists, engineers and laboratory technicians, with technical expertise in operations, scientific knowledge, engineering skills and quality management experience in order to operate our business successfully.

Our compensation program is designed to retain, motivate and, as needed, attract highly qualified employees. Accordingly, we offer a mix of competitive base salary, cash-based annual incentive compensation, performance-based equity compensation awards and other employee benefits.

Corporate Information

We were incorporated under the laws of the State of Delaware in November 2018 as Alvarado Therapeutics, Inc. In August 2019, we changed our name to MapLight Therapeutics, Inc. Our principal executive offices are located at 800 Chesapeake Drive, Redwood City, California 94063 and our telephone number is (617) 984-6300.

Available Information

We maintain an internet website at www.maplightrx.com and make available free of charge through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act. We make these reports available through our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the Securities and Exchange Commission, or the SEC.

The information on our website is not incorporated by reference into this Annual Report and should not be considered to be a part of this Annual Report. Our website address is included in this Annual Report as an inactive technical reference only.