UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.
Item 7.01 Regulation FD Disclosure.
On December 5, 2022, Longboard Pharmaceuticals, Inc. (the "Company") announced positive topline data from a Phase 1 clinical study evaluating the central nervous system (“CNS”) pharmacokinetics (“PK”) and pharmacodynamics (“PD”) of LP352, an oral, centrally acting 5-hydroxytryptamine 2C receptor subtype superagonist, in healthy volunteers. In connection with the data release, the Company compiled a presentation entitled "The Potential of LP352", which includes LP352 preclinical and clinical summary results to date, including the data from the Phase 1 clinical study referenced above.
A copy of the presentation is furnished as Exhibit 99.1. For important information about forward-looking statements, see the slide titled “Forward-Looking Statements” in Exhibit 99.1 attached hereto.
The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01, including Exhibit 99.1, shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission (“SEC”) made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 8.01 Other Events.
As noted in Item 7.01, on December 5, 2022, the Company announced positive topline data from its Phase 1 clinical study evaluating CNS PK and PD of LP352 in healthy volunteers.
The primary objectives of the open-label, Phase 1 study are to assess the central nervous system ("CNS") pharmacokinetics ("PK") and pharmacodynamics ("PD") of orally administered LP352 in healthy adult male and female participants (n=10 in each Cohort). Objectives include the characterization of plasma and cerebrospinal fluid (“CSF”) PK, the characterization of safety and tolerability of doses with titration and taper, and the assessment of the PK-PD relationships between plasma and CSF exposure, and PD endpoints of safety and efficacy, including quantitative electroencephalogram (“qEEG”) endpoints. Two doses (Cohort 1 = 6 mg and Cohort 2 = 12 mg) of LP352 three times daily were tested over a 16-day period in addition to a screening and follow-up period. Additional cohorts of the study are ongoing.
Topline data for Cohorts 1 and 2 reported include:
In addition, LP352 is being designed and dose-optimized for developmental and epileptic encephalopathies (“DEEs”). The Company is currently assessing alternative strategies to elucidate the benefits and feasibility of certain twice daily (“BID”) dosing formulations. This work is ongoing and the Company expects to complete this assessment prior to initiating a Phase 3 clinical study for LP352 for DEEs.
Forward Looking Statements
This Current Report on Form 8-K contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to Company’s expectations regarding completing its BID assessment prior to initiating a Phase 3 clinical study for LP352 for DEEs. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause the Company’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: topline data may not reflect the complete or final results of a particular study or trial, and are subject to change; the Company’s ability to advance, obtain regulatory approval of and ultimately commercialize its product candidates; the timing and results of preclinical and clinical trials; the risk that positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials and preliminary interim data readouts of ongoing trials may show results that change when such trials are completed; the Company’s ability to fund development activities and achieve development goals; the Company’s ability to protect its intellectual property; the direct and indirect impacts geopolitical and macroeconomic events on the Company’s business; and other risks and uncertainties described under the heading “Risk Factors”
in the Company’s Annual Report on Form 10-K for the year ended December 31, 2021, its subsequently filed Quarterly Reports on Form 10-Q, and the other documents the Company files from time to time with the SEC. These forward-looking statements speak only as of the date of this Current Report on Form 8-K , and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
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99.1 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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Longboard Pharmaceuticals, Inc. |
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Date: December 5, 2022 |
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By: |
/s/ Kevin R. Lind |
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Kevin R. Lind |
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President and Chief Executive Officer |
Corporate Presentation - The Potential of LP352 December 2022 CONFIDENTIAL Exhibit 99.1
Forward-Looking Statements This presentation contains forward-looking statements about Longboard Pharmaceuticals, Inc. (“we,” “Longboard” or the “Company”), including statements regarding: our future results of operations and financial position; business strategy; the timing, costs, conduct and results of our preclinical studies and clinical trials for our product candidates, such as our expectations regarding our PACIFIC Study and data from our Phase 1 Open-Label PK/PD study; the timing and likelihood of regulatory filings and approvals for our product candidates, such as our pre-IND meeting for LP659; our intellectual property; our ability to obtain regulatory approval and commercialize our product candidates; the potential of LP352, including to limit adverse events associated with currently available non-selective ASMs, make a difference across a range of DEEs, and be a best-in-class ASM, including through BID dosing; and other statements that are not historical facts, including statements that may include words such as “will”, “may”, “can”, “intend”, “plan”, “expect”, “believe”, “potential” and similar words. For such statements, we claim the protection of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: our limited operating history; net losses; our expectation that we will incur net losses for the foreseeable future, and that we may never be profitable; our need for additional funding and related risks for our business, product development programs and future commercialization activities; the timing and success of clinical trials we conduct; topline data may not reflect the complete or final results of a particular study or trial, and are subject to change; the ability to obtain and maintain regulatory approval of our product candidates; the ability to commercialize our product candidates; our ability to compete in the marketplace; risks regarding our license and dependencies on others; our ability to obtain and maintain intellectual property protection and freedom to operate for our product candidates; our ability to manage our growth; and other risks and factors disclosed in our filings with the U.S. Securities and Exchange Commission (the “SEC”). We operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. The forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Except as required by law, we assume no responsibility for the accuracy and completeness of the forward-looking statements, and we undertake no obligation to update any forward-looking statements after the date of this presentation to conform these statements to actual results or to changes in our expectations. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, research, publications, surveys and other data obtained from third-party sources and Longboard’s own internal estimates and research. While Longboard believes these third-party studies, research, publications, surveys and other data to be reliable as of the date of this presentation, it has not been independently verified, and makes no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. This presentation discusses product candidates that have not yet been approved for marketing by the U.S. Food and Drug Administration. LONGBOARD PHARMACEUTICALS CONFIDENTIAL
Longboard’s Pipeline of Next Generation GPCR Programs LONGBOARD PHARMACEUTICALS Program MOA Therapeutic Area Preclinical Ph I Ph II Ph III Anticipated Milestones LP352 5-HT2C Superagonist DEEs and other refractory epilepsies Ph 1 data at medical mtg. - H1 2022 Ph 1 CSF PK/PD qEEG data - Q4 2022 Ph 1b/2a PACIFIC Study Data - H2 2023 LP659 S1P Receptor Modulator Multiple neurological diseases Pre-IND Meeting – Q4 2022 * Through the Royalty Purchase Agreement Definitions: DEEs=developmental and epileptic encephalopathies; S1P = sphingosine 1-phosphate; PK=pharmacokinetics; PD=pharmacodynamics; EEG = electroencephalogram We hold rights to other product candidates, including LP143 and nelotanserin, through the Arena License Agreement We are eligible to receive royalties of 9.5% - 18.5% on sales of lorcaserin if approved for commercialization* CONFIDENTIAL
LP352 has the Potential to Make a Difference Across a Range of DEEs LONGBOARD PHARMACEUTICALS Penetrates the brain in a dose-dependent, consistent and sustained manner LP352 Greater Selectivity and Specificity The product of 20 years of world-class GPCR research and optimization Demonstrated consistent CNS engagement through: Transient prolactin increases Sustained qEEG activity 5-HT2 proof-of-concept observed across multiple DEEs and seizures types, however there are safety and dosing considerations with other compounds: LP352 is the only 5-HT2C agonist being dose optimized to address this patient population LP352 demonstrated predictive efficacy in several pre-clinical seizure models: Multiple zebrafish and rodent models Ph 1 data support potential best-in-class profile: SAD/MAD CSF/EEG Strong IP protection through 2041* Enrolling the Ph 1b/2a PACIFIC study in patients 12-65 years old with DEE diagnosis No echocardiograms Evaluating broad range of seizure types across DEEs *Composition of matter through 2036 with potential for PTE & PTA (2041) Definitions: DEEs=developmental and epileptic encephalopathies; CSF = cerebrospinal fluid; EEG = electroencephalogram CONFIDENTIAL
The Potential of 5-HT2C Superagonist LP352 A potential best-in-class serotonin receptor agonist anti-seizure product candidate that is designed to be highly selective and being dose-optimized to treat a broad range of DEEs effectively and safely CONFIDENTIAL
The Potential of LP352 LONGBOARD PHARMACEUTICALS Greater Selectivity and Specificity Preclinical Validation Clinical Validation SAD/MAD Clinical Validation CSF/EEG ** 5-HT2 agonist designed to only bind to the 5-HT2C receptor* 5-HT2 agonist that has no detected activity at receptors associated with significant adverse side effects: 5-HT2B (valvular heart disease and PAH) & 5-HT2A (psychiatric: insomnia, hallucinations, euphoria) Reduces seizure activity in model of neuronal hyperexcitability in zebrafish Reduced epileptiform activity in fish and rodent models of disinhibition Reduced duration and number of epileptiform events in zebrafish model of Dravet Syndrome In general, favorable safety and tolerability observed. Adverse events generally consistent with expected effects of serotonergic medications No observed food effect Potential prolactin biomarker which increased in a dose dependent and transient manner Favorable safety and tolerability results observed, adverse events generally consistent with previous clinical studies Plasma and CSF PK concentration increased in a dose dependent and consistent manner Demonstrated effects on qEEG activity within first few dose(s) Demonstrated sustained dose-dependent effects on qEEG activity after continuous dosing, thus indicating receptor engagement *Radioligand binding assays assessing >150 targets showed significant affinity only to 5-HT2C receptors ** Based on first two cohorts Definitions: PAH = pulmonary arterial hypertension CONFIDENTIAL
LONGBOARD PHARMACEUTICALS 5-HT2 Evolution in Rare Epilepsies Weight Loss Drugs Repurposed Designed for Weight Loss Compound: FINTEPLA® DS (fenfluramine, ZX008) Lorcaserin (Marketed as BELVIQ) History: Approved for weight loss in 1973, became popular in 1990s in Fen-Phen (never approved in combo) Withdrawn due to significant cardiac toxicity (1997) Repurposed for DEEs at lower dose Designed to avoid the cardiac effects seen with fenfluramine Approved for weight loss in 2012 No significant difference in major adverse cardiovascular outcomes versus placebo1 Withdrawn from market 2020; increased occurrence of cancer in safety clinical trial Current Status: Approved for the treatment of seizures with Dravet & LGS (REMS required with echocardiograms), Ph 3 CDD FDA Expanded Access Program in Dravet, Ph 3 Dravet *R=undisclosed 1 = CAMELLIA-TIMI 61 Designed & Being Dose-Optimized for DEEs LP352 Designed to be a next-generation selective 5-HT2C superagonist Dose optimization for DEEs (currently TID) BID formulation work ongoing, expected for Ph 3 No echocardiograms in PACIFIC study Ph 1b/2a clinical trial in multiple DEEs * CONFIDENTIAL
LP352 Designed to be a Next Generation 5-HT2C with Greater Selectivity and Specificity LONGBOARD PHARMACEUTICALS Serotonin Receptor Subtype EC50, nM Ki, nM Selectivity 5-HT2C vs 5-HT2B Selectivity 5-HT2C vs 5-HT2A Potential Adverse Events Per Receptor Subtype LP352 5-HT2C Superagonist 5-HT2C ~120 ~50 >200x >200x CNS, GI 5-HT2B >10,000 >10,000 n/a 5-HT2A >10,000 >10,000 n/a Nordexfenfluramine (an active metabolite of fenfluramine) 1 5-HT2C 72.4 10.4 0.94x 11.5x CNS, GI 5-HT2B 25.7 9.8 Cardiac, Pulmonary 5-HT2A 1778 120.2 Psychiatric Lorcaserin2 5-HT2C 39 13 11.3x 7.1x CNS, GI 5-HT2B 2380 147 n/a 5-HT2A 553 92 Psychiatric LP352 selectivity may limit off-target effects associated with currently available non-selective ASMs 1 Third party study previously commissioned by Arena, 2 BELVIQ FDA approved prescribing information 06/2012; Note: The above table is for illustrative purposes only and is not a head-to-head comparison. Differences exist between in vitro study designs and methodologies, and caution should be exercised when comparing data across studies Definitions: CNS= Central nervous system ; GI = Gastrointestinal; ASM = anti-seizure medication CONFIDENTIAL
LP352 Inhibited Seizure Activity in Multiple Preclinical Models LONGBOARD PHARMACEUTICALS Corneal Kindling Pentylenetetrazol (PTZ) (i.v.) Scn1aA1783V/WT Transgene scn1lab Transgene Ethyl ketopentenoate (EKP) Kainic acid (KA) Model Partial (focal) limbic seizures Acute seizure Genetic model of Dravet Syndrome Genetic model of Dravet Syndrome Generalized seizure Acute and chronic seizure Species mouse mouse mouse zebrafish zebrafish zebrafish Activity - + - + + + CONFIDENTIAL Potential ASMs are assayed in multiple relevant preclinical models based on the compound’s MOA. Models are conducted utilizing wide range panels that typically produce a mix of positive and negative results. The above are a subset of preclinical assays conducted with LP352. Preclinical models are not necessarily predictive of clinical efficacy or regulatory approval. Definitions: ASM = anti-seizure medication; MOA = mechanism of action
LONGBOARD PHARMACEUTICALS Wild-type scn -/- scn -/- LP352 * * 6 4 2 0 * DURATION OF EPILEPTIFORM ACTIVITY FREQUENCY OF EPILEPTIFORM EVENTS LP352 Significantly Reduced Epileptiform Frequency & Duration in the Zebrafish scn1lab Model of Dravet Syndrome LP352 demonstrated 85% reduction of epileptiform events N=17-23/group, *p<0.001 LP352 demonstrated 84% reduction of epileptiform duration Δ 84% Cumulative duration of epileptiform events (Mean ± SEM in msec) Wild-type scn -/- scn -/- LP352 * Δ 85% Frequency over 10 min of epileptiform events (Mean ± SEM) *LP352 30mM CONFIDENTIAL
LONGBOARD PHARMACEUTICALS LP352 Significantly Improved Seizure Activity in the Zebrafish EKP Epilepsy Model N=18-20/group, **p < 0.0001 Definitions: LFP = local field potential; EKP= Ethyl ketopentenoate; Veh = Vehicle LP352 demonstrated ~69% reduction in seizure activity Epileptiform brain activity (LFPs) in the EKP model CONFIDENTIAL
LONGBOARD PHARMACEUTICALS LP352 Significantly Reduced Seizure Activity in the Zebrafish Kainic Acid Epilepsy Model N=12-14/group Definitions: KA= Kainic Acid; Veh = Vehicle LP352 demonstrated ~82% reduction of seizure activity LP352 Normalized Power Spectral Density CONFIDENTIAL **p < 0.01 **p < 0.0001
LP352 Demonstrated Dose-Dependent Improvement in Time to Clonic Seizures in PTZ Mouse Model LONGBOARD PHARMACEUTICALS Effect of LP352 on the Threshold for Seizures Induced by the Timed Intravenous Infusion of PTZ in Male Mice Compound Animal Weight (Grams, Mean ± S.E.M.) Time of Test PTZ Dose (mg/kg, Mean ± S.E.M) Compound Animal Weight (Grams, Mean ± S.E.M.) Time of Test First Twitch Clonus Vehicle Control 32.7 ± 0.7 0.5 hr 25.1 ± 1.5 26.4 ± 1.6 LP352 3mg/kg 31.4 ± 0.4 0.5 hr 26.5 ± 0.8 30.3 ± 1.1 LP352 10mg/kg 31.8 ± 0.4 0.5 hr 28.7 ± 0.7 32.3 ± 1.2** **p < 0.01 CONFIDENTIAL
LONGBOARD PHARMACEUTICALS LP352 Ph 1 Multiple Ascending Dose (MAD) Results Favorable Safety & Tolerability Results Observed Majority of AEs were mild to moderate (most common was headache) AEs generally consistent with expected CNS effects and expected effects of serotonergic drugs At the maximum planned dose, a single SAE of anxiety was reported two days after last dose of study drug and subsequently resolved Treatment-Emergent Adverse Events by Preferred Term Occurring in ≥ 2 Subjects in Any Treatment Group – MAD (Safety Set) Preferred Term n(%) E LP352 (TID) Pooled Placebo (N=8) Cohort 1 3 mg (N=6) Cohort 2 6 mg (N=6) Cohort 3 12 mg (N=7) Cohort 4 18 mg (N=6) Pooled Placebo (N=10) n=(%) E Subjects with at least 1 TEAE 5 (83.3) 9 6 (100) 29 6 (85.7) 39 6 (100) 55 4 (50.0) 8 Headache 2 (33.3) 2 2 (33.3) 4 2 (28.6) 5 4 (66.7) 5 1 (12.5) 1 Somnolence 1 (16.7) 1 1 (16.7) 1 4 (57.1) 4 3 (50.0) 5 0 Dizziness 0 3 (50.0) 3 2 (28.6) 3 2 (33.3) 2 0 Micturition Urgency 1 (16.7) 1 0 1 (14.3) 1 5 (83.3) 5 0 Dizziness Postural 0 0 1 (14.3) 1 5 (83.3) 5 0 Diarrhoea 1 (16.7) 1 4 (66.7) 4 1 (14.3) 1 0 0 Orthostatic Hypotension 0 0 2 (28.6) 3 4 (66.7) 4 0 Constipation 1 (16.7) 1 1 (16.7) 1 2 (28.6) 3 1 (16.7) 1 1 (12.5) 1 Nausea 1 (16.7) 1 0 1 (14.3) 1 2 (33.3) 2 1 (12.5) 1 Paraesthesia 0 1 (16.7) 1 2 (28.6) 3 1 (16.7) 1 0 Chills 0 0 1 (14.3) 1 3 (50.0) 5 0 Anxiety 0 2 (33.3) 2 0 2 (33.3) 2 0 Orthostatic HR Response Increased 0 0 0 3 (50.0) 5 1 (12.5) 1 Dysmenorrhoea 1 (16.7) 1 0 0 2 (33.3) 2 1 (12.5) 1 Fatigue 0 2 (33.3) 2 0 0 0 Vessel Puncture Site Bruise 0 0 0 2 (33.3) 2 0 Hypotension 0 2 (33.3) 2 0 0 0 Presented at the American Academy of Neurology (AAN) Annual Meeting 2022 CONFIDENTIAL
LP352 Ph 1 Single Ascending Dose (SAD) Results Favorable Pharmacokinetics and Pharmacodynamics Results Observed LONGBOARD PHARMACEUTICALS Single Ascending Dose & Single-Dose Food Effect (N=40) Percent Change from Baseline in 2-Hour Prolactin Concentration Across All Dose Groups Under Fasted Conditions LP352 Demonstrated No Meaningful Food Effect Geometric Mean (95% CI) Geometric Mean (95% CI) Parameter (Unit) n Fed n Fasted Cmax (ng/mL) 6 8.8 [5.1, 15.3] 6 8.5 [4.9, 14.6] AUC0-last (h*ng/mL) 6 61.9 [33.4, 114.7] 6 49.2 [26.6, 91.2] AUC0-inf (h*ng/mL) 6 63.6 [34.7, 116.6] 6 51.0 [27.8, 93.4] Presented at the American Academy of Neurology (AAN) Annual Meeting 2022 CONFIDENTIAL
LP352 Ph 1 MAD Results Favorable Pharmacokinetics and Pharmacodynamics Results Observed LONGBOARD PHARMACEUTICALS Multiple Ascending Dose & Dose Titration (N=43) Key Summary of LP352 Pharmacokinetic Parameters by Cohort (Day 14) - MAD and Dose Titration (PK Analysis Population) Parameter (Unit) MAD 12 mg (N = 7) Cmax (ng/mL) (Mean) 44.9 Tmax (h) (Median) 1.3 AUC0-inf (h*ng/mL) (Mean) 330 T1/2 (h) (Mean) 6.0 Pharmacodynamics: Boxplot of Percent Change From Baseline in Prolactin Concentration with Dose on Day 1 at 2 Hrs - MAD and Dose Titration (Safety Population) Presented at the American Academy of Neurology (AAN) Annual Meeting 2022 CONFIDENTIAL
Cohort 1 (n=10) 6 mg TID 28 Days Day 25 Screening Daily Dosing of Liquid Formulation Follow-up Days 3-11 (target treatment) A Phase 1, Open-label Study to Assess Central Nervous System Pharmacokinetics (PK) and Pharmacodynamics (PD) of Orally Administered LP352 Key Study Objectives: Characterize the plasma and CSF PK Characterize the safety and tolerability of the doses with titration and taper Assess the PK-PD relationships between plasma and CSF exposure and PD endpoints of safety and efficacy, including qEEG endpoints as indicators of CNS target engagement LP352 102: A Phase 1 PK/PD CNS Study in Adult Healthy Volunteers LONGBOARD PHARMACEUTICALS Cohort 2 (n=10) 12 mg TID Up-Titration Days 1-2 Taper Down Day 11 (start taper after AM dose) EEG: Serial EEGs Days -1, 1, 3 & 10 (trough Day 16) EEG parameters: Five-minute resting EEG with eyes closed and five-minute resting EEG with eyes open performed with the participant seated comfortably in a sound-attenuated room Resting EEG evaluated by spectral and coherence analysis, including spectral amplitudes and coherences in clinical frequency bands Plasma: Samples Days 1-11 (and taper) PK parameters: Cmax, Tmax and AUCtau CSF: Samples Day 11 PK parameters: Cmax, Tmax and AUCtau Topline data from the 102 study are presented in this deck CONFIDENTIAL Additional Cohorts Ongoing
Steady State Plasma & CSF Concentrations for LP352 (6mg & 12mg) 12 mg TID Exceeded Ki Value for 5-HT2C Activity throughout Dosing Interval* LONGBOARD PHARMACEUTICALS *Topline data from 102 study Ki LP352 Concentration (ng/mL) LP352 Concentration (ng/mL) Time (hrs) Time (hrs) Ki CONFIDENTIAL The vast majority of participants in the 12 mg TID cohort achieved plasma and CSF levels above the relevant Ki throughout the dosing period.
Cmax and AUC CSF vs. Plasma Correlations Strong Correlation Between Plasma and CSF PK Parameters* LONGBOARD PHARMACEUTICALS *Topline data from 102 study R2 = 0.89 R2 = 0.97 CSF vs. LP352 Cmax CSF vs. LP352 AUCtau Cmax of LP352 in CSF (ng/mL) AUCtau of LP352 in CSF (hr*ng/mL) Cmax of LP352 in Plasma (ng/mL) AUCtau of LP352 in Plasma (hr*ng/mL) CONFIDENTIAL
5-Minute Resting qEEG Spectral Amplitudes in Clinical Frequency Bands (Days -1,1 and 3) LP352 Demonstrated Early qEEG Changes* *Topline data from 102 study Small and large salient contrasts (≥10%, ≥15%) are indicated by light and heavy arrows (blue=decrease, red=increase) respectively. Small and large salient Cohen’s d values (≥0.5, ≥0.8) are indicated by light and dark shading (blue=decrease, orange=increase) respectively. LONGBOARD PHARMACEUTICALS CONFIDENTIAL
5-Minute Resting qEEG Spectral Amplitudes in Clinical Frequency Bands (Days 10 and 16) LP352 Demonstrated Sustained Effects on qEEG Activity After Continuous Dosing in a Dose-Dependent Manner, Thus Indicating Receptor Engagement* LONGBOARD PHARMACEUTICALS *Topline data from 102 study ** On Day 16, all participants in Cohort 1 and 2 receive one final dose which was less than the full dose of 6 mg and 12 mg, respectively. CONFIDENTIAL ** **
LP352-102 Phase 1 Study: Key Takeaways To Date First known study of its kind for a 5HT2 agonist (e.g. fenfluramine or lorcaserin) Favorable safety and tolerability results observed, with AEs generally consistent with previous clinical studies Plasma and CSF PK concentration increased in a dose-dependent and consistent manner Demonstrated effects on qEEG activity within first few dose(s) Demonstrated sustained dose-dependent effects on qEEG activity after continuous dosing, thus indicating receptor engagement In summary, we believe the data suggest that LP352 engaged neurotransmitter systems and altered the EEG spectrum CONFIDENTIAL LONGBOARD PHARMACEUTICALS
6 mg 9 mg 12 mg Participant remains on 6, 9 or 12 mg based on tolerability during up-titration Placebo (n=10) LP352 (n=40) 5 Wks 30 Days Screening Period Randomization & Up-Titration Maintenance* Down-Titration Follow-up Period Days 1-15 Days 16-75 Days 76-80/90** Key Inclusion Criteria: Developmental and epileptic encephalopathies (DEEs) with ≥ 4 motor seizures per month in 3 mos. prior to screening and ≥ 4 motor seizures in the month of screening DEEs (multiple syndromes) may include Dravet syndrome, Lennox-Gastaut syndrome, Tuberous Sclerosis complex, CDKL5 deficiency disorder, SCN2A-related disorders, among others Key Exclusion Criteria: Use of fenfluramine & lorcaserin Basic Information: Sites: ~30 sites Ages: > 12 to <65 yrs old PACIFIC Study Initiated March 2022; Data Expected 2H 2023 A double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics of LP352 and Key Efficacy Signals: EVALUATE reduction in seizures across a broad group of epilepsies IDENTIFY potential indications for pivotal studies ANALYZE concentration response to understand dosing in different seizure types and disorders LP352 Ph 1b/2a PACIFIC Study in Patients with DEEs LONGBOARD PHARMACEUTICALS * Maintenance Dose of LP352 (TID): 6 mg, 9 mg, 12 mg or placebo TID ** Up to a 15-day down-titration/taper period (reducing dose every 5 days) depending on the last maintenance dose Open-Label Extension CONFIDENTIAL
Thank you! Nasdaq: LBPH CONFIDENTIAL