Seelos Therapeutics, Inc. · OTC:SEELQ
Seelos Therapeutics — Investor Presentation (September 2023)
49 slides from Seelos Therapeutics's investor presentation, Sep 20, 2023
Slide 1: Seelos Therapeutics September 2023
SEELOS THERAPEUTICS September 2023 “We are a company focused on achieving the most efficient development of products that address significant unmet needs in CNS disorders and in rare diseases”
Slide 2: Forward-Looking Statements
FORWARD - LOOKING STATEMENTS This corporate presentation includes certain forward - looking statements within the meaning of Section 21E of the Securities Exch ange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995. These forward - looking statements include, but are
Slide 3: Experienced Management Team
EXPERIENCED MANAGEMENT TEAM Raj Mehra, PhD Chairman, Founder, and Chief Executive Officer 23 years experience as VC/investor Michael Golembiewski Chief Financial Officer 30 years experience in public company accounting and finance Tim Whitaker, MD Chief Medical Officer 26 years experience with 19 ND
Slide 4: Seelos is a CNS and rare disease focused biotech company
Advancing multiple late - stage therapeutic candidates for CNS disorders Developing therapeutics with demonstrated mechanisms of action Identifying opportunities in large markets SEELOS IS A CNS AND RARE DISEASE FOCUSED BIOTECH COMPANY SLS - 004 Parkinson’s Disease (PD) Gene therapy program targetin
Slide 5: SLS-002 (Intranasal Racemic Ketamine)
SLS - 002 (INTRANASAL RACEMIC KETAMINE) 5
Slide 6: Suicidal ideation and behaviors among U.S. adults
SUICIDAL IDEATION AND BEHAVIORS AMONG U.S. ADULTS 12.2 million adults had serious thoughts of committing suicide 2 1.2 million adults attempted suicide 2 3.2 million adults made suicide plans 2 920,000 adults made plans and attempted suicide 2 283,000 adults made no plans and attempted suicide 2 1.
Slide 7: SLS-002-201 study title
SLS - 002 - 201 STUDY TITLE A 2 - part Phase 2 Study To Assess The Efficacy, Safety, And Tolerability Of SLS - 002 (Intranasal Racemic Ketamine) Administered To Adults With Major Depressive Disorder At Imminent Risk Of Suicide 7
Slide 8: SLS-002-201 study design
SLS - 002 - 201 STUDY DESIGN Study Design • PART 1 – open label ( OL n=17 ) • PART 2 – randomized, double blind, placebo - controlled ( DB n=147 ) • Initiated in hospital, followed by outpatient phase once stabilized • All subjects receive standard of care (SOC) therapy for duration of study • 2 - w
Slide 9: Part 1 (open label) results: clinical improvements across all scales
PART 1 (OPEN LABEL) RESULTS: SLS - 002 SHOWED CLINICAL IMPROVEMENTS ACROSS ALL SCALES BASELINE (n=17) DAY 1 (n=17) DAY 16 (n=14) MADRS (0 - 60 scale, ≤12 is remission) 39.4 14.5 7.4 CGIS - SI/B (1 - 5 scale, 1=not at all, 5=extremely suicidal) 3.8 1.6 1.1 S - STS (0 - 52 scale, higher score equated
Slide 10: SLS-002-201 Part 1 efficacy results
SLS - 002 - 201 STUDY – PART 1 EFFICACY RESULTS Clinical Improvements in Four Scales over Study Duration 10
Slide 11: Part 2 enrollment criteria: severe suicidality required
This study randomized 147 patients diagnosed with MDD requiring psychiatric hospitalization due to imminent risk of suicide and: • Baseline total score of ≥ 28 on the Montgomery - Åsberg Depression Rating Scale (MADRS) • S core of 5 or 6 on MADRS Item - 10 • Baseline CGIS - SI/B of ≥ 4 • Total s cor
Slide 12: Part 2 MADRS demonstrated early and continued benefit
PART 2 MADRS DEMONSTRATED EARLY AND CONTINUED BENEFIT THROUGHOUT THE STUDY 12 Montgomery - Åsberg Depression Rating Scale (MADRS) is a 10 - item scale with total scores ranging from 0 - 60; higher scores indicate more severe depr ession. * Denotes statistically significant differences between the tr
Slide 13: MADRS clinically meaningful differences; primary endpoint not significant
MADRS DEMONSTRATED CLINICALLY MEANINGFUL DIFFERENCES BETWEEN GROUPS THROUGHOUT THE STUDY HOWEVER, STATISTICAL SIGNIFICANCE WAS NOT ACHIEVED FOR THE PREDE FINED PRIMARY ENDPOINT ( ANCOVA MADRS 24 HOURS POST DOSING) CHANGE FROM BASELINE MADRS TOTAL SCORE MMRM ESTIMATES PRESENTED HERE 13 Visit Placebo
Slide 14: Sustained improvement on MADRS during safety follow-up
SLS - 002 - 201 SUSTAINED IMPROVEMENT ON MADRS DURING SAFETY FOLLOW - UP 14 Group Mean MADRS Baseline / Change from Baseline Placebo (N=73) SLS - 002 (N=74) Difference Baseline 37.4 38.0 0.6 Day 2 (24 hours) - 12.4 n=73 - 16.1 n=74 - 3.7 Day 16 - 22.2 n=55 - 27.9 n=63 - 5.7 Day 22 (Safety Follow - u
Slide 15: Primary analysis and ad hoc sensitivity analysis
SLS - 002 - 201 PRIMARY ANALYSIS AND AD HOC SENSITIVITY ANALYSIS 15 MADRS Day 2 (24 hours) Treatment Difference Standard Error p - Value 2 - Way ANCOVA 1 (Primary Analysis) - 3.3 1.78 0.069 1 - Way ANOVA 2 (t - test) - 3.6 1.82 0.049 1 Based on model with Treatment and Standard of Care as fixed effe
Slide 16: MADRS response and remission rates at end of treatment
MADRS RESPONSE AND REMISSION RATES AT END OF TREATMENT 16 DAY 16 Placebo DAY 16 SLS - 002 MADRS Response (≥50% reduction from baseline) 47.9% 75.7% P - value <0.001 MADRS Remission (≤12 is remission) 32.9% 62.2% P - value <0.001 Montgomery - Åsberg Depression Rating Scale (MADRS) is a 10 - item scal
Slide 17: Suicidality measures demonstrated acute differences between groups
SUICIDALITY MEASURES DEMONSTRATED ACUTE DIFFERENCES BETWEEN GROUPS CHANGE FROM BASELINE MMRM ESTIMATES 17 Visit Placebo LS Means (SE) SLS - 002 LS Means (SE) Difference LS Mean (SE) P - value S - STS total score Day 1 (4 hours) - 12.0 (0.99) - 15.1 (0.98) - 3.1 (1.35) 0.022 S - STS total score Day 2
Slide 18: Safety data summary
SAFETY DATA SUMMARY 18 • SLS - 002 showed a favorable safety profile and was well tolerated • There were no deaths • Most AEs were mild or moderate, short term/transient • No new/unique AEs identified • 52.7% (vs. 39.7% on placebo) of subjects had at least one TEAE • Most common TEAEs (≥5% and >plac
Slide 19: Group mean CADSS change from pre-dose results
GROUP MEAN CADSS CHANGE FROM PRE - DOSE RESULTS 19 Placebo SLS - 002 SLS - 002 Placebo adjusted Day 1 - 40 mins 0.2 4.1 3.9 Day 1 - 1hr Day 1 - 2hr - 0.3 - 0.6 1.5 - 0.2 1.8 0.4 Day 4 - 40 mins 0.3 2.8 2.5 Day 4 - 1hr 0.04 0.8 0.76 Day 8 - 40 mins 0.1 1.5 1.4 CADSS (Clinician - Administered Dissocia
Slide 20: Other safety measures
OTHER SAFETY MEASURES • Hemodynamic effects • 6 subjects on SLS - 002 had an adverse event reported of either increased blood pressure or hypertension, all events were mild (except 1 moderate), all were transient and resolved • In review of mean vital sign data for SLS - 002, minimal changes were ob
Slide 21: Conclusions
CONCLUSIONS • While trial did not meet its predefined primary endpoint, early and persistent improvements were observed on depressive symptoms (MADRS) – all timepoints showed clinically meaningful differences over placebo and statistically significant differences at the majority of timepoints • Stat
Slide 22: SLS-002 intranasal administration device
SLS - 002 INTRANASAL ADMINISTRATION DEVICE Manufactured by Aptar Pharma (NYSE:ATR) Seelos has Co - Exclusive use of Bidose (BDS) Liquid System Bi - dose device administers 0.1 mL sprays in each nostril Disposable device for single use Convenient, ready to use administration 22
Slide 23: SLS-002 has the potential to transform ASIB in MDD
~700,000 people die globally due to suicide annually 1 In 2019, Suicide was the 10th leading cause of deaths in the U.S. (45,000 lives per year) 2 There is one death by suicide in the U.S. every 11 minutes 5 Depression affects 264 million people globally 3 According to WHO: MDD will become a major l
Slide 24: SLS-005 (Trehalose)
| SLS-005 (TREHALOSE) seeios OI | 24
Slide 25: Current studies ongoing/planned in ALS and spinocerebellar ataxia
Current studies ongoing/planned in ALS and Spinocerebellar Ataxia SLS - 005 (TREHALOSE) FOR ALS AND SCA Dose IN ketamine hydrochloride (50 mg) or saline solution Duration Each treatment period (ketamine or placebo) consisted of 7 days. Assessments occurred at 40 min, 120 min, 240 min, 24 hrs, 48 hrs
Slide 26: Trehalose mechanism of action
TREHALOSE MECHANISM OF ACTION Immediate enhancement of autophagy 1 Prolonged enhancement of lysosomal pathway 2 Protein stabilization 1. Mayer AL, Higgins CB, Heitmeier MR, et al. SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose - induced autophagy. Scientific Reports. 2016
Slide 27: Pathogenesis and proposed approaches in ALS
• ALS is a fatal neurodegenerative disease • C haracterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord • P athogenetic mechanisms are still unclear • P roposed therapeutic strategies target only one or a few of alterati
Slide 28: Pathogenetic mechanisms involved in ALS
PATHOGENETIC MECHANISMS INVOLVED IN ALS Bonafede R, Mariotti R. ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Ves icl es. Front Cell Neurosci. 2017;11:80. Published 2017 Mar 21. doi:10.3389/fncel.2017.00080 28
Slide 29: SLS-005 (trehalose) in ALS: TFEB activation
Induces autophagy via lysosomal - mediated TFEB activation in models of motoneuron degeneration SLS - 005 (TREHALOSE) IN ALS 1 Rusmini P, Cortese K, Crippa V, et al. Trehalose induces autophagy via lysosomal - mediated TFEB activation in models of motoneuron degeneration. Autophagy. 2019;15(4):631 -
Slide 30: SLS-005 (trehalose) in ALS: mouse model survival
MTOR - independent, autophagic enhancer trehalose prolongs motor neuron survival and ameliorates the autophagic flux defect in a mouse model of ALS SLS - 005 (TREHALOSE) IN ALS *Mice can be treated orally since they do not have gut trehalase Zhang X, Chen S, Song L, et al. MTOR - independent, autoph
Slide 31: SLS-005 (trehalose) in ALS: SOD1-G93A mouse model
Trehalose decreases mutant SOD1 expression and alleviates motor deficiency in early but not end - stage ALS in a SOD1 - G93A mouse model SLS - 005 (TREHALOSE) IN ALS Li Y, Guo Y, Wang X, et al. Trehalose decreases mutant SOD1 expression and alleviates motor deficiency in early but not end - stag e a
Slide 32: SLS-005 Phase II/III in ALS
• Randomized double blind placebo - controlled trial • 160 Patients with sporadic or familial ALS with onset of ALS < 36 months • Randomized 3:1 trehalose to placebo and 24 - week treatment period • ~90% power to detect a slowing in the rate of ALSFRS - R progression of 25% Primary Efficacy Endpoint
Slide 33: SLS-005 in spinocerebellar ataxia (SCA)
SCA is a serious neurodegenerative disease caused by degeneration of the cerebellum characterized by progressive unsteadiness of gait and stance, impaired coordination of limb movements, slurred speech and abnormal eye movements SCA type 3 , also known as Machado - Joseph Disease (MJD), is character
Slide 34: SLS-005 in humans with SCA type 3
Natural History Control – (SARA) 1 • Natural history data suggests that individuals with SCA3 would be expected to show a measurable increase on SARA which is indicative of disease progression and worsening of symptoms BB - MJD - 201: 15 patients, open - label 24 - wk study 2 • Weekly infusions of S
Slide 35: SLS-005 Phase II/III in SCA
Primary Endpoint • Change from baseline in the modified Scale for Assessment and Rating Ataxia (m - SARA) total score at Week 52 in participants with SCA3 Key Secondary Endpoints • Change from baseline in Clinical Global Impression of Severity (CGI - S) at Week 52 • Change from baseline in Patient G
Slide 36: SLS-004 (Gene Therapy)
yey / oS ; . a SLS-004 (gene therapy) a, “h Htc INES) 36
Slide 37: SLS-004: alpha-synuclein as a therapeutic target
SLS - 004: ALPHA - SYNUCLEIN AS A THERAPEUTIC TARGET Brundin P, Dave KD, Kordower. Therapeutic approaches to target alpha - synuclein pathology. Experimental Neurology. 2017;298:225 - 2 35. α - SYN LEWY BODY TOXIC PROTEIN DNA mRNA 1 2 3 4 5 37
Slide 38: SLS-004: targeted epigenome-editing
All in one vector Lentiviral particles SNCA - intron 1 methylation SNCA - mRNA expression α - synuclein protein levels Cellular phenotypes SLS - 004: TARGETED EPIGENOME - EDITING Kantor B, et al. (2018) Downregulation of SNCA Expression by Targeted Editing of DNA Methylation: A Potential Strategy fo
Slide 39: SLS-004 evaluated in established PD model
SLS - 004 EVALUATED IN ESTABLISHED PD MODEL Right Hemisphere SNpc* injection Left Hemisphere SNpc* injection AAV - A53T w/ intron1 + Control Vector AAV - A53T w/ intron1 + SLS - 004 • Human A53T α - Synuclein viral vector 1 with human intron 1 • SLS - 004 directed towards human intron 2 • Well chara
Slide 40: SLS-004: CRISPR epigenetic modulation of SNCA is successful
RIGHT LEFT Loss of TH+ Dopamine neurons in SNpc with Control Recovery of TH+ Dopamine neurons in SNpc with SLS - 004 SLS - 004: CRISPR EPIGENETIC MODULATION OF SNCA IS SUCCESSFUL AAV - A53T + Control vector AAV - A53T + SLS - 004 vector 40
Slide 41: SLS-009 (Protein Targeted Autophagy)
SLS - 009 ( protein targeted autophagy ) 41
Slide 42: Toxic levels of mHTT in R6/2 HD model
TOXIC LEVELS of mHTT in R6/2 HD MODEL Characteristics of R 6/2 HD model with 120 CAG repeats ANIMALS START DYING BY DAY 64 / WEEK 9 TOXIC LEVELS OF mHTT • mHTT AGGREGATES IN STRIATUM • mHTT AGGREGATES IN CORTEX • DARPP - 32 Neuronal Dysfunction SEVERE DISEASE PROGRESSION REDUCED LIFESPAN R6/2 MICE M
Slide 43: R6/2 severe HD model experimental design
R6/2 Severe HD MODEL - EXPERIMENTAL DESIGN Treatment period Group # Group Treatment Cohorts 1 WT PD 84/ Survival 2 R6/2 vehicle PD 84/ Survival 3 R6/2 + SLS - 009* PD 84/ Survival 4 R6/2 + SLS - 005* PD 84/ Survival 43
Slide 44: mHTT significantly reduced in striatum and cortex
mHTT IS SIGNIFICANTLY REDUCED in STRIATUM and CORTEX SIGNIFICANT REDUCTION in mHTT AGGREGATES 1 2 WT TG 3 4 SLS - 009 SLS - 005 85% 77% Group 2, #106 Group 4, #26 Group 3, #32 1 WT 4 SLS - 005 2 3 TG SLS - 009 84% 87% x Striatum 85% & 77% reduction from TG levels 44 x Cortex 87% & 84% reduction from
Slide 45: Robust pipeline promises continued growth in CNS and beyond
ROBUST PIPELINE PROMISES CONTINUED GROWTH IN CNS AND BEYOND Indication(s) Pre - IND Phase I Phase II Phase III Status SLS - 002 (intranasal ketamine ) Acute Suicidal Ideation and Behavior (ASIB) in Major Depressive Disorder (MDD) Phase 2 Study Completed Topline data available SLS - 005 (trehalose) A
Slide 46: Seelos is seeking to advance innovative therapeutics for unmet medical needs
SEELOS IS SEEKING TO ADVANCE INNOVATIVE THERAPEUTICS TO ADDRESS UNMET MEDICAL NEEDS FOR PATIENTS WITH PSYCHIATRIC AND MOVEMENT DISORDERS Developing a broad portfolio of late - stage CNS product candidates with demonstrated mechanism of action Assembling a team of established industry leaders Advanci
Slide 47: Appendix
APPENDIX 47
Slide 48: Detailed summary of MADRS and MADRS Item-10 data from open label study
MADRS • 76.5% response rate on Day 1; 92.9% response rate on Day 16; and 100% response rate on Day 29 (14 days after the last dose on Day 15) • Remission rate on Day 1 = 35.3%; Day 16 = 78.6%; and Day 29 = 76.9% • Total Score (baseline) = 39.4; Day 1, mean = 14.5; Day 16, mean = 7.4; and Day 29, mea
Slide 49: Detailed summary of suicide scales data from open label study
CGIS - SI/B • 94% patients had ≥ 1 point within - patient change from their baseline on Day 1 and 100% of patients on Day 16 had ≥ 1 point change and 86% had 2 or 3 point within - patient change from their baseline • Baseline = 3.8; Day 1, mean = 1.6; and Day 16, mean = 1.1 S - STS • 94% of patients
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