Climb Bio, Inc. · NASDAQ:CLYM
Climb Bio — Eliem Therapeutics — Investor Presentation (November 2022)
33 slides from Climb Bio's investor presentation, Nov 14, 2022
Slide 1: Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders
Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders Corporate Presentation | November 14, 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding our future financial condition, results of operat
Slide 3: Rethinking treatment for nervous system disorders
Highly experienced management team Clinical and preclinical pipeline based on clinically validated mechanisms of action Two differentiated programs in depression and epilepsy with expansion opportunities in chronic pain Rethinking treatment for nervous system disorders *Cash, cash equivalents and sh
Slide 4: Powered by successful and talented executives from pioneering organizations
Powered by successful and talented executives from pioneering organizations General Management, Commercial & Corporate Development Research & Development Valerie Morisset, Ph.D. EVP R&D and Chief Scientific Officer Joanne Palmer, Ph.D. Chief Development Officer Mark Versavel, M.D., Ph.D. Interim Chi
Slide 5: Addressing multiple interrelated diseases with two distinct, clinically validated mechanisms of action
Addressing multiple interrelated diseases with two distinct, clinically validated mechanisms of action Approaching interrelated disease states with distinct MOAs (GABAA PAM and Kv7.2/3) Innovating within clinically validated mechanisms of action Multiple “pipeline-in-a-product” opportunities Chronic
Slide 6: Eliem Pipeline: Two programs with clinically validated MOAs
Product Candidate (Mechanism) Lead indications Preclinical Phase 1 Phase 2 Phase 3 ETX-155 (GABAA receptor PAM) Major depressive disorder (MDD) Epilepsy Kv7 Program (Kv7.2/3 channel opener) Epilepsy Depression Pain Eliem Pipeline: Two programs with clinically validated MOAs intended to address large
Slide 7: ETX-155
ETX-155 Proof of concept Phase 2a trial in Major Depressive Disorder (MDD) positioned for Q1 2023 initiation
Slide 8: ETX-155: A differentiated neuroactive steroid GABAA positive allosteric modulator
ETX-155: A differentiated neuroactive steroid GABAA positive allosteric modulator Dual potent activity at synaptic and extrasynaptic GABAA receptors, with high intrinsic efficacy Well tolerated at exposure levels that have translated to clinical efficacy for other GABAA PAMs No clinically meaningful
Slide 9: Clinical development focused on MDD with opportunity to expand into other large markets
Clinical development focused on MDD with opportunity to expand into other large markets with considerable unmet need Perimenopausal Depression (PMD) Estimated annual prevalence (US+EU) MoA Rationale Unmet Needs Reduced GABA levels increased MDD severity1 Clinically validated (zuranolone) Faster on
Slide 10: ETX-155 Differentiation: Similar dual GABAAR potency with differentiated pharmacokinetics
Company Molecule GABAAR Potency Pharmacokinetics Half-life Clinical Validation (positive RCT) Synaptic Extra-synaptic Food effect Half-life MDD PPD Epilepsy ETX-155 No ~40 hrs - - - zuranolone (SAGE-217) Yes 14-18 hrs - ZTALMY® (ganaxolone) Yes 2-3 hrs - - Sources: Zuranolone: Hoffmann et al, Clin P
Slide 11: ETX-155 does not have a clinically meaningful food effect
ETX-155 does not have a clinically meaningful food effect: potential to positively impact efficacy, safety, and compliance ETX-155 has not been assessed in a head-to-head study against zuranolone or ganaxolone, and the study designs and analytical methods for all product candidates may be different.
Slide 12: Phase 1 Study in Healthy Subjects: Encouraging safety and tolerability profile
Phase 1 Study in Healthy Subjects: Encouraging safety & tolerability profile observed with no severe or serious adverse events ETX-155 Phase 1 Repeat-Dose Results Favorable pharmacokinetics (PK) Steady state reached at day 8 ~40-hour half-life at steady state 60 mg evening dosing was well tolerated
Slide 13: Analysis of ETX-155 pharmacokinetic profile confirmed comparable 60 mg exposures
Analysis of ETX-155 pharmacokinetic profile confirmed comparable 60 mg exposures obtained with different batches, enabling path forward in Phase 2a MDD trial Original Phase 1 studies PSE study findings (April ‘22) Extensive Investigation SAD (5-200mg, n=6 active/cohort) MAD 7-day (60mg AM and PM, n=
Slide 14: Population PK model of 60mg at Day 3 and at steady state
Population PK model of 60mg at Day 3 and at Day 14 At Day 3 and at steady-state, modeled exposure of 60 mg ETX-155 is within the therapeutic range, and at steady-state is ~1.5-fold higher than zuranolone benchmark Mean 2248 Mean 1686 Mean (1353) Robust preclin efficacy1 Minimum (896) Actual 60mg SS
Slide 15: Positioned to progress ETX-155 into Phase 2a RCT in MDD in Q1 2023
Positioned to progress ETX-155 into Phase 2a RCT in MDD in Q1 2023 and topline data would be expected in the second half of 2024 Screening Outpatient Treatment Follow-up 28 days Week 14 days 1 2 3 4 60 mg ETX-155 qd PM x 28 days1 Placebo qd PM x 28 days MDD Phase 2a 130 patients 1:1 randomization d1
Slide 16: ETX-155 strategies to reduce variability and placebo response in Phase 2a
ETX-155 strategies to reduce variability and placebo response in Phase 2a Placebo: ETX-155 ratio 1:1 (50% get placebo) Large, well powered study Select experienced sites in one geography (USA) Minimize number of assessments and visits Video education of investigators, research staff, and subjects on
Slide 17: ETX-155 Market Opportunity
ETX-155 Market Opportunity yy elem
Slide 18: One-third of the US MDD treated patient opportunity is in 2nd line and beyond
One-third (7M) of the US MDD treated patient opportunity is in 2nd line and beyond Second Line MDD (Failed 1 ADT class) Diagnosed and Drug-treated MDD patients Third Line+ MDD (Failed ≥2 ADT classes) 21M 4.6M 2.5M US Epidemiology, 2030 estimates $14-21B Total Branded Opportunity in 2nd line + Source
Slide 19: Zuranolone precedent: GABAA PAM showed statistical significance by day 3
Zuranolone precedent GABAA PAM showed statistical significance by day 3, mild depression levels by day 15, with symptom reduction maintained out to day 42 WATERFALL1 CORAL2 2-week daily dosing, monotherapy or on top of stable ADT 2-week daily dosing co-initiated w/ ADT Zur 50mg (n=268) Placebo (n=26
Slide 20: Zuranolone precedent suggests potential GABAA PAM advantages in a direct to patient marketplace
Zuranolone precedent suggests potential GABAA PAM advantages relative to existing ADTs would be attractive in a “direct to patient” commercial marketplace Potential Differentiation Points “Treat depressive episode”: zuranolone uses a two-week regimen, 80% of patients needed only 4 weeks of therapy i
Slide 21: ETX-155: Being Developed as a Potentially Clinically Differentiated Oral Neuroactive Steroid
ETX-155: Being Developed as a Potentially Clinically Differentiated Oral Neuroactive Steroid Improve Efficacy Increased AUC observed at well-tolerated doses Absence of clinically meaningful food effect Significantly longer half-life ETX-155 Opportunities Improve Tolerability CNS AE rates similar to
Slide 22: Kv7 Opener
Kv7 Opener Pre-candidates identified IND-enabling safety studies planned for Q1 2023
Slide 23: Kv7.2/3 Program: Developing a differentiated Kv7.2/3 opener
Kv7.2/3 Program: Developing a differentiated Kv7.2/3 opener for multiple neuronal excitability indications Initiated IND-enabling studies for two pre-candidates; IND-enabling safety studies to begin in Q1 2023 Eliem Kv7 Program Goal Kv7 Opportunity Program Status Maintain efficacy with improved tole
Slide 24: Eliem's KV7 candidates incorporate novel chemistry and attractive potency, selectivity
Eliem’s KV7 candidates incorporate novel chemistry and have exhibited an attractive potency, selectivity, and in vivo activity profile to date * Putative XEN1101 molecule synthesized and tested by Eliem ETX-123 (BEFORE FORMULATION) ETX-963 (BEFORE FORMULATION) XEN1101 (putative)* (AFTER FORMULATION)
Slide 25: ETX-123 demonstrated modulation of neuronal excitability in rat DRG neurons
ETX-123 demonstrated modulation of neuronal excitability through hyperpolarization and inhibition of repeat firing in rat dorsal root ganglion (DRG) neurons Hyperpolarization of resting membrane potential (RMP) Inhibition of repeat action potential firing SYG-00514123 = ETX=123 baseline 1 μM ETX-123
Slide 26: ETX-123 demonstrated 7-fold separation between MES efficacy and rotarod side effects
ETX-123 demonstrated 7-fold separation between the dose that inhibits tonic convulsions in the rat MES model and the dose that induces side effects in the rotarod model ETX-123 (mg/kg oral) Retigabine pos control (mg/kg oral) ETX-123 has demonstrated a favorable in vivo efficacy/tolerability profile
Slide 27: Rethinking treatment for nervous system disorders
Highly experienced management team Clinical and preclinical pipeline based on clinically validated mechanisms of action Two differentiated programs in depression and epilepsy with expansion opportunities in chronic pain Rethinking treatment for nervous system disorders ~$130M* cash runway into 2025
Slide 28: For more information
For more information: www.eliemtx.com InvestorRelations@eliemtx.com
Slide 29: BACKUP
BACKUP
Slide 30: Comprehensive root cause investigation did not reveal any CMC differences
Comprehensive root cause investigation did not reveal any CMC differences or issues with exposures from any batch or tablet size Activities Conducted Outcome CMC investigations for API and DP batches Particle size distribution, Scanning Electron Microscopy, Modulated Differential Scanning Calorimetr
Slide 31: ETX-155 75 mg does not provide clear advantages over 60 mg
ETX-155 75 mg does not provide clear advantages over 60 mg on either exposure or tolerability 60 mg pooled 7-day and 14-day studies 75 mg 10-day study ETX-155 N=24 Placebo N=11 ETX-155 N=12 Placebo (n=6) n (%) n (%) n (%) n (%) ≥1 TEAE 14 (58.3) 7 (63.6) 11 (91.7) 2 (33.3) Somnolence 7 (29.2) 4 (36.
Slide 32: Zuranolone precedent: GABAA PAM efficacy in line with approved MDD drugs
Zuranolone precedent GABAA PAM efficacy in line with approved MDD drugs, achieving statistical significance and ~50% reduction in HAMD17 despite smaller delta to placebo Drug: Study* Reference Year of Study Baseline HAMD17 Duration of Treatment Mean HAMD17 change from Baseline Estimated Mean HAMD17
Slide 33: Zuranolone's Shoreline study: durable effects with ~2 courses in a year
Zuranolone’s Shoreline study: demonstrated durable effects with the average patient only needing ~2 courses (~4 weeks) in a year ~80% of 50 mg responders* needed only 1 or 2 treatment courses over 1 year Source: Sage Therapeutics *Only responders at Day 15 of the initial treatment period (≥50% reduc
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