Climb Bio, Inc. · NASDAQ:CLYM
Climb Bio — Eliem Therapeutics — Investor Presentation (May 2023)
20 slides from Climb Bio's investor presentation, May 11, 2023
Slide 1: Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders
Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders Corporate Presentation | May 2023
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: Highly experienced team with deep expertise in neuroscience and ion channel drug discovery
Highly experienced team with deep expertise in neuroscience and ion channel drug discovery and development Highly differentiated Kv7 program with broad potential to pursue across multiple neuronal excitability indications Rethinking treatment for nervous system disorders * cash, cash equivalents and
Slide 4: Addressing multiple interrelated diseases by focusing on core mechanisms of neuronal excitability
Addressing multiple interrelated diseases by focusing on core mechanisms of neuronal excitability Approaching interrelated disease states with distinct MOAs Innovating within clinically validated mechanisms of action Pursuing products with multiple potential indications Pain, other hyper-excitabilit
Slide 5: Eliem Portfolio: Focused on clinically validated Kv7.2/3 mechanism
Product Candidate (Mechanism) Potential Indications Lead selection / optimization IND-enabling studies Phase 1 Phase 2 Phase 3 ETX-123 (Kv7.2/3 channel opener) Epilepsy Depressive disorders Chronic Pain Other CNS hyperexcitability disorders Epilepsy Backup Kv7.2/3 openers ETX-155* (GABAA PAM neurost
Slide 6: Kv7 Opener
Kv7 Opener Lead candidate ETX-123 selected Phase 1 planned 1H 2024
Slide 7: Kv7.2/3 potassium channel: a clinically validated regulator of neuronal hyperexcitability
Kv7.2/3 potassium channel: a clinically validated regulator of neuronal hyperexcitability with significant commercial potential K+ Kv7.2/Kv7.3 heteromers mediate the neuronal M-current, widely regulating neuronal excitability by enabling the outflow of potassium ions, to dial down action potential f
Slide 8: 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 Eliem Kv7 Program Objectives Kv7 Opportunity Program Status Identify novel Kv7 openers with: Potent activity at Kv7.2/3 Better selectivity over other Kv7 subtypes (Kv7.4 / 7.1) Improved metabol
Slide 9: Kv7 channels provide a convergent mechanism to control hyperexcitability
Kv7 channels provide a convergent mechanism to control hyperexcitability in CNS, PNS, and other tissues Source: Soldovieri et al., 2011 The Kv7 family consists of 5 different subtypes with different electrophysiological properties and tissue expression: Kv7.1: cardiac tissue Kv7.2 and Kv7.3: CNS and
Slide 10: Mechanism: Kv7.2/3 openers decrease neuronal excitability
Mechanism: Kv7.2/3 openers decrease neuronal excitability by hyperpolarizing the membrane potential and reducing of action potential firing in excitable cells afterhyperpolarization Hyperpolarization and decrease of resting membrane potential Decrease of action potential firing 400 pA Baseline Kv7 c
Slide 11: Discovery and optimization of novel class of Kv7 openers
Discovery and optimization: leveraged existing target knowledge and deep ion channel expertise to identify novel class of Kv7 openers Compound design and synthesis informed by published series, structural analysis, computational chemistry, IP ETX-123 selected as lead clinical candidate based on comp
Slide 12: Electrophysiology: ETX-123 demonstrates best-in-class Kv7.2/3 potency and selectivity
Electrophysiology: ETX-123 demonstrates best-in-class Kv7.2/3 potency and selectivity Kv7.2/3 Kv7.4 - EDTT XVII ETX-123 (μM) Retigabine (μM) Kv7.2/3 0.0007-0.002 2 Kv7.4 >10 12-14 Kv7.3/5 0.02 4-7 Kv7.1 >30 >30* In vitro, ETX-123 is significantly more potent and selective than retigabine, and other
Slide 13: Translational pharmacology: ETX-123 decreases rat DRGs excitability
Translational pharmacology: ETX-123 decreases rat DRGs excitability by hyperpolarization and significant inhibition of repeat firing of action potentials Control ETX-123 wash-out ****p < 0.0001, **p < 0.01 and *p <0.05 – comparisons all groups vs. the control group 1 Free clinical anticonvulsant exp
Slide 14: In vivo efficacy: ETX-123 showed dose-dependent anticonvulsant activity in rat MES model
In vivo efficacy: ETX-123 showed dose-dependent anticonvulsant activity in the rat MES model, with encouraging separation vs doses showing CNS side effects in the rotarod model Day 0 ETX-123 dosing Day 0 Rotarod testing Day 0 MES testing Terminal PK samples Day -3 to-1 Rotarod Habituation Image Sour
Slide 15: Human bladder contractility assay
Human bladder contractility assay: Free anticonvulsant concentration of ETX-123 are 700–fold lower than concentration relaxing human bladder, vs only ~4-fold for retigabine Urinary retention adverse events, or related voiding dysfunctions were reported with retigabine/ezogabine in 2% of patients Act
Slide 16: Broad Selectivity: multiple screens confirm no off-target activity
Broad Selectivity: multiple screens confirm no off-target activity ETX-123 shows at least a >1000-fold separation vs. Kv7.2/3 EC50 in multiple screen, including a 48-Target Cerep screening panel
Slide 17: ETX-123 profile to date is significantly superior to retigabine
ETX-123 profile to date is significantly superior to retigabine * ETX-123 data before formulation optimized to improve solubility and oral bioavailability ETX-123 (pre-formulation*) Retigabine In vitro profile Potency at Kv7.2/3 0.7- 2 nanoM 2-14 microM Selectivity over Kv7.1 Selectivity over Kv7.4
Slide 18: Progressing ETX-123 through IND-enabling activities in 2023, Phase 1 in 1H 2024
Progressing ETX-123 through IND-enabling activities in 2023, with Phase 1 anticipated to begin in 1H 2024 Opportunity to pursue multiple neuronal excitability indications in Phase 2 and beyond Key activities Status Novel “non-retigabine” chemotype (COM IP filed August 22) Potency and selectivity
Slide 19: Highly experienced team with deep expertise in neuroscience and ion channel drug discovery
Highly experienced team with deep expertise in neuroscience and ion channel drug discovery and development Highly differentiated Kv7 program with broad potential to pursue across multiple neuronal excitability indications Rethinking treatment for nervous system disorders * cash, cash equivalents and
Slide 20: For more information
For more information: www.eliemtx.com InvestorRelations@eliemtx.com
Eliem Therapeutics — Investor Presentation (May 2023) on 6ix