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Item 7.01 Regulation FD Disclosure.
A copy of a slide presentation that Eliem Therapeutics, Inc. (Eliem, or the Company) will use at investor conferences and presentations is attached to this Current Report as Exhibit 99.1 and is incorporated herein solely for purposes of this Item 7.01 disclosure.
The information in this Item 7.01 (including Exhibit 99.1) is being furnished, not filed, pursuant to Regulation FD. Accordingly, the information in this Item 7.01 will not be incorporated by reference into any registration statement filed by the Company under the Securities Act of 1933, as amended, unless specifically identified therein as being incorporated therein by reference. The furnishing of the information in this Item 7.01 is not intended to, and does not, constitute a determination or admission by the Company that this information is material or complete, or that investors should consider this information before making an investment decision with respect to any security of the Company.
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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.
Eliem Therapeutics, Inc. | ||||||
Date: March 28, 2022 | By: | /s/ James B. Bucher | ||||
James B. Bucher | ||||||
Executive Vice President and General Counsel |
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Exhibit 99.1
Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders Corporate Presentation | March 28, 2022
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 operations, business strategy and plans, and objectives of management for future operations, as well as statements regarding industry trends, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as anticipate, believe, continue, could, estimate, expect, intend, may, plan, potentially, predict, should, will or the negative of these terms or other similar expressions. We have based these forward-looking statements largely on our current expectations and projections about future events and trends that we believe may affect our financial condition, results of operations, business strategy and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things, risks related to: the success, cost and timing of our product development activities and clinical trials; our expectations about the timing of achieving regulatory approval and the cost of our development programs; our ability to obtain funding for our operations, including funding necessary to complete further development and commercialization of our product candidates; the impact of the COVID-19 pandemic on our operations; the commercialization of our product candidates, if approved; our plans to research, develop and commercialize our product candidates; our plans to develop additional product candidates; our ability to obtain, maintain, expand, protect and enforce our intellectual property rights; our ability to operate our business without infringing, misappropriating or otherwise violating the intellectual property rights of third parties; our ability to attract collaborators with development, regulatory and commercialization expertise; future agreements with third parties in connection with the commercialization of our product candidates; the size and growth potential of the markets for our product candidates and our ability to serve those markets; the rate and degree of market acceptance of our product candidates; regulatory developments in the United States and foreign countries; regulatory application, review and approval processes and our compliance with applicable legal and regulatory requirements; our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately; the success of competing products that are or may become available; and our ability to attract and retain key scientific or management personnel. These risks are not exhaustive. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, 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, or implied by, any forward-looking statements. More information about the risks and uncertainties faced by Eliem is contained under the caption Risk Factors set forth in Eliems Annual Report on Form 10-K for the fiscal year ended December 31, 2021, which is available on the SECs website at www.sec.gov, and in other subsequent reports and filings Eliem will make with the SEC from time to time. You should not rely upon forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation. Certain information contained in this presentation relates to, or is based on, studies, publications, surveys and other data obtained from third-party sources and the Companys own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. These and other factors could cause results to differ materially from those expressed in the estimates made by the independent parties and by us. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. In addition, statements that we believe and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this presentation, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements.
Highly experienced management team Clinical and preclinical pipeline based on clinically validated mechanisms of action Rethinking treatment for Two clinically differentiated lead product candidates with top-line nervous system data readouts across five indications over next 24 months disorders ~$160M* cash runway to late 2023 allows for top line data readouts and advancement of preclinical assets
Powered by Successful and Talented Deep expertise in neuroscience Executives from Pioneering Organizations research, clinical development and commercialization Lyrica, Neurontin, Trobalt, Vyepti, Vixotrigine, Nimotop, Aptiom, Lunesta, General Management, Commercial & Corporate Development Geodon Leadership experience in both large pharma and small biotech Robert Azelby, MBA Erin Lavelle James Bucher, J.D. Large: Amgen, GSK, Novartis, Biogen, Chief Executive Officer Chief Operating Officer & EVP and General Counsel Bayer, Pfizer Chief Financial Officer Small: Alder, Juno, Convergence, Cavion, Exelixis Research & Development Highly skilled in public/private capital raising and corporate development with successful exits Valerie Morisset, Ph.D. Joanne Palmer, Ph.D. Mark Versavel, M.D., Ph.D. EVP R&D and Chief Scientific Officer Chief Development Officer Interim Chief Medical Officer Exits: Alder, Convergence, Juno, Immunomedics, Cascadian, Cavion
Eliem is Developing Novel Therapies With Multiple Opportunities to Address Interrelated Diseases Chronic Pain Approaching interrelated disease states with ETX-810 multiple MOAs ETX-155 Kv7 Innovating within clinically validated mechanisms of action Depression Epilepsy / Anxiety ETX-155 ETX-155 Kv7 Kv7 Multiple pipeline-in-a-product opportunities Next-gen anxiolytic
Eliem Pipeline: Four Programs with Clinically Validated MOAs and Multiple Upcoming Clinical Catalysts Product Candidate Anticipated Clinical Lead indications Preclinical Phase 1 Phase 2 Phase 3 (Mechanism) Milestones Topline Phase 2a Diabetic peripheral neuropathic pain data (1H 2022) ETX-810 (PEA prodrug) Topline Phase 2a Lumbosacral radicular pain (sciatica) data (2H 2022) Topline Phase 2a Major depressive disorder (MDD) data (2H 2023) ETX-155 Topline Phase 2a Perimenopausal depression (PMD) (GABA receptor PAM) data (2H 2023) A Phase 1b photosensitive Focal onset seizure (FOS) epilepsy data (1H 2022) Kv7 Program Pain, Epilepsy, Depression (Kv7.2/3 channel opener) Next Gen Anxiolytic Generalized anxiety disorder (GAD) (2,3-benzo)
Anticipated Milestones Diabetic Peripheral Neuropathic Pain (DPNP) ETX-810 Phase 2a Data 1H 2022 Lumbosacral Radicular Pain (LSRP) Phase 2a Data 2H 2022
Chronic Pain: Large Commercial Opportunity with High Unmet Need Current Treatment Paradigm Unmet Need >36m <50% of patients achieve ?50% reduction in pain ? significant residual pain 1st line Antidepressants Significant tolerability issues (e.g., dizziness, nausea, US+EU (e.g., Cymbalta) somnolence, weight gain) Pain Patients Anticonvulsants (e.g., Lyrica) Chronic NSAIDs Poor compliance / frequent switching Treated Opioids Est. Abuse liabilities (e.g., opioids) Other ~$20b Rx market (2018) Novel MoAs? polypharmacy/ combination therapy ETX-810 has opportunity to be preferred 2nd line monotherapy or used in combination
ETX-810: Prodrug of PEA (palmitoylethanolamide), an Endogenous Bioactive Lipid Acting as a Master Regulator of Neuroinflammation and Pain Signaling Reduced PEA levels hypothesized in PEA is a master regulator of neuroinflammation and chronic pain pathology1 pain signaling with a pleiotropic mechanism1 Inhibition of inflammatory mediator release from mast ETX-810 cells/monocytes/macrophages Agonism of PPAR-alpha ? inhibition of pro-inflammatory gene expression Agonism of GPR55 ? action on microglia activation and phagocytic activity Entourage effect via FAAH inhibition ? increase endocannabinoid levels (AEA, 2-AG, OEA) ETX-810 is being developed to restore PEA levels to reduce persistent neuroinflammation and pain signaling in chronic pain
Clinical Validation of PEA: Compelling Body of Evidence Highlighting PEAs Activity and Tolerability in Chronic Pain PEA in Chronic Pain Meta-Analyses of PEA Chronic Pain Clinical Studies Reference Key Conclusions >2,500 patients treated with PEA in >35 published clinical studies of PEA Paladini 20161 81% achieved mild pain by day 60 (12 studies) (compared to 41% in control) Artukoglu 20172 2-point pain score reduction* vs control >1,500 patients studied in 15 RCTs (8 RCTs) ~900 patients treated with PEA *Mean pain score delta vs placebo for benchmark chronic pain drugs: Cymbalta0.8 to 1.23; Lyrica0.5 to 1.14 Consistent, clinically meaningful Activity across a broad range of Benign tolerability profile reductions in pain chronic pain conditions
Clinical Validation of PEA: Two Large Placebo-Controlled Studies Demonstrate Clinical Activity and Dose-Dependent Response Guida 20101 Low back pain / sciatica Steels 20193 Knee osteoarthritis N=636, PEA monotherapy 300 mg / 600 mg vs placebo, N=111, PEA monotherapy 300 mg / 600 mg vs placebo, 21-day BID dosing 8-week BID dosing Pain Score Reduction WOMAC total score Placebo 300 mg PEA 600 mg PEA Baseline Week 4 Week 8 score 50 0 -1 40 -2 10) -2 Placebo Score 2.9WOMAC 30 0 -3 * * PEA 300 mg Pain -0.9 20 (scale -4 Ä vs placebo -5 Mean ** PEA 600 mg VAS -5 10 -6 -3 * Ä vs placebo * Anova p<0.001 * 300 mg p=0.037 ** 600 mg p=0.001 Statistically significant reduction in pain vs placebo at d21 Significant reduction in WOMAC total score (pain, stiffness, and function) vs placebo at Wk 8, with dose-dependent response 600 mg significantly better than 300 mg 2 Statistically significant reduction in NRS pain vs placebo at Wk 8 (-2.1 pain 82% of 600 mg group had ?50% reduction in pain reduction vs placebo at 600mg, data not shown) Higher neuropathic pain correlated with higher efficacy2
ETX-810: Opportunity to Be a First-in-Class PEA Prescription Therapeutic for Chronic Pain Program Rationale ETX-810 Absorption Clear dose response in PEA RCTs Opportunity to enhance exposure Develop new chemical entity (NCE) Ester prodrug Protected PEA Hydrolysis in Active PEA through prodrug approach moiety tissue & serum Rapid oral absorption and release of biologically active PEA through series of enzymatic hydrolysis Program Goals steps Favorable pharmacokinetics increased half-life and dose-dependent increase in exposure Optimize PK of bioactive PEA Maximize probability of clinical trial Strong preclinical activity and dose-dependent effect in models of inflammatory pain and success Bring regulated PEA product to market neuropathic pain supported by robust RCTs New IP generated with patent protection to 2037
ETX-810 Has an Improved PK Profile and 3X Higher Exposure Compared to Dietary Supplement PEA Prodrug pharmacokinetics results in higher PEA concentration over time and 3x exposure improvement PEA concentration over time PEA exposure 80 400 1000 mg ETX-810 (delivering 490 mg PEA) 600 mg PEA dietary supplement 60 30012h) 3x higher 40 200 exposure* Concentration(0 PEA (ng/mL) AUC Mean 20 100 0 0 0 2 4 6 8 10 12 600mg PEA 1000 mg ETX-810 Time (h) Dietary supplement (= 490 mg PEA) Longer half-life of bioactive PEA 1000 mg BID dosing expected to Significantly higher area under the curve yield 6x higher PEA exposure
Encouraging Tolerability in Phase 1 Study With All AEs Being Mild and at Similar Rates as Placebo, With No Discontinuations SAD Study (n=60) MAD Study (n=20) ETX-810 Placebo ETX-810 1000mg ETX-810 500mg BID Placebo Adverse Event Adverse Event (50-1200mg) (n=48*) (n=12) BID (n=8) (n=8) (n=4) Any AE 29% 33% Any AE 38% 38% 50% Somnolence 10% 8% Dizziness 8% 0% Nausea 25% 0% 25% Headache 4% 0% Vomiting 0% 0% 25% Disorientation 2% 0% Menorrhagia 0% 25% 0% Euphoric mood 2% 0% Paraesthesia 2% 0% Dysmenorrhea 0% 13% 0% Nausea 6% 17% Insomnia 0% 13% 0% Diarrhoea 2% 0% Headache 13% 0% 25% Dry mouth 2% 0% Dyspepsia 0% 8% Dizziness 13% 0% 0% Fatigue 2% 17% Muscle twitching 13% 0% 0% Pallor 2% 0% Palpitations 2% 0% Muscle spasms 13% 0% 0% Phase 2 dose Participants were dosed every 12 hrs for 6 consecutive days; a single dose was administered on day 7 * same subjects participated in both the 150mg fasted and fed dosing conditions All doses were administered following a meal Highly differentiated Phase 1 tolerability profile for a chronic pain drug
ETX-810: Two Phase 2a Proof of Concept Studies With Topline Data Expected in 2022 Diabetic Peripheral Neuropathic Pain (DPNP) Objectives: 4 Weeks Study + 1 Week Follow up Fully enrolled Demonstrate clinically meaningful R ETX-810 (1000mg BID) Anticipated topline data improvement in neuropathic pain 1H 2022 Confirm safety & tolerability N = 162 Placebo BID NCT04688671 Primary Outcome Measure: Lumbosacral Radicular Pain (LSRP) Change from baseline to Week 4 in weekly average of the daily pain score 4 Weeks Study + 1 Week Follow up Rated on 11-point pain intensity Anticipated topline data numerical rating scale (PI-NRS) R ETX-810 (1000mg BID) 2H 2022 80% power to detect a 1-point difference from placebo N = 122 Placebo BID NCT04778592 Implementing clinical development strategies to refine patient population and limit placebo effect
There are a total of ~10 million treated patients in the DPNP and LSRP indications in the US DPNP LSRP Diabetes overall prevalence 34.2 M Chronic LBP overall prevalence 32.4 M DPNP overall prevalence 9.6 M Neuropathic pain in chronic LBP 13.7 M DPNP diagnosis rate 4 468 .6 M Chronic LBP diagnosis rate 8.9 M DPNP Drug Treated patients 3.0 M LSRP Drug Treated patients 7.0 M
~60% of the treated US patient opportunity is in 2nd line and beyond (2L+) Treated patient opportunity by LOT DPNP Total 2L+ <50% of patients achieve ?50% Line 1 Line 2 Line 3 Line 4+ reduction in pain ? significant % Pts 59% (40%) (27%) (19%) (14%) residual pain across all lines Significant tolerability issues # Pts 1.2m 0.8m 0.6m 0.4m 1.8m (e.g., dizziness, nausea, somnolence) LSRP Total 2L+ Abuse liabilities (e.g., opioids) Line 1 Line 2 Line 3 Line 4+ Compliance challenges % Pts 64% (35%) (27%) (21%) (17%) Polypharmacy # Pts 2.5m 1.9m 1.5m 1.1m 4.5m
A $15B+ branded opportunity exists in LoT2+ Drug Branded Dollar Both Cymbalta and Lyrica achieved Treated Opportunity >$1B in US peak sales in pain DPNP ~3.0 M ~$5 B Peak year: 2013 Assumptions: Pain revenue: ~$1.3B ? 60% LOT2+ LSRP ~7.0 M 195 Average DoT ~$11 B ? ~$ WAC Peak year: 2018 ? 5000 Pain revenue: ~$3.1B Both ~10.0 M ~$16 B Indications
Each 10% share of the LoT2+ patients is a $1.5B+ opportunity Percentage of Patients in LoT2+ across DPNP and LSRP Opportunity 11% Opioids 43% ~40%+ of patients are taking Total Branded Patients opioids consistently Opportunity = $16B of 31% Anti-Epileptics / Anti-Depressants Share of Lot2+ patients Nearly every patient is on an 10% 20% 30% Percentage 74% anti-epileptic or an anti- $ Opportunity $1.6B $3.2B $4.8B depressant Overall (LoT2+) Anti-epileptic Opioid Anti-depressant Others
We believe we can target 70% of the market (~75k HCPs) with a field team of ~500-550 HCP Universe Top specialties across DPNP & LSRP by NRx volume 8% PM & R LSRP 8% DPNP PAIN MEDICINE 10% 17k 31k 27k 14% ANESTHESIOLOGY NRx % INTERNAL MEDICINE 34% FAMILY MEDICINE ~75k unique HCPs
Aiming to Develop a NCE with Desired Clinical Profile to Address the Large Chronic Pain Market Target Profile for a New Chronic Pain Treatment Commercial Opportunity Non-opioid, with no abuse liability 2028 US+EU Forecast: ~50m 2nd line or later drug-treated chronic pain patients Novel mechanism of action ~10m ?2nd line treated LSRP and Chronic Low DPNP patients in US+EU Back Pain LSRP (neuropathic At ~$5K annual price, every 2% Efficacy as monotherapy and in combination back pain) patient market share is worth DPNP ~$1b/year in LSRP and DPNP alone Benign side effect profile OA Pain Broad expansion opportunities into large chronic low back pain and OA Fibromyalgia, RA pain, pain indications No drug-drug interactions (DDIs) Cancer Pain, PHN A novel chronic pain therapy with a desirable product profile is a multi-billion dollar opportunity
Anticipated Milestones Photosensitive Epilepsy ETX-155 Data Expected 1H 2022 Major Depressive Disorder Topline Phase 2a Expected 2H 2023 Perimenopausal Depression Topline Phase 2a Expected 2H 2023
ETX-155: A Differentiated Neuroactive Steroid GABAA Positive Allosteric Modulator Clinical validation for MOA (GABAA PAM) Dual potent activity at synaptic and extrasynaptic GABAA receptors, with high intrinsic efficacy No clinically meaningful food effect Convenient once-daily dosing with ~40-hr half-life Well tolerated at exposure levels that have translated to clinical efficacy for other GABAA PAMs Strong IP position with patent protection to 2039
Clinical Development Focused on Depressive Disorders and Focal Onset Seizure Large Markets With Considerable Unmet Need Major Depressive Perimenopausal Epilepsy / Focal Disorder (MDD) Depression (PMD) Onset Seizure (FOS) Reduced GABA levels ? Reduced neurosteroid levels ? GABAergic deficits ? increased MDD severity1 PMD symptoms epileptic state MoA Rationale Clinically validated (SAGE-217) Clinically validated in neurosteroid- Clinically validated in orphan driven PPD (SAGE-217) epilepsies (ganaxolone) Faster onset of action Same as MDD Novel MoAs? better seizure control Unmet Needs Improved tolerability/efficacy Novel MoAs directly addressing reduced neurosteroid levels Positive impact on mood as #1 Novel MoAs comorbidity is depression4 Estimated annual ~32m ~8m ~2m prevalence (US+EU) (~9m failed ?1 prior therapy)2 (~2m with no history of MDD)3 (~0.8m with uncontrolled seizures)5
ETX-155 Differentiation: Significantly Longer Half-Life, Lack of Food Effect, Favorable Bioavailability and Broad GABAAR Activity GABAAR Clinical Validation Pharmacokinetics Activity (positive RCT) Company Molecule Extra- Synaptic Food effect Half-life Oral Bioavailability MDD PPD or PMD Epilepsy synaptic ~70% ETX-155 No ~40 hrs 2H 2023 2H 2023 2024 (tablet) SAGE-217 68% Yes 14-18 hrs(zuranolone) (capsule) 10% ganaxolone Yes 2-3 hrs (capsule) PRAX-114 Yes 1215 hrs Not disclosed TBD TBD
Phase 1 Study in Healthy Subjects: Excellent Pharmacokinetics and Safety & Tolerability Profile with No Severe or Serious Adverse Events Most common treatment-emergent AEs ETX-155 Phase 1 Repeat-Dose Results (In ?10% of ETX-155 treated subjects across repeat dose studies) Favorable pharmacokinetics 7-day Repeat 14-day Repeat Steady state reached at day 8 Combined Dose Dose ~40-hour half-life at steady state ETX-155 ETX-155 ETX-155 60 mg evening dosing was well tolerated Placebo Placebo Placebo 60 mg 60 mg 60 mg No SAEs or discontinuations (n=6) (n=5) (n=11) (n=9) (n=15) (n=24) All AEs were mild/moderate and transient n (%) n (%) n (%) n (%) n (%) n (%) CNS AE details The rate of CNS AEs were comparable in ETX-155 and ?1 TEAE 5 (56) 3 (50) 9 (60) 4 (80) 14 (58) 7 (64) placebo groups Most CNS AEs occurred at Tmax (3-4 hrs post-dose) Somnolence 1 (11) 2 (33) 6 (40) 2 (40) 7 (29) 4 (36) 7 reports of somnolence out of 24 ETX-155-treated Fatigue 0 0 4 (27) 1 (20) 4 (17) 1 (9) patients (no subject reported somnolence more than once during dosing period) Leeds Sleep Evaluation Questionnaire indicates no Headache 2 (22) 2 (33) 1 (7) 0 3 (13) 2 (18) difference in next-morning alertness or disruption in sleep quality compared to placebo Dizziness 1 (11) 0 2 (13) 0 3 (13) 0
ETX-155 Does Not Have a Clinically Meaningful Food Effect: Potential to Impact Efficacy, Safety, and Compliance Reported Fed/Fasted Ratios for GABAA PAM class Presence of a food effect may impact: Efficacy 3.5 Cmax AUC(0-t) Exposure reduced or increased if medication not 3 3.0x taken with food 2.5 2.9x 2.6x FOOD EFFECT Safety and Tolerability Clinically meaningful higher Ratio 2 exposure if taken with food Timing/severity of AEs associated with Cmax 1.5 1.6x 1.25x Compliance 1 NO FOOD EFFECT4 Fed/Fasted More strict daily routine required to maintain 0.8x FOOD EFFECT drug levels within the required range for 0.5 0.6x Clinically meaningful lower exposure if taken with food efficacy and safety 0 ETX-155 PRAX-1141 SAGE-2172 Ganaxolone3 Tablet, 30mg, Suspension, Capsule, 30mg, Capsule, human 30mg, human human 5 mg/kg, dog
Progressing ETX-155 in Epilepsy: Phase 1b Proof-of-Concept Trial in Photosensitive Epilepsy (PSE) to De-risk Focal Onset Seizure Study Rationale Study Details PSE is characterized by a photoparoxysmal response (PPR) Design: Phase 1b, single-center, randomized, double-blind, triggered by light stimulation placebo-controlled, 2-sequence crossover study Objective: Provide evidence of inhibition of PPR in subjects Single dose PSE trials are valuable in predicting efficacy in with PSE epilepsy and aiding in dose selection for later phase trials Dose: Single dose of 135 mg (MTD), then titrate down until Reduction of an induced PPR EEG response in PSE has proven loss of effect a reliable biomarker of anticonvulsant activity in epilepsy for most approved ASMs1 N= 6 Primary Outcome Measure: Change in PPR range vs placebo at 1, 2, 4, 6, and 8hr Data anticipated 1H 2022
Progressing ETX-155 in Depressive Disorders: Two Phase 2a RCTs of ETX-155 in MDD and PMD, with Topline Data Anticipated in 2H 2023 Screening Outpatient Treatment Follow-up Primary Endpoint (both PMD and MDD studies) Week 28 days 14 days Change from baseline in HAMD17 1 2 3 4 over days 3, 8, 15, 22, and 29 MDD Phase 2a ETX-155 60 mg tablets Key Secondary Endpoints ~80 subjects qd x 28 days Change from baseline in HAMD17 at day 3, 8, 15, 22, 29, and 43 PMD Phase 2a RANDOMIZATION Placebo ~80 subjects1:1 qd x 28 days 50% response rate in HAMD17 at day 3, 8, 15, 22, 29 d1 d8 d15 d22 d29 d43 Topline data from both studies anticipated 2H 2023
ETX-155: Potentially Clinically Differentiated Oral Neuroactive Steroid in Markets with Significant Unmet Needs Unmet Needs ETX-155 Opportunities Depressive Disorders Improve Efficacy Leverage absence of food effect & significantly longer half-life Slow onset of efficacy (~6+ wks) Improve Tolerability High refractory rates Highly encouraging CNS AE rates in healthy subjects Tolerability issues limit compliance Improve Durability Leverage longer half-life and evaluate longer dosing periods (i.e., ?28 days) Novel MoA Focal Onset Seizure Clinicians combine different MoAs to improve seizure control 30% of patients on ASMs have uncontrolled seizures Well Tolerated #1 co-morbidity is depression Encouraging Phase 1 tolerability data when considering use as an add-on therapy Positive impact on mood Potential to provide differentiated benefit on common depression comorbidity
Kv7.2/3 Program: Developing a Differentiated Kv7.2/3 Opener For Multiple Neuronal Excitability Indications Kv7 Opportunity Eliem Kv7 Program Goal Maintain efficacy with improved tolerability Chronic Pain Human genetic validation and safety Strong clinical validation in pain and epilepsy Program Status Kv7 (retigabine, flupirtine, XEN1101) Multiple lead and backup Depression Epilepsy chemotypes in novel IP space Metabolic/safety liabilities with existing molecules Improved metabolic stability Potent at Kv7.2/3 and selective vs Clear translational path to Kv7.1/4 Opportunity across clinical efficacy multiple indication areas IND-enabling studies anticipated to initiate in 2022
Multiple Catalysts and Value-Creating Milestones Across Pipeline Existing Cash Runway Through Five Topline Data Catalysts Anticipated Catalysts and Key Milestones 1H 2022 2H 2022 1H 2023 2H 2023 Ph 2a DPNP Topline Ph 2b Dose Range Finding data ETX-810 Ph 2a LSRP Topline data Potential Ph 2b Dose Range Finding Ph 2a MDD Topline data ETX-155 Ph 2a PMD Topline data Ph1b PSE data Ph 2 FOS Kv7 program preclinical development and Preclinical IND-enabling studies GAD program preclinical development ~$160 million* cash runway into late 2023
Highly experienced management team Clinical and preclinical pipeline based on clinically validated mechanisms of action Rethinking treatment for Two clinically differentiated lead product candidates with top-line nervous system data readouts across five indications over next 24 months disorders ~$160M* cash runway to late 2023 allows for top line data readouts and advancement of preclinical assets
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