UNITED STATES
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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).
Emerging growth company
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Item 2.02. Results of Operations and Financial Condition.
On November 14, 2022, Eliem Therapeutics, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2022. A copy of such press release is attached to this Current Report as Exhibit 99.1.
Item 7.01. Regulation FD Disclosure.
A copy of a slide presentation that the Company will use at investor conferences and presentations is attached to this Current Report as Exhibit 99.2 and is incorporated herein solely for purposes of this Item 7.01 disclosure.
The information in Items 2.02 and 7.01 (including Exhibits 99.1 and 99.2) are being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any filing under the Exchange Act or the Securities Act of 1933, as amended, whether filed before or after the date hereof and regardless of any general incorporation language in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
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Description |
99.1 |
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Press release of Eliem Therapeutics, Inc., dated November 14, 2022 |
99.2 |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
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1
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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Eliem Therapeutics, Inc. |
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Date: November 14, 2022 |
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By: |
/s/ Robert Azelby |
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Robert Azelby |
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President and Chief Executive Officer |
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Exhibit 99.1
Eliem Therapeutics Reports Third Quarter Financial and Business Highlights
Positioned to initiate ETX-155 Phase 2a trial in major depressive disorder in the first quarter of 2023 with 60-milligram dose
Progressing IND-enabling studies for two Kv7 pre-candidates with safety studies planned in the first quarter of 2023
Cash runway expected to fund operations into 2025
SEATTLE and CAMBRIDGE, UK, --(GLOBE NEWSWIRE) – November 14, 2022 – Eliem Therapeutics, Inc. (Nasdaq: ELYM), a clinical-stage biotechnology company focused on developing novel therapies for neuronal excitability disorders to address unmet needs in psychiatry, epilepsy, chronic pain, and other disorders of the peripheral and central nervous systems, today provided a business update and reported financial results for the quarter ended September 30, 2022.
“I am proud of the rigorous analysis done by our team over the past six months, and we are now positioned to initiate our ETX-155 Phase 2a MDD trial in the first quarter of 2023 with the 60-milligram dose,” said Bob Azelby, chief executive officer of Eliem Therapeutics. “We believe ETX-155 has the potential to be a best-in-class molecule in a growing depression market in search of new medicines to tackle this crisis. In parallel, we have advanced two pre-candidates from our Kv7 program into IND-enabling studies, and we are very excited about our rapidly emerging preclinical data for this important program. We remain well financed with our cash runway expected to fund operations into 2025, funding key data catalysts on each program.”
Program Updates and Anticipated Key Milestones
ETX-155 in depression and epilepsy: ETX-155 is a novel GABAA receptor positive allosteric modulator (GABAA PAM) that is being developed for the treatment of major depressive disorder (MDD) and epilepsy.
Kv7.2/3 channel opener program: The Company’s preclinical program targets the Kv7.2/3 potassium channel (Kv7), a target that has clinical validation in pain and epilepsy.
Third Quarter 2022 Financial Results
About Eliem Therapeutics, Inc.
Eliem Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing novel therapies for neuronal excitability disorders to address unmet needs in psychiatry, epilepsy, chronic pain, and other disorders of the peripheral and central nervous systems. These disorders often occur when neurons are overly excited or inhibited, leading to an imbalance, and our focus is on restoring homeostasis. We are developing a pipeline of clinically differentiated product candidates focused on validated mechanisms of action with broad therapeutic potential to deliver improved therapeutics for patients with these disorders. Eliem channels its experience, energy, and passion for improving patients’ quality of life to fuel our efforts to develop life-changing novel therapies. At its core, the Eliem team is motivated by the promise of helping patients live happier, more fulfilling lives. https://eliemtx.com/
Forward-Looking Statements
This press release contains forward-looking statements, including, without limitation, statements relating to: the advancement of Eliem’s pipeline; the continued development and clinical and therapeutic potential of ETX-155 and Eliem’s Kv7 channel opener program; the commencement of the referenced Phase 2a trial of ETX-155 in MDD in the first quarter of 2023 and the availability of topline data for that trial; Eliem’s plans to continue to pursue development of ETX-155 in focal onset seizures; Eliem’s planned activities and expectations for the Kv7 channel opener program, including the initiation of IND-enabling safety studies and Phase 1 studies, and the timing thereof; Eliem’s belief that it is well financed and that its current cash, cash equivalents and short- and long-term marketable securities will fund operations into 2025; and Eliem’s commitment to developing therapies targeting neuronal excitability disorders. Words such as “advanced,” “believe,” “encouraging,” “excited,” “expected,” “focus,” “initiate,” “planned,” “positioned,” “potential,” “progressing,” “remain,” “reported,” “would,” or other similar expressions, identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. The forward-looking statements in this press release are based upon Eliem’s current plans, assumptions, beliefs, expectations, estimates and projections, and involve substantial risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements due to these risks and uncertainties as well as other factors, which include, without limitation: the clinical, therapeutic and commercial value of ETX-155 and the Kv7 program; risks related to the potential failure of ETX-155 or the Kv7 program to demonstrate safety and efficacy in clinical testing; Eliem’s ability to initiate and conduct clinical trials and studies of ETX-155 or the Kv7 program sufficient to achieve a positive completion; the availability of data at the expected times; Eliem’s ability to obtain and protect intellectual property rights, and operate without infringing on the intellectual property rights of others; the uncertain timing and level of expenses associated with Eliem’s preclinical and clinical development activities; the sufficiency of Eliem’s capital and other resources; risks and uncertainties related to regulatory application, review and approval processes and Eliem’s compliance with applicable legal and regulatory requirements; market competition; changes in economic and business conditions; impacts on Eliem’s business due to external events, including health pandemics or other contagious outbreaks, such as the current COVID-19 pandemic; and other factors discussed under the caption “Risk Factors” in Eliem’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2022. This filing, when available, is available on the SEC’s website at www.sec.gov. Additional information will also be set forth in Eliem’s other reports and filings it will make with the SEC from time to time. The forward-looking statements made in this press release speak only as of the date of this press release. Eliem expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Eliem’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
Investors
Chris Brinzey
ICR Westwicke
chris.brinzey@westwicke.com
339-970-2843
Media
Marites Coulter
Verge Scientific
Mcoulter@vergescientific.com
415.819.2214
Eliem Therapeutics, Inc.
Condensed Consolidated Balance Sheets
(In thousands, except share and per share amounts)
(unaudited)
Assets |
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September 30, 2022 |
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December 31, 2021 |
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Current assets: |
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Cash and cash equivalents |
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$ |
35,944 |
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$ |
46,922 |
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Short-term marketable securities |
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86,675 |
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89,558 |
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Prepaid expenses and other current assets |
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10,552 |
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11,772 |
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Total current assets |
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$ |
133,171 |
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$ |
148,252 |
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Operating lease right-of-use assets |
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585 |
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— |
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Long-term marketable securities |
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6,961 |
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24,919 |
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Other long-term assets |
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141 |
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70 |
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Total assets |
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$ |
140,858 |
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$ |
173,241 |
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Liabilities and stockholders’ equity |
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Current liabilities: |
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Accounts payable |
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1,494 |
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1,404 |
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Accrued expenses |
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4,434 |
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4,627 |
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Operating lease liabilities |
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352 |
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— |
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Total current liabilities |
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$ |
6,280 |
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$ |
6,031 |
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Other long-term liabilities |
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— |
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7 |
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Operating lease liabilities, net of current portion |
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219 |
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— |
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Total liabilities |
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$ |
6,499 |
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$ |
6,038 |
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Stockholders’ equity |
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Common stock, $0.0001 par value per share, 250,000,000 shares authorized; 26,567,681 shares issued and outstanding at September 30, 2022 and December 31, 2021, respectively |
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3 |
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3 |
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Additional paid-in capital |
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248,035 |
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242,939 |
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Accumulated other comprehensive loss |
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(581 |
) |
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(123 |
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Accumulated deficit |
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(113,098 |
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(75,616 |
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Total stockholders’ equity |
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$ |
134,359 |
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$ |
167,203 |
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Total liabilities and stockholders’ equity |
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$ |
140,858 |
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$ |
173,241 |
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Eliem Therapeutics, Inc.
Condensed Consolidated Statements of Operations
(In thousands, except share and per share amounts)
(unaudited)
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Three Months Ended September 30, |
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Nine Months Ended September 30, |
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2022 |
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2021 |
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2022 |
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2021 |
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Operating expenses: |
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Research and development |
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$ |
4,258 |
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$ |
5,989 |
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$ |
21,287 |
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$ |
16,443 |
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General and administrative |
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4,490 |
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3,394 |
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14,294 |
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8,526 |
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Total operating expenses |
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8,748 |
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9,383 |
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35,581 |
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24,969 |
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Loss from operations |
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(8,748 |
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(9,383 |
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(35,581 |
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(24,969 |
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Other income (expense): |
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Change in fair value of redeemable convertible preferred stock tranche liability |
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— |
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— |
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— |
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(11,718 |
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Foreign currency loss |
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(1,317 |
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(252 |
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(2,516 |
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(268 |
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Other income, net |
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383 |
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20 |
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615 |
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20 |
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Total other income (expense) |
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(934 |
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(232 |
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(1,901 |
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(11,966 |
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Net loss |
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$ |
(9,682 |
) |
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$ |
(9,615 |
) |
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$ |
(37,482 |
) |
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$ |
(36,935 |
) |
Accretion of redeemable convertible preferred stock to redemption value and cumulative preferred stock dividends |
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— |
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(1,322 |
) |
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— |
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(4,548 |
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Net loss attributable to common stockholders |
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$ |
(9,682 |
) |
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$ |
(10,937 |
) |
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$ |
(37,482 |
) |
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$ |
(41,483 |
) |
Net loss per share attributable to common stockholders, basic and diluted |
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$ |
(0.37 |
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$ |
(0.70 |
) |
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$ |
(1.43 |
) |
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$ |
(5.49 |
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Weighted-average number of shares outstanding used to compute net loss per share attributable to common stockholders, basic and diluted |
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26,336,029 |
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15,585,611 |
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26,290,868 |
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7,554,300 |
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Clinical Stage Neurology Company Focused on Neuronal Excitability Disorders Corporate Presentation | November 14, 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 Eliem’s Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2022, which is available on the SEC’s 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 Company's 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 Two differentiated programs in depression and epilepsy with expansion opportunities in chronic pain Rethinking treatment for nervous system disorders *Cash, cash equivalents and short- and long-term marketable securities of $129.6M as of September 30, 2022 ~$130M* cash runway into 2025 allows for topline clinical data readouts and advancement of preclinical asset into clinic
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 Chief Medical Officer Robert Azelby, MBA Chief Executive Officer Erin Lavelle Chief Operating Officer & Chief Financial Officer James Bucher, J.D. EVP and General Counsel Deep expertise in neuroscience research, clinical development and commercialization Lyrica, Neurontin, Trobalt, Vyepti, Vixotrigine, Nimotop, Aptiom, Lunesta, Geodon Leadership experience in both large pharma and small biotech Large: Amgen, GSK, Novartis, Biogen, Bayer, Pfizer Small: Alder, Juno, Convergence, Cavion, Exelixis Highly skilled in public/private capital raising and corporate development with successful exits Exits: Alder, Convergence, Juno, Immunomedics, Cascadian, Cavion 4
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 Pain Epilepsy Depression / Anxiety ETX-155 Kv7
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 markets GABAA PAM: GABAA receptor positive allosteric modulator IND-enabling safety studies planned in Q1 2023 Positioned for Phase 2a initiation in Q1 2023
ETX-155 Proof of concept Phase 2a trial in Major Depressive Disorder (MDD) positioned for Q1 2023 initiation
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 food effect Convenient once-daily dosing with ~40-hr half-life Strong IP position with patent protection to 2039 Clinical validation for MOA (GABAA PAM)
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 onset of action Improved tolerability/efficacy Novel MoAs Same as MDD Novel MoAs directly addressing reduced neurosteroid levels Reduced neurosteroid levels PMD symptoms Clinically validated in neurosteroid-driven PPD (zuranolone) ~32m (~9m failed ≥1 prior therapy)2 ~8m (~2m with no history of MDD)3 GABAergic deficits epileptic state Clinically validated in orphan epilepsies (ganaxolone) Novel MoAs better seizure control Positive impact on mood, as #1 comorbidity is depression4 ~2m (~0.8m with uncontrolled seizures)5 Epilepsy / Focal Onset Seizure (FOS) Major Depressive Disorder (MDD) Luscher et al, Mol Psychiatry, 2011;16(4):383-406 Decision Resources Group (DRG)– Unipolar Depression Disease Landscape and Forecast Freeman et al, JAMA Psychiatry, 2014;72(1):36-43 Kanner AM, Biol Psychiatry, 2003;54(3):388-98 DRG – Epilepsy Disease Landscape and Forecast, May 2021 Proof of concept planned Potential future indication opportunities
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 Pharmacokinet, 2020;59(1):111-120; Hoffmann et al, ASCP 2018, poster #782; Botella et al, J Med Chem, 2017;60(18)7810-7819; Phase 3 WATERFALL topline data press release Ganaxolone: ZTALMY Prescribing Information; Hulihan et al., American Epilepsy Society Annual Meeting 2020, poster * Evening QD dosing for ETX-155, zuranolone; TID dosing for ganaxolone ETX-155 Differentiation: Similar dual GABAAR potency to clinically validated GABAA PAMs, with differentiated pharmacokinetics
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. As a result, such data may not be directly comparable. Presence of a food effect may negatively impact: Efficacy Exposure reduced or increased if medication not taken with food Safety and Tolerability Timing/severity of AEs associated with Cmax Compliance More strict daily routine required to maintain drug levels within the required range for efficacy and safety Zuranolone1 Ganaxolone2 NO FOOD EFFECT3 ETX-155 AUC(0-t) Cmax FOOD EFFECT Clinically meaningful higher exposure if taken with food FOOD EFFECT Clinically meaningful lower exposure if taken with food 1.25x 0.8x 1.6x 2.9x 2.6x 3.0x Fed/Fasted Ratio Tablet, 30mg, human Capsule, 30mg, human Capsule, 5 mg/kg, dog Reported Fed/Fasted Ratios for GABAA PAM class Hoffmann et al, Clin Pharmacokinet, 2020;59(1):111-120; Hoffmann et al, ASCP 2018, poster #782 U.S. Patent No. 9,029,355 Range of fed/fasted ratios for AUC and Cmax required to claim absence of food effect on bioavailability, per FDA Guidance For Industry, Food-Effect Bioavailability and Fed Bioequivalence Studies, December 2002
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 No SAEs or discontinuations All AEs were mild/moderate and transient CNS AE details The rate of CNS AEs were comparable in ETX-155 and placebo groups Most CNS AEs occurred at Tmax (3-4 hrs post-dose) 7 reports of somnolence out of 24 ETX-155-treated patients (no subject reported somnolence more than once during dosing period) Leeds Sleep Evaluation Questionnaire indicates no difference in next-morning alertness or disruption in sleep quality compared to placebo 7-day Repeat Dose 14-day Repeat Dose Combined ETX-155 60 mg (n=9) Placebo (n=6) ETX-155 60 mg (n=15) Placebo (n=5) ETX-155 60 mg (n=24) Placebo (n=11) n (%) n (%) n (%) n (%) n (%) n (%) ≥1 TEAE 5 (56) 3 (50) 9 (60) 4 (80) 14 (58) 7 (64) Somnolence 1 (11) 2 (33) 6 (40) 2 (40) 7 (29) 4 (36) Fatigue 0 0 4 (27) 1 (20) 4 (17) 1 (9) Headache 2 (22) 2 (33) 1 (7) 0 3 (13) 2 (18) Dizziness 1 (11) 0 2 (13) 0 3 (13) 0 Most common treatment-emergent AEs (In ≥10% of ETX-155 treated subjects across repeat dose studies)
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=9 active/cohort) MAD 14-day (60mg PM, n=15 active/cohort) Well tolerated, especially with PM dosing Encouraging PK profile Moderate CV% of ~30% Half-life of ~40 hrs Steady state at day 8 Moderate acc. ratio of ~2 No food effect Exposures within preclinical efficacy range Enabled selection of a Phase 2 clinical dose of 60mg Single-dose of 135 mg N=3 patients with photosensitive epilepsy (PSE) Evaluation of activity in this model inconclusive due to ~50% lower-than-expected exposures Achievement of predicted therapeutic exposure levels is critical for success of planned Phase 2a MDD trial Prompted investigation to understand potential root causes prior to progressing to MDD trial CMC investigations on all batches of API and DP No findings Dog PK to compare preclinical exposure across all batches Comparable across batches 5 single dose cohorts of healthy subjects to confirm PK profile Comparable exposure across batches with variability remaining moderate Comparison of exposures from all batches with population PK model based on original Phase 1 data Exposures at 60mg fit the model Evaluated 75 mg in repeat-dose cohort to determine any advantage over 60 mg 60 mg dose selected for Phase 2a based on favorable exposure and AE profile relative to 75 mg dose
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 AUCtau Mean 2289 5th % 95th % 5th % 95th % 1. Mean AUC derived from male rats with 3 mg/kg PO dose of ETX-155; 3 mg/kg dose of ETX-155 was an efficacious across multiple preclinical depression, anxiety, and seizure models in mice and rats 2. Derived from 5-day repeat dose 30mg pharmacokinetic data in Bullock et al, Marcé of North America Congress, Oct 21-24, 2021, and Hoffmann et al, 2018 Annual Meeting of the American Society for Clin Pharm and Ther, March 2018 extrapolated to 50 mg based on dose linearity; Day 3 zuranolone exposures have not been disclosed 3. Estimated preclinical AUC for robust efficacy for zuranolone derived from Althaus et al, Neuropharmacology, 2020;181:108333, extrapolated from reported 10 mg/kg PO AUC in male mice, assuming dose linearity The two graphs are not generated from head-to-head trials and therefore are not direct comparisons. ETX-155 preclinical AUC ranges are derived from rat PK study for 1 mg/kg and 3 mg/kg groups, which were efficacious dose levels in depression, anxiety, seizure, and EEG preclinical models; SS: Steady State Benchmark zuranolone modeled AUC0-24 for 30mg and 50mg capsules at steady-state2 Mean 1540 CV% Mean: 924 CV% Mean robust preclin efficacy (1216)3 Zuranolone has demonstrated a dose response with improved efficacy when moving from 20 mg to 30 mg (Mountain) and from 30 mg to 50 mg (Waterfall, Shoreline) in Phase 3 MDD trials
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 d8 d15 d22 d29 d42 Primary Endpoint Change from baseline in HAMD17 over days 4, 8, 15, 22, and 29 Secondary Endpoints Change from baseline in HAMD17 and HAMD6 at days 4, 8, 15, 22, 29 and 422 HAMD17 response and remission rates at days 4, 8, 15, 22, 29 and 42 Day 1 dose will be split and given bid, in AM and PM Day 42 assessments are exploratory HAMD17: Hamilton Depression Rating Scale Study is 90% powered to detect a placebo-adjusted reduction of 4 points from baseline Phone visit
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 differences between clinical research and care provided by an HCP, and inclusion/exclusion criteria Closely monitor study drug compliance (AiCure app) and eDiary Independent SAFER process: MGH clinician interview to confirm HAMD-17 clinical assessments and trial eligibility Implementation of a placebo control reminder script for use at every visit Exclude patients who experience a substantial change (increase/decrease) in HAMD-17 score between screening and baseline assessments If currently taking an antidepressant drug, subjects must be on a stable dose for at least 4 weeks before baseline assessment
ETX-155 Market Opportunity
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: DRG Unipolar Depression Disease Landscape and Forecast, 2021 Assumes $6,000 WAC, 6 months on therapy/yr Reference branded MDD drug peak sales Drug Class Peak Sales Peak Year Lexapro SSRI $3.0B 2011 Effexor SNRI $2.7B 2008 Zoloft SSRI $2.6B 2005 Cymbalta SNRI $2.6B 2013 Prozac SSRI $2.4B 2001
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=269) Zur 50mg + ADT (n=215) Placebo + ADT (n=210) Baseline HAMD17 26.8 26.9 26.8 26.6 Mean day 3 HAMD17 17 20.1 17.9 (endpt: -1.9 vs pbo) 19.6 Mean day 15 HAMD17 12.7 (endpt: -1.7 vs pbo) 14.6 13.1 13.7 Mean day 42 HAMD17 13.3 14.3 11.9 11.7 HAMD17 severity categories3 ≥24 Severe depression 17-23 Moderate depression 8-16 Mild depression 0-7 No depression Sage Therapeutics / Biogen – WATERFALL topline data presentation, June 15, 2021 Sage Therapeutics / Biogen – CORAL topline data presentation, Feb 16, 2022 Zimmerman et al, J Affect Disord, 2013;150(2):384-8
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 in a year Rapid onset: zuranolone achieved activity by day 3, with no titration, which should enable patient to know within two weeks if product is working Transient side effects: somnolence/fatigue but no weight gain, sexual dysfunction, or withdrawal observed in zuranolone trials Enhanced adherence: two-week course of therapy should dramatically improve adherence Short treatment duration combined with rapid effect enables dosing aligned with the depressive episode Background SSRI’s treatment duration undefined – many patients on SSRIs for multiple years/life SSRI’s can take 6 to 8 weeks to work, if they work; not accounting for titration period Side effects including weight gain, sexual dysfunction, withdrawal symptoms Unsatisfied market with new MDD patient on therapy for ~ 5.5 months, adherence rates of 51% at week 16, 21% at week 331 1. Sawada et al, BMC Psychiatry, 2009;9(38).
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 placebo in healthy subjects No difference from placebo in sleep quality and next day alertness No reports of somnolence on more than one day in repeat dosing studies Improve Durability Evaluate longer dosing regimens (i.e., 28 days) Statements are not based on data resulting from head-to-head trials and are not direct comparisons of safety or efficacy
Kv7 Opener Pre-candidates identified IND-enabling safety studies planned for Q1 2023
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 tolerability and safety Multiple lead and backup candidates in novel chemical space Improved metabolic stability Potent at Kv7.2/3, selective vs Kv7.1/4, and active in MES rat model* Human genetic validation Strong clinical validation in pain and epilepsy (retigabine, flupirtine, XEN1101) Clear translational path to clinical efficacy Metabolic/safety liabilities with existing molecules Foundational IP filed *MES: maximal electroshock seizure, a preclinical model where efficacy has been historically shown to be highly translatable to humans with recurrent seizures
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) Retigabine In vitro profile Potency at Kv7.2/3 +++ (7 nM) ++ (70 nM) ++ (20 nM) + (2 uM) Selectivity over Kv7.4 ++++ (14,000-fold) ++ (45-fold) + (10-fold) + (7.8-fold) Selectivity over Kv7.1 +++ +++ +++ +++ In vivo profile Rat MES / rotarod ++++ (2 mg/kg oral MES efficacy / 14 mg/kg rotarod side effects) +++ (sc dosing) +++ +++ Oral bioavailability (rat) + + +++ +++ Chemistry Structural features Novel scaffold, not disclosed analogue of retigabine Substituted aniline IP COM IP Filed August 2022 2028 expiry (initial issued patents) n/a (off-market)
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 Washout
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 to date; additional oral formulation optimization and IND-enabling studies ongoing Efficacious in rat maximal electroshock seizure (MES) model Well tolerated in rat rotarod model *** *** *** *** V 0.5 2 8 14 50 % of animals 0 25 50 75 100 *** p<0.01 Latency on Rotarod (s) Vehicle ETX-123 (mg/kg oral) Retigabine (mg/kg oral) ** V 0.5 2 8 14 50 0 100 200 300 ** p<0.01
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 allows for topline clinical data readouts and advancement of preclinical asset into clinic *Cash, cash equivalents and short- and long-term marketable securities of $129.6M as of September 30, 2022
For more information: www.eliemtx.com InvestorRelations@eliemtx.com
BACKUP
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 Calorimetry, Powder X-Ray Diffraction, Zeta Potential, dissolution profile, presence of crystalline material, roller compaction, compression Documentation review No differences were found between the 3 different batches of drug substance, and drug product No deviations recorded in executed batch records or clinical trial documentation No evidence of a quality event or manufacturing or dosing errors Preclinical exposure comparison (Dog PK) 6 cohorts of n=6 dogs, to compare exposure between all drug product batches (2020, 2021 and 2022) and tablet sizes No differences in exposure between any batches and tablets size tested Clinical exposure comparison (HV PK) Completed 5 single dose cohorts (n=19-24 each, 42 total w/ some subjects participating in several cohorts) 60mg (4 cohorts) and 75mg (one cohort) Planned repeat dose cohort with 75mg, data in November (n≤18) No differences in exposure between all batches and tablet sizes at 60mg single dose – Variability remains moderate Population PK model comparison Mathematical analysis of exposures from all batches and tablet sizes with PopPK model established with original Phase 1 data No difference in mathematical analysis of the 60mg exposure data from ongoing HV study compared to the pop PK model
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 (36.4) 8 (66.7) (1 moderate) 2 (33.3) Fatigue 4 (16.7) 1 (9.1) 0 0 Headache 3 (12.5) 2 (18.2) 0 0 Dizziness 3 (12.5) 0 2 (16.7) 0 Drowsiness 0 0 2 (16.7) 1 (16.7) Euphoric mood 2 (8.3) 0 2 (16.7) 0 75 mg 75 mg 60 mg Day 3 exposures (by subject) Steady state exposures (by subject) Repeat dose exposures for 60 mg and 75 mg ETX-155 (PM dosing) Most common TEAEs for 60 mg and 75 mg ETX-155 (PM dosing)* * Treatment-emergent adverse events (TEAEs) in ≥10% of subjects in any arm; drowsiness TEAE includes reports coded as “feeling tired” or “drowsiness”, Euphoric mood TEAE includes reports coded as “feeling high” or “euphoric mood” 60 mg dose yields exposures within the robust therapeutic range by day 3, with a more favorable tolerability profile than 75 mg
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 at end of treatment Active (top dose, if >1 arm) Placebo Delta to placebo Active Placebo 38 studies of SSRIs/SNRIs Kirsch 2002 1980s-1990s 21.0 – 29.7 4-8 weeks -10.4 (range: -5.9 to -14.2) -7.6 (range: -3.0 to -10.5) -2.8 ~14 ~17 Cymbalta: Study 1 Cymbalta label 2001 21 9 weeks -10.9 -6.1 -4.9 10.1 14.9 Cymbalta: Study 2 Cymbalta label 2001 20 9 weeks -10.5 -8.3 -2.2 9.5 11.7 Cymbalta: Study 3 Cymbalta label 2001 18 8 weeks -8.6 -5.0 -3.6 9.4 13 Cymbalta: Study 4 Cymbalta label 2001 20 8 weeks -12.1 -8.8 -3.3 7.9 11.2 Pristiq: Study 332 Liebowitz et al 2008 23 8 weeks -11.5 -9.5 -2.0 11.5 13.5 Pristiq: Study 333 Boyer et al 2008 24 8 weeks -13.7 -10.7 -3.0 10.3 13.3 Rexulti: Pyxis Study Thase et al (a) 2013 21 6 weeks -5.89 -3.59 -2.29 15.1 17.4 Rexulti: Polaris Study Thase et al (b) 2013 21 6 weeks -6.26 -4.57 -1.69 14.7 16.4 Rexulti: Sirius Study Hobart et al 2016 21 6 weeks -7.1 -5.9 -1.16 13.9 15.1 Average of all drugs (range) Average of all drugs (range) 6-8 wks -9.7 (-5.9 to -13.7) -7.0 (-3.6 to -10.7) -2.7 (-1.16 to -4.9) 11.6 (7.9 to 15.1) 14.4 (11.7 to 17.4) Sage zuranolone data Waterfall 2020-21 26.8 2 weeks -14.1 -12.3 -1.7 12.7 14.6 Coral 2021 26.8 2 weeks -13.7 -12.9 -0.8 13.1 13.7 * Studies reporting HAMD as primary endpoint shown here; recent MDD registrational trials for Trintellix, Spravato, and Axsome used MADRS as endpoint, rather than HAMD17, so are not included ~50% reduction in mean HAMD17 from severe depression (>24) to mild depression (8-16)
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% reduction in HAMD17 total score from baseline) could continue to get retreatment in the SHORELINE study ~70% of 30 mg responders* Needed only 1 or 2 treatment courses over 1 year Median time to first retreatment: 249 days Median time to first retreatment: 135 days