Financial Data and Key Metrics Changes - For Q1 2023, total research and development expenses were approximately $15.9 million, down from $25 million in the same period of 2022, primarily due to the completion of Study 301 and Study 303 [29] - General and administrative expenses for Q1 2023 were approximately $12.3 million, compared to $13.3 million in Q1 2022, reflecting a decrease of about $1 million [30] - The net loss for Q1 2023 was $26.3 million or $0.87 per share, compared to a net loss of $39.7 million or $1.40 per share in Q1 2022 [32] - Cash, cash equivalents, and short-term investments as of March 31, 2023, totaled approximately $132.4 million, down from $148.3 million as of December 31, 2022 [34] Business Line Data and Key Metrics Changes - The ongoing Study 302 is expected to enroll approximately 300 patients, with over one-third already enrolled, and is anticipated to complete in the first half of 2024 [24] - The new Study 304 is planned to initiate in mid-2023, also with a target enrollment of approximately 300 patients, expected to complete in the second half of 2024 [24] Market Data and Key Metrics Changes - The company is focusing on optimizing the design of clinical trials to enhance signal detection and control placebo response, which has been a significant issue in previous studies [16][19] - The company has identified and is working with clinical sites that have demonstrated better control over placebo responses in past trials [50] Company Strategy and Development Direction - The company intends to primarily focus on REL-1017 as an adjunctive treatment for major depressive disorder (MDD) and has implemented changes to improve trial designs based on previous learnings [12][16] - The management emphasizes the importance of recruiting appropriately diagnosed subjects and controlling for placebo response in ongoing and upcoming studies [22][23] - The company is confident in its funding position to execute plans through the end of 2024, supported by the completion of certain studies [31] Management's Comments on Operating Environment and Future Outlook - Management remains optimistic about the approval of REL-1017 and believes that the right plans and team are in place to optimize chances for success [87] - The management acknowledges the challenges faced in previous studies but is focused on improving patient selection and trial design to ensure better outcomes [79] Other Important Information - The open-label one-year safety study for REL-1017 is concluding, with final safety follow-up visits occurring soon, and data is expected to be released later this year [25] - The company has had two late-breaking posters accepted for presentation at the upcoming 2023 American Society of Clinical Psychopharmacology meeting [26] Q&A Session Summary Question: Overlap between Study 302 and Study 304 sites - Management confirmed that there is no overlap between the sites for Study 302 and Study 304, with approximately 50 sites expected for each trial [45] Question: Duration of trials and quality of patient selection - Management emphasized that quality of patients and sites is prioritized over speed, with a focus on controlling placebo response [50] Question: Open-label safety study expectations - The open-label study is expected to provide insights into real-world effects of treatment, with various patient subsets being analyzed [62] Question: FDA interactions and protocol amendments - Management confirmed ongoing dialogue with the FDA regarding protocol amendments and emphasized adherence to regulatory approvals [73] Question: Onset of action and differences in study populations - Management acknowledged challenges in transitioning from controlled inpatient studies to outpatient populations, affecting the observed onset of action [76]

PART I - FINANCIAL INFORMATION [Item 1. Unaudited Condensed Consolidated Financial Statements](index=4&type=section&id=Item%201.%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Relmada Therapeutics, Inc.'s unaudited condensed consolidated financial statements for Q1 2023 and 2022, including balance sheets, operations, equity, cash flows, and detailed notes [Condensed Consolidated Balance Sheets](index=4&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets and stockholders' equity decreased from December 31, 2022, to March 31, 2023, due to reduced short-term investments and increased accumulated deficit | Metric | March 31, 2023 (Unaudited) | December 31, 2022 | | :-------------------------- | :------------------------- | :------------------ | | Cash and cash equivalents | $28,894,360 | $5,395,905 | | Short-term investments | $103,547,634 | $142,926,781 | | Total current assets | $135,531,574 | $152,870,304 | | Total assets | $135,566,449 | $152,905,179 | | Total current liabilities | $10,097,257 | $12,468,877 | | Total stockholders' equity | $125,469,192 | $140,436,302 | | Accumulated deficit | $(488,432,511) | $(462,110,935) | [Unaudited Condensed Consolidated Statements of Operations](index=5&type=section&id=Unaudited%20Condensed%20Consolidated%20Statements%20of%20Operations) Net loss decreased for Q1 2023 compared to Q1 2022, driven by lower operating expenses, especially R&D, and increased other income | Metric | Three months ended March 31, 2023 | Three months ended March 31, 2022 | | :-------------------------- | :-------------------------------- | :-------------------------------- | | Research and development | $15,861,010 | $25,012,853 | | General and administrative | $12,292,599 | $13,284,570 | | Total operating expenses | $28,153,609 | $38,297,423 | | Loss from operations | $(28,153,609) | $(38,297,423) | | Total other income (expenses) | $1,832,033 | $(1,448,360) | | Net loss | $(26,321,576) | $(39,745,783) | | Loss per common share | $(0.87) | $(1.40) | [Unaudited Condensed Consolidated Statements of Stockholders' Equity](index=6&type=section&id=Unaudited%20Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) Stockholders' equity decreased from **$140.4 million** to **$125.5 million** due to net loss, partially offset by stock-based compensation | Metric | December 31, 2022 | March 31, 2023 | | :-------------------------- | :---------------- | :------------- | | Total Stockholders' Equity | $140,436,302 | $125,469,192 | | Stock based compensation | - | $11,354,466 | | Net loss | - | $(26,321,576) | - For the three months ended March 31, 2022, the company raised **$29,583,542** from an ATM offering, **$300,006** from warrant exercises, and **$64,800** from option exercises[15](index=15&type=chunk) [Unaudited Consolidated Statements of Cash Flows](index=7&type=section&id=Unaudited%20Consolidated%20Statements%20of%20Cash%20Flows) Cash and cash equivalents significantly increased to **$28.9 million** from **$5.4 million** due to net cash from investing activities, despite operating cash usage | Metric | Three months ended March 31, 2023 | Three months ended March 31, 2022 | | :-------------------------------------- | :-------------------------------- | :-------------------------------- | | Net cash used in operating activities | $(16,505,094) | $(19,429,743) | | Net cash provided by (used in) investing activities | $40,003,549 | $(10,027,668) | | Net cash provided by financing activities | $- | $29,948,348 | | Net increase in cash and cash equivalents | $23,498,455 | $490,937 | | Cash and cash equivalents at end of period | $28,894,360 | $44,934,376 | [Notes to Unaudited Condensed Consolidated Financial Statements](index=8&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) Detailed notes explain the company's business, accounting policies, financial instruments, equity, and commitments, providing context to the financial statements [NOTE 1 - BUSINESS](index=8&type=section&id=NOTE%201%20-%20BUSINESS) Relmada Therapeutics, Inc. is a clinical-stage biotechnology company developing esmethadone (REL-1017) for CNS diseases, facing inherent industry risks - Relmada Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing esmethadone (REL-1017), an N-methyl-D-aspartate (NMDA) receptor antagonist, for central nervous system (CNS) diseases[21](index=21&type=chunk) - The company faces risks common to the biotechnology industry, including dependence on collaborative arrangements, new technological innovations, key personnel, proprietary technology protection, and compliance with FDA and other governmental regulations[22](index=22&type=chunk) [NOTE 2 - SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES](index=8&type=section&id=NOTE%202%20-%20SUMMARY%20OF%20SIGNIFICANT%20ACCOUNTING%20POLICIES) This section outlines accounting principles including basis of presentation, consolidation, liquidity, estimates, and policies for cash, investments, patents, leases, fair value, taxes, R&D, stock compensation, and EPS [Basis of Presentation](index=8&type=section&id=Basis%20of%20Presentation) Unaudited condensed consolidated financial statements adhere to U.S. GAAP for interim reporting, including normal adjustments, and should be read with the annual 10-K - Financial statements are prepared in accordance with U.S. GAAP for interim unaudited condensed consolidated financial information, including normal recurring adjustments[23](index=23&type=chunk) - Interim results are not necessarily indicative of full-year results and should be read with the Company's Annual Report on Form 10-K for the year ended December 31, 2022[23](index=23&type=chunk) [Principles of Consolidation](index=8&type=section&id=Principles%20of%20Consolidation) Consolidated financial statements include Relmada Therapeutics, Inc. and its wholly-owned subsidiary, with all significant intercompany transactions eliminated - The unaudited condensed consolidated financial statements include the Company's accounts and those of its wholly-owned subsidiary, with all significant intercompany accounts and transactions eliminated[24](index=24&type=chunk) [Liquidity](index=8&type=section&id=Liquidity) Negative operating cash flow of **$16.5 million** and **$488.4 million** accumulated deficit as of March 31, 2023; management expects current funds to cover 12 months - The Company incurred negative operating cash flows of **$16,505,094** for the three months ended March 31, 2023, and has an accumulated deficit of **$488,432,511**[25](index=25&type=chunk) - Management believes existing cash and cash equivalents and short-term investments will fund operating expenses and capital expenditure requirements for at least 12 months from the issuance date[26](index=26&type=chunk) - Beyond 12 months, management will evaluate additional financings through equity/debt sales, loans, or strategic collaborations[26](index=26&type=chunk) [Use of Estimates](index=8&type=section&id=Use%20of%20Estimates) Financial statements require management estimates and assumptions, especially for stock-based compensation and income taxes, which may differ from actual results - Preparation of financial statements requires management to make estimates and assumptions, with significant estimates including stock-based compensation expenses and income taxes[27](index=27&type=chunk) [Cash and Cash Equivalents](index=8&type=section&id=Cash%20and%20Cash%20Equivalents) Cash and cash equivalents comprise highly liquid investments with maturities under three months, held at high-credit institutions, exceeding insured limits - Cash and cash equivalents include cash deposits and highly liquid investments with maturities of three months or less when purchased[28](index=28&type=chunk) - The Company's cash and cash equivalents balance of **$28,894,360** at March 31, 2023, exceeds federally insured limits[28](index=28&type=chunk) [Short-term Investments](index=10&type=section&id=Short-term%20Investments) Short-term investments, mainly mutual funds, are measured at fair value with changes in earnings; totaled **$103.5 million** at March 31, 2023, using Level 1 inputs - Short-term investments consist entirely of mutual funds, measured at fair value based on net asset value (NAV), with changes recognized in earnings[31](index=31&type=chunk) - At March 31, 2023, short-term investments were **$103,547,634**, classified using Level 1 inputs within the fair value hierarchy[32](index=32&type=chunk)[40](index=40&type=chunk) - The company recorded an unrealized gain of **$1,291,110** for the three months ended March 31, 2023, compared to an unrealized loss of **$1,763,287** for the same period in 2022[40](index=40&type=chunk) [Patents](index=10&type=section&id=Patents) Patent application costs are expensed as incurred due to uncertain recoverability - Costs related to filing and pursuing patent applications are expensed as incurred due to uncertain recoverability[33](index=33&type=chunk) [Leases](index=10&type=section&id=Leases) Operating leases over one year are recognized as right-of-use assets and lease liabilities; short-term leases (12 months or less) are expensed straight-line - The Company recognizes leases with terms greater than a year on the balance sheet as right-of-use assets and lease liabilities, classified as operating leases for office space[34](index=34&type=chunk) - Short-term leases (12 months or less) are expensed on a straight-line basis over the lease term and are not recognized on the balance sheet[34](index=34&type=chunk) [Fair Value of Financial Instruments](index=10&type=section&id=Fair%20Value%20of%20Financial%20Instruments) Financial instruments, including cash, short-term investments, and accounts payable, are valued using a fair value hierarchy, with short-term investments primarily using Level 1 inputs - The Company's financial instruments (cash, short-term investments, accounts payable) are valued at fair value, with short-term investments of **$103,547,634** classified using Level 1 inputs[35](index=35&type=chunk)[40](index=40&type=chunk) - Fair value hierarchy prioritizes quoted prices in active markets (Level 1) over unobservable inputs (Level 3)[36](index=36&type=chunk)[37](index=37&type=chunk)[38](index=38&type=chunk) [Income Taxes](index=12&type=section&id=Income%20Taxes) The company uses the asset and liability method for income taxes, with a full valuation allowance against net deferred tax assets due to realization uncertainty, and no uncertain tax position liabilities - The Company accounts for income taxes using the asset and liability method, recognizing deferred tax assets and liabilities[43](index=43&type=chunk) - A full valuation allowance is recognized against net deferred tax assets as of March 31, 2023, and December 31, 2022, due to the likelihood of realization not meeting the 'more likely than not' threshold[43](index=43&type=chunk) - No liabilities were recorded for uncertain tax positions at March 31, 2023, and December 31, 2022[44](index=44&type=chunk) [Research and Development](index=12&type=section&id=Research%20and%20Development) R&D costs, including contracts, salaries, stock-based compensation, and consultants, are expensed as incurred, with clinical study estimates based on progress and contracted costs - Research and development costs, primarily for product development contracts, salaries, benefits, stock-based compensation, and consultants, are expensed in the period incurred[45](index=45&type=chunk) - Estimates for clinical study contracts are made by analyzing study progress, invoices, and contracted costs[45](index=45&type=chunk) [Stock-Based Compensation](index=12&type=section&id=Stock-Based%20Compensation) Employee equity award costs are measured at grant-date fair value using Black-Scholes and recognized over the service period - The cost of employee services for equity instruments is measured at grant-date fair value using the Black-Scholes option pricing model and recognized over the requisite service period[46](index=46&type=chunk) [Net Loss per Common Share](index=12&type=section&id=Net%20Loss%20per%20Common%20Share) Basic and diluted loss per common share are based on net loss and weighted-average shares; dilutive securities are excluded from diluted EPS due to net losses - Basic and diluted loss per common share are calculated by dividing net loss by the weighted-average number of common shares outstanding[47](index=47&type=chunk) - Potentially dilutive securities (stock options and warrants) are excluded from diluted net loss per share calculations for all periods presented due to the Company's net losses, making them anti-dilutive[47](index=47&type=chunk)[48](index=48&type=chunk) | Anti-Dilutive Securities | March 31, 2023 | March 31, 2022 | | :----------------------- | :------------- | :------------- | | Stock options | 12,487,917 | 10,262,184 | | Common stock warrants | 3,027,441 | 3,175,443 | | Total | 15,515,358 | 13,437,627 | [Recent Accounting Pronouncements](index=13&type=section&id=Recent%20Accounting%20Pronouncements) ASU 2016-13 adoption, 'Financial Instruments - Credit Losses (Topic 326),' did not significantly impact the condensed consolidated financial statements - The adoption of ASU 2016-13, 'Financial Instruments - Credit Losses (Topic 326),' did not have a significant impact on the Company's condensed consolidated financial statements[50](index=50&type=chunk) [Subsequent Events (Note 2)](index=13&type=section&id=Subsequent%20Events%20(Note%202)) Management reviewed all material events through the financial statement issuance date for subsequent event disclosure - Management reviewed all material events through the date the financial statements were issued for subsequent event disclosure consideration[51](index=51&type=chunk) [NOTE 3 - PREPAID EXPENSES](index=13&type=section&id=NOTE%203%20-%20PREPAID%20EXPENSES) Prepaid expenses decreased from **$4.0 million** to **$3.1 million** due to reduced prepaid R&D costs | Prepaid Expenses | March 31, 2023 | December 31, 2022 | | :--------------------- | :------------- | :---------------- | | Insurance | $211,700 | $313,200 | | Research and Development | $2,589,800 | $3,619,800 | | Other | $288,100 | $102,200 | | Total | $3,089,600 | $4,035,200 | [NOTE 4 - ACCRUED EXPENSES](index=13&type=section&id=NOTE%204%20-%20ACCURUED%20EXPENSES) Accrued expenses decreased from **$7.2 million** to **$5.7 million**, primarily due to lower accrued R&D costs | Accrued Expenses | March 31, 2023 | December 31, 2022 | | :--------------------- | :------------- | :---------------- | | Research and development | $4,806,000 | $5,809,800 | | Professional fees | $125,000 | $116,500 | | Accrued bonus | $331,000 | $492,100 | | Accrued vacation | $332,400 | $529,800 | | Other | $80,900 | $258,700 | | Total | $5,675,300 | $7,206,900 | [NOTE 5 - STOCKHOLDERS' EQUITY](index=14&type=section&id=NOTE%205%20-%20STOCKHOLDERS'%20EQUITY) This section details common stock, option, and warrant activity, and stock-based compensation expense, noting no common stock issued in Q1 2023 but 620,000 options granted [Common Stock](index=14&type=section&id=Common%20Stock) No common stock shares were issued in Q1 2023; an Open Market Sale Agreement for up to **$100 million** remains unused - No shares of common stock were issued during the three months ended March 31, 2023[55](index=55&type=chunk) - The Company has an Open Market Sale Agreement with Jefferies to sell up to **$100,000,000** of common stock, but no shares have been issued under this agreement as of March 31, 2023[56](index=56&type=chunk) [Options and Warrants](index=14&type=section&id=Options%20and%20Warrants) Two equity incentive plans allow up to **10,552,942** options; **620,000** options granted in Q1 2023, with **$84.5 million** unrecognized stock-based compensation expense - The 2014 Stock Option and Equity Incentive Plan and the 2021 Equity Incentive Plan (as amended) allow for granting up to **10,552,942** options or other stock awards[57](index=57&type=chunk)[58](index=58&type=chunk)[59](index=59&type=chunk) - From January 1, 2023, through March 31, 2023, **620,000** options were issued to consultants and employees with an aggregate fair value of approximately **$1.9 million**[64](index=64&type=chunk) - As of March 31, 2023, the Company has approximately **$84.5 million** of unrecognized stock-based compensation expense related to unvested stock options, to be recognized over a weighted average remaining service period of **2.62** years[66](index=66&type=chunk) | Options Activity (3 months ended March 31, 2023) | Number of Options | Weighted Average Exercise Price Per Share | | :----------------------------------------------- | :---------------- | :---------------------------------------- | | Outstanding at December 31, 2022 | 12,122,606 | $18.19 | | Granted | 620,000 | $3.60 | | Forfeited | (93,750) | - | | Cancelled | (160,939) | - | | Outstanding at March 31, 2023 | 12,487,917 | $17.35 | | Options exercisable at March 31, 2023 | 4,774,660 | $21.33 | - As of March 31, 2023, the Company had approximately **$5.5 million** of unrecognized compensation expense related to outstanding warrants[68](index=68&type=chunk) [Stock-based compensation by class of expense](index=15&type=section&id=Stock-based%20compensation%20by%20class%20of%20expense) Total stock-based compensation decreased to **$11.4 million** from **$11.9 million**, with most allocated to general and administrative expenses | Stock-based Compensation | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :----------------------- | :-------------------------------- | :-------------------------------- | | Research and development | $1,994,200 | $1,258,400 | | General and administrative | $9,360,300 | $10,672,300 | | Total | $11,354,500 | $11,930,700 | [NOTE 6 - COMMITMENTS AND CONTINGENCIES](index=16&type=section&id=NOTE%206%20-%20COMMITMENTS%20AND%20CONTINGENCIES) This section details license agreements with Wonpung, third-party licensors, Inturrisi/Manfredi, and Arbormentis, LLC, covering fees, milestones, royalties, legal proceedings, and lease commitments [License Agreements](index=16&type=section&id=License%20Agreements) Relmada holds license agreements with Wonpung, third-party licensors, Inturrisi/Manfredi, and Arbormentis, LLC, covering territorial rights, royalties, milestones, and a psilocybin program - Relmada has a License Development and Commercialization Agreement with Wonpung Mulsan Co. for exclusive territorial rights in Asia for up to two drugs, with potential royalties of up to **12%** of net sales[72](index=72&type=chunk)[73](index=73&type=chunk) - The Company has an obligation to pay third parties (Dr. Charles E. Inturrisi and Dr. Paolo Manfredi) royalty payments up to **2%** on net sales and up to **20%** of sublicense royalties, plus milestone payments up to **$4 million**[74](index=74&type=chunk) - Under an agreement with Inturrisi and Manfredi, Relmada pays **$45,000** every three months and tiered royalties up to **2%** on net sales of licensed products[75](index=75&type=chunk) - Relmada acquired development and commercial rights to a novel psilocybin program from Arbormentis, LLC, for an upfront fee of **$12.7 million** (cash and warrants) and potential milestone payments up to approximately **$160 million**, plus a low single-digit royalty on net sales[77](index=77&type=chunk) [Legal](index=17&type=section&id=Legal) The company is unaware of any legal proceedings or claims that would materially adversely affect its business, financial condition, operating results, or cash flows - The Company is not currently aware of any legal proceedings or potential claims that would have a material adverse effect on its business, financial condition, operating results, or cash flows[79](index=79&type=chunk) [Leases and Sublease](index=17&type=section&id=Leases%20and%20Sublease) Relmada leases corporate headquarters in Coral Gables and New York, with Q1 2023 and 2022 lease expenses of **$51,700** and **$19,500**, respectively - The Company leases corporate headquarters in Coral Gables, FL, and additional office space in New York, NY[80](index=80&type=chunk) - Lease expense for the three months ended March 31, 2023, and 2022, was approximately **$51,700** and **$19,500**, respectively[80](index=80&type=chunk) [NOTE 7 - OTHER POST-RETIREMENT BENEFIT PLAN](index=18&type=section&id=NOTE%207%20-%20OTHER%20POST-RETIREMENT%20BENEFIT%20PLAN) Relmada participates in a multiemployer 401(k) plan, matching employee contributions, with Q1 2023 expense of **$40,400**, up from **$31,600** in Q1 2022 - Relmada participates in a multiemployer 401(k) plan, matching **100%** of the first **3%** of employee contributions and **50%** of contributions exceeding **3%** up to **5%**[84](index=84&type=chunk) - The Company's 401(k) contribution expense was approximately **$40,400** for the three months ended March 31, 2023, compared to **$31,600** for the same period in 2022[85](index=85&type=chunk) [NOTE 8 - SUBSEQUENT EVENTS (Note 8)](index=18&type=section&id=NOTE%208%20-%20SUBSEQUENT%20EVENTS%20(Note%208)) Subsequent to March 31, 2023, **15,000** options were granted to two new employees with exercise prices between **$2.28** and **$2.51** - Subsequent to March 31, 2023, **15,000** options were granted to two new employees with an exercise price ranging from **$2.28** to **$2.51**[86](index=86&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=19&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial condition and Q1 2023 operational results, focusing on its clinical-stage biotechnology business and esmethadone (REL-1017) development for MDD [FORWARD-LOOKING STATEMENT NOTICE](index=19&type=section&id=FORWARD-LOOKING%20STATEMENT%20NOTICE) This section warns that the report contains forward-looking statements with risks and uncertainties, and actual results may differ; the company assumes no obligation to update - The report contains forward-looking statements that involve risks and uncertainties, particularly in the 'Risk Factors' and 'Management's Discussion and Analysis of Financial Condition and Results of Operations' sections[88](index=88&type=chunk) - Readers are cautioned not to place undue reliance on forward-looking statements, which are based on information available as of the report date, and the company assumes no obligation to update them[89](index=89&type=chunk) [Business Overview](index=19&type=section&id=Business%20Overview) Relmada is a clinical-stage biotechnology company developing esmethadone (REL-1017) for MDD, with positive Phase 2 results, ongoing Phase 3 trials (RELIANCE I, II, III), Fast Track designation, and upcoming milestones - Relmada Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing esmethadone (REL-1017), an NMDA receptor antagonist, for CNS diseases, with a lead product candidate for depression[90](index=90&type=chunk)[91](index=91&type=chunk) [Phase 2 Clinical Trial](index=19&type=section&id=Phase%202%20Clinical%20Trial) The REL-1017-202 Phase 2 study demonstrated statistically significant improvements in depression symptoms across multiple measures for both 25 mg and 50 mg doses, with rapid onset and favorable tolerability - The REL-1017-202 Phase 2 study showed statistically significant improvement on all efficacy measures (MADRS, CGI-S, CGI-I, SDQ) for both REL-1017 **25 mg** and **50 mg** treatment groups compared to placebo[93](index=93&type=chunk) - Improvements on the MADRS endpoint appeared on Day 4 and continued through Day 14, with P values < **0.03** and large effect sizes (**0.7** to **1.0**)[94](index=94&type=chunk) - The study confirmed REL-1017's tolerability profile, with only mild and moderate adverse events (AEs) and no serious AEs, psychotomimetic/dissociative AEs, or withdrawal signs[95](index=95&type=chunk) [Phase 3 Program](index=20&type=section&id=Phase%203%20Program) Relmada initiated three Phase 3 MDD trials (RELIANCE I, II, III) for REL-1017; RELIANCE I and III missed primary endpoints, but RELIANCE I showed meaningful difference; FDA granted Fast Track designation - Relmada initiated Phase 3 clinical trials RELIANCE I (adjunctive MDD, Dec 2020), RELIANCE II (adjunctive MDD, Apr 2021), and RELIANCE III (monotherapy MDD, Oct 2021) for REL-1017[96](index=96&type=chunk)[97](index=97&type=chunk) - RELIANCE III (monotherapy) did not achieve its primary endpoint, showing a MADRS reduction of **14.8** points vs. **13.9** points for placebo, with a higher than expected placebo response[98](index=98&type=chunk) - RELIANCE I (adjunctive) did not achieve its primary endpoint but showed a clinically meaningful MADRS reduction of **2.2** points (**15.1** vs. **12.9**) and a nominally statistically significant response rate (**39.8%** vs. **27.2%**, p<**0.05**)[99](index=99&type=chunk) - The FDA granted Fast Track designation to REL-1017 as a monotherapy for MDD and confirmed no two-year carcinogenicity study or Thorough QT (TQT) cardiac study is required[97](index=97&type=chunk)[101](index=101&type=chunk) [Human Abuse Potential (HAP) Studies](index=21&type=section&id=Human%20Abuse%20Potential%20(HAP)%20Studies) HAP studies showed REL-1017 had significantly lower 'likability' than oxycodone and ketamine, and was equivalent to placebo, indicating no opioid or dissociative abuse potential - REL-1017 (**25 mg**, **75 mg**, **150 mg**) demonstrated a highly statistically significant difference in 'likability' compared to oxycodone **40 mg** in recreational opioid users (p<**0.05**) and was statistically equivalent to placebo[102](index=102&type=chunk) - REL-1017 also showed a substantial and statistically significant difference in 'likability' compared to intravenous ketamine **0.5 mg/kg** in recreational drug users and was statistically equivalent to placebo[103](index=103&type=chunk) [Key Upcoming Anticipated Milestones](index=21&type=section&id=Key%20Upcoming%20Anticipated%20Milestones) Upcoming milestones include RELIANCE II results in H1 2024, new Phase III adjunctive MDD trial initiation in mid-2023, and RELIANCE – OLS study results in mid-2023 - Results of RELIANCE II, the second adjunctive MDD trial, are expected in the first half of 2024[104](index=104&type=chunk) - Initiation of a new Phase III adjunctive MDD trial is anticipated in mid-2023, with completion in the second half of 2024[104](index=104&type=chunk) - Results of the RELIANCE – OLS (Long-term, Open-label) study in MDD are expected in mid-2023[104](index=104&type=chunk) [Our Development Program](index=22&type=section&id=Our%20Development%20Program) Relmada's program focuses on esmethadone (REL-1017) for MDD, a rapid-acting NMDA channel blocker differentiated by its mechanism and lack of opioid/ketamine-like adverse effects [Esmethadone (d-Methadone, dextromethadone, REL-1017) as a treatment for MDD](index=22&type=section&id=Esmethadone%20(d-Methadone,%20dextromethadone,%20REL-1017)%20as%20a%20treatment%20for%20MDD) Esmethadone is developed as a rapid-acting oral MDD agent, addressing treatment gaps; its low-affinity, non-competitive NMDA channel blocker mechanism differentiates it - **21.0 million** adults in the U.S. had at least one major depressive episode in the past year, with only about half receiving treatment, and **33%** of drug-treated patients not achieving adequate therapeutic benefits[105](index=105&type=chunk) - Esmethadone is being developed as a rapidly acting, oral agent for MDD, differentiated by its mechanism as a low affinity, non-competitive NMDA channel blocker, potentially lacking adverse side effects of ketamine/esketamine[107](index=107&type=chunk) - Esmethadone, as the dextro isomer of racemic methadone, possesses NMDA antagonist properties with virtually no traditional opioid or ketamine-like adverse events at therapeutic doses, unlike l-methadone which is responsible for opioid activity[109](index=109&type=chunk) [Esmethadone (d-methadone, dextromethadone, REL-1017) in other indications](index=22&type=section&id=Esmethadone%20(d-methadone,%20dextromethadone,%20REL-1017)%20in%20other%20indications) Current focus is adjunctive MDD, but Relmada may explore esmethadone as monotherapy for MDD and other indications like restless leg syndrome in the future - Current strategy focuses on esmethadone as an adjunctive treatment for MDD, but future plans may include re-commencing testing as a monotherapy for MDD[111](index=111&type=chunk) - Relmada is evaluating other potential indications for esmethadone, including restless leg syndrome and other glutamatergic system activation-related diseases[111](index=111&type=chunk) [Our Corporate History and Background](index=23&type=section&id=Our%20Corporate%20History%20and%20Background) Relmada is a clinical-stage biotechnology company with no revenues, a **$26.3 million** Q1 2023 net loss, and **$488.4 million** accumulated deficit, requiring trials and approvals for commercialization - Relmada is a clinical-stage biotechnology company developing NCEs and novel drug products for CNS diseases[112](index=112&type=chunk) - The Company has not generated revenues and does not anticipate doing so in the foreseeable future, requiring clinical trials and regulatory approvals for product commercialization[113](index=113&type=chunk)[114](index=114&type=chunk) - Net loss for the three months ended March 31, 2023, was **$26,321,576**, with an accumulated deficit of **$488,432,511**[114](index=114&type=chunk) [Business Strategy](index=23&type=section&id=Business%20Strategy) Relmada's strategy is to develop and commercialize CNS product candidates for unmet needs, prioritizing esmethadone development, IP generation, and resource-based activity prioritization - The Company's strategy is to identify, develop, and commercialize product candidates for high unmet medical needs in CNS diseases, leveraging industry experience and development expertise[115](index=115&type=chunk) - The priority program is the further development of esmethadone, which requires a full clinical development program for NDA submission[116](index=116&type=chunk) - Plans include generating intellectual property (IP) to protect products and prioritizing development activities based on resources, market dynamics, and value potential[116](index=116&type=chunk) [Market Opportunity](index=23&type=section&id=Market%20Opportunity) The CNS disease treatment market, especially for depression, offers a large revenue opportunity, affecting nearly **2 billion** people globally, with antidepressants as the largest segment - The market for addressing high unmet medical needs in CNS diseases is believed to be large, with CNS diseases affecting nearly **2 billion** people globally (**40%** of total disease burden)[117](index=117&type=chunk) - The depression treatment market is segmented by antidepressant drugs, devices, and therapies, with antidepressants being the largest segment, including major pharmaceutical and generic companies[118](index=118&type=chunk) [Intellectual Property Portfolio and Market Exclusivity](index=23&type=section&id=Intellectual%20Property%20Portfolio%20and%20Market%20Exclusivity) Relmada holds over **50** patents for REL-1017, potentially covering beyond 2033, and secured Orphan Drug Designation for d-methadone, granting 7-year FDA exclusivity and potential 10-year EU exclusivity - The Company has over **50** issued patents and pending patent applications related to REL-1017 for multiple uses, potentially providing coverage beyond 2033[119](index=119&type=chunk) - Relmada secured an Orphan Drug Designation from the FDA for d-methadone for 'the treatment of postherpetic neuralgia,' which, upon potential NDA approval, carries 7-year FDA Orphan Drug marketing exclusivity[119](index=119&type=chunk) - REL-1017 may be eligible for **5** years of market exclusivity in the U.S. (Hatch Waxman Act) plus an additional **6** months of pediatric exclusivity, and up to **10** years of exclusivity in the European Union[119](index=119&type=chunk) [Key Strengths](index=24&type=section&id=Key%20Strengths) Relmada's strengths include REL-1017 in Phase 3 for adjunctive MDD, robust Phase 2 efficacy, safety, potential in multiple indications, expert scientific support, and a substantial IP portfolio - Compelling lead product opportunity: REL-1017 is in Phase 3 trials for adjunctive treatment of MDD[122](index=122&type=chunk) - Robust and highly statistically significant efficacy seen with esmethadone in a randomized Phase 2 trial, with primary endpoint at **7** days and onset of action at **4** days[122](index=122&type=chunk) - Potential in additional multiple indications in underserved markets with large patient populations in other affective and cognitive disorders[122](index=122&type=chunk) - Scientific support from leading experts affiliated with institutions like Harvard, Cornell, Yale, and University of Pennsylvania[122](index=122&type=chunk) - Substantial IP portfolio and market protection with approved and filed patent applications providing coverage beyond 2033[122](index=122&type=chunk) [Results of Operations](index=24&type=section&id=Results%20of%20Operations) Total operating expenses decreased by **$10.1 million** in Q1 2023 due to lower R&D, leading to a reduced net loss despite increased other income from higher interest rates | Operating Expenses | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | Decrease | | :------------------------ | :-------------------------------- | :-------------------------------- | :------- | | Research and development | $15,861,010 | $25,012,853 | $(9,151,843) | | General and administrative | $12,292,599 | $13,284,570 | $(991,971) | | Total | $28,153,609 | $38,297,423 | $(10,143,814) | [Research and Development Expense](index=24&type=section&id=Research%20and%20Development%20Expense) R&D expense decreased by **$9.2 million** to **$15.9 million** in Q1 2023, mainly due to lower study costs after RELIANCE I and III completion, partially offset by increased compensation - Research and development expense decreased by approximately **$9,151,900** to **$15,861,000** for the three months ended March 31, 2023, compared to **$25,012,900** in the prior year[122](index=122&type=chunk) - The decrease was primarily driven by a **$9,050,700** reduction in study costs and a **$1,124,900** decrease in other research expenses due to the completion of RELIANCE I and RELIANCE III late in 2022[123](index=123&type=chunk) - Offsetting factors included an increase of **$735,700** in stock-based compensation expense and **$639,200** in employee compensation expense[123](index=123&type=chunk) [General and Administrative Expense](index=25&type=section&id=General%20and%20Administrative%20Expense) G&A expense decreased by **$992,000** to **$12.3 million** in Q1 2023, primarily due to lower stock-based compensation, partially offset by higher employee and consulting costs - General and administrative expense decreased by approximately **$992,000** to **$12,292,600** for the three months ended March 31, 2023, compared to **$13,284,600** in the prior year[124](index=124&type=chunk) - The change was primarily due to a **$1,312,000** decrease in stock-based compensation expense, offset by a **$229,200** increase in compensation expense and a **$90,800** increase in other general and administrative expenses[129](index=129&type=chunk) [Other Income (Expense)](index=25&type=section&id=Other%20Income%20(Expense)) Other income significantly increased to **$1.2 million** from **$329,900** due to higher interest rates, with a **$666,700** realized loss and **$1.3 million** unrealized gain on short-term investments - Interest/investment income, net, increased to approximately **$1,207,600** for the three months ended March 31, 2023, from **$329,900** in the prior year, due to higher interest rates and investment yields[124](index=124&type=chunk) - Realized loss on short-term investments was approximately **$666,700**, and unrealized gain was **$1,291,100** for the three months ended March 31, 2023[124](index=124&type=chunk) [Income Taxes](index=25&type=section&id=Income%20Taxes) No income tax provision was made for Q1 2023 and 2022 due to net losses and a full valuation allowance against deferred tax assets - The Company did not provide for income taxes for the three months ended March 31, 2023, and 2022, due to a net loss and a full valuation allowance against all deferred tax assets[125](index=125&type=chunk) [Net Loss](index=25&type=section&id=Net%20Loss) Net loss for Q1 2023 was **$26.4 million**, down from **$39.7 million**, resulting in a loss per common share of **$0.87** compared to **$1.40** - Net loss for the three months ended March 31, 2023, was approximately **$26,351,600**, compared to **$39,745,800** in the prior year[126](index=126&type=chunk) - Loss per common share, basic and diluted, was **$0.87** for the three months ended March 31, 2023, compared to **$1.40** in the prior year[126](index=126&type=chunk) [Liquidity](index=25&type=section&id=Liquidity) Relmada had **$16.5 million** negative operating cash flow and **$488.4 million** accumulated deficit in Q1 2023; cash increased due to investing activities, sufficient for 12 months - The Company incurred negative operating cash flows of **$16,505,094** for the three months ended March 31, 2023, and has an accumulated deficit of **$488,432,511**[127](index=127&type=chunk) - Management believes existing cash and cash equivalents and short-term investments will fund operating expenses and capital expenditure requirements for at least 12 months[128](index=128&type=chunk) | Cash Flow Activity | Three Months Ended March 31, 2023 | Three Months Ended March 31, 2022 | | :---------------------------------- | :-------------------------------- | :-------------------------------- | | Cash used in operating activities | $(16,505,094) | $(19,429,743) | | Cash provided by (used in) investing activities | $40,003,549 | $(10,027,668) | | Cash provided by financing activities | $- | $29,948,348 | | Net increase in cash and cash equivalents | $23,498,455 | $490,937 | - Cash provided by investing activities for Q1 2023 was **$40,003,549**, primarily from the sale of short-term investments (**$74,770,836**) exceeding purchases (**$34,767,287**)[131](index=131&type=chunk) [Effects of Inflation](index=26&type=section&id=Effects%20of%20Inflation) Monetary assets are not directly affected by inflation, and equipment replacement costs are immaterial; however, inflation could increase compensation and contract service expenses - The Company's assets are primarily monetary (cash and cash equivalents) and not directly affected by inflation[133](index=133&type=chunk) - Inflation could increase expenses for employee compensation and contract services, potentially affecting the rate at which resources are used[133](index=133&type=chunk) [Commitments and Contingencies (MD&A)](index=26&type=section&id=Commitments%20and%20Contingencies%20(MD%26A)) No material changes to commitments, contingencies, or risk factors previously disclosed in the Annual Report on Form 10-K for December 31, 2022 - No material changes to commitments and contingencies or risk factors previously disclosed in the Company's Annual Report on Form 10-K for the year ended December 31, 2022[134](index=134&type=chunk) [Critical Accounting Policies and Estimates](index=26&type=section&id=Critical%20Accounting%20Policies%20and%20Estimates) Financial statements adhere to U.S. GAAP, requiring management estimates and assumptions, which are continuously reviewed, with no current high estimation uncertainty - Financial statements are presented in accordance with U.S. GAAP, requiring management to make estimates and assumptions that affect reported amounts[136](index=136&type=chunk) - Management continuously reviews estimates and assumptions, and currently, none involve a high level of estimation uncertainty[136](index=136&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=28&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) No material changes to market risk exposures were disclosed in the Annual Report on Form 10-K for December 31, 2022 - No material changes to market risk exposures as disclosed in the annual MD&A contained in Form 10-K for the year ended December 31, 2022[137](index=137&type=chunk) [Item 4. Controls and Procedures](index=28&type=section&id=Item%204.%20Controls%20and%20Procedures) This section confirms effective disclosure controls and procedures as of March 31, 2023, with no material changes in internal control over financial reporting during the quarter [Evaluation of Disclosure Controls and Procedures](index=28&type=section&id=Evaluation%20of%20Disclosure%20Controls%20and%20Procedures) The CEO and CFO concluded that disclosure controls and procedures were effective as of March 31, 2023, ensuring timely and accurate material information reporting - The Chief Executive Officer and Chief Financial Officer concluded that the Company's disclosure controls and procedures were effective as of March 31, 2023[138](index=138&type=chunk) - Disclosure controls are designed to ensure material information is accumulated, communicated, processed, summarized, and reported within specified time periods[138](index=138&type=chunk) [Changes in Internal Control over Financial Reporting](index=28&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) No material changes in internal control over financial reporting occurred during Q1 2023 that affected or are likely to affect the company's controls - No material changes in internal control over financial reporting occurred during the three months ended March 31, 2023[139](index=139&type=chunk) PART II - OTHER INFORMATION [Item 1. Legal Proceedings](index=29&type=section&id=Item%201.%20Legal%20Proceedings) The company is unaware of any legal proceedings or claims that would materially adversely affect its business, financial condition, operating results, or cash flows - The Company is not currently aware of any legal proceedings or potential claims that would have a material adverse effect on its business, financial condition, operating results, or cash flows[142](index=142&type=chunk) [Item 1A. Risk Factors](index=29&type=section&id=Item%201A.%20Risk%20Factors) No material changes to risk factors previously disclosed in the Annual Report on Form 10-K for December 31, 2022 - No material changes to the risk factors under Part I, Item 1A of the Form 10-K for the year ended December 31, 2022[143](index=143&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=29&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) No unregistered sales of equity securities or use of proceeds were reported for the period - None[144](index=144&type=chunk) [Item 3. Defaults Upon Senior Securities](index=29&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) No defaults upon senior securities were reported for the period - None[145](index=145&type=chunk) [Item 4. Mine Safety Disclosures](index=29&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[146](index=146&type=chunk) [Item 5. Other Information](index=29&type=section&id=Item%205.%20Other%20Information) No other information to report for the period - None[147](index=147&type=chunk) [Item 6. Exhibits](index=30&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with Form 10-Q, including CEO and CFO certifications (Sarbanes-Oxley Sections 302 and 906) and Inline XBRL documents | Exhibit No. | Title of Document | Location | | :---------- | :----------------------------------------------------------------------------------- | :------- | | 31.1 | Certification of the Chief Executive Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 | Attached | | 31.2 | Certification of the Principal Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002 | Attached | | 32.1 | Certification of the Chief Executive Officer pursuant to U.S.C. Section 1350 as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002* | Attached | | 32.2 | Certification of the Principal Financial Officer pursuant to U.S.C. Section 1350 as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002* | Attached | | 101.INS | Inline XBRL Instance Document. | Attached | | 101.SCH | Inline XBRL Taxonomy Extension Schema Document. | Attached | | 101.CAL | Inline XBRL Taxonomy Extension Calculation Linkbase Document. | Attached | | 101.DEF | Inline XBRL Taxonomy Extension Definition Linkbase Document. | Attached | | 101.LAB | Inline XBRL Taxonomy Extension Label Linkbase Document. | Attached | | 101.PRE | Inline XBRL Taxonomy Extension Presentation Linkbase Document. | Attached | | 104 | Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101). | Attached | [SIGNATURES](index=31&type=section&id=SIGNATURES) The report is signed by Relmada Therapeutics, Inc.'s CEO, Sergio Traversa, and CFO, Maged Shenouda, as of May 11, 2023 - The report is signed by Sergio Traversa, Chief Executive Officer, and Maged Shenouda, Chief Financial Officer, on May 11, 2023[153](index=153&type=chunk)

Relmada Therapeutics, Inc. (NASDAQ:RLMD) Q4 2022 Earnings Conference Call March 23, 2023 4:30 PM ET Company Participants Tim McCarthy - LifeSci Advisors Sergio Traversa - CEO Maged Shenouda - CFO Cedric O'Gorman - Chief Medical Officer Conference Call Participants Uy Ear - Mizuho Health Guofang Li - SVB Securities Andrea Tan - Goldman Sachs Andrew Tsai - Jefferies Jay Olson - Oppenheimer Operator Greetings and welcome to Relmada Therapeutics Fourth Quarter and Full Year 2022 Earnings Conference Call. [Opera ...

Drug Development and Clinical Trials - Relmada Therapeutics is developing esmethadone (REL-1017) as a rapidly acting oral agent for the treatment of major depressive disorder (MDD) and other CNS diseases[21]. - In the Phase 2 clinical trial (REL-1017-202), subjects receiving 25 mg and 50 mg doses of REL-1017 showed statistically significant improvements in MADRS scores compared to placebo, with reductions of 8.7 and 10.4 points respectively on Day 7[25][24]. - The RELIANCE I and II Phase 3 trials for REL-1017 as an adjunctive treatment for MDD were initiated in December 2020 and April 2021, respectively[27]. - The RELIANCE III study, evaluating REL-1017 as a monotherapy for MDD, did not achieve its primary endpoint, showing a MADRS reduction of 14.8 points compared to 13.9 points for placebo[29]. - The RELIANCE I study also did not meet its primary endpoint, with a MADRS reduction of 15.1 points in the REL-1017 arm versus 12.9 points for placebo, indicating a clinically meaningful difference of 2.2 points[30]. - Esmethadone is currently in the second of three Phase 3 trials for the adjunctive treatment of Major Depressive Disorder (MDD)[63]. - The Phase 2 trial of esmethadone showed robust efficacy with a primary endpoint at 7 days and onset of action at 4 days[63]. - The company faces significant risks related to clinical trials, including potential adverse effects and the need for additional trial sites, which could delay progress[128]. - Regulatory approval for esmethadone is uncertain and subject to extensive clinical trials, which are lengthy and costly[127]. - Clinical trials are expensive and complex, with potential delays impacting the timing and commercialization of drug candidates[167][169]. - The company may need to shift its strategic focus to other therapeutic areas if its drug development efforts in depression fail[186]. - Delays in clinical trials can arise from various factors, including regulatory changes, which may adversely affect the commercial prospects of product candidates[195]. Financial Performance and Position - Relmada reported a net loss of approximately $157.04 million for the year ended December 31, 2022, compared to a net loss of $125.75 million for 2021[46]. - The company has an accumulated deficit of approximately $462.11 million as of December 31, 2022[46]. - The company has generated no revenue from commercial sales to date, and future profitability remains uncertain[138]. - The company expects to continue operating at a net loss for at least the next several years due to ongoing research and development efforts[138]. - The company had cash, cash equivalents, and short-term investments of approximately $148.3 million at December 31, 2022[140]. - The company has Federal, New York State, and New York City net operating loss carryforwards of approximately $118.9 million, $74.8 million, and $74.6 million, respectively, beginning to expire in 2028 and 2033[144]. Regulatory and Compliance Issues - The FDA granted Fast Track designation to REL-1017 as a monotherapy for MDD on August 9, 2022[28]. - The FDA requires a substantial application user fee for NDA submissions, which typically increases annually[67]. - FDA has a performance goal to review most standard drug applications within twelve months and non-NMEs within ten months from NDA submission[68]. - Orphan Drug Designation can provide a seven-year exclusive marketing period for drugs treating rare diseases affecting fewer than 200,000 individuals in the U.S.[76]. - The active ingredients in esmethadone are regulated as controlled substances under the Comprehensive Drug Abuse Prevention and Control Act[89]. - FDA may require a risk evaluation and mitigation strategy (REMS) as a condition of NDA approval to ensure drug benefits outweigh risks[72]. - Changes to approved applications require submission of a new NDA or NDA supplement, which must include clinical data similar to the original application[73]. - FDA may conduct inspections of clinical sites and manufacturing facilities before approving an NDA to ensure compliance with regulations[70]. - The first NDA applicant to receive FDA approval for a drug with Orphan Drug Designation is entitled to exclusive marketing rights for that indication[76]. - Post-approval requirements include adverse event reporting and compliance with current good manufacturing practices (cGMPs)[82]. - Compliance with federal and state pharmaceutical regulations is mandatory, and failure to comply could result in fines and reputational damage[122]. - The company is subject to ongoing FDA obligations and regulatory review, which may result in significant expenses and limit commercialization[177]. - Compliance with the Controlled Substances Act (CSA) and DEA regulations is critical, as failure to comply may adversely affect the business[189]. - The DEA's quota system may limit the availability of active ingredients for clinical trials and commercial demand, potentially causing delays[175]. - The DEA's quota system limits the availability and production of controlled substances, which may impact the company's development and commercialization plans if the FDA approves its formulations[191]. Market and Competitive Landscape - The market for CNS diseases is estimated to affect nearly 2 billion people globally, representing approximately 40% of the total disease burden[49]. - The company faces intense competition from large pharmaceutical companies with more resources and established R&D capabilities[59]. - The market for esmethadone may be competitive, with existing products potentially reaching approval before esmethadone[131]. - The company may face significant obstacles in international commercialization due to limited foreign regulatory and commercial resources[139]. - The company intends to seek market clearances in foreign markets deemed to generate significant opportunities, despite currently having no foreign operations[213]. - International development activities may suffer due to inherent risks such as regulatory changes, export restrictions, and currency fluctuations[214]. Intellectual Property and Licensing - The company has over 50 issued patents and pending applications related to REL-1017, providing potential coverage beyond 2033[51]. - The company has secured a 7-year FDA Orphan Drug marketing exclusivity for d-methadone upon NDA approval, with potential for up to 10 years in the EU[51]. - The company received an upfront license fee of $1.5 million from Wonpung Mulsan Co and will earn royalties of up to 12% on net sales for licensed products[57]. - The company executed a License Agreement with Arbormentis, LLC for a novel psilocybin program, involving an upfront fee of $12.7 million and potential milestone payments totaling up to $160 million[58]. - The company's patent position is uncertain, and it may face challenges in obtaining and enforcing patents, which could materially harm its business[207]. - The commercialization of patented inventions requires appropriate FDA authorization, regardless of patent status, which could limit the company's ability to market its products[212]. - There are risks related to intellectual property rights, including the possibility that current and future patent applications may not lead to issued patents[216]. Human Capital and Organizational Structure - As of December 31, 2022, the company had a total of 14 employees, emphasizing the importance of human capital for innovation and operational excellence[111]. - The company focuses on inclusion and diversity, with approximately 60% of its employee population being female as of December 31, 2022[112]. - The company maintains a competitive compensation and benefits package, including performance-based incentives tied to both company and individual performance[113]. - The company currently employs only 14 full-time employees and plans to hire additional qualified personnel to support its operations[146]. - The company has engaged a third-party consultant to evaluate pay practices, finding no meaningful differences in compensation based on demographic characteristics[114]. Risks and Challenges - The company faces significant risks related to clinical trials, including potential adverse effects and the need for additional trial sites, which could delay progress[128]. - The company relies on third parties for preclinical and clinical studies, and any failure in their performance could materially harm product development and commercialization efforts[123]. - The company is vulnerable to business interruptions from various risks, including health epidemics like COVID-19, which could materially affect its operations[150]. - The company may encounter public controversy regarding its products containing controlled substances, which could lead to marketing restrictions[188]. - The company may be exposed to liability claims associated with the use of hazardous materials, which could adversely affect its financial condition[203]. - If the company is found to infringe on patents owned by others, it may need to cease or alter product development efforts, which could consume substantial financial resources[211]. - The company may seek acquisitions of drug candidates or technologies, which could involve substantial cash expenditures and potential dilution of current stockholders' ownership interests[148]. - The company anticipates that managing growth to support larger clinical trials will strain its financial and operational resources[147]. - The company faces intense competition from larger pharmaceutical companies, which may have greater financial resources and development capabilities[202]. - The company does not currently carry product liability insurance, which could inhibit the commercialization of its product candidates if serious adverse reactions occur[204].

Relmada Therapeutics, Inc. (NASDAQ:RLMD) Q3 2022 Earnings Conference Call November 10, 2022 4:30 PM ET Company Participants Brian Ritchie - LifeSci Advisors Sergio Traversa - Chief Executive Officer Maged Shenouda - Chief Financial Officer Maurizio Fava - Chairman, Harvard Psychiatry Department Conference Call Participants Guofang Li - SVB Securities Uy Ear - Mizuho Yatin Suneja - Guggenheim Partners Andrea Tan - Goldman Sachs Andrew Tsai - Jefferies Jay Olson - Oppenheimer Joon Lee - Truist Securities Oper ...

Drug Development and Clinical Trials - Relmada Therapeutics is developing esmethadone (REL-1017) as a rapidly acting oral agent for the treatment of major depressive disorder (MDD) and other CNS diseases[115]. - In the Phase 2 clinical trial (REL-1017-202), subjects receiving 25 mg and 50 mg doses of REL-1017 showed statistically significant improvements in MADRS scores compared to placebo, with P values < 0.03 and effect sizes ranging from 0.7 to 1.0[118][119]. - The Phase 3 program for REL-1017 includes two placebo-controlled trials across 55 clinical sites in the U.S., with the primary endpoint being the change in MADRS score at Day 28[123]. - The FDA granted Fast Track designation to REL-1017 as a monotherapy for MDD, indicating potential expedited review[124]. - The RELIANCE III study did not achieve its primary endpoint, showing a MADRS reduction of 14.8 points for REL-1017 compared to 13.9 points for placebo at Day 28[125]. - Esmethadone is currently in Phase 3 trials for the adjunctive treatment of major depressive disorder (MDD), with robust efficacy demonstrated in a randomized Phase 2 trial[148]. - In a Human Abuse Potential study, all doses of REL-1017 showed a statistically significant difference in abuse potential compared to oxycodone, supporting the lack of opioid effects[128]. - Esmethadone's mechanism of action as a non-competitive NMDA antagonist differentiates it from currently approved antidepressants, potentially offering rapid effects without adverse side effects[133]. - The urgent need for faster-acting antidepressant treatments is highlighted by the fact that severe depression can be life-threatening, with a significant portion of patients not achieving adequate therapeutic benefits[132]. Financial Performance - For the nine months ended September 30, 2022, the net loss was approximately $119,099,500, compared to a net loss of $91,373,300 for the same period in 2021, representing an increase of approximately 30.3%[161]. - Research and development expenses for the nine months ended September 30, 2022, were approximately $86,454,600, an increase of approximately $21,106,900 from $65,347,700 for the same period in 2021, reflecting a 32.3% increase[157]. - The total operating expenses for the nine months ended September 30, 2022, were approximately $122,546,656, compared to $91,520,718 for the same period in 2021, marking an increase of approximately 35.9%[156]. - The company incurred negative operating cash flows of $67,918,717 for the nine months ended September 30, 2022[162]. - The company has not generated revenues and does not anticipate generating revenues for the foreseeable future[142]. - For the nine months ended September 30, 2022, cash used in operating activities was $67,918,717, an increase of 24.9% compared to $54,213,231 for the same period in 2021[166]. - The net loss for the nine months ended September 30, 2022, was $119,099,458, compared to a net loss of $91,373,316 for the same period in 2021, reflecting a year-over-year increase of 30.3%[167]. - Cash provided by investing activities for the nine months ended September 30, 2022, was $21,389,056, a decrease of 42.3% from $37,064,696 in 2021[168]. - Net cash provided by financing activities for the nine months ended September 30, 2022, was $44,610,591, an increase of 70.9% compared to $26,102,432 in 2021[169]. - Sales of common stock contributed $42,728,599 to financing activities for the nine months ended September 30, 2022, compared to $23,416,036 in 2021, indicating an increase of 82.5%[170]. - The company experienced a net decrease in cash and cash equivalents of $1,919,070 for the nine months ended September 30, 2022, contrasting with an increase of $8,953,897 in the same period of 2021[166]. Market and Patent Information - The market for CNS diseases is estimated to affect nearly 2 billion people globally, representing approximately 40% of the total disease burden, indicating a significant revenue opportunity[145]. - The company has over 50 issued patents and pending patent applications related to REL-1017, potentially providing coverage beyond 2033[147]. Risk Factors and Financial Reporting - Inflation affects the company's expenses, particularly in employee compensation and contract services, which could increase the level of expenses[171]. - There have been no material changes to the risk factors previously disclosed in the company's Annual Report on Form 10-K for the year ended December 31, 2021[172]. - The company’s financial statements are prepared in accordance with U.S. GAAP, requiring management to make estimates and assumptions that affect reported amounts[174]. - There have been no material changes to the company's exposures to market risks as disclosed in the annual MD&A contained in the Form 10-K for the year ended December 31, 2021[175].

Relmada Therapeutics, Inc. (NASDAQ:RLMD) Q2 2022 Earnings Conference Call August 11, 2022 4:30 PM ET Company Participants Brian Ritchie - LifeSci Advisors Sergio Traversa - Chief Executive Officer John Hixon - Head of Commercial Maged Shenouda - Chief Financial Officer Conference Call Participants Andrew Tsai - Jefferies Yatin Suneja - Guggenheim Andrea Tan - Goldman Sachs Joon Lee - Truist Securities Jay Olson - Oppenheimer Uy Ear - Mizuho Securities Operator Good day, ladies and gentlemen, and welcome to ...

Drug Development and Clinical Trials - Relmada Therapeutics is developing esmethadone (REL-1017) as a rapidly acting oral agent for the treatment of major depressive disorder (MDD) and other CNS diseases[103]. - In the Phase 2 clinical trial (REL-1017-202), subjects receiving REL-1017 (25 mg and 50 mg) showed statistically significant improvements in MADRS scores compared to placebo, with P values < 0.03 and effect sizes ranging from 0.7 to 1.0[106][107]. - The Phase 3 program for REL-1017 includes two pivotal trials (RELIANCE I and RELIANCE II) with a primary endpoint of change from baseline on the MADRS score at day 28[112]. - The FDA granted Fast Track designation to REL-1017 as a monotherapy for MDD, indicating potential expedited review[111]. - Relmada's studies indicate that REL-1017 has a favorable tolerability profile, with only mild to moderate adverse events reported and no serious adverse events observed[109]. - The company plans to report results from the RELIANCE III monotherapy trials and the RELIANCE I and II adjunctive trials in the second half of 2022[116]. - Esmethadone is being evaluated for other indications, including restless leg syndrome and other glutamatergic system activation-related diseases[122]. - The Human Abuse Potential study showed that REL-1017 demonstrated a statistically significant difference in abuse potential compared to oxycodone, supporting its safety profile[114]. - The mechanism of action for esmethadone as an NMDA receptor antagonist differentiates it from traditional antidepressants, potentially offering rapid effects without typical opioid side effects[118][120]. Financial Performance - The company reported a net loss of approximately $79,680,800 for the six months ended June 30, 2022, compared to a net loss of $48,767,100 for the same period in 2021, representing an increase of approximately 63.3%[142]. - Research and development expenses for the six months ended June 30, 2022, were approximately $55,925,500, an increase of approximately 78.3% from $31,353,700 for the same period in 2021[140]. - The company had cash and short-term investments of $211,955,077 as of June 30, 2022, despite incurring negative operating cash flows of $41,055,884 for the six months ended June 30, 2022[146]. - The company raised net proceeds of $42,728,599 from the sale of common stock through its ATM equity offering during the six months ended June 30, 2022[147]. - The company reported a loss per share of $2.73 for the six months ended June 30, 2022, compared to a loss per share of $2.90 for the same period in 2021[142]. - Total operating expenses for the six months ended June 30, 2022, were approximately $83,809,495, an increase of approximately 71.5% from $48,867,083 for the same period in 2021[139]. - Net cash provided by financing activities for the six months ended June 30, 2022, was $44,041,499, an increase from $25,917,276 in the same period of 2021, representing a growth of approximately 70%[153][154]. - Proceeds from options exercised for common stock amounted to $417,544 in 2022, compared to $517,271 in 2021, indicating a decrease of about 19%[153][154]. - Proceeds from warrants exercised for common stock were $895,356 in 2022, down from $1,941,955 in 2021, reflecting a decline of approximately 54%[153][154]. - Sales of common stock reached $42,728,599 in 2022, up from $23,458,050 in 2021, marking an increase of around 82%[153][154]. Market and Intellectual Property - The market for CNS diseases is estimated to affect nearly 2 billion people globally, representing approximately 40% of the total disease burden, indicating a significant revenue opportunity for the company[128]. - The company has over 50 issued patents and pending patent applications related to its product candidates, potentially providing coverage beyond 2033[130]. - The company has secured an Orphan Drug Designation from the FDA for d-methadone, which carries 7-year marketing exclusivity upon NDA approval[130]. Risk Factors and Management Assumptions - There have been no material changes to the risk factors previously disclosed in the company's Annual Report on Form 10-K for the year ended December 31, 2021[156]. - Management's estimates and assumptions are based on historical experience and reasonable assumptions, which may differ from actual results under different circumstances[158]. - There have been no material changes to the company's exposures to market risks as disclosed in the annual MD&A contained in the Form 10-K for the year ended December 31, 2021[159].

Financial Data and Key Metrics Changes - For Q1 2022, total research and development expenses were approximately $25 million, up from $14 million in Q1 2021, primarily due to increased costs associated with the broader clinical program for REL-1017 [24] - General and administrative expenses for Q1 2022 were approximately $13.3 million, compared to $8.4 million in Q1 2021, reflecting an increase of about $4.9 million mainly due to higher stock-based compensation [25] - The net loss for Q1 2022 was $39.7 million, or $1.40 per share, compared to a net loss of $22.2 million, or $1.34 per share, in the same period of 2021 [26] - As of March 31, 2022, cash, cash equivalents, and short-term investments totaled $220.6 million, compared to approximately $211.9 million at December 31, 2021 [26] Business Line Data and Key Metrics Changes - The ongoing RELIANCE Phase 3 trials for REL-1017 are expected to yield clinical data readouts beginning mid-year 2022, with enrollment completion anticipated for RELIANCE III [8][13] - RELIANCE I and RELIANCE II are designed to evaluate REL-1017 as an adjunctive treatment for major depressive disorder (MDD), with both studies including two arms: placebo and 25 milligrams of REL-1017 [15][17] Market Data and Key Metrics Changes - The company is focusing on the potential market for REL-1017, particularly in the adjunctive treatment space where it would be the only antidepressant available, thus allowing for greater pricing power and reduced competition [50] - In the monotherapy market, competition includes generic drugs, which poses challenges in terms of pricing and market share [51] Company Strategy and Development Direction - The company aims to position REL-1017 as a potential Schedule IV drug, with the possibility of it becoming a non-scheduled drug after one to two years of marketing experience [12] - The strategic focus includes maximizing the success of the Phase 3 studies by controlling the placebo effect through careful site and rater selection [34] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the efficacy of REL-1017 based on previous Phase 2 data and the expected outcomes of the ongoing Phase 3 trials [30][33] - The management team is optimistic about the potential for REL-1017 to improve treatment outcomes for patients with MDD, particularly in light of the anticipated clinical data [54] Other Important Information - The company appointed Gino Santini as Corporate Development Strategic Advisor to enhance its strategic capabilities in the biopharmaceutical industry [19] - REL-1017 data were presented at the Ketamine & Related Compounds International Hybrid Conference 2022, highlighting its safety profile [21] Q&A Session Summary Question: What are the expectations for the kinetics of the Phase 3 monotherapy data? - Management indicated that they do not expect any loss of efficacy over time based on strong adjunctive treatment data and experiences with similar compounds [30] Question: What measures have been taken to maximize the success of the Phase 3 study? - The company has implemented strategies to control the placebo effect, including careful site selection and training for raters [34] Question: What is the expected placebo effect in the outpatient setting? - Management expects a placebo delta of 12 points from baseline to day 28, which would indicate a successful trial if REL-1017 performs as anticipated [65] Question: What is the current status of the psilocybin compound? - The psilocybin compound is progressing well, with the company finishing up the manufacturing process [129]

1 Targeting Major of CNS Disorders Advances in Treatment May 5th, 2022 I Nasdaq: RLMD Disclosures Certain statements contained in this presentation or in other documents of Relmada Therapeutics, Inc. (the "Company"), along with certain statements that may be made by management of the Company orally in presenting this material, may contain "forward-looking statements." These statements can be identified by the fact that they do not relate strictly to historic or current facts. They use words such as "estimat ...