TRPC4

Submitted New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for KarXT for the treatment of schizophrenia in the third quarter of 2023 Initiated the Phase 3 ADEPT-2 and ADEPT-3 trials evaluating KarXT for the treatment of psychosis in Alzheimer’s disease in the third quarter of 2023 $1.3 billion in cash expected to fund operations through 2026 Conference call and webcast to take place today at 8:00 a.m. ET BOSTON--(BUSINESS WIRE)-- Karuna Therapeutics, Inc. (NASDAQ: KRTX), a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced financial results for the third quarter of 2023 and provided a general business update. “The third quarter was highlighted by our NDA submission to the FDA for KarXT for the treatment of schizophrenia, a significant milestone for Karuna, as well as for patients living with this serious mental illness,” said Bill Meury, president and chief executive officer of Karuna Therapeutics. “There remains an unmet need for new treatment options and, if approved, KarXT would represent the first novel pharmacological approach to treating schizophrenia in decades.” “In parallel to our submission, we continue to advance our commercialization plans ahead of the potential approval and launch of KarXT in the U.S. in the second half of next year,” Mr. Meury added. "Additionally, we have made important progress across our ongoing KarXT Phase 3 programs, highlighted by the initiation of the ADEPT-2 and ADEPT-3 trials in psychosis in Alzheimer’s disease. Beyond our primary indications in schizophrenia and Alzheimer’s disease, we’re also focused on building our pipeline with potential new opportunities for KarXT, as well as advancing other early-stage compounds across a broad range of neuropsychiatric conditions.” KEY PIPELINE HIGHLIGHTS Karuna is advancing a pipeline of novel drug candidates for the treatment of various psychiatric and neurological conditions led by KarXT (xanomeline-trospium), an oral, investigational M1/M4-preferring muscarinic agonist. KarXT KarXT is being evaluated in Phase 3 clinical trials as a potential treatment for schizophrenia, for adjunctive treatment in schizophrenia, as well as for psychosis in Alzheimer’s disease. Schizophrenia Submitted an NDA to the FDA for KarXT for the treatment of schizophrenia in adults in the third quarter of 2023. The Company anticipates the potential approval and launch of KarXT in the second half of 2024. Presented additional data analyses from the EMERGENT program at the 36th European College of Neuropsychopharmacology (ECNP) Congress in the fourth quarter of 2023. Poster presentations included previously reported cognition data from the EMERGENT-2 and EMERGENT-3 trials, as well as new efficacy and safety analyses from the EMERGENT-3 trial where: KarXT demonstrated a statistically significantly greater percentage of Positive and Negative Syndrome Scale (PANSS) responders (≥30% reduction in PANSS total score) at week 5 compared to placebo (p<0.01), a pre-specified secondary endpoint in the trial. KarXT was associated with statistically significant improvements from baseline to week 5 compared to placebo in the PANSS Marder 5-Factor symptom domains, including the PANSS Marder positive (p<0.001), disorganized thoughts (p<0.05), uncontrolled hostility/excitement (p<0.001), and anxiety/depression (p<0.01) factors. While not meeting the threshold for statistical significance at week 5, KarXT did demonstrate a statistically significant reduction in the PANSS negative Marder factor score compared to placebo at week 4 (p<0.05). KarXT was generally well-tolerated, with the most common treatment emergent adverse events (TEAEs) being cholinergic in nature, consistent with prior trials of KarXT. The majority of these common TEAEs occurred within the first two weeks of treatment, were mild in severity, and transient in nature. Additional data analyses to be presented at upcoming medical congresses in the fourth quarter of 2023. Presentations will highlight new pooled efficacy and safety data from the EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials. Topline data from the EMERGENT-4 and EMERGENT-5 trials evaluating the long-term safety of KarXT in schizophrenia are anticipated in the second half of 2024. The Company remains on track to report topline data from the Phase 1b trial evaluating the effect of KarXT on 24-hour ambulatory blood pressure in the fourth quarter of 2023. Adjunctive treatment in schizophrenia Topline data from the Phase 3 ARISE trial evaluating the efficacy and safety of KarXT in schizophrenia when combined with a background antipsychotic is anticipated in the second half of 2024. Psychosis in Alzheimer’s disease The Phase 3 ADEPT-2 and ADEPT-3 trials initiated in the third quarter of 2023. Topline data from ADEPT-1 and ADEPT-2 are anticipated in 2025. Early-stage and discovery programs The Karuna pipeline also includes clinical-stage candidate KAR-2618, a TRPC4/5 inhibitor for the treatment of mood and anxiety disorders, as well as pre-clinical muscarinic, TRPC4/5, and target-agnostic compounds for the treatment of psychiatric and neurological conditions. The Company plans to evaluate KAR-2618 for the treatment of major depressive disorder (MDD). The initiation of a Phase 1b clinical trial of KAR-2618 is anticipated in 2024, with additional details to be shared early next year. ANTICIPATED UPCOMING MILESTONES Topline data from the Phase 3 EMERGENT-4 trial (2H 2024) Topline data from the Phase 3 EMERGENT-5 trial (2H 2024) Launch of KarXT in schizophrenia, if approved (2H 2024) Topline data from the Phase 3 ARISE trial (2H 2024) Initiation of the Phase 1b trial of KAR-2618 (2024) Topline data from the Phase 3 ADEPT-1 trial (2025) Topline data from the Phase 3 ADEPT-2 trial (2025) THIRD QUARTER 2023 FINANCIAL RESULTS The Company reported a net loss of $119.1 million for the third quarter of 2023, as compared to $77.0 million for the prior year period. The increase in net loss for the quarter was driven by research and development expenses related to the Company’s ongoing KarXT clinical programs, pre-commercialization activities, increased employee headcount across the organization, and higher stock-based compensation. Research and development expenses were $104.0 million for the third quarter of 2023, as compared to $62.0 million for the prior year period. The increase in research and development expenses for the quarter was primarily driven by expenses related to the KarXT clinical programs, increased employee headcount, and higher stock-based compensation. General and administrative expenses were $32.3 million for the third quarter of 2023, as compared to $19.1 million for the prior year period. The increase in general and administrative expenses for the quarter was primarily driven by the Company’s pre-commercialization activities, increased employee headcount, and higher stock-based compensation. The Company ended the quarter with $1.3 billion in cash, cash equivalents, and available-for-sale investment securities compared to $1.1 billion as of December 31, 2022. The increase was primarily the result of the completion of the Company’s follow-on public offering in March 2023, which resulted in net proceeds of $436.7 million. The Company expects that current cash, cash equivalents, and available-for-sale investment securities as of September 30, 2023, will enable the Company to fund its operating expenses and capital expenditure requirements through 2026. CONFERENCE CALL AND WEBCAST DETAILS The third quarter 2023 financial results and business update will be discussed during a conference call and webcast today at 8:00 a.m. ET. A webcast of the live call may be accessed on the Investor Relations page of Karuna’s website at investors.karunatx.com. A replay of the webcast will be available for up to 30 days following the event. About Karuna Therapeutics Karuna Therapeutics is a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions. At Karuna, we understand there is a need for differentiated and more effective treatments that can help patients navigate the challenges presented by serious mental illness. Utilizing our extensive knowledge of neuroscience, we are harnessing the untapped potential of the brain in pursuit of novel pathways to develop medicines that make meaningful differences in peoples’ lives. For more information, please visit . Forward Looking Statements This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding our expectations about the timing of our ongoing and planned clinical trials and regulatory filings, our goals to develop and commercialize our product candidates, our liquidity and capital resources, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to obtain necessary funding, our ability to generate positive clinical trial results for our product candidates and other risks inherent in clinical development, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, risks relating to business interruptions, and other risks set forth under the heading “Risk Factors” of our Annual Report on Form 10-K for the year ended December 31, 2022 and in our subsequent filings with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Karuna Therapeutics, Inc. Unaudited Consolidated Statements of Operations (in thousands, except share and per share data) Three Months Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 License and other revenue $ - $ 81 $ 654 $ 5,359 Operating expenses: Research and development 103,952 61,950 281,909 158,243 General and administrative 32,266 19,125 83,936 51,756 Total operating expenses 136,218 81,075 365,845 209,999 Loss from operations (136,218 ) (80,994 ) (365,191 ) (204,640 ) Other income, net: Interest income 16,952 3,884 44,894 4,611 Sublease income 147 147 441 433 Total other income, net 17,099 4,031 45,335 5,044 Net loss before income taxes (119,119 ) (76,963 ) (319,856 ) (199,596 ) Income tax provision — — — (528 ) Net loss attributable to common stockholders $ (119,119 ) $ (76,963 ) $ (319,856 ) $ (200,124 ) Net loss per share, basic and diluted $ (3.16 ) $ (2.38 ) $ (8.72 ) $ (6.52 ) Weighted average common shares outstanding used in computing net loss per share, basic and diluted 37,689,144 32,349,111 36,682,056 30,693,117 Karuna Therapeutics, Inc. Unaudited Consolidated Balance Sheet Data (in thousands) September 30, 2023 December 31, 2022 Cash, cash equivalents and investments $ 1,339,477 $ 1,124,044 Working capital 1,316,429 1,120,823 Total assets 1,385,097 1,163,334 Total stockholders’ equity $ 1,322,316 $ 1,126,238 View source version on businesswire.com: Contacts Investors: Alexis Smith +1 (617) 352-9917 asmith@karunatx.com Media: Julie Ciardiello +1 (917) 647-0159 julie.ciardiello@karunatx.com Source: Karuna Therapeutics, Inc. View this news release online at:

On track to submit New Drug Application (NDA) for KarXT in schizophrenia with the U.S. FDA in the third quarter of 2023, with a product launch in the second half of 2024, assuming approval Initiated the Phase 3 ADEPT-3 open label extension trial in the third quarter of 2023, and on track to commence the Phase 3 ADEPT-2 trial in the second half of 2023 Announced the appointment of Jonathan Rosin to Chief Human Resources Officer and the promotion of Jason Brown to Chief Financial Officer $1.4 billion in cash expected to fund operations through 2026 Conference call and webcast to take place today at 8:00 a.m. ET BOSTON--(BUSINESS WIRE)-- Karuna Therapeutics, Inc. (NASDAQ: KRTX), a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced financial results for the second quarter of 2023 and provided a general business update. “We’ve made significant progress in the second quarter across our business, but most importantly in generating, analyzing, and preparing the data required for our NDA submission in schizophrenia,” said Bill Meury, president and chief executive officer of Karuna Therapeutics. “Looking ahead, we remain focused on our NDA submission, which is on track for later this quarter, and building the commercial infrastructure in preparation for the potential launch of KarXT in the second half of 2024.” “Beyond the EMERGENT program, we continue to activate additional clinical trial sites to support recruitment in our ARISE trial, with data on track for the second half of 2024. We also initiated the ADEPT-3 open label extension trial in psychosis in Alzheimer’s earlier this quarter, with the full Phase 3 ADEPT program expected to be underway in the coming months following the initiation of ADEPT-2, our second pivotal safety and efficacy trial in this program,” added Mr. Meury. KEY PIPELINE HIGHLIGHTS Karuna is advancing a pipeline of novel drug candidates for the treatment of various psychiatric and neurological conditions led by KarXT (xanomeline-trospium), an oral, investigational M1/M4-preferring muscarinic agonist. KarXT KarXT is being evaluated in Phase 3 clinical trials as a potential treatment for schizophrenia as a monotherapy and adjunctive therapy, as well as for psychosis in Alzheimer’s disease. Schizophrenia Presented additional data analyses from the EMERGENT program evaluating KarXT in schizophrenia at the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting and the 2023 Congress of the Schizophrenia International Research Society (SIRS) in the second quarter of 2023. In the EMERGENT-3 trial, KarXT demonstrated a statistically significant and clinically meaningful improvement in the Clinical Global Impression – Severity (CGI-S) score, a prespecified secondary endpoint, compared to placebo starting at week 2 and maintained such improvement throughout the trial to week 5 (-1.1 KarXT vs. -0.6 placebo; p<0.0001), consistent with the EMERGENT-1 and EMERGENT-2 trials. In an exploratory pooled analysis of the EMERGENT-2 and EMERGENT-3 trials, KarXT was associated with statistically significant and clinically meaningful improvements in cognitive function compared to placebo at week 5 in patients with cognitive impairment at baseline (0.41 KarXT vs. 0.13 placebo; p<0.01, Cohen’s d=0.52) as measured by the CANTAB composite score. Additionally, there was no significant correlative relationship between changes in Positive and Negative Syndrome Scale (PANSS) total score and changes in CANTAB composite score in the KarXT group, suggesting that improvements observed in cognition were largely independent of improvements in PANSS-related symptoms. Completed enrollment in the EMERGENT-5 trial in the second quarter of 2023. Topline data from the EMERGENT-4 and EMERGENT-5 trials evaluating the long-term safety of KarXT in schizophrenia are anticipated in 2024. The Phase 1b trial evaluating the effect of KarXT on 24-hour ambulatory blood pressure in adults with schizophrenia completed enrollment in the second quarter of 2023. Topline data from the trial is expected in the fourth quarter of 2023. The Company remains on track to submit an NDA for KarXT in schizophrenia with the FDA in the third quarter of 2023, with a launch in the second half of 2024, if approved. Adjunctive treatment in schizophrenia Topline data from the ARISE trial evaluating the efficacy and safety of KarXT in schizophrenia when combined with a background antipsychotic is anticipated in the second half of 2024. Psychosis in Alzheimer’s disease The ADEPT-1 trial is ongoing, with the ADEPT-2 trial on track to initiate in the second half of 2023. Topline data from the ADEPT-1 and ADEPT-2 trials are anticipated in 2025. Initiated the ADEPT-3 open-label extension trial in the third quarter of 2023. Early-stage and discovery programs The Karuna pipeline also includes clinical-stage candidate KAR-2618, a TRPC4/5 inhibitor for the treatment of mood and anxiety disorders, as well as pre-clinical muscarinic, TRPC4/5, and target-agnostic compounds for the treatment of psychiatric and neurological conditions. The Company plans to share next steps on the development of KAR-2618 for the treatment of mood and anxiety disorders in the second half of 2023. BUSINESS UPDATES Announced key leadership appointments. In a separate press release, the Company today announced the appointment of Jonathan Rosin to Chief Human Resources Officer in July 2023, and the promotion of Jason Brown to Chief Financial Officer. Mr. Brown succeeds Troy Ignelzi who will remain at Karuna for a transition period through the end of the third quarter of 2023. ANTICIPATED UPCOMING MILESTONES NDA submission of KarXT in schizophrenia (3Q 2023) Initiation of the Phase 3 ADEPT-2 trial (2H 2023) Topline data from the Phase 3 EMERGENT-4 trial (2024) Topline data from the Phase 3 EMERGENT-5 trial (2024) Launch of KarXT in schizophrenia, if approved (2H 2024) Topline data from the Phase 3 ARISE trial (2H 2024) Topline data from the Phase 3 ADEPT-1 trial (2025) Topline data from the Phase 3 ADEPT-2 trial (2025) SECOND QUARTER 2023 FINANCIAL RESULTS The Company reported a net loss of $103.2 million for the second quarter of 2023, as compared to $64.9 million for the prior year period. The increase in net loss for the quarter was driven by research and development expenses related to the Company’s ongoing KarXT clinical programs, NDA-supporting activities, pre-commercialization activities, increased employee headcount across the organization, and higher stock-based compensation. Research and development expenses were $92.5 million for the second quarter of 2023, as compared to $52.5 million for the prior year period. The increase in research and development expenses for the quarter was primarily driven by expenses related to the KarXT clinical programs, NDA-supporting activities, increased employee headcount, and higher stock-based compensation. General and administrative expenses were $27.4 million for the second quarter of 2023, as compared to $17.8 million for the prior year period. The increase in general and administrative expenses for the quarter was primarily driven by the Company’s pre-commercialization activities, increased employee headcount, and higher stock-based compensation. The Company ended the quarter with $1.4 billion in cash, cash equivalents, and available-for-sale investment securities compared to $1.1 billion as of December 31, 2022. The increase was primarily the result of the completion of the Company’s follow-on public offering in March 2023, which resulted in net proceeds of $436.7 million. The Company expects that current cash, cash equivalents, and available-for-sale investment securities as of June 30, 2023 will enable the Company to fund its operating expenses and capital expenditure requirements through the end of 2026. CONFERENCE CALL AND WEBCAST DETAILS The second quarter 2023 financial results and business update will be discussed during a conference call and webcast today at 8:00 a.m. ET. A webcast of the live call may be accessed on the Investors section of the Karuna website at investors.karunatx.com. A replay of the webcast will be available for up to 30 days following the event. About Karuna Therapeutics Karuna Therapeutics is a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions. At Karuna, we understand there is a need for differentiated and more effective treatments that can help patients navigate the challenges presented by these severe and disabling disorders. Utilizing our extensive knowledge of neuroscience, we are harnessing the untapped potential of the brain in pursuit of novel pathways to develop medicines that make meaningful differences in peoples’ lives. For more information, please visit . Forward Looking Statements This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding our expectations about the timing of our ongoing and planned clinical trials and regulatory filings, our goals to develop and commercialize our product candidates, our liquidity and capital resources and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to obtain necessary funding, our ability to generate positive clinical trial results for our product candidates and other risks inherent in clinical development, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, risks relating to business interruptions resulting from the coronavirus (COVID-19) pandemic, and other risks set forth under the heading “Risk Factors” of our Annual Report on Form 10-K for the year ended December 31, 2022 and in our subsequent filings with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Karuna Therapeutics, Inc. Unaudited Consolidated Statements of Operations (in thousands, except share and per share data) Three Months Ended Six Months Ended June 30, June 30, 2023 2022 2023 2022 License and other revenue $ - $ 5,278 $ 654 $ 5,278 Operating expenses: Research and development 92,490 52,487 177,957 96,293 General and administrative 27,417 17,843 51,670 32,631 Total operating expenses 119,907 70,330 229,627 128,924 Loss from operations (119,907 ) (65,052 ) (228,973 ) (123,646 ) Other income, net: Interest income 16,597 490 27,942 727 Sublease income 147 147 294 286 Total other income, net 16,744 637 28,236 1,013 Net loss before income taxes (103,163 ) (64,415 ) (200,737 ) (122,633 ) Income tax provision — (528 ) — (528 ) Net loss attributable to common stockholders $ (103,163 ) $ (64,943 ) $ (200,737 ) $ (123,161 ) Net loss per share, basic and diluted $ (2.75 ) $ (2.17 ) $ (5.55 ) $ (4.13 ) Weighted average common shares outstanding used in computing net loss per share, basic and diluted 37,524,640 29,896,332 36,170,166 29,851,396 Karuna Therapeutics, Inc. Unaudited Consolidated Balance Sheet Data (in thousands) June 30, 2023 December 31, 2022 Cash, cash equivalents and investments $ 1,434,477 $ 1,124,044 Working capital 1,413,344 1,120,823 Total assets 1,472,103 1,163,334 Total stockholders’ equity $ 1,419,563 $ 1,126,238 View source version on businesswire.com: Contacts Investor: Alexis Smith +1 (518) 338-8990 asmith@karunatx.com Source: Karuna Therapeutics, Inc. View this news release online at:

Announced positive topline data from the Phase 3 EMERGENT-3 trial of KarXT in schizophrenia in the first quarter of 2023 On track to submit New Drug Application (NDA) for KarXT in schizophrenia with the U.S. FDA in the third quarter of 2023, with a launch in the second half of 2024, if approved Phase 3 ADEPT-2 and ADEPT-3 trials of KarXT in psychosis in Alzheimer’s disease to initiate in the second half of 2023 $1.5 billion in cash expected to fund operations through 2026 Conference call and webcast to take place today at 8:00 a.m. ET BOSTON--(BUSINESS WIRE)-- Karuna Therapeutics, Inc. (NASDAQ: KRTX), a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced financial results for the first quarter of 2023 and provided a general business update. “We’ve had a very strong start to the year,” said Bill Meury, president and chief executive officer of Karuna Therapeutics. “We announced positive data from EMERGENT-3, our third consecutive registrational trial of KarXT in schizophrenia, which further reinforces KarXT’s potential to be a completely novel and differentiated treatment for people living with schizophrenia. On the regulatory front, we remain on track to submit our NDA mid-year – specifically the third quarter – following an encouraging pre-NDA meeting with the FDA last month. We’ve also made significant progress advancing EMERGENT-4 and 5, our Phase 3 open-label trials evaluating the long-term safety of KarXT in schizophrenia, which will provide valuable information for both the NDA and medical education pre- and post-launch, with data to share next year.” “As we continue to build the infrastructure to support the potential commercialization of KarXT in schizophrenia, we maintain a sharp focus on the execution of our ARISE program evaluating KarXT as an adjunctive treatment for schizophrenia, with anticipated topline data from the Phase 3 ARISE trial in the second half of 2024, as we activate additional sites to support recruitment in the study. We remain on track for the ADEPT program evaluating KarXT in psychosis in Alzheimer’s disease and expect topline data from the Phase 3 ADEPT-1 & 2 trials in 2025,” Mr. Meury added. “Beyond KarXT, we continue to grow our pipeline both organically and inorganically, most notably with our exclusive global in-license agreement for TRPC4/5 inhibitors for the treatment of mood and anxiety disorders announced in February, and we look forward to sharing next steps in the program later this year.” KEY PIPELINE HIGHLIGHTS Karuna is advancing a pipeline of novel drug candidates for the treatment of various psychiatric and neurological conditions led by KarXT (xanomeline-trospium), an oral, investigational M1/M4-preferring muscarinic agonist. KarXT KarXT is being evaluated in Phase 3 clinical trials as a potential treatment for schizophrenia as a monotherapy and adjunctive therapy, as well as for psychosis in Alzheimer’s disease. Schizophrenia Announced positive results from the Phase 3 EMERGENT-3 trial in schizophrenia in the first quarter of 2023. The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-20.6 KarXT vs. -12.2 placebo; p<0.0001) at week 5. KarXT was generally well tolerated, with a side effect pro consistent with prior trials of KarXT. Additional data analyses from the EMERGENT-2 and EMERGENT-3 trials to be presented at upcoming medical congresses in the second quarter of 2023. Presentations will highlight additional new efficacy and safety data from EMERGENT-3 and data from the cognitive exploratory endpoint analyses from EMERGENT-2 and EMERGENT-3. Topline data from the EMERGENT-4 and EMERGENT-5 trials evaluating the long-term safety of KarXT in schizophrenia are anticipated in 2024. EMERGENT-4 completed enrollment in the fourth quarter of 2022, and EMERGENT-5 is estimated to complete enrollment in the second quarter of 2023. The Phase 1b trial evaluating the effect of KarXT on 24-hour ambulatory blood pressure in adults with schizophrenia initiated in the second quarter of 2023. Topline data from the trial is expected in the fourth quarter of 2023. The Company remains on track to submit an NDA for KarXT in schizophrenia with the FDA in the third quarter of 2023 following the completion of a pre-NDA meeting in the second quarter of 2023. Adjunctive treatment in schizophrenia The Company now anticipates topline data from the Phase 3 ARISE trial in the second half of 2024. The Company is increasing the number of sites in the trial, including additional clinical trial sites in Europe, to support recruitment. Psychosis in Alzheimer’s disease Topline data from the Phase 3 ADEPT-1 trial is anticipated in 2025. The Company is on track to initiate the Phase 3 ADEPT-2 and ADEPT-3 trials in the second half of 2023. Topline data from the Phase 3 ADEPT-2 trial is anticipated in 2025. Early-stage and discovery programs The Karuna pipeline also includes clinical-stage candidate KAR-2618, a TRPC4/5 inhibitor for the treatment of mood and anxiety disorders, as well as pre-clinical muscarinic, TRPC4/5, and target-agnostic compounds for the treatment of psychiatric and neurological conditions. Announced exclusive global license of TRPC4/5 inhibitors, including lead clinical-stage candidate KAR-2618, in the first quarter of 2023. The Company plans to share next steps on the development of KAR-2618 for the treatment of mood and anxiety disorders in the second half of 2023. ANTICIPATED UPCOMING MILESTONES NDA submission of KarXT in schizophrenia (3Q 2023) Initiation of the Phase 3 ADEPT-2 trial (2H 2023) Initiation of the Phase 3 ADEPT-3 trial (2H 2023) Topline data from the Phase 3 EMERGENT-4 trial (2024) Topline data from the Phase 3 EMERGENT-5 trial (2024) Launch of KarXT in schizophrenia, if approved (2H 2024) Topline data from the Phase 3 ARISE trial (2H 2024) Topline data from the Phase 3 ADEPT-1 trial (2025) Topline data from the Phase 3 ADEPT-2 trial (2025) FIRST QUARTER 2023 FINANCIAL RESULTS The Company reported a net loss of $97.6 million for the first quarter of 2023, as compared to $58.2 million for the prior year period. The increase in net loss for the quarter was primarily attributable to higher operating expenses of $109.7 million compared to $58.6 million for the prior year period, driven by expenses related to the EMERGENT, ARISE and ADEPT clinical programs, NDA-supporting activities, the $15.0 million upfront license payment for Goldfinch Bio’s TRPC4/5 channel candidates, increased employee headcount across the organization, and higher stock-based compensation expense. Operating expenses were slightly offset by higher interest income driven by the increase in cash equivalents and short-term investments, as well as higher interest rates. The Company recognized licensing revenue of $0.7 million for the first quarter of 2023 associated with sales of clinical drug supply to Zai Lab (Shanghai) Co., Ltd. No license revenue was recognized for the prior year period. Research and development expenses were $85.5 million for the first quarter of 2023, as compared to $43.8 million for the prior year period. The increase in research and development expenses for the quarter was primarily driven by the EMERGENT, ARISE and ADEPT clinical programs, NDA-supporting activities, the upfront license payment for Goldfinch Bio’s TRPC4/5 channel candidates, personnel-related costs due to the increase in employee headcount, and higher stock-based compensation expense. General and administrative expenses were $24.3 million for the first quarter of 2023, as compared to $14.8 million for the prior year period. The increase in general and administrative expenses for the quarter was primarily driven by an increase in pre-commercialization activities, professional fees, employee headcount, and higher stock-based compensation expense. The Company ended the quarter with $1.5 billion in cash, cash equivalents, and available-for-sale investment securities compared to $1.1 billion as of December 31, 2022. The increase was primarily the result of the completion of the Company’s follow-on public offering in March 2023, which resulted in net proceeds of $436.7 million. The Company expects that current cash, cash equivalents, and available-for-sale investment securities as of March 31, 2023 will enable the Company to fund its operating expenses and capital expenditure requirements through the end of 2026. CONFERENCE CALL AND WEBCAST DETAILS The first quarter 2023 financial results and business update will be discussed during a conference call and webcast today at 8:00 a.m. ET. A webcast of the live call may be accessed on the Investors section of the Karuna website at investors.karunatx.com. A replay of the webcast will be available for up to 30 days following the event. About Karuna Therapeutics Karuna Therapeutics is a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions. At Karuna, we understand there is a need for differentiated and more effective treatments that can help patients navigate the challenges presented by these severe and disabling disorders. Utilizing our extensive knowledge of neuroscience, we are harnessing the untapped potential of the brain in pursuit of novel pathways to develop medicines that make meaningful differences in peoples’ lives. For more information, please visit . Forward Looking Statements This press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding our expectations about the timing of our ongoing and planned clinical trials and regulatory filings, our goals to develop and commercialize our product candidates, our liquidity and capital resources and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to obtain necessary funding, our ability to generate positive clinical trial results for our product candidates and other risks inherent in clinical development, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, risks relating to business interruptions resulting from the coronavirus (COVID-19) pandemic, and other risks set forth under the heading “Risk Factors” of our Annual Report on Form 10-K for the year ended December 31, 2022 and in our subsequent filings with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Karuna Therapeutics, Inc. Unaudited Consolidated Statements of Operations (in thousands, except share and per share data) Three Months Ended March 31, 2023 2022 License and other revenue $ 654 $ — Operating expenses: Research and development 85,467 43,806 General and administrative 24,253 14,788 Total operating expenses 109,720 58,594 Loss from operations (109,066 ) (58,594 ) Other income, net: Interest income 11,345 237 Sublease income 147 139 Total other income, net 11,492 376 Net loss before income taxes (97,574 ) (58,218 ) Income tax provision — — Net loss attributable to common stockholders $ (97,574 ) $ (58,218 ) Net loss per share, basic and diluted $ (2.80 ) $ (1.95 ) Weighted average common shares outstanding used in computing net loss per share, basic and diluted 34,800,643 29,805,961 Karuna Therapeutics, Inc. Unaudited Consolidated Balance Sheet Data (in thousands) March 31, 2023 December 31, 2022 Cash, cash equivalents and investments $ 1,474,454 $ 1,124,044 Working capital 1,482,522 1,120,823 Total assets 1,516,168 1,163,334 Total stockholders’ equity $ 1,488,135 $ 1,126,238 View source version on businesswire.com: Contacts Investors: Alexis Smith +1 (518) 338-8990 asmith@karunatx.com Media: Bob Josefsberg +1 (646) 734-3584 bjosefsberg@karunatx.com Source: Karuna Therapeutics, Inc. View this news release online at: