UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 Regulation FD Disclosure.
On March 20, 2023, Karuna Therapeutics, Inc. (the “Company”) announced topline results from its Phase 3 EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium), in adults with schizophrenia. A copy of this press release is attached hereto as Exhibit 99.1 and is incorporated into this Item 7.01 by reference.
The information in this Item 7.01 and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
In connection with the announcement of its Phase 3 EMERGENT-3 trial results, the Company is hosting an investor call to present the data from the trial. A copy of the slide presentation to be presented during the investor call is attached hereto as Exhibit 99.2 and is incorporated into this Item 8.01 by reference. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
99.1 |
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Press Release issued by Karuna Therapeutics, Inc., dated March 20, 2023 |
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99.2 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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KARUNA THERAPEUTICS, INC. |
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Date: |
March 20, 2023 |
By: |
/s/ Troy Ignelzi |
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Troy Ignelzi |
Exhibit 99.1
Karuna Therapeutics Announces Positive Results from Phase 3 EMERGENT-3 Trial of KarXT in Schizophrenia
Third positive registrational trial met its primary endpoint, with KarXT demonstrating an 8.4-point reduction in PANSS total score compared to placebo at Week 5 (p<0.0001)
KarXT was generally well tolerated, with a side effect profile substantially consistent with previous trials of KarXT in schizophrenia
Company is on track to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration (FDA) in mid-2023, with a potential launch in the second half of 2024, if approved
Pre-NDA meeting is scheduled for early second quarter of 2023
Conference call and webcast to take place today at 8:00 a.m. ET
BOSTON—March 20, 2023— 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 positive topline results from its Phase 3 EMERGENT-3 trial evaluating the efficacy, safety, and tolerability of its lead investigational therapy, KarXT (xanomeline-trospium) in adults with schizophrenia. 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 (Cohen’s d effect size of 0.60). Consistent with prior trials, KarXT demonstrated an early and sustained statistically significant reduction of symptoms from Week 2 (p<0.05) through the end of the trial as assessed by PANSS total score.
“KarXT has now demonstrated a robust and consistent reduction of symptoms across all three registrational trials, providing a compelling picture of the potential of KarXT in schizophrenia. With these data, we are one step closer to a potential treatment option that could provide the first new mechanism of action to treat schizophrenia in several decades,” said Bill Meury, president and chief executive officer of Karuna Therapeutics. “We look forward to working closely with the FDA as we focus our attention on the regulatory process, including our upcoming pre-NDA meeting in early second quarter, and remain on track for an NDA submission in mid-2023. I would like to thank all of the participants in the EMERGENT trials and the study investigators – without their commitment and trust, none of this would be possible.”
“Schizophrenia is a persistent and disabling condition that presents with symptoms which are often difficult to treat and manage. Despite the number of currently available treatments, there remains a significant need for new treatment options for the 21 million people living worldwide with schizophrenia,” said David Walling, Ph.D., chief clinical officer at Cenexel - CNS and investigator on the EMERGENT-3 trial. “The results from the EMERGENT-3 trial add to the growing body of data which suggest KarXT could address the symptoms of schizophrenia without the common side effects we see with current treatment options.”
KarXT also demonstrated reductions in positive and negative symptoms of schizophrenia as measured by PANSS positive, PANSS negative, and PANSS negative Marder factor subscales – secondary endpoints in the trial. KarXT demonstrated a clinically meaningful and statistically significant 3.5-point reduction in PANSS positive subscale compared to placebo at Week 5 (-7.1 KarXT vs. -3.6 placebo; p<0.0001). While not meeting the threshold for statistical significance at Week 5, KarXT did demonstrate a statistically significant reduction in PANSS negative subscale and PANSS negative Marder factor subscale compared to placebo at Week 4 (p<0.05).
KarXT was generally well tolerated, with a side effect profile substantially consistent with prior trials of KarXT. The overall discontinuation rate in the trial was 33% (37% KarXT vs. 29% placebo). The overall treatment emergent adverse event (TEAE) rates for KarXT and placebo were 70% and 50%, respectively. Discontinuation rates related to TEAEs were similar between treatment arms (6% KarXT vs. 5% placebo), consistent with the EMERGENT-1 and EMERGENT-2 trials. The only serious TEAE reported in the KarXT arm was related to gastroesophageal reflux disease (acid reflux) and deemed not to be related to study drug. There were no serious TEAEs reported in the placebo group. The most common KarXT TEAEs (>5%) were nausea, dyspepsia, vomiting, constipation, headache, hypertension, diarrhea, and insomnia, which were all rated mild or moderate in severity. There were no discontinuations due to TEAEs of hypertension. Mean blood pressure measures were similar between KarXT and placebo, and no syncopal events were observed. Similar to prior trials, an increase in heart rate was associated with KarXT treatment and decreased in magnitude by the end of the trial. Measures of weight gain, somnolence, and extrapyramidal symptoms of KarXT were similar to placebo, consistent with prior trials of KarXT in schizophrenia.
The NDA submission for KarXT in schizophrenia will incorporate the efficacy and safety data from the three placebo-controlled registrational trials, EMERGENT-1, EMERGENT-2, and EMERGENT-3, in addition to long-term safety data from the ongoing EMERGENT-4 and EMERGENT-5 trials. The Company is on track to submit an NDA to the FDA in mid-2023, with a potential launch in the second half of 2024, if approved.
Conference Call and Webcast Information
Karuna will hold a webcast and conference call this morning at 8:00 a.m. ET to share topline results from its Phase 3 EMERGENT-3 trial of KarXT in schizophrenia.
A live webcast of the presentation will be available on the Investor Relations page of Karuna’s website at investors.karunatx.com. A replay of the webcast will also be archived for up to 30 days on Karuna’s website following the conference.
About the EMERGENT-3 Trial
The Phase 3 EMERGENT-3 trial is a double-blind, placebo-controlled, five-week, inpatient trial evaluating the efficacy, safety, and tolerability of our lead investigational therapy, KarXT, compared to placebo in adults with schizophrenia in the United States and Ukraine. The primary endpoint was change from baseline in Positive and Negative Syndrome Scale (PANSS) total score, a scale for measuring schizophrenia symptom severity, of KarXT compared to placebo at Week 5. Prespecified secondary endpoints included change from baseline in PANSS positive, PANSS negative and PANSS negative Marder factor subscale of KarXT compared to placebo at Week 5.
A total of 256 adults (between the ages of 18-65 years) with schizophrenia enrolled in the trial. Enrolled patients had a confirmed diagnosis of schizophrenia and were experiencing symptoms of psychosis at the time of enrollment.
Patients were randomized 1:1 to receive either a flexible dose of KarXT or placebo two times a day (BID) for five weeks. On Days 1-2, patients received a dose of 50/20 KarXT (50mg xanomeline/20mg trospium) BID or matching placebo. On Day 3, patients escalated to a dose of 100/20 BID, and on Day 8, patients had the option to increase to 125/30 BID based on tolerability. In the trial, 79% of patients on KarXT compared to 91% on placebo titrated to the highest dose level (125/30 BID).
About KarXT
KarXT (xanomeline-trospium) is an oral, investigational M1/M4-preferring muscarinic agonist in development for the treatment of psychiatric and neurological conditions, including schizophrenia and psychosis in Alzheimer’s disease. KarXT is the first potential medicine of its kind with a truly new and unique dual mechanism of action. Unlike current therapies, KarXT does not rely on the dopaminergic or serotonergic pathways, and it is designed to harness the therapeutic potential of xanomeline while managing peripheral side effects through trospium. This approach has the potential to provide a differentiated therapy, and, if approved, to beneficially impact the lives of millions of people with serious mental illness.
About Schizophrenia
Schizophrenia is a persistent and often disabling mental illness affecting how a person thinks, feels, and behaves. It is characterized by positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making) – all of which can severely impact functioning, with only 10% of people gainfully employed and many struggling to meet adult milestones such as living independently. The life expectancy of people living with schizophrenia is reduced by 10-20 years compared to the general population. Schizophrenia affects more than 21 million people worldwide and is most commonly treated with antipsychotics. Unfortunately, many people with schizophrenia continue to experience limited efficacy or problematic side effects while on antipsychotic therapy, and approximately 75% of patients discontinue medication before 18 months. When schizophrenia treatment is discontinued, it can lead to impacts on health including relapse, hospitalization, and longer time to remission.
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 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 www.karunatx.com.
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. 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.
Investor Contact:
Alexis Smith
518-338-8990
asmith@karunatx.com
Media Contact:
Bob Josefsberg
646-734-3584
bjosefsberg@karunatx.com
Phase 3 EMERGENT-3 Trial of KarXT in Schizophrenia Topline Data Results March 20, 2023 Exhibit 99.2
Forward looking statements This presentation and other related material may contain a number of “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding Karuna’s expectation about any or all of the following: (i) the timing, progress and results of preclinical studies and clinical trials for KarXT and other product candidates it may develop, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work and the period during which the results of the trials will become available; (ii) Karuna’s research and development plans, including its plans to explore the therapeutic potential of KarXT in additional indications; (iii) Karuna’s plans to develop and commercialize KarXT, KAR-2618 and other product candidates; and (iv) the timing of and Karuna’s ability to submit for, obtain and maintain marketing approvals for its product candidates. Forward-looking statements can be identified by terms such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negative of those terms. Karuna has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that it believes may affect its business, financial condition and results of operations. Although Karuna believes that such statements are based on reasonable assumptions, forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond Karuna’s control, you should not rely on these forward-looking statements as predictions of future events. These risks and uncertainties include, among others: outcomes of Karuna’s planned and ongoing clinical trials and studies may not be favorable; one or more of Karuna’s product candidate programs may not proceed as planned for technical, scientific or commercial reasons; availability and timing of results from preclinical studies and clinical trials; uncertainty about regulatory approval to conduct clinical trials or to market products; uncertainties regarding intellectual property protection; risks relating to business interruptions resulting from the coronavirus (COVID-19) pandemic; and those risk and uncertainties described under the heading “Risk Factors” in Karuna’s Annual Report on Form 10-K for the year ended December 31, 2022, and filed with the Securities and Exchange Commission on February 23, 2023, and in any other subsequent filings made by Karuna with the U.S. Securities and Exchange Commission, which are available at www.sec.gov. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. Karuna disclaims any obligation or undertaking to update or revise any forward-looking statements contained in this presentation, other than to the extent required by law.
Introduction Bill Meury President and Chief Executive Officer Phase 3 EMERGENT-3 trial results Steve Brannan, M.D. Chief Medical Officer Building a leading neuroscience company Bill Meury Q&A Agenda 3 Bill Meury Steve Brannan, M.D. Steve Paul, M.D. President of R&D and Chief Scientific Officer Andrew Miller, Ph.D. Founder and Chief Operating Officer Troy Ignelzi Chief Financial Officer Will Kane Chief Commercial Officer
5 Sources: GBD 2017, Patel et al. 2014, Remington et al. 2016, Goff et al. 2011, Liebermann et al. 2005 One of the leading causes of disability worldwide, with onset in late-teens / early-adulthood 21M+ people living with schizophrenia globally Estimated potential life lost is 10-20 years compared to general population – partly attributed to cardiovascular & metabolic comorbidities and increased suicide rate Chronic psychiatric syndrome affecting how one thinks, feels, and behaves Schizophrenia
Up to 30% of patients do not respond to therapy ~50% experience only a partial improvement in positive symptoms or unacceptable side effects ~75% of patients discontinue treatment in the first 18 months 10-15M U.S. prescriptions annually, within 1 class of medicine Need for new pharmacological approach for treatment of schizophrenia Sources: IQVIA Factored Rx Data, 2022, Kane et al. 2019, Patel et al. 2014, Lieberman et al. 2005
Phase 3 EMERGENT-3 trial topline results Steve Brannan, M.D. Chief Medical Officer 7
Third positive registrational trial in the EMERGENT program NDA = New Drug Application; *Additional analyses ongoing EMERGENT-1 NCT03697252 EMERGENT-2 NCT04659161 EMERGENT-3 NCT04738123 EMERGENT-4 NCT04659174 EMERGENT-5 NCT04820309 Phase 2 Phase 3 Phase 3 Phase 3 Phase 3 Efficacy and safety of KarXT vs. placebo Efficacy and safety of KarXT vs. placebo Efficacy and safety of KarXT vs. placebo Long-term safety & tolerability of KarXT Long-term safety & tolerability of KarXT 5-week, 1:1 randomized, flexible-dose, double-blind, placebo-controlled inpatient trial 5-week, 1:1 randomized, flexible-dose, double-blind, placebo-controlled inpatient trial 5-week, 1:1 randomized, flexible-dose, double-blind, placebo-controlled inpatient trial 52-week, open-label, outpatient extension of EMERGENT-2 & 3 52-week, open-label, outpatient trial Complete Complete Complete* Ongoing Enrolling
EMERGENT-3 trial design KarXT dose is expressed as xanomeline/trospium (mg/mg); Reflective of intent to treat (iTT) population *Washout of prior oral lithium and/or antipsychotics; †Optional increase in dose based on tolerability determined by a clinician; ‡Analyses not available at topline data PANSS = Positive & Negative Syndrome Scale; CFB = change from baseline; BID = twice daily Double-blind Inpatient Treatment Period Days 1-35 Screening Period* <2 weeks KarXT (n=125) Placebo (n=131) KEY Patients randomized Start of trial (Day 0) End of trial & primary endpoint (Week 5) Flexible dosing & titration schedule of KarXT BID vs. matching placebo BID R KarXT 50/20 Days 1-2 KarXT 100/20 Day 3 KarXT 125/30† Day 8 R 9 Select Eligibility Criteria: 18-65 years of age Confirmed diagnosis of schizophrenia and experiencing symptoms of psychosis PANSS total score between 80 and 120 Primary Endpoint: CFB in PANSS total score compared to placebo at Week 5 Prespecified Secondary Outcome Measures: PANSS positive subscale, PANSS negative subscale, PANSS negative Marder factor subscale, CGI-S‡, PANSS responder‡
Demographics and baseline characteristics *Mean age represented in years; PANSS = Positive & Negative Syndrome Scale ITT population 10 KarXT (n=125) Placebo (n=131) Mean age, n (SD)* 43.6 (11.4) 42.6 (12.2) Sex, n (%) Male Female 87 (69.6) 38 (30.4) 104 (79.4) 27 (20.6) Race, n (%) Asian Black White Not Reported 1 (0.8) 79 (63.2) 45 (36.0) 0 0 77 (58.8) 53 (40.5) 1 (0.8) Baseline PANSS total score 97.3 96.7 Baseline PANSS positive score 26.9 26.4 Baseline PANSS negative score 22.6 22.0 Baseline PANSS negative Marder factor score 22.0 21.8
KarXT was generally well tolerated, consistent with prior EMERGENT trials Summary of safety and tolerability of safety population (KarXT n=125, placebo n=128) TEAE = treatment emergent adverse event, GERD = gastroesophageal reflux disease, EPS = extrapyramidal symptoms KarXT was generally well tolerated Overall discontinuation rate was 33% (37% KarXT vs. 29% placebo) Discontinuation rates related to TEAEs were similar between treatment arms (6% KarXT vs. 5% placebo) Overall TEAE rates for KarXT and placebo were 70% and 50%, respectively Only serious TEAE reported in the KarXT group related to GERD and deemed not to be related to study drug The most common KarXT TEAEs (>5%) were all mild to moderate in severity Common KarXT TEAEs (>5%) were nausea, dyspepsia, vomiting, constipation, headache, hypertension, diarrhea, and insomnia, with rates consistent with EMERGENT-2 Cholinergic TEAEs mostly occurred within the first two weeks of treatment and were generally transient in nature Rates of headache and insomnia were similar to placebo TEAEs of hypertension (6% KarXT vs. 2% placebo) did not lead to trial discontinuation Vital signs were consistent with prior trials of KarXT in schizophrenia Mean blood pressure change from baseline was similar between KarXT and placebo An increase in heart rate was associated with KarXT treatment and decreased in magnitude by the end of the trial No syncope observed Measures of weight gain, somnolence and EPS were similar between KarXT and placebo 15
Building a leading neuroscience company Bill Meury 16
Robust antipsychotic effect across three registrational trials *Cohen’s d is a standardized effect size for measuring the difference between two group means KEY METRICS EMERGENT-3 EMERGENT-2 EMERGENT-1 Primary endpoint PANSS total score KarXT vs. placebo at Week 5 -8.4 (-20.6 KarXT vs. -12.2 placebo) -9.6 (-21.2 KarXT vs. -11.6 placebo) -11.6 (-17.4 KarXT vs. -5.9 placebo) p-value p<0.0001 p<0.0001 p<0.0001 Cohen’s d* 0.60 0.61 0.75 TEAE-related discontinuation rate (KarXT vs. placebo) 6% vs. 5% 7% vs. 6% 2% vs. 2% 17
18 KarXT has the potential to be a completely new and advanced treatment for people with schizophrenia Novel mechanism of action Early and sustained reduction of positive and negative symptoms of schizophrenia Generally well tolerated, with consistent side effect profile May not be associated with common AEs of current medications
KarXT serves as the foundation of our neuroscience pipeline *In-licensed KAR-2618 (formerly GFB-887) from assignment estate of Goldfinch Bio in January 2023; currently in planning stage †In collaboration with PsychoGenics COMPOUND INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA SUBMISSION KarXT (xanomeline-trospium) M1/M4 muscarinic agonist Schizophrenia Schizophrenia Adjunctive therapy Psychosis in Alzheimer's disease KAR-2618* TRPC4/5 inhibitor Mood & anxiety disorders KAR-201 Muscarinic-targeted drug candidate Undisclosed KAR-301 Muscarinic-targeted drug candidate Undisclosed KAR-401 Muscarinic-targeted drug candidate Undisclosed KAR-501 Target-agnostic drug candidate† Undisclosed
Maintaining momentum with multiple milestones ahead $1.1 billion in cash expected to fund operations through 2025* *Reflects cash, cash equivalents, and available-for-sale investments as of December 31, 2022; †In-licensed KAR-2618 (formerly GFB-887) from assignment estate of Goldfinch Bio in January 2023 2023 Announced exclusive license agreement for TRPC4/5 inhibitors, including clinical-stage asset KAR-2618† Positive data from Phase 3 EMERGENT-3 trial NDA submission of KarXT in schizophrenia (mid-2023) Initiate Phase 3 ADEPT-2 trial (2H 2023) Initiate Phase 3 ADEPT-3 open-label extension trial (2023) Announce next steps on KAR-2618 clinical development program in mood and anxiety (2H 2023) 2024 & 2025 Topline data from ARISE (1H 2024) Launch of KarXT in schizophrenia, if approved (2H 2024) Topline data from ADEPT-1 (2025) Topline data from ADEPT-2 (2025)
Q&A 21