8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 18, 2019

 

 

KARUNA THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38958   27-0605902

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

33 Arch Street, Suite 3110

Boston, Massachusetts

  02110
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code: (857) 449-2244

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

   Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
   Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
   Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
   Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange

on which registered

Common stock, par value $0.0001   KRTX   The Nasdaq Global Market

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 8.01 Other Events.

On November 18, 2019, Karuna Therapeutics, Inc. (the “Company”) announced results from its Phase 2 clinical trial of KarXT for the treatment of acute psychosis in patients with schizophrenia. A copy of this press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference. The presentation containing the initial data from the Phase 2 clinical trial is attached hereto as Exhibit 99.2 and is incorporated by reference herein.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits

 

99.1    Press Release issued by Karuna Therapeutics, Inc., dated November 18, 2019.
99.2    Company presentation, dated November 18, 2019.


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.

 

    Karuna Therapeutics, Inc.
Date: November 18, 2019     By:   /s/ Troy Ignelzi
      Troy Ignelzi
      Chief Financial Officer
EX-99.1

Exhibit 99.1

 

LOGO

Karuna Therapeutics Announces KarXT Met Primary Endpoint in Phase 2 Clinical Trial of Acute Psychosis in Patients with Schizophrenia

KarXT Demonstrated Statistically Significant and Clinically Meaningful Improvement in Total PANSS Score at All Time Points Over Five Weeks and was Well-Tolerated Compared to Placebo

Improvement in Total PANSS Score at Five Weeks was 11.6 Points Compared to Placebo (p<0.0001)

No Evidence of Somnolence, Extrapyramidal Side Effects or Weight Gain Relative to Placebo

Data Support Advancing KarXT to Phase 3 and Continued Development in Other CNS Disorders

Conference Call and Webcast to Take Place Today at 8:30 a.m. EST

BOSTON—Nov. 18, 2019—Karuna Therapeutics, Inc. (Nasdaq: KRTX), a clinical-stage biopharmaceutical company committed to developing novel therapies with the potential to transform the lives of people with disabling and potentially fatal neuropsychiatric disorders and pain, today announced results from its Phase 2 clinical trial of KarXT for the treatment of acute psychosis in patients with schizophrenia. In the clinical trial, KarXT demonstrated a statistically significant and clinically meaningful 11.6 point mean reduction in total Positive and Negative Syndrome Scale (PANSS) score compared to placebo (p<0.0001) and also demonstrated good overall tolerability. A statistically significant reduction in the secondary endpoints of PANSS-Positive and PANSS-Negative scores were also observed (p<0.001).

KarXT was well tolerated in the Phase 2 trial, with similar discontinuation rates between KarXT (20%) and placebo (21%). The number of discontinuations due to treatment emergent adverse events (AEs) were equal in the KarXT and placebo arms (N=2 in each group).

KarXT is an oral coformulation of xanomeline (a novel muscarinic receptor agonist) and trospium (a muscarinic receptor antagonist) designed to treat psychosis and related symptoms through preferential stimulation of muscarinic receptors in the central nervous system (CNS). This combination has the potential to be a new option for treating the difficult symptoms of debilitating CNS disorders, such as schizophrenia, without subjecting patients to the problematic side effects associated with current antipsychotic standard of care therapies.

“The results of the Phase 2 trial are impressive and encouraging because they indicate that KarXT, if approved, could represent a game-changing therapeutic advance in the treatment of patients with schizophrenia,” said Jeffrey Lieberman, M.D., professor and chairman of the Department of Psychiatry, Columbia University, College of Physicians and Surgeons and a member of Karuna’s scientific advisory board. “The effectiveness of antipsychotics has been limited by the frequent and serious side effects of first- and second-generation drugs which are difficult for many patients to tolerate, are potentially harmful, and lead to high rates of discontinuation and relapse. In addition to its novel mechanism of action, KarXT could be a new therapeutic option that has the potential to offer robust efficacy devoid of weight gain, metabolic effects and extrapyramidal side effects.”

In the clinical trial, patients demonstrated a clinically meaningful and statistically significant 11.6 point mean reduction over placebo in total PANSS score, the trial’s primary efficacy endpoint. Historically, changes as small as five points have supported the approval of current antipsychotics.


LOGO

 

Overall, KarXT was well tolerated in the clinical trial, with similar discontinuation rates of patients on KarXT, 20%, and placebo, 21%. The number of discontinuations due to treatment emergent AEs were equal in the KarXT and placebo arms (N=2 in each group). The overall AE rate of patients on KarXT was 54% vs. 43% on placebo, with the most common AEs being constipation, nausea, dry mouth, dyspepsia, and vomiting. The tolerability of KarXT was also reflected in the trial’s high rate of dose escalation. In the trial, 91% of KarXT treated patients escalated to the increased dose which was similar to the escalation rate with placebo. Occurrences of somnolence, weight gain, and extrapyramidal symptoms were also similar to placebo. One serious adverse event (SAE) was experienced in the drug treatment arm, in which the patient discontinued treatment and subsequently sought hospital care for worsening psychosis, meeting the regulatory definition of an SAE.

“The schizophrenia treatment landscape has remained rather stagnant for decades with therapeutic options relying on discoveries dating back to the 1950s,” said Steve Paul, M.D., chief executive officer, president, and chairman of Karuna. “KarXT and its novel muscarinic receptor mechanism of action represent the potential to become a true advancement in how schizophrenia is treated, allowing patients relief from their debilitating psychotic symptoms without experiencing some of the very troubling side effects associated with current treatments.”

Muscarinic acetylcholine receptors emerged in the 1990s as a promising alternative target to dopamine-receptor based treatments for treating psychosis, but adverse side effects limited their development as a therapeutic option. It is believed that these side effects were the result of the stimulation of muscarinic receptors in peripheral tissues. Karuna addressed this issue by combining xanomeline, a novel muscarinic receptor agonist that preferentially stimulates M1 and M4 muscarinic receptors, with trospium, an approved muscarinic receptor antagonist that does not measurably cross the blood-brain barrier, confining its effects to peripheral tissues. The resulting therapeutic, known as KarXT, was designed to activate muscarinic receptors in the CNS while avoiding the side effects associated with activating muscarinic receptors in peripheral tissues.

“We are extremely pleased with these results, as the 11.6-point PANSS score separation from placebo far exceeded the five-point minimum improvement that has historically supported approval of current antipsychotics,” said Stephen Brannan, M.D., chief medical officer of Karuna. “With this information, and following our anticipated end-of-Phase 2 meeting with the FDA in the second quarter of 2020, we will work to initiate a Phase 3 clinical trial of KarXT in patients with schizophrenia by the end of 2020. We also plan to further analyze these results to better understand the potential of KarXT in patients with schizophrenia experiencing negative and cognitive symptoms, and to explore other CNS disorders that could benefit from this approach, such as psychosis in Alzheimer’s disease as well as the management of pain.”

About the Trial

The Phase 2, randomized, double-blind, placebo-controlled, inpatient trial enrolled 182 adult patients, age 18 to 60, who had been diagnosed with DSM-5 schizophrenia and were experiencing acute psychosis. Patients were washed-out of antipsychotic medicines and randomized 1:1 to receive either KarXT or placebo for five weeks. The primary outcome measure of the trial was the change from baseline on the total PANSS score on KarXT vs. placebo treatment at week five.

KarXT was dosed as xanomeline 50 mg/trospium 20 mg twice a day for two days and then increased to xanomeline 100 mg/trospium 20 mg starting on day three. Beginning on day eight, if KarXT was well tolerated, an option was given to escalate the dose of KarXT to xanomeline 125 mg/trospium 30 mg twice a day. If a patient escalated to the highest dose, the dose could be decreased back to xanomeline 100 mg/trospium 20 mg twice per day, based on tolerability, if needed. No dose changes were allowed during the last two weeks of the trial.


LOGO

 

About Schizophrenia

Schizophrenia is a chronic, disabling disorder typically diagnosed in late teenage years or early adulthood. Characterized by recurring episodes of psychosis requiring long-term treatment with antipsychotic drugs in most patients, it affects more than 21 million people worldwide and 2.7 million Americans (0.5% - 1.0% of U.S. population).

At least one-third of patients with schizophrenia fail to respond to current treatments, with 74% of patients discontinuing within 18 months of initiation. People with schizophrenia have a 10- to 15-year reduction in life expectancy and struggle to maintain meaningful interpersonal relationships. The World Health Organization ranks psychosis as the third-most disabling medical condition in the world.

Conference Call and Webcast Information

Karuna will hold a webcast and conference call this morning at 8:30 a.m. EST to provide results from its Phase 2 clinical trial of KarXT for the treatment of acute psychosis in patients with schizophrenia. The dial-in numbers are 1-855-548-1216 for domestic callers and 1-409-216-6318 for international callers. The conference ID number for the live call will be 9498519. A live webcast of the conference call will also be available on the investor relations page of the Karuna Therapeutics corporate website at www.karunatx.com. After the live webcast, the event will remain archived on the Karuna Therapeutics website for three months.

About Karuna

Karuna is a clinical-stage biopharmaceutical company committed to developing and delivering first-in-class therapies with the potential to transform the lives of people with CNS disorders – which remain among the most disabling and potentially fatal disorders worldwide. Galvanized by the understanding that today’s neuropsychiatric and pain management patients deserve better, Karuna’s mission is to harness the untapped potential of the brain’s complex biology in pursuit of novel therapeutic pathways that will advance the standard of care. For more information, please visit karunatx.com.

Investor Contact:

Chris Brinzey

Westwicke, an ICR Company

+1 339 970-2843

chris.brinzey@westwicke.com

Media Contact:

Jenn Gordon

GlobalHealthPR

+1 202 587-2580

jgordon@globalhealthpr.com

EX-99.2

Slide 1

Developing novel therapies to dramatically improve the lives of people with psychiatric and neurological disorders Topline Data from Phase 2 Trial of KarXT in Acute Psychosis in Patients with Schizophrenia Exhibit 99.2


Slide 2

Legal Disclaimer OVERVIEW These slides and the accompanying oral presentation contain forward-looking statements and information. You should not place undue reliance on forward-looking statements, as these statements are based upon our current expectations, forecasts, and assumptions and are subject to significant risks and uncertainties. These statements may be identified by words such as “may,” “will,” “should,” “could,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “forecast,” “continue,” or the negative of these terms or other words or terms of similar meaning. Statements, including forward-looking statements, speak only to the date they are provided (unless an earlier date is indicated), and we do not undertake any obligation to publicly update any statements, including forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, achievements or events and circumstances reflected in the forward-looking statements will occur. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.


Slide 3

IntroductionTroy Ignelzi / Chief Financial Officer Summary of Phase 2 ResultsSteve Paul, M.D. / Chairman, CEO and President Phase 2 Results AnalysisStephen Brannan, M.D. / Chief Medical Officer KarXT Development PlanAndrew Miller, Ph.D. / Founder & Chief Operating Officer Summary RemarksSteve Paul, M.D. / President & Chief Executive Officer Questions & AnswersSteve Paul, M.D. / President & Chief Executive Officer Andrew Miller, Ph.D. / Founder & Chief Operating Officer Stephen Brannan, M.D. / Chief Medical Officer Agenda Overview


Slide 4

KarXT Phase 2 Trial Results in Acute Psychosis in Patients with Schizophrenia


Slide 5

Chronic, disabling disorder typically diagnosed in late teenage years or early adulthood Characterized by recurring episodes of psychosis requiring long-term treatment with antipsychotic drugs in most patients Affects over 21 million people worldwide 2.7 million Americans (0.5% - 1.0% of U.S. population) had schizophrenia in 2017 Today’s standard of care rely on same mechanism as drugs of the 1950s (first antipsychotic drug, chlorpromazine, discovered in 1952) In many patients, approved antipsychotics offer modest efficacy and significant side effects Schizophrenia: The “cancer of psychiatry” Summary of Phase 2 Results


Slide 6

Summary of Topline Phase 2 Results Summary of Phase 2 Results KarXT is a novel mechanism of action therapeutic targeting central nervous system (CNS) indications representing large and underserved patient populations characterized by psychosis and cognitive impairment Met the primary endpoint with a statistically significant (P<0.0001) and clinically meaningful 11.6 point improvement on the PANSS total score from baseline vs. placebo. The PANSS total improvement over placebo was significant at all assessed time points. Statistically significant reduction in the secondary endpoints of PANSS-positive and PANSS-negative subscales at all assessed time points. KarXT was well tolerated: The overall discontinuation rate and the discontinuation rate due to treatment emergent adverse events on KarXT was similar to placebo 91% of patients escalated to the high dose of KarXT as part of the flexible dose design No evidence of somnolence, extrapyramidal side effects or weight gain Data supports entering Phase 3 development with a completely unique new mechanism to treat psychosis in schizophrenia


Slide 7

KarXT Phase 2 Trial Results Analysis


Slide 8

Phase 2 Trial Design Overview Same fundamental trial design and primary endpoint used in pivotal studies to support registration of other antipsychotic drugs Randomized, double-blind, placebo-controlled, five week, inpatient trial Enrolled 182 schizophrenia patients with acute psychosis (N=90 on KarXT, N=92 on Placebo) Patients were washed out of any antipsychotic drugs prior to randomization Flexible dose, two-arm trial with 1:1 randomization to KarXT or placebo with a five-week treatment period Days 1-2: 50/20 KarXT BID (50 mg xanomeline/20 mg trospium) Days 3-7: 100/20 KarXT BID Days 8-35: 100/20 KarXT BID with optional increase to 125/30 KarXT BID; titration based only on tolerability Primary endpoint of change in total PANSS from baseline vs. placebo at week 5 in the modified intent to treat population (mITT) Other endpoints: PANSS-positive and –negative subscales, CGI, PANSS Marder factor, cognitive battery, and others Phase 2 Results Analysis


Slide 9

Demographics and Baseline Characteristics Phase 2 Results Analysis   Placebo KarXT Mean age (years) 41.8 43.7 Sex, male (%) 74 81 Race (%white / %non-white) 20/80 23/77  Baseline PANSS 96.6 97.3 Baseline PANSS-positive 26.3 26.3 Baseline PANSS-negative 22.9 22.5 mITT population No significant differences between the treatment groups


Slide 10

Baseline Week 2 Week 4 Week 5 *** *** *** Clinically meaningful and statistically significant improvement in total PANSS vs placebo 11.6 point improvement at week 5 with p<0.0001 (-17.4 KarXT vs. -5.9 placebo) Statistical separation at every assessed time point Primary Endpoint: PANSS Total Score at Week 5 Phase 2 Results Analysis ***P<0.0001 mITT population


Slide 11

Clinically meaningful and statistically significant improvement in total PANSS-positive vs placebo 3.2 point improvement at week 5 with p<0.0001 (-5.6 KarXT vs. -2.4 placebo) Statistical separation at every assessed time point Secondary Endpoint: PANSS-Positive Subscore Phase 2 Results Analysis Baseline Week 2 Week 4 Week 5 *** *** *** ***P<0.0001 mITT population


Slide 12

Clinically meaningful and statistically significant improvement in PANSS-negative vs placebo 2.3 point improvement at week 5 with p<0.001 (-3.2 KarXT vs. -0.9 placebo) Statistical separation at every assessed time point Secondary Endpoint: PANSS-Negative Subscore Phase 2 Results Analysis Baseline Week 2 Week 4 Week 5 ** ** * *p<0.05 **P≤0.001 mITT population


Slide 13

KarXT was well tolerated Overall discontinuation rate on KarXT (20%) similar to placebo (21%) The number of discontinuations due to treatment emergent adverse events was equal in the KarXT and placebo arms (N=2 in each group) Dose escalation rate on KarXT was high and similar to placebo 91% of KarXT subjects escalated to 125/30 KarXT (vs. 97% on placebo); 4% percent de-escalated back to 100/20 KarXT dose (vs. 1% on placebo) Overall treatment emergent adverse event rate on KarXT was 54% vs. 43% on placebo Most common adverse events were constipation, nausea, dry mouth, dyspepsia, and vomiting, which were all mild or moderate in severity and did not lead to discontinuations Somnolence, weight gain, and extrapyramidal symptoms/akathisia similar to placebo No syncope, no mean change in BP, 5.5 bpm peak mean placebo adjusted resting HR increase with downward trend after week 2, and one discontinuation due to elevated GGT One serious adverse event on KarXT: patient discontinued treatment and subsequently sought hospital care for worsening psychosis, meeting the regulatory definition of an SAE. All other TEAEs were mild or moderate Summary of Safety and Tolerability Phase 2 Results Analysis data from safety population


Slide 14

KarXT Development Plan


Slide 15

Achieved the initial goals of KarXT development: Improve tolerability of xanomeline Maintain and confirm previous therapeutic benefits of xanomeline Three double-blind, placebo-controlled studies supporting therapeutic benefit of xanomeline/KarXT KarXT Phase 2 study in patients with schizophrenia Small Phase 2 study in patients with schizophrenia with xanomeline-alone Phase 2 study in patients with Alzheimer’s disease with xanomeline-alone Large existing safety database with xanomeline and KarXT: >1000 patients enrolled in studies with KarXT or xanomeline 68 Alzheimer’s disease patients treated with xanomeline for at least one year Robust data including 3 efficacy studies and long-term safety going into Phase 3 Multiple efficacy and safety studies support Phase 3 Development of KarXT KarXT Development Plan


Slide 16

Complete final analysis of all data and endpoints to further inform path forward Plan an end of Phase 2 meeting with FDA to discuss data and development path including Phase 3 trial design Meeting anticipated in Q2 2020 Pending FDA meeting, we anticipate advancing to Phase 3 using a similar trial design as our Phase 2 trial with trial initiation anticipated by the end of 2020 Topline Phase 1b data in pain expected in mid 2020 Topline Phase 1b data in healthy elderly volunteers expected in 2H 2020 KarXT Development Moving Forward KarXT Development Plan


Slide 17

Karuna’s portfolio of muscarinic receptor-targeted programs THE KarXT Development Plan Indication Discovery/ Preclinical Phase 1 Phase 2 Phase 3 Upcoming Milestone Schizophrenia Psychosis Schizophrenia Cognitive Symptoms Schizophrenia Negative Symptoms Alzheimer’s Disease Psychosis Pain Muscarinic Targeted Drug Candidate KarXT Other End Phase 2 Meeting Q2 2020 Phase 1b initiation 1H 2020 Phase 1b initiation 1H 2020 Phase 1b topline data 2H 2020 Phase 1b topline data Mid 2020 IND-enabling studies 2020


Slide 18

Summary Comments


Slide 19

Developing novel therapies to dramatically improve the lives of people with psychiatric and neurological disorders