Karuna Therapeutics Stock

Karuna Therapeutics, Inc. operates as a clinical-stage biopharmaceutical company. The company is driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions. The company’s pipeline is primarily built on the broad therapeutic potential of its proprietary lead product candidate, KarXT (xanomeline-trospium), an oral modulator of muscarinic receptors that are located both in the central nervous system, or CNS, and various peripheral tissues. KarXT combines xanomeline, a novel muscarinic agonist, with trospium, an approved muscarinic antagonist, to preferentially stimulate muscarinic receptors in the CNS. The company is initially developing KarXT for the treatment of acute psychosis in adults with schizophrenia, as well as for the treatment of psychosis in Alzheimer's disease, or AD.

Schizophrenia is a chronic disabling disorder that is characterized by recurring episodes of psychosis requiring long-term treatment with antipsychotic drugs in most patients. Psychotic symptoms, also known as positive symptoms, include hallucinations and delusions. As a result of the disease, patients with schizophrenia also experience negative symptoms, such as apathy, reduced social drive, loss of motivation and lack of social interest, as well as cognitive impairment. It is estimated that more than 24 million people are living with schizophrenia worldwide, with approximately 2.8 million in the United States.

The company is initially developing KarXT for the treatment of acute psychosis in adults with schizophrenia, as well as for the treatment of psychosis in AD. KarXT combines xanomeline, a muscarinic receptor agonist that preferentially stimulates M1 and M4 muscarinic receptors, and trospium, an approved muscarinic receptor antagonist that does not measurably cross the blood-brain barrier, confining its effects to peripheral tissues. M1 and M4 muscarinic receptors are the receptor subtypes believed to mediate the antipsychotic and procognitive effects of xanomeline and other muscarinic agonists. Results from preclinical studies and clinical trials conducted by third parties support the hypothesis that xanomeline can reduce psychosis and improve cognition. To its knowledge, xanomeline is the only muscarinic orthosteric agonist that has demonstrated therapeutic benefit in clinical trials in both schizophrenia and AD. Like all muscarinic orthosteric agonists studied to date, however, xanomeline’s tolerability has been limited by side effects arising from muscarinic receptor stimulation in peripheral tissues, leading to nausea, vomiting, diarrhea and increased salivation and sweating, collectively referred to as cholinergic adverse events. Trospium is a muscarinic receptor antagonist approved in the United States and Europe for the treatment of overactive bladder that inhibits all five muscarinic receptor subtypes in peripheral tissues. The combination of xanomeline and trospium in KarXT has the potential to preferentially stimulate M1 and M4 muscarinic receptors in the brain without stimulating muscarinic receptors in peripheral tissues, enabling KarXT to achieve meaningful therapeutic benefit in patients with psychotic and cognitive disorders.

In September 2023, the company submitted its New Drug Application, or NDA, for KarXT for the treatment of schizophrenia in adults to the FDA. In November 2023, the company received an acceptance of its NDA by the FDA with a Prescription Drug User Fee Act, or PDUFA, action date of September 26, 2024. If approved, the company is targeting a potential commercial launch of KarXT for the treatment of schizophrenia in the second half of 2024.

Development Programs

The EMERGENT program is the company’s clinical program evaluating KarXT for the treatment of schizophrenia as a monotherapy and includes its completed positive Phase 2 EMERGENT-1 and Phase 3 EMERGENT-2 and EMERGENT-3 trials evaluating the efficacy and safety of KarXT compared to placebo, as well as two Phase 3 trials, EMERGENT-4 and EMERGENT-5, evaluating the long-term safety of KarXT. Topline data from the EMERGENT-4 and EMERGENT-5 trials is anticipated in the second half of 2024.

In November 2023, the company announced positive topline results from its Phase 1b ambulatory blood pressure monitoring trial of KarXT in patients with schizophrenia. Results demonstrate KarXT was not associated with clinically meaningful increases in blood pressure in adults with schizophrenia. KarXT demonstrated a mean change from baseline to week 8 in 24-hour ambulatory systolic blood pressure of -0.59 mmHg, the primary endpoint in the trial, and was generally well tolerated, with a side effect profile consistent with prior trials in the EMERGENT program evaluating KarXT in schizophrenia.

The company plans to utilize the data from the EMERGENT and ARISE clinical programs to help inform future potential development plans for KarXT in negative and cognitive symptoms of schizophrenia, for which there are currently no approved treatments.

The company is also developing KarXT as a potential treatment for psychosis related to AD. The ADEPT program, which is the clinical program evaluating KarXT as a potential treatment for psychosis related to AD, consists of three Phase 3 trials: ADEPT-1, ADEPT-2 and ADEPT-3. The Phase 3 ADEPT-1 trial is evaluating the efficacy and safety of KarXT compared to placebo in adults with moderate to severe psychosis related to AD. Enrollment for this trial began in the third quarter of 2022 and topline data is anticipated in 2026. This trial consists of a 12-week, single-blind treatment period, followed by a 26-week, double-blind, randomized withdrawal period in which subjects who meet the response criteria will be randomized to receive KarXT or placebo. The single-blind treatment period is designed to enroll approximately 380 adults with AD between 55 and 90 years old, with moderate to severe hallucinations or delusions, who are living at home or at an assisted living facility. The company’s Phase 3 ADEPT-2 trial is a 14-week, flexible-dose, double-blind, placebo-controlled trial evaluating the efficacy and safety of KarXT versus placebo in up to 400 patients. This trial initiated in the third quarter of 2023 and topline data is anticipated in 2026. The company’s Phase 3 ADEPT-3 trial is an open-label extension trial of ADEPT-1 and ADEPT-2 evaluating the long-term safety of KarXT in adults with psychosis related to AD. Enrollment for this trial commenced in the third quarter of 2023.

In January 2023, the company entered into an exclusive global license agreement for Goldfinch Bio, Inc.'s, or Goldfinch Bio's, investigational transient receptor potential canonical 4 and 5 (TRPC4/5) channel candidates, including the lead clinical-stage TRPC4/5 candidate, KAR-2618. KAR-2618 has been dosed in over 100 humans across Goldfinch Bio’s clinical trials. The company intends to evaluate KAR-2618 for the treatment of major depressive disorder, and plan to initiate a Phase 1b clinical trial in 2024.

Pipeline

The company is advancing a pipeline of therapeutic programs with KarXT to address psychiatric conditions, such as schizophrenia and psychosis related to AD. The company is leveraging its expertise and experience to explore the development of KarXT for additional CNS disorders, as well as advance its other muscarinic-targeted drug candidates and a target-agnostic drug discovery program through its collaboration with PsychoGenics, Inc.

KarXT Programs

The company specifically designed KarXT, a proprietary combination of xanomeline and trospium, to unlock the therapeutic potential of xanomeline by overcoming its limiting side effects resulting from the stimulation of muscarinic receptors in peripheral tissues. The company initially selected xanomeline based on the results of the two third-party, randomized, double-blind, placebo-controlled clinical trials, as well as the results of a wide variety of preclinical studies conducted by third parties, which supported the further development of xanomeline, in the form of KarXT, as an antipsychotic and procognitive therapeutic agent. The company’s Phase 1, Phase 2 and Phase 3 clinical trial data suggests that each of xanomeline and trospium do not affect the other’s pharmacokinetics or systemic exposure.

The company obtained an exclusive license to xanomeline from Eli Lilly along with a large database of preclinical and clinical data generated by Eli Lilly supporting xanomeline’s development.

Proof of Concept of KarXT

Phase 1 Clinical Trials

The company observed KarXT’s ability to ameliorate the side effects of xanomeline in its randomized, double-blind, placebo-controlled, Phase 1 clinical trial in 70 healthy volunteers conducted under its investigational NDA. In this trial, the company compared the tolerability profile and pharmacokinetics of xanomeline administered with placebo against KarXT co-administered as xanomeline in combination with trospium. The company selected the 225-mg (75 mg TID) dose for evaluation in its trial due to the results of this dose in Eli Lilly’s schizophrenia and AD trials of xanomeline.

Phase 1 Multiple Ascending Dose Clinical Trial

The company has also completed a randomized, double-blind, placebo-controlled multiple ascending dose Phase 1 clinical trial of KarXT. This trial evaluated BID dosing of the company’s proprietary KarXT co-formulation containing fixed ratios of xanomeline and trospium, rather than the TID dosing previously used with xanomeline. The company designed its Phase 1 clinical trial based on the improved tolerability of KarXT over xanomeline plus placebo observed in its prior Phase 1 clinical trial and the dose-dependent clinical activity observed in the Eli Lilly AD trial of xanomeline. In particular, Eli Lilly observed that the antipsychotic effect of xanomeline improved when the dose was increased from 25 mg to 50 mg to 75 mg, all administered TID, suggesting that the dose response may extend beyond 75 mg TID and that doses of xanomeline higher than 75 mg TID may lead to additional therapeutic benefit.

In this Phase 1 clinical trial, the company observed that KarXT doses containing either 100 mg or 125 mg of xanomeline administered BID were well-tolerated when paired with trospium. Importantly, the 100 mg BID dose level administered in the company’s co-formulation provided blood exposures equal to or greater than those observed by the company and Eli Lilly with 75 mg TID xanomeline, which was observed to have beneficial effects on psychosis and cognition in both schizophrenia and AD. Based on the results of this trial, the company identified 100/20 mg and 125/30 mg BID as the doses and ratios of xanomeline to trospium to evaluate in its Phase 2 clinical trial of KarXT for acute psychosis in patients with schizophrenia.

The company submitted an Investigational New Drug, or IND, application to the FDA for KarXT for the treatment of schizophrenia which went into effect in August 2016.

Completed EMERGENT-1 Phase 2 Clinical Trial for the Treatment of Acute Psychosis in Adults with Schizophrenia

In September 2018, the company initiated EMERGENT-1, a multi-site, double-blind, placebo-controlled, five-week, inpatient Phase 2 clinical trial of KarXT in adults with schizophrenia with acute psychosis. The company enrolled 182 patients in this trial and patients were randomized 1:1 to receive either KarXT or placebo. Patients were washed out of any existing antipsychotic medications before entering the five-week active treatment or placebo phase. The company’s trial had the same fundamental design and primary endpoint as the previous xanomeline trial in psychosis in schizophrenia, which is also the design that has been used in pivotal trials for several approved antipsychotic medicines. Additional endpoints of the company’s trial included changes in PANSS negative Marder Factor subscale, a cognitive battery and the clinical global impression (CGI-S).

In November 2019, the company announced topline results from its EMERGENT-1 trial, in which KarXT met the trial’s primary endpoint with a statistically significant (p<0.0001) and clinically meaningful 11.6 point mean reduction in PANSS total score over placebo (-17.4 KarXT vs. -5.9 placebo) at week 5 (Cohen’s d effect size of 0.75). The company also observed a statistically significant 3.2 point mean reduction from baseline in the PANSS-positive subscale (-5.6 KarXT v. -2.4 placebo) and a statistically significant 2.3 point mean reduction from baseline in the PANSS-negative subscale (-3.2 KarXT v. -0.9 placebo) at week five (p<0.0001 and p<0.001, respectively). The PANSS total score, PANSS-positive subscale, and the PANSS-negative subscale had statistically significant separation at every assessment throughout the trial.

The company also analyzed additional pre-specified secondary endpoints, including PANSS negative Marder factor subscale, CGI-S frequency counts and percentage of CGI-S responders, defined as a CGI-S rating of either 1 or 2 at week five. The company observed a statistically significant 2.5 point mean reduction from baseline in the PANSS negative Marder factor subscale (-3.9 KarXT v. -1.3 placebo) at week five (p<0.001). The PANSS negative Marder factor subscale had statistically significant separation at every assessment point through the trial. The company also observed statistically significant different CGI-S frequency counts for KarXT compared to placebo at week five (p<0.001). A 4:1 ratio of CGI-S responders (5.6% KarXT v. 1.4% placebo) was also observed, however this result was not statistically significant (p=0.151). KarXT was observed to be well tolerated in the Phase 2 EMERGENT-1 trial.

Completed Phase 3 EMERGENT-2 Clinical Trial for the Treatment of Acute Psychosis in Adults with Schizophrenia

In 2020, the company initiated EMERGENT-2, a multi-site, double-blind, five-week, inpatient Phase 3 clinical trial evaluating the efficacy, safety and tolerability of KarXT compared to placebo for the treatment of acute psychosis in adults with schizophrenia. In August 2022, the company announced positive topline results from EMERGENT-2 trial, in which KarXT met the primary endpoint, demonstrating a statistically significant and clinically meaningful 9.6-point reduction in PANSS total score compared to placebo (-21.2 KarXT vs. -11.6 placebo, p<0.0001) at Week 5 (Cohen’s d effect size of 0.61).

Completed Phase 3 EMERGENT-3 Clinical Trial for the Treatment of Acute Psychosis in Adults with Schizophrenia

In 2020, the company initiated EMERGENT-3, a multi-site, double-blind, five-week, inpatient Phase 3 clinical trial evaluating the efficacy, safety and tolerability of KarXT compared to placebo for the treatment of acute psychosis in adults with schizophrenia. The company enrolled 252 patients in this trial and patients were randomized 1:1 to receive either KarXT or placebo.

In March 2023, the company announced positive topline results from its Phase 3 EMERGENT-3 trial evaluating the efficacy, safety and tolerability of KarXT compared to placebo for the treatment of acute psychosis in adults with schizophrenia. KarXT met the primary endpoint, demonstrating a statistically significant and clinically meaningful 8.4-point reduction in 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).

Additional EMERGENT Clinical Trials and NDA Status

In addition to its completed Phase 2 EMERGENT-1 and Phase 3 EMERGENT-2 and EMERGENT-3 trials, the company’s EMERGENT program that is evaluating KarXT for the treatment of schizophrenia as a monotherapy includes the following Phase 3 trials:

EMERGENT-4: A 52-week outpatient, open-label extension trial evaluating the long-term safety and tolerability of KarXT in adults with schizophrenia who completed EMERGENT-2 or EMERGENT-3. Enrollment for this trial completed in the fourth quarter of 2022 and topline data is expected in the second half of 2024.

EMERGENT-5: A 52-week outpatient, open-label trial conducted in the United States and Puerto Rico evaluating the long-term safety and tolerability of KarXT in adults with schizophrenia who were not enrolled in EMERGENT-2 or EMERGENT-3. Enrollment for this trial completed in the second quarter of 2023 and topline data is expected in the second half of 2024.

In September 2023, the company submitted its NDA for KarXT for the treatment of schizophrenia in adults to the FDA. In November 2023, the company received an acceptance of its NDA by the FDA with a PDUFA action date of September 26, 2024. If approved, the company is targeting a potential commercial launch of KarXT for the treatment of schizophrenia in the second half of 2024.

Completed Ambulatory Blood Pressure Monitoring Study

In 2023, the company announced positive topline results from its Phase 1b ambulatory blood pressure monitoring trial of KarXT in patients with schizophrenia. The ambulatory blood pressure monitoring trial was designed in line with FDA guidance (Assessment of Pressor Effects of Drugs, Guidance for Industry, February 2022) to provide an accurate assessment of the potential pressor effects of KarXT over a 24-hour period using ambulatory monitoring at baseline and at week 8 in adults with schizophrenia.

Ongoing ARISE Program for KarXT as Adjunctive Therapy in Adults with Schizophrenia

In 2021, the company initiated its Phase 3 ARISE trial to evaluate the safety and efficacy of KarXT compared to placebo as an adjunctive treatment in adults with schizophrenia who have an inadequate response to their current antipsychotic therapy. The company anticipates topline data from the ARISE trial in 2025.

Development Plans for KarXT for the Negative and Cognitive Symptoms of Schizophrenia

The company is collecting data on the potential benefit of KarXT on negative and cognitive symptoms of schizophrenia as part of the ongoing EMERGENT and ARISE programs, which will help inform future potential development plans specifically directed towards the negative and cognitive symptoms of schizophrenia, for which there are no approved treatments.

In 2020, the company presented the results of an exploratory endpoint analysis evaluating the impact of KarXT on cognition in the Phase 2 EMERGENT-1 trial at the European College of Neuropsychopharmacology Annual Meeting. The analysis demonstrated trends towards improvements in cognition for patients receiving KarXT relative to placebo, with larger benefits seen in patients with greater cognitive impairment at baseline.

In 2023, the company presented the results of an exploratory endpoint analysis evaluating the impact of KarXT on cognition in the Phase 3 EMERGENT-2 and EMERGENT-3 trials at the American Society of Clinical Psychopharmacology. In a pooled analysis of both studies, patients with cognitive impairment of greater than one standard deviation below normative standards at baseline, KarXT showed a statistically significant (p<0.01) improvement in cognition from baseline with an effect size of 0.52.

Completed Phase 1b Healthy Elderly Volunteer Clinical Trial

Based on Eli Lilly’s Phase 2 clinical trial of xanomeline in patients with AD, and the improved tolerability profile of KarXT as compared to xanomeline, in 2019, the company initiated a Phase 1b dose-ranging clinical trial to assess the safety and tolerability of KarXT in healthy elderly volunteers. The company utilized a flexible dosing protocol titrated over approximately two to three weeks in order to select the doses and titration protocol for future trials of KarXT in elderly patients with psychosis related to AD.

Ongoing ADEPT program for the Treatment of Psychosis Related to Alzheimer’s Disease

The ADEPT program, which is the clinical program evaluating KarXT as a potential treatment for psychosis related to AD, consists of the following ongoing Phase 3 trials:

ADEPT-1: A trial evaluating the efficacy and safety of KarXT compared to placebo in up to 400 adults with moderate to severe psychosis related to AD. This trial consists of a 12-week, single-blind treatment period, followed by a 26-week, double-blind, randomized withdrawal period in which subjects who meet the response criteria will be randomized to receive KarXT or placebo. The single-blind treatment period is designed to enroll approximately 380 adults with AD between 55 and 90 years old, with moderate to severe psychosis associated with AD as measured by the Neuropsychiatric Inventory-Clinical (NPI-C): Hallucinations and Delusions (H+D) score. This trial is being conducted in the United States and Europe. Enrollment for this trial began in the third quarter of 2022 and topline data is anticipated in 2026.

ADEPT-2: A 14-week, flexible-dose, double-blind, placebo-controlled trial evaluating the efficacy and safety of KarXT versus placebo designed to enroll up to 400 adults with AD, between 55 and 90 years old, with moderate to severe psychosis associated with AD as measured by the Neuropsychiatric Inventory-Clinical (NPI-C): Hallucinations and Delusions (H+D) score. This trial is being conducted in the United States, Europe and other territories, including in China with its partner Zai Lab. This trial initiated in the third quarter of 2023 and topline data is anticipated in 2026.

ADEPT-3: A 52-week open-label extension trial evaluating the long-term safety and tolerability of KarXT in adults with psychosis related to AD who completed ADEPT-1 or ADEPT-2. Enrollment for this trial began in the third quarter of 2023.

Planned Additional Formulations of KarXT

The company’s ongoing research efforts include the development of advanced oral and long-acting injectable formulations. In the fourth quarter of 2023, it completed a Phase 1 MAD study of an advanced oral formulation of KarXT and plans to initiate a Phase 1 study of an advanced oral formulation of KarXT in healthy elderly volunteers in the second half of 2024. The company continues to evaluate the optimal xanomeline to trospium dose ratios, as well as dosing regimens, for advanced oral formulations.

Other Research and Development Programs

In January 2023, the company entered into an exclusive global license agreement for Goldfinch Bio, Inc.'s, or Goldfinch Bio's, investigational transient receptor potential canonical 4 and 5 (TRPC4/5) channel candidates, including the lead clinical-stage TRPC4/5 candidate, KAR-2618, after confirming select properties of KAR-2618 under a material transfer agreement. KAR-2618 has been dosed in over 100 humans across Goldfinch Bio’s clinical trials. The company intends to evaluate KAR-2618 for the treatment of major depressive disorder, and plans to initiate a Phase 1b clinical trial in 2024.

The company also continues to build its early stage pipeline. The company has a novel series of compounds focused on muscarinic receptor targets. In particular, the company has synthesized lead compounds for further development as potential therapeutic agents in several CNS disorders, including schizophrenia and psychosis in AD.

In February 2020, the company announced a drug discovery partnership with Charles River Laboratories to accommodate continued growth in its muscarinic receptor drug discovery efforts. The company continues to evaluate other opportunities focused on muscarinic and non-muscarinic targets for CNS disorders.

Manufacturing and Supply

The company uses CMOs who act in accordance with the FDA’s good laboratory practices, or GLP, and current good manufacturing practices, or cGMP, for the manufacture of drug substance and product. The company contracts with Neuland Laboratories Limited and Esteve Quimica, S.A., for the manufacture of xanomeline and source trospium from Procos, S.p.A. and Midas Pharmaceuticals, Inc. The company’s drug product is manufactured by Catalent Pharma Solutions, LLC.

Intellectual Property

Product Candidates

KarXT

The company exclusively licenses KarXT from PureTech Health LLC, or PureTech Health, a patent family that, as of February 15, 2024, comprises two issued U.S. patents with claims directed to an oral medicament comprising certain doses of xanomeline and/or the salt thereof and certain doses of trospium chloride, three issued U.S. patents with claims directed to methods for treating CNS disorders using an oral medicament comprising certain doses of xanomeline and/or salts thereof and certain doses of trospium chloride, issued patents in Canada, Europe, Japan and Hong Kong, and a total of five patent applications pending, one in each of the U.S., Europe and Hong Kong, and two in Japan. The patents and the pending patent applications, if issued, are expected to expire in 2030 without taking into account any possible Patent Term Extension, or PTE, or any possible patent term adjustments.

The company also owns five issued U.S. patents, issued patents in Australia, Brazil, Canada, Israel, India, Japan, Korea, Mexico, and New Zealand; allowed patent applications in Japan, the Philippines, and South Africa; one pending U.S. patent application; and a total of 21 pending patent applications in Australia, Canada, Chile, China, Costa Rica, the Eurasian Patent Office, Egypt, Europe, Hong Kong, Indonesia, Israel, Japan, the Philippines, Saudi Arabia, Singapore, Thailand, Ukraine, and Vietnam with claims directed towards the KarXT drug product, including claims to an oral pharmaceutical composition comprising a plurality of xanomeline beads having a core comprising xanomeline or a salt thereof, and a plurality of trospium beads having a core comprising a salt of trospium, and related methods of treatment using the KarXT drug product. The patents and the pending patent applications, if issued, are expected to expire in 2039 without taking into account any possible PTE or any possible patent term adjustments.

The company also owns one pending U.S. non-provisional patent application and a total of five pending patent applications, one in each of Canada, China, Europe, Japan, and Hong Kong, with claims directed to the use of KarXT for treating schizophrenia or a disease related to schizophrenia in a patient in need thereof. The patent applications, if issued, are expected to expire in 2040 without taking into account any possible PTE or any possible patent term adjustments.

The company also owns ten pending applications, one in each of the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, Japan, and Taiwan, with claims directed towards treating a disorder ameliorated by activating muscarinic receptors in an elderly patient in need thereof using xanomeline and/or a salt thereof and a salt of trospium. The pending patent applications, if issued, are expected to expire in 2042 without taking into account any possible PTE or any possible patent term adjustments.

The company also owns one pending U.S. patent application, one European application, and one Hong Kong application with claims directed towards treating CNS disorders with xanomeline and/or a salt thereof and an antipsychotic. The pending patent applications, if issued, are expected to expire in 2042 without taking into account any possible PTE or any possible patent term adjustments.

The company also owns one pending PCT application with claims directed towards treating CNS disorders with xanomeline and/or a salt thereof and a second therapeutic agent. The pending patent applications, if issued, are expected to expire in 2043 without taking into account any possible PTE or any possible patent term adjustments.

The company also owns one issued U.S. patent, one pending U.S. patent application, one pending U.S. provisional application, and a total of six pending applications in Australia, Canada, China, Europe, Japan, and New Zealand with claims directed to compounds targeting muscarinic receptors and methods of treatment using such compounds. The pending patent applications, if issued, are expected to expire in 2040 without taking into account any possible PTE or any possible patent term adjustments. The company’s U.S. and foreign patent applications also disclose combinations of muscarinic activators to treat CNS disorders.

KAR-2618

With respect to KAR-2618, the company exclusively licenses from GFB (ABC), LLC, or GFB, assignee of the assignment estate of Goldfinch Bio, six patent families that are collectively directed to the compound KAR-2618, along with formulations, biomarker technology, combination therapy, and methods of use. The company’s first exclusively licensed patent family from GFB is directed to a genus of TRPC4/5 compounds and methods of use and, as of February 15, 2024, contains one pending U.S. patent application along with patent applications pending in Europe, Hong Kong, Australia, and Canada. Any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2038, without taking into account any patent term adjustment, PTE, or supplementary protection certificate, or SPC.

The company’s second exclusively licensed patent family from GFB describes KAR-2618 and methods of use and, as of February 15, 2024, contains nine issued patents, including two in the United States, one pending U.S. patent application, allowed applications in Europe and Taiwan, and patent applications pending in Japan, Australia, Canada, China, and over 20 additional foreign countries. These U.S. patents, and any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2039, without taking into account any patent term adjustment, PTE, or SPC.

The company’s third patent family exclusively licensed from GFB is directed to polymorphic forms of KAR-2618 and methods of use and, as of February 15, 2024, contains one pending U.S. patent application and patent applications pending in Europe, Japan, Australia, Canada, China, and two additional foreign countries. Any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2040, without taking into account any patent term adjustment, PTE, or SPC.

The company’s fourth patent family exclusively licensed from GFB is directed to formulations containing KAR-2618 and methods of use thereof and, as of February 15, 2024, contains one pending U.S. patent application and patent applications pending in Europe, Japan, Australia, Canada, China, and over five additional foreign countries. Any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2040, without taking into account any patent term adjustment, PTE, or SPC.

The company’s fifth patent family exclusively licensed from GFB is directed to combination therapy using KAR-2618 and, as of February 15, 2024, contains one pending U.S. patent application and patent applications pending in Europe, Japan, Australia, Canada, China, and over five additional foreign countries. Any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2040, without taking into account any patent term adjustment, PTE, or SPC.

The company also exclusively licensed from GFB a patent family directed to biomarker technology and certain methods of use, which, as of February 15, 2024, contains one pending U.S. patent application and patent applications pending in Europe, Japan, Australia, Canada, and over 15 additional foreign countries. Any U.S. or foreign patents that issue based on the pending patent applications, if granted and if all appropriate maintenance fees are paid, are expected to expire in year 2040, without taking into account any patent term adjustment, PTE, or SPC.

License Agreements

License Agreement with Eli Lilly and Company

In 2012, the company entered into an exclusive license agreement, or the Lilly License Agreement, with Eli Lilly and Company (Eli Lilly), pursuant to which Eli Lilly assigned to it all of its rights to certain patents (now expired), regulatory documentation, data records and materials related to xanomeline. The company are also entitled to sublicense or otherwise transfer the rights granted in connection with the Lilly License Agreement. Under the Lilly License Agreement, the company is obligated to use commercially reasonable efforts to develop, manufacture, commercialize and seek and maintain regulatory approval for xanomeline, in any formulation, for use in humans.

Patent License Agreement with PureTech Health LLC

In 2011, the company entered into an exclusive license agreement, or the PureTech License Agreement, with PureTech Health, pursuant to which PureTech Health granted it an exclusive license to patent rights relating to combinations of a muscarinic activator with a muscarinic inhibitor for the treatment of CNS disorders.

License Agreement with Zai Lab

In 2021, the company entered into a License Agreement, or the Zai License Agreement, with Zai Lab (Shanghai) Co., Ltd, or Zai, pursuant to which it granted to Zai the right to exclusively develop, manufacture and commercialize KarXT in mainland China, Hong Kong, Macau, and Taiwan, referred to as the Licensed Territory.

License Agreement with GFB

In January 2023, the company entered into an exclusive license agreement, or the GFB License Agreement, with GFB, assignee of the assignment estate of Goldfinch Bio, pursuant to which GFB granted it the exclusive right and license to develop, manufacture, and commercialize GFB’s TRPC4/5 candidates, or the GFB Compounds, including the lead clinical-stage candidate known as KAR-2618 (formerly GFB-887).

History

The company was founded in 2009. It was incorporated under the laws of the state of Delaware in 2009. The company was formerly known as Karuna Pharmaceuticals, Inc. and changed its name to Karuna Therapeutics, Inc. in 2019.