PharmaShots Interview: Zai Lab’s Jonathan Wang Shares Insights on KarXT (xanomeline-trospium) for the Treatment of Schizophrenia And Psychosis

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PharmaShots Interview: Zai Lab’s Jonathan Wang Shares Insights on KarXT (xanomeline-trospium) for the Treatment of Schizophrenia And Psychosis

In an interview with PharmaShots, Jonathan Wang, Executive Vice President and Head of Business Development at Zai Lab shares his views on the license agreement with Karuna Therapeutics for KarXT (xanomeline-trospium) to treat schizophrenia and psychosis


  • The companies collaborate to develop, manufacture & commercialize KarXT in Greater China including mainland China, Hong Kong, Macau & Taiwan
  • Zai Lab gets exclusive rights to develop & commercialize KarXT in Greater China & will be responsible to fund all development, regulatory & commercialization activities in Greater China
  • In the P-II (EMERGENT-1) trial, KarXT showed improvements in 1EPs of PANSS total score & 1EPs includes PANSS-positive & negative subscore @5wk., was well-tolerated for schizophrenia & AD. The therapy is being studied in the P-III (ARISE) trial of KarXT for schizophrenia & is expected to initiate the P-III program for psychosis in mid-2022, based on P-Ib trial results

Tuba: Can we discuss the deal details between Zai Labs and Karuna Therapeutics (such as upfront, milestones and royalties, geographical coverage?

Jonathan Wang: Zai Lab’s collaboration with Karuna Therapeutics represents a significant milestone in our commitment to bring transformative medicines like KarXT to patients in China and around the world. As part of this collaboration, Zai Lab and Karuna Therapeutics will be developing, manufacturing, and commercializing KarXT in the Greater China area including mainland China, Hong Kong, Macau, and Taiwan. We are proud to be working with Karuna Therapeutics to not only expand the global footprint of KarXT, but to also address an unmet need for meaningful therapies in psychiatric and neurological diseases.

Under the terms of the agreement, Karuna will receive a $35 million upfront payment, with the potential to receive up to $80 million milestone payment for development, regulatory milestones and up to $72 million in potential sales milestones.


Tuba: Let’s discuss KarXT. Its MoA, RoA, formulations, modality among other details?

Jonathan Wang: KarXT is currently being evaluated in late-stage clinical trials for the treatment of schizophrenia and psychosis in Alzheimer’s disease. As an oral, investigational M1/M4-preferring muscarinic agonist, KarXT stimulates receptors in the central nervous system (CNS), implicated in various psychiatric conditions. KarXT was designed to unlock the therapeutic potential of xanomeline, a muscarinic acetylcholine receptor agonist, which has previously demonstrated significant benefits in Phase 2 studies in reducing symptoms of psychosis in schizophrenia and Alzheimer’s disease.


Tuba: Can we talk about the global epidemiology of schizophrenia, Alzheimer’s, and other neurological indications that were assessed?

Jonathan Wang: Schizophrenia is a chronic and severe neurological brain disorder. Schizophrenia is a very common mental disorder which affects approximately 24 million people worldwide including 8 million people in Greater China. Significant proportion of these patients are inadequately treated due to tolerability and efficacy outcomes from the current standard of care.  There are about 44 million people worldwide that live with Alzheimer’s disease, yet only 1 in 4 receive a diagnosis. There is a significant unmet need to provide new treatment options that offer meaningful results for the millions of patients living with these hard-to-treat neurological diseases.


Tuba: Can we talk about the trial designs of the trials in which KarXT is being studied?

Jonathan Wang: Zai Lab is excited to be working with Karuna to bring KarXT to Greater China. Currently, KarXT is being evaluated in the EMERGENT clinical program for the treatment of schizophrenia. The EMERGENT program is comprised of the previously completed Phase 2 EMERGENT-1 trial and four ongoing Phase 3 trials, with data from EMERGENT-2 and EMERGENT-3, the two Phase 3 acute efficacy and safety trials, expected later this year.

We are evaluating other indications for KarXT as an adjunctive treatment for schizophrenia in adults with inadequate response to other medication. Additionally, Karuna also plans to initiate a Phase 3 program evaluating KarXT for the treatment of dementia related psychosis later this year following encouraging results from the completed Phase 1b trial.


Tuba: Can you tell us more about BLU-945 & BLU-701 such as MoA, RoA, formulations, modality among other details?

Jonathan Wang: In 2021, Zai Lab and Blueprint Medicines Corporation announced an exclusive collaboration to develop and commercialize two investigational therapies for the treatment of epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer (NCSLC). With this partnership, Zai Lab and Blueprint Medicines will be accelerating the global development of these next-generation EFGR inhibitors to bring clinical trials of both BLU-945 and BLU-701 to Greater China, including mainland China, Hong Kong, Macau, and Taiwan.

BLU-945 and BLU-701 are designed to address challenges with resistance to current EGFR targeted therapies and have the potential to be used either as a monotherapy or in combination, together or with other agents, to overcome or prevent on-target resistance across multiple lines of treatment. In addition, this collaboration enables opportunities to combine BLU-945 or BLU-701 with other Zai Lab lung cancer drug candidates to address off-target resistance mutations. Both Blu-945 and Blu701 are selective, potent EGFR tyrosine kinase inhibitors with activity against EGFR-activating mutations combined with the C797S resistance mutation.


Tuba: Please shed some light on the epidemiology of NSCLC (broader & EGFR-driven) in China and present treatment options (SoC, other approved therapies & pipeline products)

Jonathan Wang: Every year, there are more than 800,000 newly diagnosed lung cancer patients and approximately 85% of those cases are NSCLC. EGFR mutation rates is also much higher than the rest of the world at ~40-50% of NSCLC. As the leading cause of cancer death in China, there is an opportunity to bring innovative patient care to this significant patient population. While targeted medicines have made improvements in the treatment of EGFR-driven NSCLC, there is currently no approved standard of care to address on-target resistance to early-generation EGFR therapies.


Tuba: What about Zai Lab’s approach to partnerships positions Zai Lab as a trusted partner of choice for other companies?

Jonathan Wang: Zai Lab is a fully-integrated, patient-focused global biopharmaceutical company with a long-standing track record of execution that has established the company as a leading strategic partner for global clinical development. Inspired by the opportunity to address an underserved patient population in China and around the world, Zai Lab leverages an open innovation model. With tenured leadership with unique global expertise at the helm, we have in-house end-to-end clinical development capabilities to advance innovative product candidates with our partners and also for our own internal pipeline assets, creating a sustainable product pipeline. Through strategic partnerships with leading global biopharmaceutical companies, Zai Lab aims to deliver transformative medicines to patients in China and around the world to impact human health globally.


Tuba: What are you most excited about regarding Zai Lab’s 2022 outlook?

Jonathan Wang: Today we have a strong position in the world’s two largest pharmaceutical markets, China and the United States. We have a derisked, late-stage pipeline with 28 potential first-in-class or best-in-class assets and 11 internally developed compounds. Last year, we added 8 new partners to our efforts, including Karuna and Blueprint. We’re building toward our goal of becoming a global pharmaceutical company, and we’re redefining the standards of what that means across all aspects of our business.

When our CEO and Chair, Samantha Du PhD., founded Zai Lab, providing equal opportunities for women within the biopharmaceutical industry was at the core of the company’s ethos. We are immensely proud that Zai Lab is among the first of global biopharmaceutical companies to achieve gender pay parity across all levels of the company. Currently, Zai Lab has established and maintained female representation in senior management and representing 57% of the workforce and 53.8% of women in key management positions. As we look ahead, we aim to establish Zai Lab as an example for the industry on how to foster an environment in which diversity and inclusion can thrive. We will see a number of important business catalysts in 2022 while we continue to differentiate Zai Lab as a place where talented scientific and business leaders can build a career while they are building a company.

Image Source: Pexels

About Author: Jonathan Wang is the Executive Vice President and Head of Business Development at Zai Lab. Mr. Wang holds a Master of Business Administration in healthcare management from Wharton Business School.


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This content piece was prepared by our former Senior Editor. She had expertise in life science research and was an avid reader. For any query reach out to us at connect@pharmashots.com

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