Season 1 (2011-2020)

Completed project

(KDDF-201506-05) Development of oral VVZ-149, a non-opioid analgesic candidate for nociceptive and neuropathic pain

CNS Disease, Chemical
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  • Development and Market Objectives

    VVZ-149 is a small molecule that inhibits both GlyT2 and 5HT2a. GlyT2 plays an important role for pain transmission in spinal dorsal horn area. Inhibition of GlyT2 increases the amount of glycine released from glycinergic inhibitory interneuron so that pain transmission from periphery to central dorsal horn can be reduced. 5HT2a is expressed in both peptidergic and non-peptidergic nociceptive nerve terminal in periphery so that blocking of 5HT2a can decrease the activation of nociceptive nerve terminal. 5HT2a also plays an important role in spinal dorsal horn area via descending facilitatory tract increasing the sensitivity for pain. Thus, inhibiting both GlyT2 and 5HT2a can provide more efficient way to control pain. VVZ-149 has shown morphine comparable efficacies in various animal studies. Currently, Clinical phase 2 trials of VVZ-149 injections for treatment of postoperative pain are ongoing in US and Korea. If the phase 2 studies are successful, the application of VVZ-149 injections can be expanded to pain for terminal cancer patient or chemotherapy induced neuropathic pain.

     

    This project is to accelerate the development of oral VVZ-149 by conducting preformulation studies and GLP toxicology studies although the GLP toxicology studies had already conducted as an injection form. After oral administration of VVZ-149, most of the VVZ-149 is metabolized to an active metabolite, VVZ-368, in liver. Thus, the GLP study will elucidate any potential toxicity of the active metabolite, VVZ-368. Oral form of VVZ-149 will provide various development opportunities for various chronic pain including neuropathic pain.

     

    Licensing-out to global pharmaceutical companies will be expedited once the phase 2 studies of VVZ-149 injections are successful and phase 1 study for the oral form of VVZ-149 is ready.

     

  • Unmet Medical Need & Target Patients

    Analgesic market (>$60B) is a second biggest market, behind the market for anticancer drugs. Nevertheless, there are huge unmet medical needs in perspectives of safety and efficacy.

     

    So far, opioid analgesics and NSAIDs accounting for almost half of the market have been commonly used, but their various adverse effects have limited their use. The opioid analgesics induce nausea, respiratory depression, vomiting, itching, addiction, and tolerance etc. seriously limiting its flexible usage. The NSAIDs is widely used, however, they are not that effective for moderate-to-sever pain and cause a mechanism based ulcer in stomach or duodenum limiting their long-term use.

     

    Oral form of VVZ-149 will be developed for most chronic pain including migraine or neuropathic pain. The analgesic effect in arthritis (rheumatoid- or osteo-) has not been confirmed yet. 

     

  • Current Progress

    Preformulation studies have been started focusing various physicochemical properties of VVZ-149. The GLP toxicology study will be initiated at early 2016. 

     

  • Intellectual Property

    A. Patent Status

    Substance Patent:               

    Applied in 2011 (PCT/KR2012/010257 : NOVEL BENZAMIDE DERIVATIVE AND USE THEREOF)

    Registered in Korea in 2015 (10-1542939)

     

    Mode of Action Patent:     

    Applied in 2011 (PCT/KR2012/005145 : COMBINATION OF EFFECTIVE SUBSTANCES CAUSING SYNERGISTIC EFFECTS OF MULTIPLE TARGETING AND USE THEREOF

     

    B. Scope

    Worldwide

     

  • Competitive Advantages

    A. First-in-Class, non-opioid and non-NSAID analgesic

    B. Clear MoA : Dual-target Synergism, acting on both CNS and PNS

    C. Efficacy in animal studies : Comparable efficacy to morphine, clear dose-dependency, and proven PK/PD relationship in animal studies. All studies were conducted under complete randomization and blind test.

    D. Well studied plasma exposure levels for efficacy : Repetitive and consistent plasma exposure level for efficacy was confirmed in various animal models for neuropathic pain, formalin-induced pain, and postoperative pain. Human proof-of-concept is expected soon from the ongoing Phase 2 studies of VVZ-149 injections for post-operative pain and neuropathic pain providing early opportunity of out-licensing for the oral VVZ-149.  

     

  • Disease Target

    CNS Diseases, Pain

  • Project duration

    Oct. 01, 2015 ~ Sep. 30, 2016

  • Organization

    Vivozon, Inc.

  • Phase of Development

    Pre-clinical

  • Contact

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