Pipeline

Current Pipeline as of August 2019

  • Product
  • Indication
  • Target
  • Nonclinical
  • Phase 1
  • Phase 2
    • AntibodyNOV1105

    • Solid cancers (ph1) , Colorectal cancer (ph2)
    • HGF

    NOV1105Solid cancers (ph1) , Colorectal cancer (ph2)

    NOV1105 is an anti-hepatocyte growth factor (HGF) antibody effectively down-regulating the signaling HGF/c-Met pathway. This Humanized IgG4 with a KD of 1.2 x 10-10 M demonstrates excellent safety and PK profiles. In vivo studies show tumor growth inhibition and increased survival in Glioblastoma Multiforme (GBM), soft tissue sarcoma (STS) and ovarian cancer models alone or in combination with other drugs. With delicate roles of HGF in the tumor microenvironment and with recently found novel biomarkers strongly related with HGF, the clinical POC of first in human is expected to not only uncover the optimal population of responders but also to give us the more clues for HGF in tumorigenesis.

    We completed Phase 1 studies for solid tumors(MFDS) with several cases of stable diseases and partial responses* and have started to enroll the patients for phase 2 study for colorectal cancers this Summer 2019.
    * First-in-human phase I trial of anti-hepatocyte growth factor (HGF) antibody (YYB101) in refractory solid tumor patients: Integrative pathologic-genomic analysis and the final results. ASCO poster 2019 ⇒ 

     

    • Target
      Hepatocyte Growth Factor (HGF)
    • MOA
      Inhibition of Hypoxia-induced HGF – cMET signaling by anti-HGF antibody
    • Dev. Stage
      Phase 1 completed, Phase 2 study oncoing
    • Profile
      Humanized anti-HGF antibody(IgG4), No CDC, ADCC effect.
      Affinity 3.6pM, Half Life 21 days in Monkey, 11 days in mouse
      4 weeks repeated Tox: NOAEL 200mpk, well tolerate
    • Efficacy
      Potent inhibition in in vitro /in vivo model of Glioblastoma and Leiomyosarcoma.
      Several cases of stable disease or partial response reported in sebacious carcinoma, melanoma and colon cancers in phase I study.
    • Dosing
      IV, infusion, once every 2 weeks
    • Indication
      – Solid tumors including Melanoma, NSCLC, CRC, Sebacious carcinoma (ph 1)
      – CRC in combination with Irinotecan (Ph 2)
    • Competition
      Ficlatuzumab (Phase II)
    • Originator
      YOOYOUNG Pharm.
    • Small moleculeNOV1201 (Licensed Out)

    • NSCLC, Breast cancer
    • Pan-HER

    NOV1201 (Licensed Out)NSCLC, Breast cancer

    Poziotinib (NOV120101) is an oral, irreversible inhibitor of EGFR, HER2 and HER4. Preclinical studies conducted in cell lines and xenograft models of NSCLC revealed that Poziotinib has more potent activity than gefitinib, erlotinib and even afatinib in lung cancer models with activating EGFR mutations or T790M mutation. A phase I study to investigate the safety and maximum tolerated dose (MTD) of Poziotinib in genetically-unselected patients with advanced solid cancers including NSCLC and Breast cancer showed that 14% (7/51) of patients experienced partial response (PR), with the MTD of 24 mg once daily and acceptable toxicity profile, supporting further clinical development of Poziotinib. In phase II open-label, single-arm study was conducted to explore the anti-cancer activity and safety of Poziotinib in patients with advanced or metastatic lung adenocarcinoma with activating EGFR mutations, who developed acquired resistance (AR) to EGFR TKIs based on the Jackman criteria. A Prospective, Open-label, Single-arm, Multi-Center, Phase II Trial of NOV120101 in Patients With HER2-overexpressed Recurrent Stage IV Breast Cancer Who Have Received at Least 2 Prior HER2-directed Regimens is now in progress. It was licensed out to Spectrum Pharmaceuticals for global development in 2015.

    • Target
      pan-HER receptor
    • MOA
      Inhibition of HER signaling
    • Dev. Stage
      Phase 2
    • Efficacy
      in phase 1, response rate was 20% in solid tumors and overall response rate was 60% in breast cancers
    • Dosing
      PO
    • Indication
      Breast cancer, NSCLC
    • Competition
      afatinib,neratinib
    • Originator
      Hanmi Pharmaceuticals
    • Licensee
      Spectrum pharmaceuticals, Inc.
    • Small moleculeNOV1204

    • Solid tumors (ph 1), Colorectal cancer (ph2/3)
    • Tubulin

    NOV1204Solid tumors (ph 1), Colorectal cancer (ph2/3)

    NOV1204 (CKD-516) is a tubulin inhibitor under development for the treatment of advanced solid tumors (ph1,IV and oral) and colorectal cancer (ph1b/2a on going, pivital in plan, oral form). NOV1204 is a benzophenone derivative and water-soluble valine prodrug which binds to tubulin and prevents its polymerization in the tumor blood vessel and tumor cells (vascular disrupting agent: VDA). It blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent not only disrupts the tumor vasculature and tumor blood flow, deprives tumor cells of nutrients and induces tumor cell apoptosis, but also has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization. In vivo studies showed tumor inhibition and tumor regression, alone or in combination, while demonstrating good safety and PK profiles. Having a wider therapeutic margin and good bioavailability, NOV1204 is expected to be the only market drug of the VDAs which can be administrated orally with little concern about cardiovascular toxicity issue. These characteristics make it possible to design the patient-friendly dosing plan of daily oral low dose. It was proven to have efficacy in colorectal cancers in combination with irinotecan at phase 1b. With the promising result from phase 1b, We are planning to expand this study as a pivotal study in the 2nd half of this year 2019.
    Currently, a lot of proofs indicate that clinical outcomes have to do not only with the main characteristics of vascular disruption but also with its immune-boosting ability, one of the unique features of NOV1204. It was shown to increase DC maturation, antigen presentation, CD8+ T cell proliferation, and tumor infiltration in animal models. In syngeneic mice model, NOV1204 had the synergistic effect in combination with anti-PD-1, PD-L1 or CTLA-4 antagonists. Being an oral agent, flexible dosing schedule optimization is possible.

    • Target
      Microtubule Destabilization
    • MOA
      Vascular disrupting agent
    • Dev. Stage
      –Phase 1b/2a. Combination study (with irinotecan) in CRC at phase 1a completed and pivotal trial in plan (PO)
    • Profile
      – An orally active potent small molecule inhibitor
      – Excellent aqueous solubility
      – Excellent PK w/ good oral bioavailability
    • Efficacy
      – Good anticancer effects in various solid tumors including advanced drug-resistant tumors
      – Suitable for combination therapy (with Irinotecan, with ImmunoOncology drugs)
    • Dosing
      IV (once or twice per week) or PO (5d on / 2d off)
    • Indication
      – Solid tumors (ph 1)
      – CRC in combination with Irinotecan (ph1b/2a)
    • Competition
      Plinabulin (Ph3), phosbretabulin(CA4P,Ph3), BNC-105P(Ph2)
    • Originator
      CHONG KUN DANG Pharm.
    • Small moleculeNOV1301

    • Solid cancers (HCC, CRC, NSCLC) and hematologic cancers ( MDS, MM, etc)
    • ALK-5 (TGFβ type I receptor)

    NOV1301Solid cancers (HCC, CRC, NSCLC) and hematologic cancers ( MDS, MM, etc)

    NOV1301 (TEW-7197) is an ALK5 (TGF ß type I receptor) inhibitor under development for the treatment of solid tumors and CML.  It reduces the signaling of TGF ß, typically increased during cancer by inhibiting its receptor ALK5, whilst normalizing the tumor microenvironment by modulating the extracellular matrix, allowing angiogenesis and enhancing immune surveillance. In vivo it reduced metastasis and inhibited tumor growth in breast, melanoma, HCC, GBM and CML models, leading to extended survival. NOV1301 exhibits good safety and PK profiles in an oral once a day dosing.
    – It is at the completion stage of phase 1 FIH under the US FDA IND approval. We are actively enrolling patients to several phase 2 studies.
    – Currently the biomarker study is ongoing for patient selection strategy. It is based on the status of the TBRS (TGF Beta Response Signature), which will show us who will get benefit from this drug.

    • Target
      TGFβ type I receptor inhibitor
    • MOA
      Inhibits EMT and metastasis & activates immune surveillance
    • Dev. Stage
      Phase 2 (US)
    • Profile
      – An orally active potent small molecule inhibitor
      – Potent & selective
      – Good ADME & PK profile
    • Efficacy
      – Good efficacy in various in vivo animal models
      – Suitable for combination therapy
    • Dosing
      PO
    • Indication
      – Solid tumors (Breast, Melanoma, HCC, GBM at Ph1)
      – Hematologic tumors (MM, MDS, CML at ph2)
      – CRC in combination with Keytruda (ph2)
      – NSCLC in combination with Imfinzi (ph2)
    • Competition
      Galunisertib (Phase II)
    • Originator
      MedPacto Inc.
    • Small moleculeNOV1401

    • Solid tumors
    • PARP1/2

    NOV1401Solid tumors

    NOV1401 selectively binds to and inhibits ADP-ribose polymerase-1 and 2, inhibiting PARP-mediated repair of single-strand DNA breaks leading programmed cell death. It inhibits PARP-1,2 in nanomolar level and shows greater anti-tumor effects than the other market PARP inhibitors in various cell lines and animal models with BRCA mutations and HRD. Upon confirmation of its clinical feasibility at phase 1, parallel clinical-development of companion diagnostics will be initiated using biomarkers for prognostic and monitoring purpose for this drug responses.

    • Target
      Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor
    • MOA
      Inhibition of PARP-mediated repair of single-strand DNA
    • Dev. Stage
      Phase 1a (FIH)
    • Profile
      – An orally active potent small molecule inhibitor
      – Excellent aqueous solubility
      – Potent & selective
      – Good ADME & PK profile
    • Efficacy
      – Good efficacy in various in vivo animal models
      – Suitable for combination therapy
    • Dosing
      PO
    • Indication
      Solid tumors (HGS-OV, Breast, Prostate, Gastric Cancer)
    • Competition
      Olaparib, Rucaparib, Niraparib, Talazoparib (ph III)
    • Originator
      ILDONG Pharmaceutical
    • Small moleculeNOV1402

    • Solid tumors
    • PARP/TNKS

    NOV1402Solid tumors

    NOV1402 acts by targeting both poly ADP-ribose polymerases (PARPs) and tankyrase (TNKS). PARP is a DNA nick-sensor that signals the presence of DNA damage and facilitates DNA repair. Inhibition of PARP increases the activity of DNA damaging agents and causes cancer cell death. Inhibition of tankyrase not only induces interruption of the Wnt/β-catenin signaling by stabilizing axin and promoting β-catenin degradation but prevents non-homologous end joining (NHEJ) activation that repairs double-strand breaks in DNA, which lead to prevention of tumor growth.
    NOV1402 is expected to be superior to olaparib or the similar class of PARP inhibitors in its efficacy and to talazoparib in its toxicity based on its dual mode of actions and physicochemical properties. Upon confirmation of its clinical feasibility, parallel development of companion diagnostics is planned.

    • Target
      Poly (ADP-ribose) polymerase-1,2,3 and tankyrase
    • MOA
      Inhibition of PARP-mediated repair of single-strand DNA and Wnt/b-catenin signaling
    • Dev. Stage
      Phase 1a (FIH)
    • Profile
      – An orally active potent small molecule inhibitor
      – Excellent aqueous solubility
      – Potent & selective
    • Efficacy
      Good efficacy in various in vivo animal models
    • Indication
      Solid tumors (HGS OC, TNBC, CRPC, Gastric, CRC, NSCLC, etc)
      Dosing
      PO
    • Competition
      PARP inhibitors (Olaparib, Rucaparib, Niraparib), TNK inhibitors(G007-LK,JW-55,XAV-939, NVP-TANKS656)
    • Originator
      Jeil Pharmaceuticals Inc.
    • AntibodyNOV1501 (Licensed Out)

    • Solid tumors
    • DLL4/VEGF

    NOV1501 (Licensed Out)Solid tumors

    VEGF is a key inducer of angiogenesis in cancer, forms new blood vessels and results in tumor growth beyond a certain size. Anti-VEGF therapy has been widely used in patients with various tumor types, but the effects are variable and resistance is frequently encountered. VEGF induces DLL4 expression in endothelial tip cells. VEGF-induced expression of DLL4 in vascular endothelium leads to the activation of Notch signaling. Blocking the Notch/DLL4 signaling results tumor growth due to the formation of immature and poorly functional vessels that result in reduced tumor perfusion. Blockade of DLL4 can have potent inhibition effects on tumor growth that are resistant to anti-VEGF therapies. Furthermore, the simultaneous targeting of DLL4 and VEGF has produced additive of synergistic anti-tumor effects compared to single agents in a number of tumor models.
    NOV1501 is an anti-DLL4/anti-VEGF bispecific monoclonal antibody. It inhibits both DLL4/Notch and VEGF/VEGFR2 interactions in nanomolar level. It shows greater anti-cancer effects in various animal models in comparison to anti-DLL4 or anti-VEGF agents. NOV1501’s unique design of the bispecific antibody helps simpler purification and higher anti-cancer efficacy.

    • Target
      DLL4 and VEGF
    • MOA
      Anti-angiogenesis by inhibiting DLL4/Notch and VEGF/VEGFR2 interaction
    • Dev. Stage
      Phase 1 (FIH)
    • Profile
      – Unique design bispecific Antibody
      – Good synergy in vivo
      – Active in Avastin-resistant tumors
    • Efficacy
      – Good efficacy in various in vivo animal models
      – Suitable for combination therapy
    • Dosing
      IV infusion, Q2W
    • Indication
      Solid tumors (Gastric, Colon, Ovarian cancer)
    • Competition
      Navicixizumab(Ph I), ABT-165 (Ph I)
    • Originator
      ABL Bio, Inc.
    • Licensee
      TRIGR pharmaceuticals
    • Small moleculeNOV1601

    • Solid tumors with TRK gene rearrangements or certain TRK mutations
    • Pan TRK

    NOV1601Solid tumors with TRK gene rearrangements or certain TRK mutations

    NOV1601(CHC2014) selectively inhibits not only pan-TRK(TRKA, TRKB, and TRKC), but also mutated forms of TRKAs(G595R & G667C). TRK is known to be involved in several diseases, and especially TRK gene fusion has been reported in many types of cancers. NOV1601 blocks the activity of tyrosine kinases and the signaling pathways they activate, thereby exhibiting the therapeutic effect. NOV1601 is currently on phase 1 FPI trial. Identification of TRK gene fusion will be performed using the companion diagnostic platforms that are under development.

    • Target
      Pan-TRK
    • MOA
      TRK has been shown to be highly expressed in the form of fusion proteins in some cancers. In recent years, abnormal genetic mutations, including the fusions of the TRK genes, have emerged as new targets for cancer treatment. A variety of carcinogenic genetic alterations, including NTRK gene rearrangements, have been found in several types of tumors, and promising results have been reported in clinical trials in suppressing TRK as a therapeutic target. The approach to target oncogenic TRK in cancer treatment is expected to show a higher response rate than any targeted therapeutics so far.
    • Dev. Stage
      Phase 1
    • Profile
      – An orally active potent small molecule inhibitor
      – Potent & selective
      – Good ADME & PK profile
      – Parallel Development of companion diagnostics for TRK detection
    • Efficacy
      – Good efficacy in various in vivo animal models
      – It overcomes LOX-101 resistance
    • Dosing
      PO
    • Indication
      Solid tumors with TRK gene rearrangements or certain TRK mutations
    • Competition
      Larotrectinib (market), Loxo-195 (Ph2)
    • Originator
      Handok, CMG Pharma
    • Small moleculeNOV1701

    • Solid tumors & Hematologic tumors
    • Myc

    NOV1701Solid tumors & Hematologic tumors

    NOV 1701 is a synthetic compound program that directly inhibits MYC.
    Unlike many other Myc inhibitors that have been developed so far, NOV1701 has a new mechanism that directly inhibits the binding of Myc / Max dimers to DNA. In other words, other c-Myc inhibitors indirectly inhibit Myc by modulating the universal Leucine-Zipper protein PPI of the surrounding regulators, while NOV1701 specifically and directly inhibits Myc, a substantial target protein.
    While the attempt to develop other platform materials (siRNA, peptide) or synthetic compounds that were under development as Myc direct inhibitors has not been very successful, NOV1701 has been proved to be the only one with high selectivity, efficacy and safety (in vivo).

    • Target
      c-Myc
    • MOA
      It directly inhibits the binding of Myc / Max dimers to DNA
    • Dev.Stage
      Non GLP development
    • Profile
      first in class Myc direct inhibitor
    • Efficacy
      Good efficacy in several cancer models (Lung, Colon, etc)
    • Indication
      Solid tumors and Hematological tumors(Lymphoma, etc)
    • Competition
      -direct inhibitor: AVI-4126 (ph II/III)
      -indirect inhibitor: TEN-10 (ph IB), OTX015 (Ph IB)
    • Originator
      National Cancer Center and KRICT
    • Gene therapyNOV1702

    • HPV-associated disease (CIN, cervical cancer)
    • E6 and E7 of HPV 16, 18 type

    NOV1702HPV-associated disease (CIN, cervical cancer)

    NOV1702 (GX-188E) is a therapeutic DNA vaccine, in the form of a plasmid that codes the E6 and E7 oncoproteins of HPV 16 and 18 types. It enhances the immune response by simultaneously expressing tPA for the extracellular secretion of expressed E6/E7 and Flt-3L, which promotes dendritic cells and its uptake of these antigens. When DNA injected by electroporator produces E6 / E7 protein, the human body induces the cytotoxic T lymphocyte response to tumor cells that express E6/E7 oncoprotein.

    We are doing phase 1b/2a study for cervical cancer in combination with anti-PD1 antibody pembrolizumab based on the result of the phase 1 study where 8 out of 9 CIN3 patients showed an enhanced antigen-specific immune response and 7 of them had a complete loss of lesion and removal of HPV 16 or 18 types,* expecting its anti-cancer immune response to cervical cancer can be enhanced if we prevent CD8+ T Cell exhaustion by PD-1 Immune checkpoint inhibition(NCT03444376).

    * Kim TJ et al. Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients. Nat Commun. 2014 Oct 30;5:5317 ⇒ 

    • Target
      E6 and E7 of HPV 16, 18 type
    • MOA
      Promoting a tumor-specific, CD8+ immune response against HPV E6 and E7 epitopes through vaccination (GX-188E)
    • Dev.Stage
      Phase 1b/2 started in 2018
    • Profile
      6,085 base pair plasmid DNA vaccine containing E6/E7 genes of HPV16 and 18, fused to Flt3 (Fms-like tyrosine kinase 3) ligand
    • Efficacy
      Therapeutic potential (regression of lesions and viral clearance) in CIN3 patients
    • Dosing
      Intramuscular administration
    • Indication
      HPV-associated cervical cancer
    • Competition
      VGX-3100(INOVIO, Phase III), ADXS11-001(Advaxis, Phase II-III)
    • Originator
      Genexine Inc.
    • AntibodyNOV1801

    • Solid tumors
    • 4-1BB/TNFRSF9/CD137

    NOV1801Solid tumors

    4-1BB is a receptor of T lymphocyte and its signal is required for proper T cell activation. NOV1801 is an anti-4-1BB therapeutic monoclonal antibody. Co-stimulatory receptor, 4-1BB is not expressed in resting T cells and is up-regulated following activation. In other words, 4-1BB is induced on CD8+ T cell upon stimulation and generate proliferation and anti-apoptotic signaling with ligation of NOV1801. In addition, agonistic anti-4-1BB antibody NOV1801 induce secretion of INF-gamma which plays a pivotal role in promoting immune reaction against primary and metastatic tumors. In study of humanized mice which possess human immune system, NOV1801 eradicate human tumor and show synergistic anti-tumor activity with immune checkpoint blockade. Thus, NOV1801 represent diverse advantages in anti-cancer therapy;

    • Excellent anti-tumor efficacy
    • Minimize adverse event of cancer therapy
    • Inhibit recurrence of tumor through memorized immune system
    • Synergize anti-cancer effect with immune checkpoint modulator or chemotherapy

    • Target
      4-1BB/TNFRSF9/CD137(CD66c)
    • MOA
      Activation of cytotoxic CD8+ T cell
    • Dev. Stage
      Preclinical stage
    • Profile
      Humanized anti-human 4-1BB antibody. KD: 7.975E-10 (M)
    • Efficacy
      Excellent anti-tumor efficacy in humanized mice model
    • Dosing
      IV
    • Indication
      Solid tumors
    • Competition
      Urelumab (BMS, phase I or II), Utomilumab (Pfizer, phase I or II)
    • Originator
      Eutilex Co., Ltd.
    • AntibodyNOV1803

    • Solid tumors
    • CEACAM6 (CD66c)

    NOV1803Solid tumors

    NOV1803 (DNP002) is a humanized anti-CEACAM6 antibody. It can bind and destroy both cancer cells and MDSC. NOV1803’s epitope is B domain of CEACAM6, therefore it does not block the CEACAM1 and CEACAM6 interaction. Rather, by binding the membrane proximal region of CEACAM6, NOV1803 strongly induces ADCC. Ex vivo studies with advanced gastric cancer (AGC) patients showed the almost complete depletion of cancer cells following the activation of autologous immune cells. Besides, NOV1803 effectively depleted the MDSC (myeloid-derived suppressor cells) in Ex Vivo studies using the whole blood of AGC patients. Also, strong tumor growth inhibition was shown in several mouse models including NSCLC, gastric cancer and colon cancer.
    In terms of mode of action of NOV1803, it was confirmed that NOV1803 induced not only the NK cells activation but also the activation of T cells and other immune cells. In addition to the ability to remove MDSC, induction of various immune effector cells activation is expected to lead to the overall activation of the immune system, especially in the tumor microenvironment and thus influence positively the anticancer effect of NOV1803.

    It is currently in the preclinical stage, and will be conducting the IND for Phase I study in US next year 2019.

     

    • Target
      CEACAM6 (CD66c)
    • MOA
      Enhanced ADCC by afucosylation, Both Tumor & MDSC depleting
    • Dev. Stage
      Preclinical, IND for phase I planned for 2019
    • Profile
      Humanized anti-CEACAM6 antibody(IgG1), Affinity KD 6.64E-10 (M),
      MCB established; Ab. Titer > 4.5 g/L
    • Efficacy
      Good efficacy in various in vivo animal models,
      Tumor cell killing by autologous immune cells of Gastric cancer patients in Ex vivo.
    • Dosing
      IV, infusion, once every weeks
    • Indication
      Solid tumors (NSCLC, gastric cancer, colon cancer)
    • Competition
      NEO-201 (Precision Biologics, Phase I), BAY 1834942 (Bayer, Phase I)
    • Originator
      DINONA Inc.
antibody : Antibody small_molecule : Small molecule small_molecule : Gene therapy small_molecule : Cell therapy small_molecule : etc