NOV1105Solid cancers (Ovarian, Melanoma)

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.

It is under development for the treatment of solid tumors at Phase 1 studies (MFDS) with several cases of stable diseases and partial responses(interim result). We are planning to initiate the phase 2 study in the first quarter of 2019.

• Target

  Hepatocyte Growth Factor (HGF)

• MOA

  Inhibition of Hypoxia-induced HGF – cMET signaling by anti-HGF antibody

• Dev. Stage

  Phase 1b (FIH) completed (DB lock), Phase 2 study planned for 1Q of 2019

• 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

• Competition

  Ficlatuzumab (Phase II)

• Originator

  YOOYOUNG Pharm.

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 Luye Pharmaceuticals for Chinese market in 2014 and 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

• Licensees

  Spectrum pharmaceuticals, Inc , Luye pharmaceuticals, Inc.

NOV1204Solid tumors

NOV1204 (CKD-516) is a tubulin inhibitor under development for the treatment of advanced solid tumors in phase 1 (IV and oral formulation). NOV1204 is a benzophenone derivative and water-soluble valine prodrug which binds to tubulin and prevents its polymerization in 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. We are planning to expand this study in phase 2 at the 2nd half of this year.
Currently, a lot of proofs indicate that clinical outcomes will have to be related not only to its main characteristics of vascular disruption but also 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 1 completed (IV, PO)
  – Phase 1b/2a combination study  (with irinotecan) in CRC on going  (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, Colorectal Cancers

• Competition

  Plinabulin (Phase III), phosbretabulin(CA4P,Phase III), BNC-105P(Phase II)

• Originator

  CHONG KUN DANG Pharm.

NOV1301HCC & MDS

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 end of phase 1 FIH under the US FDA IND approval. We are actively enrolling patients to phase 2 of MDS (US). Additional INDs for Phase 2 were approved for HCC (US and Korea) and Gastric cancer. Recently in ASCO 2018, the IIT clinical trial was presented for multiple myeloma.
– 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

  -SIT: Solid tumors (HCC, Gastric cancer) or Hematologic tumor (MDS)
  -IIT: Solid tumors (Pancrease cancer) or Hematologic tumor (MM)

• Competition

  Galunisertib (Phase II)

• Originator

  MedPacto Inc.

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

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.

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.

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 in the non-clinical development phase with the goal of conducting clinical trials for solid tumors with TRK gene fusion. Identification of TRK gene fusion will be performed using the companion diagnostic platforms that are under development and 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

  pre-IND

• 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

  Loxo-101 (Ph II/III), RXDX-101 (Phase II/III)

• Originator

  Handok, CMG Pharma

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

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 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.
NOV1702 has been studied for its efficacy and safety in nine patients with cervical intraepithelial lesions (CIN3). In this study, NOV1702 induced an enhanced antigen-specific immune response in 8 patients, 7 of which reported complete loss of lesion and removal of HPV 16 or 18 type (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).
NOV1702 enhances tumor-specific CD8+ immune response to HPV E6 and E7 epitopes. Therefore, we expect that its anti-cancer immune response to cervical cancer can be enhanced if we prevent CD8+ T Cell exhaustion by PD-1 Immune checkpoint inhibition.

• 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 disease (CIN, cervical cancer)

• Competition

  VGX-3100(INOVIO, Phase III), ADXS11-001(Advaxis, Phase II-III)

• Originator

  Genexine Inc.

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.

NOV1802Solid tumors

NOV1802 (YSC-02) is an oncological virus that expresses multiple shRNA and cytokine combinations. It not only can be used as a universal therapeutic agent for a variety of tumors but also has a safety profile based on a tumor-selective target anti-cancer mechanism. To date, almost all virus-based anti-cancer drugs on the market or in development now have GM-CSF only, whereas NOV1802 (oncologic virus) is loaded with additional genes that can lead to high immune responding activities (mouse animal test).
NOV1802 can be administered systemically by using mesenchymal stem cells modified to be easily infected with this viruses and to replicate more viruses with high producibility. Therefore, it is possible to distribute a large number of viruses to tumors, and the antitumor effect can be expected to be maximized.

• Target

  tumor-related multitarget

• MOA

  • Tumoricidal activity of recombinant oncolytic adenovirus
  • anti-tumor immunity as well as direct tumor cell killing

• Dev. Stage

  Preclinical

• Profile

  first-in-class of oncolytic viral therapeutics in various types of cancers

• Efficacy

  Enhanced tumor cell killing and immune activation with both versatility and selectivity to tumor

• Dosing

  IV

• Indication

  Solid tumors

• Competition

  ImlygicTM (T-Vec) (Amgen, on the market), Pexa-Vec (Sillajen, Phase 3)

• Originator

  Yonsei University

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.