• Pipeline

  Nonspecific cell cycle disruption with standard chemotherapeutic agents has been the backbone of cancer therapy. The addition of targeted agents, both small molecules and biologics, to the armamentarium of anti-cancer agents has had limited improvement in patient survival. Too many patients continue to suffer disease relapse and progression. The cancer cells bypass the inhibitory effects of chemotherapeutic and targeted agents by activating alternate signaling and survival pathways, thereby escaping death.

  Niiki Pharma's strives to meet the challenge of improving patient survival by taking a new direction: developing agents that inhibit the core of tumor cell survival and resistance signaling cascade.

  
  

NKP-1339

• Compound

  

  NKP-1339 is a first-in-class ruthenium-based small molecule.
  NKP-1339 is administered to patients as an intravenous injection.

  
  

• Mechanism of Action

  NKP-1339 targets the GRP78 pathway. GRP78 is a master regulator of endoplasmic reticulum stress and plays a significant role in tumor cell survival and resistance. Normal healthy cells have low levels of stress and express low basal levels of GRP78. Cancer cells, however, are under significant stress due to intrinsic and extrinsic factors (e.g. relative hypoxia, acidosis and glucose deprivation), and therefore have constitutive up-regulation of GRP78. The dependency ("addiction") of the tumor cells on high levels of GRP78 for survival has been recognized as a critical factor for tumor survival¹. NKP-1339 down-regulates GRP78 levels in the tumor cells leading to tumor cell death. NKP-1339 is the most advanced agent in clinical trials that down-regulates this critical cancer cell survival pathway.

  The high levels of GRP78 in cancer cells has been correlated with drug resistance in many tumor types including breast, melanoma, gliomas, hepatocellular and lung cancers². In addition, treatment with many anti-cancer agents further induces GRP78, which boosts the tumor cells resistance to the treatment. Anti-cancer agents which induce GRP78 include platinums, taxanes, anthracyclines, anti-metabolites, proteosome inhibitors and kinase inhibitors³. NKP-1339 exhibits synergistic anti-tumor activity when combined with these agents⁴.

  Click to see larger version of image.
  
  

  ¹ Lee, Cancer Res 2007
  ² Lee, Cancer Res 2007; Li et al, Curr Mol Med 2006; Ma et al, Nat Rev Cancer 2006
  ³ Chiou et al, Ann Surg Oncol 2010; Jiang et al, Carcinogenesis 2009; Kern et al, Blood 2009; Pyrko et al, Cancer Res 2007; Wang et al, BMC Cancer 2008
  ⁴ Baerga et al, AACR-NCI-EORTC 2011

• Clinical Trial

  The dose escalation portion of a single agent NKP-1339 Phase I clinical trial has been completed in in patients with metastatic solid tumors resistant to standard therapies.

  For more information on the NKP-1339 trial visit ClinicalTrials.gov.

  

  For the latest update on the clinical trial please visit: News

• Companion Diagnostic

  A GRP78 based companion diagnostic assay is under development in parallel with all NKP-1339 trials.

• Projected Target Indications

  In the Phase I clinical trial to date, NKP-1339 as a single agent, has shown activity signals in several tumor types including neuroendocrine tumors and non-small cell lung cancers. Based on the synergy of NKP-1339 in combination with other anti-cancer agents seen in preclinical models, potential additional NKP-1339 indications include hepatocellular carcinoma, gastric and pancreatic cancers.

• Commercials Rights

  Niiki Pharma owns global commercial rights and all patents for NKP-1339, related compounds, and companion diagnostics.

• Intellectual Property

  NKP-1339 has an extensive international patent portfolio including issued patents and pending patent applications with coverage up until 2032.

• Scientific Presentations

  
  
  

NKP-2235

• Compound

  

  NKP-2235 is a first-in-class targeted gallium-based small molecule. It is orally bioavailable and given as a tablet.

  
  

• Mechanism of Action

  NKP-2235 targets the endoplasmic reticulum. Unlike normal cells, tumor cells are known to be under high levels of stress due to factors such as hypoxia, acidosis and glucose deprivation. This leads to high levels of protein misfolding and other stress effects. Endoplasmic reticulum is the cell machinery that repairs protein misfolding. In tumor cells, the endoplasmic reticulum in is under stress due to the high levels of misfolded proteins and other factors. NKP-2235 induces additional endoplasmic reticulum stress, leading to an overload of the system, which triggers tumor cell death.

  Preclinical studies indicate that NKP-2235 has a unique pattern of tumor cell cytotoxicity, which markedly differs from gallium salts such as gallium nitrate. The many differences between NKP-2235 and gallium salts is believed to arise from the fact that NKP-2235 remains intact, while gallium salts form free gallium ion in the aqueous phase.

  In addition to its anti-tumor activity, preclinical studies have demonstrated that NKP-2235 at low doses can prevent bone resorption (breakdown).

• Clinical Trial

  NKP-2235 IND was approved in 2011 and the Phase I trial is scheduled to begin shortly in the US. NKP-2235 will be administered as oral tablets once daily. The Phase I trial will be conducted in patients with metastatic solid tumors resistant to standard therapies.

• Companion Diagnostic

  A NKP-2235 based companion diagnostic is under development in parallel with the NKP-2235 clinical trial.

• Projected Target Indications

  In addition to its direct anti-tumor effects, NKP-2235 inhibits bone resorption. NKP-2235 target indications therefore would be cancers with high incidence of bone metastases such as NSCLC, breast and prostate cancers, as well as multiple myeloma. NKP-2235 could potentially be the first dual action agent with both anti-tumor as well as anti-bone resorption activities.

• Commercial Rights

  Niiki Pharma owns global commercial rights and all patents for NKP-2235, related compounds and companion diagnostics.

• Intellectual Property

  NKP-2235 has an extensive international patent portfolio including issued patents and pending patent applications with coverage up until 2032.