PIPELINE

Indication
Discovery
Preclinical
IND enabling
Phase 1

Cancer Immunotherapy

Local oxygen delivery reverses multiple immunosuppressive pathways to enhance anti-cancer immune responses
Cancer Immunotherapy

The hypoxic tumor microenvironment suppresses anti-cancer immune responses by modulating multiple signaling pathways including, but not limited to, hypoxia-inducible factor (HIF-1) signaling.

Hypoxia has been shown through HIF-1 signaling to:

  1. activate PD-1/PD-L1 pathways that inhibit recruitment and activation of helper and cytotoxic T-cells (Th and Tc ) and natural killer (NK) cells, key effectors of anti-tumor responses;
  2. recruit and activate inhibitory regulatory T cells (Treg ), tumor associated macrophages (TAM) and other myeloid-derived suppressor cells (MDSC); and
  3. directly inhibit the ability of tumor cells to be recognized by the immune system.

By delivering oxygen to the hypoxic tumor microenvironment, OMX reverses these effects and stimulates an immune attack on tumor cells resulting in tumor cell death.

References:
  1. Lee CT, Mace T, Repasky EA. Hypoxia-driven immunosuppression: a new reason to use thermal therapy in the treatment of cancer? Int J Hyperthermia. 2010;26(3):232-46.
  2. Wei L, et al. Blocking HIF-1α following radiotherapy to prolong and enhance the immune effects of radiotherapy: a hypothesis. Med Sci Monit. 2014 Oct 31;20:2106-8.
  3. Noman MZ, et al. Hypoxia: a key player in antitumor immune response. A Review in the Theme: Cellular Responses to Hypoxia. Am J Physiol Cell Physiol. 2015 Nov 1;309(9):C569-79.
  4. Melero I, et al. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 2015 Aug;15(8):457-72.
  5. Chaturvedi P, et al. Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment. Proc Natl Acad Sci U S A. 2014 May 20;111(20):E2120-9.
  6. Corzo CA, et al. HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010 Oct 25;207(11):2439-53.
  7. Siemens DR, et al. Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: role of nitric oxide. Cancer Res. 2008 Jun 15;68(12):4746-53.
  8. Hasan A, Mazzone M. Sixty shades of oxygen-an attractive opportunity for cancer immunotherapy. Ann Transl Med. 2015 Aug;3(13):187.
  9. Sitkovsky MV, et al. Hostile, hypoxia-A2- adenosinergic tumor biology as the next barrier to overcome for tumor immunologists. Cancer Immunol Res. 2014 Jul;2(7):598-605.

Stroke

Local oxygen delivery into ischemic brain tissue prevents multiple cell death cascades and preserves long term brain function
Stroke

Within minutes of a stroke, a severe reduction of blood flow and oxygen supply causes cell death in the part of the brain tissue surrounding the blocked blood vessel (black). In the immediate vicinity of the dead tissue is a hypoxic zone (green) - tissue that is severely deprived of oxygen and at risk of dying. If left untreated, the oxygen-deprived tissue will die, resulting in further impairments in speech, motor, and cognitive function. By restoring oxygen levels in brain tissue affected by stroke, Omniox’s drug candidate for stroke (OMX-IS) can delay or prevent this progressive neuronal death, saving brain tissue and preserving brain function.

Cardiovascular Ischemia

Local oxygen delivery into hypoxic myocardial tissue preserves cardiac function and systemic oxygenation to support life

In cardiovascular ischemia, such as during a heart attack or acute blood loss, hypoxia drives a vicious cycle in which the heart tissue is damaged, negatively affecting blood flow and reducing oxygen levels, and depriving all organ systems of oxygen. This in turn results in a number of complications, including reduced heart function, long-term neurological deficits, and organ failure. OMX-CV oxygenates the hypoxic heart tissue to break this cycle and preserve heart and other major organ function.