In 1964, researchers demonstrated that a single leukemic cell could cause fatal disease. The logical implication is that a high cure rate depends on the elimination of every cancer cell in the body. Curative therapy for metastatic cancer must:

Have sufficient specificity to be effective without producing unacceptable patient toxicity. In other words, the drugs must be far more toxic to cancer cells than normal cells.

Reach all cancer cells, wherever they may be in the body.

Address the resistance problem. Drugs are needed that can kill all the different types of cancer cells that evolve in the patient.

A patient with metastatic cancer can have billions of cancer cells spread throughout his or her body. A treatment that kills 99% of the cancer cells would leave millions of live cancer cells that could multiply and cause progressive disease. Major log reductions are needed for cure.

The term “log reduction” or “log kill” refers to the percentage of cancer cells that a drug eliminates. Each log reduction corresponds to a 90% decrease in the number of cancer cells. For example, in a patient with one hundred billion (100,000,000,000 or 10¹¹) cancer cells, a 1-log reduction leaves ten billion (10,000,000,000) cancer cells. A 2-log reduction leaves 1,000,000,000 cancer cells. An 11-log reduction leaves 1 cancer cell. A 12-log reduction leaves 0.1 cancer cells, which corresponds to a 10% probability that one cancer cell remains. The 11-log reduction would therefore correspond to at least a 90% cure rate. A 13-log reduction would be required to get a 99% cure rate.

**Effect of Different Log Reductions on a**

**Patient With 100 Billion Malignant Cancer Cells**

Log reduction | Cancer Cells Killed | Expected number of Surviving Malignant Cancer Cells |

0 | 0% | 100,000,000,000 |

1 | 90% | 10,000,000,000 |

2 | 99% | 1,000,000,000 |

3 | 99.9% | 100,000,000 |

4 | 99.99% | 10,000,000 |

5 | 99.999% | 1,000,000 |

6 | 99.9999% | 100,000 |

7 | 99.99999% | 10,000 |

8 | 99.999999% | 1,000 |

9 | 99.9999999% | 100 |

10 | 99.99999999% | 10 |

11 | 99.999999999% | 1 |

12 | 99.9999999999% | 0.1 (i.e., a 10% probability that 1 cell survives) |

13 | 99.99999999999% | 0.01 (i.e., a 1% probability that 1 cell survives) |

The figure below shows the probability of cure that corresponds to a given log reduction for tumor burdens ranging from 10 million cancer cells to 100 billion cancer cells.

The graph is conservative and overestimates the number of log reductions required for cure, as not all cancer cells that evolve will be able to proliferate and sustain the disease.

The design of most current cancer drugs and immunotherapies **rarely results in even a 2-log reduction** in cancer cell survival.

General Oncology’s pipeline is designed to achieve **major log reductions** in cancer cell survival.

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