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Koronis Pipeline


KP-1461 for HIV Treatment

KP-1461 is an oral prodrug of KP-1212, a nucleoside analog designed to target HIV-1 and HIV-2, including strains with resistance to current treatments. This approach leverages the concept of "lethal mutagenesis," wherein a virus is subjected to an elevated rate of mutation, pushing it beyond its ability to survive as a stable population.

Mechanism of Action:

KP-1461 is converted in the body into its active metabolite, KP-1212-triphosphate. This active form integrates into the viral genome during replication via the viral reverse transcriptase enzyme. The presence of KP-1212-triphosphate introduces random transitional mutations in the viral genome. Over successive replication cycles, the accumulation of errors destabilizes the virus, leading to its collapse. This process does not harm host cells, as demonstrated in preclinical studies. 

Advantages of KP-1461: 


  • Targets resistant strains of HIV, making it suitable for patients with limited treatment options.
  • Does not rely on suppressing viral replication alone but disrupts the virus's ability to maintain genetic integrity.
  • Offers potential synergy with existing antiretroviral approaches by complementing suppression-based therapies.

Clinical Development Stages:

​Phase 1a: 

Conducted in healthy volunteers, this trial assessed the safety and pharmacokinetics of single and escalating doses of KP-1461. Results confirmed that the compound was well-tolerated at all tested doses, with no significant adverse events.

​Phase 1b: 

Currently enrolling HIV-positive patients with prior treatment failures and resistance to multiple drug classes. This study focuses on evaluating safety, tolerability, and pharmacokinetics in this population.

Phase 2a: 

Planned to investigate the efficacy of KP-1461 in achieving virological outcomes in a broader patient group.

Research on Viral Mutagenesis in Other RNA Viruses 

The principles behind KP-1461 are also being extended to other RNA viruses, such as HCV. RNA viruses are characterized by high mutation rates due to the low fidelity of their replication enzymes. This intrinsic instability makes them particularly vulnerable to strategies involving mutagenesis.