Comanche is a preclinical biopharmaceutical company developing novel siRNA compounds for the treatment of preeclampsia. Our purpose is to lower the risks of pregnancy and prematurity worldwide by safely sustaining natural pregnancy and allowing for fetal maturation. We envision a world where all pregnant women have access to safe and effective therapies that are evidence-based, cost-effective and sustainable. Our mission is to prevent or treat preeclampsia at its root cause.
What is Preeclampsia?
The burden of preeclampsia is substantial and growing in frequency and severity. It results in 10M patients worldwide with more than 500,000 infant and nearly 80,000 maternal deaths every year. Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality with significant short-term costs to healthcare systems and long-term societal losses. It disproportionately affects women who are the youngest, the oldest, black, and the poorest.
Characterized by hypertension and proteinuria developing after gestational week 20, there exists no definitive treatment other than pre-term delivery of the baby and removal of the placenta. Serious adverse outcomes for the mother include seizures, stroke, renal failure and death. For the baby, either iatrogenic termination or, if delivered prematurely, serious events like intraventricular hemorrhage, periventricular leukomalacia, retinopathy and bronchopulmonary dysplasia. These outcomes are more severe in low and middle income areas of the world where healthcare resources can be scarce and access to care delayed. Current standard of care is non-specific and involves hospitalization, bedrest and symptomatic treatment (“expectant management”). The objective is to prolong pregnancy and allow the fetus to mature sufficiently to survive ex utero; the trade off is continued risk to the mother for the complications of the disease.
Our founding scientists have created hsiRNA compounds capable of specifically and durably silencing the sFLT-1 gene in the placenta thereby halting production of the protein responsible for preeclampsia. Our approach to this deadly disease unifies three remarkable achievements:
sFLT-1 recognized as an unambiguous cause of preeclampsia
This protein, produced by the placenta and measurable in the plasma of pregnant women, is both diagnostic and prognostic for preeclampsia and is causally responsible for its disease manifestations when over-expressed.
Gene silencing via short-interfering RNA (siRNA) molecules
Small snippets of RNA, which typically serve as the blueprint for manufacturing the body’s proteins, can also be used ubiquitously by cells to silence or modulate the expression of target genes. This biological phenomenon, for which the Nobel Prize in Physiology or Medicine was awarded in 2006, has revolutionized scientific inquiry into gene and protein function and spawned an entirely new class of pharmacologic agents.
Three decades of oligonucleotide chemistry
Chemically stabilized double-stranded RNA compounds that function as potent, durable and safe pharmaceutical agents have now been approved by regulatory agencies around the world for indications ranging from orphan disease to population health. Our chemists have improved upon this successful track record and conjugated siRNA compounds that accumulate in the placenta where they selectively down-regulate multiple mRNA isoforms coding for sFLT-1 while leaving important angiogenic factors unaffected.