Mirvie cofounder and CEO Maneesh Jain, chief medical advisor Michal Elovitz and cofounder and scientific advisory board chair Stephen Quake.
Mirvie
This year, more than 3.6 million women will give birth in the U.S. Around 4% of them will have a potentially fatal high blood pressure condition known as preeclampsia. It will be three times more likely to kill Black mothers than white ones. And the main tools to identify who’s at risk haven’t changed in decades: a checklist of risk factors and a blood pressure cuff.
Maneesh Jain and Stephen Quake are hoping to change that. The cofounders of South San Francisco-based Mirvie are developing non-invasive diagnostic tools to help predict the risk of conditions like preeclampsia and premature birth from a vial of blood. Up until now, this technology, known as liquid biopsy, has mainly been used for early cancer detection.
“We believe we have a historic opportunity to address what is just an absolutely staggering, unmet need in pregnancy health,” says CEO Jain, 52. “At a scientific level, what’s really driving all this, is that we’ve never before been able to see the underlying biology in pregnancy health, because you can’t do any kind of invasive sampling.”
Earlier this month, Mirvie’s preeclampsia test received breakthrough device designation from the FDA, which is an accelerated track prioritizing the review of products that could help better treat or diagnose life-threatening conditions. On Tuesday, the company announced it raised $60 million in Series B funding led by Decheng Capital, which will help fund a 10,000-person clinical trial to validate Mirvie’s technology as it moves towards commercialization. BlackRock, Foresite Capital, General Catalyst, GV, Khosla Ventures, and Mayfield participated in the round, which brings Mirvie’s valuation to $155 million, according to a person familiar with the deal. Olympic runner Allyson Felix, whose daughter was born eight weeks early due to preeclampsia complications, also invested in the round. The company has raised a total of $90 million to date.
The investors are backing a team with a proven track record in the liquid biopsy space. Quake, 52, a bioengineering professor at Stanford and president of the Chan Zuckerberg Biohub, has invented new sequencing technologies and diagnostic tools, including the first non-invasive prenatal test for Down syndrome. He chairs Mirvie’s scientific advisory board. Jain has spent two decades commercializing sequencing and diagnostic technology, including as CEO of Cirina, which developed a liquid biopsy test for the early cancer detection, and merged with Grail in 2017.
“The nature of a lot of the science in this space hasn’t been as developed as what we’ve seen in areas like cancer, where there’s just been so much investment,” says Krishna Yeshwant, a general partner at GV (formerly known as Google Ventures). “That means there are opportunities for people to bring some of the learnings from these different fields to women’s health.”
“The answer to racial disparities in average pregnancy outcomes has fallen to genetics, which is just false. We’re not really attending to the cause of the disease.”
Mirvie’s secret sauce is its RNA platform, which is essentially able to read through the tens of thousands of messages that a mom and baby’s cells are sending through the body. The human genome, the unique set of instructions that make up each person, is made up of DNA. But it’s RNA that unzips that information in the nucleus of a cell and sends out the orders to make proteins. While the DNA code inherited from your parents is fixed, its interpretation through these tens of thousands of RNA messages can generate a snapshot of what’s going on in your cells, which could indicate whether you have a particular condition at that moment in time (or may be at risk for developing it).
“Doctors simply can’t identify today who is at risk for these conditions early in the pregnancy. And if you can’t identify who’s at risk, then you’re not able to effectively deploy the interventions at your disposal,” says Jain. “As a result, we find ourselves in this place for pregnancy health that is stuck in this reactive mode.”
Today a woman goes to a doctor or midwife and is asked a series of questions to determine preeclampsia risk. The number one risk factor is having had preeclampsia before, which is entirely unhelpful to any first-time mom. “We do a lot of guessing in pregnancy and maternal health,” says Michal Elovitz, a maternal fetal medicine doctor and professor at the University of Pennsylvania Perelman School of Medicine who serves as Mirvie’s chief medical advisor. Other risk factors include high blood pressure, obesity, age and being Black. What’s happened is there’s now an assumption that these risk factors are causative rather than associative, says Elovitz. “The answer to racial disparities in average pregnancy outcomes has fallen to genetics, which is just false,” she says. “We’re not really attending to the cause of the disease.”
It starts with the idea that preeclampsia doesn’t just happen out of the blue. There is some underlying biological cause. And the one thing that every single person who has preeclampsia has in common is a placenta. It’s an organ that forms during pregnancy to provide oxygen and food to the fetus. “If we can understand how the placenta should normally function, and how its function may get perturbed around pregnancy, we can then begin to say how do those perturbations identify women at risk for the disease months before it happens.”
More than a decade ago, Elovitz worked on a study that aimed to identify the proteins in maternal blood that might help predict who would be at highest risk for preterm birth. “Everything we thought we knew about pregnancy did not predict,” she recalls. It’s because that approach – seeking out individual proteins – was too limited. And it’s only been through technological developments in the past couple of years, including sequencing of the entire transcriptome (the collection of RNA messages) combined with machine learning, that has ushered in the possibility of these new diagnostics.
In 2018, Elovitz and Quake collaborated on a proof-of-concept study published in Science that set the foundation for Mirvie. That research, funded by the Bill and Melinda Gates Foundation, March of Dimes Foundation and Chan Zuckerberg Biohub, established that measuring certain of these RNA messages in a vial of blood could help retrospectively predict the age of a fetus with the same accuracy as an ultrasound, which is essentially within a 2-week window. A separate blood test was also able to differentiate between women who delivered prematurely and full-term. Early on, the team also engaged Stan Lapidus, the founder of Cytyc Corporation, which developed the modern pap smear, and who later went on to found Exact Sciences, which developed the noninvasive Cologuard test for colon cancer, among other companies. Lapidus chairs Mirvie’s board of directors.
This year the Mirvie team published two more significant peer-reviewed studies. A January study in Nature found that Mirvie’s technology could, after combing through messages from the mom, baby and placenta across 2,500 blood samples, accurately predict preeclampsia with a sensitivity rate of 75% and a predictive positive rate of 32.3%. This means it correctly identified people who had the disease 75% of the time and the probability that someone with a positive test would go on to develop the disease 32.3% of the time. While that may not seem particularly high, Elovitz puts it in context for her current patients: “We have nothing to empower women. We have nothing to inform risk,” she says. An April study in the American Journal of Obstetrics and Gynecology demonstrated the technology could predict risk of premature birth from a second trimester blood draw.
The Series B capital will go towards further increasing the clinical evidence that is needed to bring Mirvie’s tests to market. “We have underway the largest clinical study of its kind in pregnancy health,” says Jain, which will enroll up to 10,000 women and sequence the full transcriptome for each – all of the RNA messages from mom, baby and placenta. In the end, Jain expects to discover that issues like preeclampsia or preterm birth “will actually fall into multiple sub-conditions, which might be treated quite differently, and much more effectively.” Further down the line, Mirvie hopes to predict other issues, including gestational diabetes or placenta accreta, which can lead to severe blood loss. “Even if we can make a small impact, it’ll be huge just considering it’s almost approaching a million women every year in the U.S. experience these complications.”
