Through its revolutionary early-stage detection blood test, biotech company AOA will save half the women diagnosed with ovarian cancer.

Oriana Papin-Zoghbi

Co-founder and CEO

Location / Year Founded / Industry:

New York, NY / 2020 / Women's Health

What is AOA:

The first liquid biopsy test that accurately enables early diagnosis of ovarian cancer through the analysis of tumor marker gangliosides.

Why it matters:

Dubbed the “silent killer” with a five-year survival rate due to late diagnosis, ovarian cancer is the deadliest gynecological disease and the fifth leading cause of cancer-related deaths in women. Ninety-four percent of women experience symptoms starting from Stage 1, but 80 percent of cases are diagnosed too late (Stage III+). Not only are early-stage ovarian cancer symptoms continuously mistaken for benign conditions (including cysts, endometriosis, fibroids and other similar gynecological conditions), but due to a lack of accurate testing methods, it is incredibly difficult to diagnose the disease in the early stages.

Why you should care:

Current methods of ovarian cancer diagnosis fall into three categories: biomarkers, imaging, and clinical assessment. A clinician will typically conduct an assessment followed by imaging, usually in the form of a transvaginal ultrasound. These assessments usually take nine months to complete and lack the ability to detect early cancer, thus typically diagnosing women already in late-stage disease. For many years, researchers have strived to develop a feasible and reliable way to detect early-stage ovarian cancer in women who do not have any symptoms. AOA’s early-stage liquid biopsy diagnostic test will improve clinical practice, reduce patient mortality, and—as the second most expensive cancer to treat, second only to brain cancer—deliver cost savings to payers

After graduating from college, Oriana Papin-Zoghbi stumbled into women’s health, fell in love with it, and then never left. “I worked for a very early stage company focused on diagnostic tests in the maternal fetal medicine space,” she remembers. “I learned what it took to get a product off the ground, to convince physicians to use something novel in women’s health, as well as the barriers to innovating in women’s health and how challenging this space is—from the lack of funding to the lack of prioritization. It was serendipitous that I started my career in women’s health but it was purposeful that I stayed in this space.”

It was at that first diagnostics company, where she stayed through acquisition, that Oriana met Anne Jeter and Alex Fisher, her co-founders. Together, they developed a passion and expertise for finding solutions that disproportionately affect women. “After that, we helped build and sell another women’s health company together, so it seemed natural to take on the next challenge as founders.” They set out to find an area that needed innovation and landed on ovarian cancer—specifically, the first blood test that accurately enables early diagnosis of the disease.

We are thrilled to back AOA’s vision to revolutionize the future of ovarian cancer diagnostics, for which they have raised a $2.5 million seed round with investors including The Helm, Avestria Ventures, AlleyCorp, and Life Science. Read more in our interview with Oriana below.

Why did you decide to tackle ovarian cancer specifically?

Less than 10 percent of all funding goes into innovating for women’s health and 90 percent of all medical innovation stays in academia and research—it never gets developed. There’s a huge disconnect there, with so many disease areas lacking consumer-facing innovation: endometriosis, preeclampsia, ovarian cancer. We started with a long list of diseases that disproportionately affect women. We wanted to bridge that gap and started looking at patents, meeting with academics and tech transfer offices to find IP that had never been developed. We did diligence on tools for preeclampsia, for endometriosis, and then for ovarian cancer and ended up landing on ovarian cancer, primarily because of the innovation that stemmed out of Professor Uri Saragovi’s lab, our chief scientific officer. We dove into understanding there was nothing available for these women, that this disease is so deadly, and that what he had invented was—for the first time in over 30 years—something that could actually have an impact on these women’s lives. Essentially, those pieces came together for us to form AOA around this problem.

Can you tell us about Professor Saragovi’s innovation? Why is it so revolutionary?

Currently, the diagnostic process for ovarian cancer takes over nine months—it’s a wait and see process: to see if symptoms are persistent, to see if CA-125 levels are continuously rising, to see if there is a need for a biopsy procedure. These women have no alternative to the current “gold standard” test, the CA-125, which detects an antigen that indicates inflammation in the pelvic area. It’s often interchangeably used to try to understand if a woman has endometriosis, fibroids, or potentially ovarian cancer. Typically, high CA-125 levels in young women is attributed to having endometriosis or a pelvic inflammatory disease. Typically for endometriosis, the high CA-125 level will not change much over time, but with ovarian cancer, that level usually increases every three months. But what’s the problem with that? You’re waiting for that number to increase to know whether you have ovarian cancer, and as you’re waiting for that level to increase, that tumor is growing and you’re catching that woman at a later stage of cancer. 

This is why what is available today is so incredibly confusing—testing for CA-125 can’t effectively differentiate between these conditions, it’s simply telling you that something is wrong in your pelvic area. This is why, even though over 90 percent of women with ovarian cancer start experiencing symptoms at stage one, 80 percent of them are diagnosed when they’re already at stage three or four, which is too late. 

For Professor Saragovi, his initial research started with the theory that ganglioside markers (a group of complex lipids) are expressed on tumors. From there, he reduced that theory to practice, which took him 10 years. He then had to figure out a way to not only identify those markers, but to extract them, and he created proprietary antibodies as the mechanism to detect and extract these ganglioside markers on ovarian cancer cells. These markers are present only in ovarian cancer and not in endometriosis, not in fibroids, so we are able to detect ovarian cancer as early as stage one, giving women a 90 percent survival rate compared to women diagnosed at stage three and four, who have a 28 percent survival rate. 

You mentioned earlier that innovations in academia never get developed. Why is that?  

Funding is one part of it, expertise is another. Typically, those developing the innovations are your researchers, academics, or physicians who understand the technology and the science. Rarely do they have the expertise to form a company, raise the funds, put it through FDA approval and commercialize it. On the flip side, you also have fantastic business teams who have the experience of going through FDA, of commercializing a drug, but that don’t have the scientific background to invent something. That connection is often what’s missing. That’s where we formed a beautiful partnership between Professor Saragovi and our team: his scientific expertise, his know-how, his invention, and our really strong business and development team combined allows us to take something that’s in academia and translate it. 

If startups like AOA didn’t exist, would pharmaceutical companies buy these inventions from academia instead? And if that’s the case, is this why treatments in women’s health are so sorely lacking: because the solutions may exist but larger companies are perhaps ignoring them—leaving it to smaller startups to bring them to life, which often lack funding to do so.

I don’t know if it’s the bigger companies purposefully turning a blind eye, but if you think about what big companies are doing to expand their portfolio, it’s usually something that’s already within their domain that they’re looking to expand, rather than going after a complete unknown. That level of risk to go after something completely unknown, to start from scratch, is rarely the appetite of a big company. And it’s also rarely how they function. That’s where startups are really taking up that space, because there’s an appetite and comfort level for risk, and an understanding of the mechanics of what it takes to go from start to finish on bringing something to market. We are bridging that gap between starting in academia and ending up in Big Pharma, because those startups get acquired and these products then get embedded into big diagnostics companies. But that starting point of taking it out of academia, developing it, going through regulatory, de-risking it—that’s where we fit in really nicely.

Several larger pharmaceutical companies have eliminated their women’s health research divisions over the last couple of years. We know there is a prevailing thought that there’s no money to be made in women’s health. Do you think that’s changing?

There is certainly this notion that women’s health can be less lucrative, from a revenue perspective, but it’s more systemic than that in the sense that it’s hard for people— anybody—to invest in, believe in, and follow things that don’t necessarily affect them. If you look at who has managed these projects historically, it’s all men. The majority of large health company CEOs are men. The majority of investors are men. The majority of CEOs and founders of startups have been men. We lived this—at the last two companies we helped to build, our CEOs were male, our boards were entirely male and all of our investors were male. If you think about it, it’s hard for them to relate to ovarian cancer and understand it at that level. But what we’re seeing in the last few years is a changing tide in leadership. You’re seeing more female CEOs. For the first time, the American Cancer Foundation has a female leader. You’re seeing an increase in female founders. This is systematically changing the interest in women’s health. 

Which speaks to the fact that there has been an annual prostate cancer screening test on the market for years, but nothing for ovarian cancer. Can you tell us about your fundraising process as a female founder in the women’s health space? And do you have any advice for other early-stage founders?

I come from a sales background, so I knew I needed to have a really, really big funnel—it’s playing the numbers game, but doing so in a very strategic manner. The first thing I did was look at who was investing in women’s health while also looking for female investors. I only contacted people who I knew would find my story impactful. The next level was people who invested in diagnostics, who were at least going to understand the diagnostic pathway. But more than anything, it was playing the numbers game—my lead list of everyone I spoke to for this round is close to 200 people. Eventually, that narrowed down significantly to the number of people I had second and third calls with. For this reason, it was really important to be on top of my followup list and to stay incredibly organized. I managed my calendar to make sure I followed up with people within a day, never letting things sit in my inbox. Fundraising is thrilling, but it’s also exhausting. It’s about mentally preparing for that. You never know how long it’s going to take, but for a certain amount of time, it’s going to be a wild ride. Knowing that it’s a marathon and not a sprint really helps. 

One other thing as founder is to remember you’re an investor on the other side, as well. It’s not just the investor doing diligence on you, it’s you doing diligence on the investor. Are they the right fit for you? They may be a wonderful team and really nice to speak with, but if they don’t understand or believe in your mission, then they are going to be more challenging to work with down the line because you may have to hand-hold them a little bit more, or you may have to explain how clinical studies get delayed and make them feel more comfortable. I really tried to focus on finding a match and understanding, okay, do I resonate with them? Do they resonate with me? 

Do you have any favorite platforms or tools you used for fundraising tracking?

I used a simple Excel file and OneNote notebook. In my notebook I have one page per investor and I track every call so that I can also see the order. I number the calls so I know it took me six calls to close them, for example. Then in my Excel file, it’s very simple: who my main point of contact is and how interested they are. I have a funnel from “lead” to “interested” to “meeting completed” to “committed”, or whatever it is. 

Every day I would use my Excel file to see where I was at. If I needed further details, I would go into my notebook. I also have a process where at the end of every call, I add that investor on LinkedIn as a simple thank you. Because again, that’s just raising awareness. We publish a lot on our social media so the more they see us, the more they’ll learn about us and stay updated with our story. Then I just make sure I do my follow up within 24 hours.

Did you encounter any differences when talking to male investors versus female investors? Many female-founded companies struggle to get female investors on board, which surprises them. Oftentimes, it’s because of that risk appetite. 

It was definitely a struggle to find female investors. It required a lot of conscious effort. I could have closed our round with all male investors but we made the conscious effort not to do that and let it take a little longer. It’s similar to the way you handle hiring. If you think about the pool of wealth and historically how it’s worked, men have much more generational wealth. We’re starting to get to the stage where women are having more generational wealth or women are becoming partners at VC firms, but if you’re playing the numbers game and you’re speaking with 100 people, you’re lucky if 20 of them are women.

If you need to funnel down from there, then you need to make an effort to get more than 20. You have to hunt harder. We made the conscious effort to do that because that was something that was incredibly important to myself and Alex. Once we spoke to female investors, I don’t think I got turned away more by women than by men. People really resonated with the fact that they were going to a doctor’s office and it was hard for them to find a solution—plus, the number of people who actually knew someone with an ovarian cancer diagnosis. With women, it clicked a lot faster. With men, I would say the most common question was, “How does this compare to the prostate cancer screening test?” And again, that comes down to “How can I relate to this?” We were always checking our numbers, making sure that we had a certain amount of female investors at all times, even if they were female partners in a fund who were going to be supportive of what we were doing. It did take an enormous amount of conscious effort.

What is your plan for this round of funding? What will it be used for?

Three important things. First, we’re at the stage now where we can develop the assay from a proof of concept in academia to an industry standard test. The second is starting our regulatory process, submitting the first part of our package to the FDA before the end of 2021. The third is preparing for our prospective clinical trial, which will happen in 2022. That includes identifying which hospitals and which doctors we’re going to be doing the trial with, aligning on the protocol, getting the ethics approval. All of this takes a lot of time and a lot of organization. It’s likely we’ll work with 20 different hospitals, multiple sets of different doctors, so we need to get everybody on the same page before the clinical trial begins. 

We are also going to add one more person to our team in the short term, which is the director of clinical operations, who is going to be to help lead the clinical trial. Then next year, we’re also adding scientists to our team for development. In general, our team is going to remain very lean. This is the model that we’ve run in the past. We do this in the early days from a cash perspective, but also because the expertise that we need changes quite frequently as we get through the development process. We think about what kind of expertise we need through certain stages and then engage with consultants who are experts.

Finally, where do you see AOA in five years? 

My grand vision is twofold. First, I want to get an ovarian cancer diagnostic on the market for patients as soon as possible. Tactically thinking, it’s about getting this test into the hands of doctors so that when women show up, there’s an option for them. Long-term from there, I want to develop AOA to be the next big diagnostics company focused on catching cancer early from blood, really filling in gaps where there is a lack of tests today to catch cancer earlier: breast cancer, small cell lung cancer, glioma, and multiple myelomas. Those four are on our radar; from what we know about where our targets are present and where there’s a need in the market, that seems like a natural next step for us.