Jim Posillico has a long academic and commercial pedigree in reproductive medicine, having spent time as a researcher at Harvard Medical School, Serono Laboratories, the Ares-Serono Group, InterMune Life Sciences and SAGE BioPharma.
So when he learned of a metabolomics platform being developed at McGill University, he was quick to realize its applicability to a variety of potential conditions and disease states. The technology allows the comparison of biomarkers produced by cell metabolism monitor the progress of diseases like Parkinson’s and Alzheimer’s.
Based on his recognition of the possibilities Posillico’s four-year-old venture, Molecular Biometrics Inc., bought the intellectual property for the platform from McGill and began using it to compare biomarkers from embryos that produced successful pregnancies with those that did not. The company’s flagship product, ViaMetrics-E, is based on that research. It’s a point-of-care diagnostic that doctors can use to help determine the most viable embryos to transplant following in vitro fertilization. In January, the company raised $12.5 million in Series B financing, which it used to accelerate the ViaMetrics-E launch, which came in March.
MassDevice spoke with Posillico about his firm’s technology, which is on the market in Europe, Turkey and Australia, it’s plans for a U.S. launch next year and why it could help cut the costs and burdens to the healthcare system stemming from pre-mature and multiple births.
MassDevice: Molecular Biometrics seems to have its hand in a number of areas — reproductive health, degenerative brain disease, pulmonary metabolism and fetal medicine, for example. Can you give us a primer on the company’s origins and how its metabolomics technology is applicable in so many different disciplines?
Jim Posillico: The fundamental IP behind the technology was developed at McGill University and the applications, at that point, were in therapeutic fields other than assisted reproduction. The field of maternal fetal medicine and neurology were all areas that had been explored by the primary investigator early on. When I became aware of the technology and saw how it worked or what the scientific rationale for it was, I thought I might be able to solve an age-old problem in the IVF arena, based on my background and experience in that field. So what we did when we built the company, we took the options on the license from McGill, we got the existing intellectual property but we drafted additional new IP to look at the application of this technology, as a metabolomics platform, to look at embryo assessment.
That worked out pretty well for us. Our company is focused on assisted reproduction and we’ve developed our first product using this platform to assess embryo viability for in vitro fertilization; the original patents in which the technology was first applied or tested were IP that the company owns, but they weren’t really being explored at that time for obvious human and financial resources of a small co. We have a nice portfolio of IP based on this platform of metabolomics using infrared spectroscopy and we selected, for a variety o reasons, mostly my familiarity with the marketplace and my understanding of the the opportunity, we decided to focus on IVF.
The second part of the question is that, as a platform, this is one of those technologies that looks like it’s going to be probably applicable to several therapeutic fields. That’s evidenced by a lot of the IP that we’ve already been working on. What we’re doing with our technology is looking at metabolomic biomarkers that exist in cells as they differentiate and grow and function. And so one would conceivably feel that this could be useful in several fields. What we’ve been able to show with the embryo, for example, is that when the embryo is as small as maybe four or eight cells combined together, we can get biomarker signals from those cells that give us a good idea as to whether that embryo has the potential to produce a baby or not, or whether that embryo may be malfunctioning or the cells may be malfunctioning to the extent that it has a low probability of producing a baby. If you take that same fundamental concept and apply it to just about any other cellular mechanism you want to look at, it becomes a nice platform for looking at diagnostic biomarkers of other diseases, namely Alzheimer’s or Parkinson’s. Although our primary focus is on the embryo, we do have a substantial grant from the Michael J. Fox Foundation to use this technology as a methodology to diagnose and monitor Parkinson’s disease. We’re doing that with grant money, so it’s non-dilutive to our financing, so our board doesn’t mind that we go ahead and try to expand our therapeutic applications.
In one sense, while we’re really a 95 percent assisted reproduction company, we also have the opportunity to develop in parallel the applications in Parkinson’s disease. That’s very exciting to us, because of course it’s a very different disease state, it has a lot of regulatory barriers, but nevertheless gives us the opportunity for corporate growth, perhaps through other partnerships and licensing this technology to other pharmaceutical groups.
The Michael J. Fox Foundation support has allowed is to put together a study involving some of the most impressive opinion leaders in the Parkinson’s disease field. We’ve been able to tap into a cohort group of patients that are being followed longitudinally over several years, so we get access to these historical specimen databases on which to build our analysis. That’s crucial in terms of being able to develop this technology. Really the way you develop this technology is you get a bunch of patients who have confirmed Parkinson’s disease and begin looking at the metabolomic biomarker profiles in those patients’ blood serum samples, compared to age-matched controls who are disease-free.
That’s very analogous to the way we studied the embryo. We looked at the metabolized biomarker populations and profiles of embryos that we know went on to produce a pregnancy, and compared those to the biomarker profiles of embryos that did not produce a pregnancy. And then through some sophisticated algorithm development, we can separate those two populations and create predictive algorithms for identifying healthy versus unhealthy embryos. The same applies to Parkinson’s disease, Alzheimer’s disease, fetal development, pulmonary edema and so forth.
The interest that we see in this technology, not just our own, there are many companies who see the value of metabolomic platforms, we just happen to use a very, we think, simple, much more cost-effective technology of near-infrared spectroscopy to mine this data. Rather than more expensive technologies like mass spectrometry or nuclear magnetic resonance imaging, both of which are more expensive and not practical for point-of-care diagnostics instruments because of their size and cost.
We actually developed this technology in less than four years, which I’m very proud of and proud of our team for doing. Now that we’re in the market, we’re very excited about getting established. The technology as a platform allows us to look at some very logical extensions in the IVF field. We see this as not a one-product or one-technology company.
MassDevice: You have an extensive background in endocrinology, pharmaceuticals and reproductive medicine. What prompted you to co-found Molecular Biometrics?
JP: I saw the data they had amassed looking at amniotic fluid and looking at metabolomic information in the biomarker profiles that were associated with pre-term deliveries and final birthrate in babies and I thought, “Gee, that’s really remarkable.” If you think about the baby and amniotic fluid, it’s an extension of the embryo and culture media fluid in the laboratory. We were very excited about the fact that we were able to access the technology, build the company around it and then we took all of our energy and all of our, at that time few dollars, to probe the application of the IVF market. Not only did I know the market well and have experience in it, just from a business point of view IVF is a very classical, very nice little niche market compared to maternal fetal medicine or neuro-degenerative diseases, which are huge and have challenges in their own right. And they have also very extensive and complicated regulatory pathways with the Food & Drug Administration to get products approved.
So we felt we could, from a business point of view, be more successful with this technology in this market niche of IVF, rather than in a much larger market space that was going to require much more money as well as more time to be successful. So the business case was easy to make with the IVF application, versus some of the other applications that were potentially wrapped up in the IP.
MassDevice: Your first product, ViaMetrics-E, is a non-invasive method of assessing embryo viability. It’s on the market in Australia, Japan, Greece, Ireland and the U.K. Where are you on the pathway to getting that to market in the U.S.?
JP: It’s been launched in several countries in Europe as well — Italy, Spain and we have others pending, Turkey, actually — we just literally launched in the first part of March and we’re still in the frenzy of getting into the marketplace. It’s a pretty exciting time. It’s a CE Mark and just by comparison, we do have an FDA trial underway. We hope to get that done and a submission in place by the end of the year and go through the regulatory review process in 2011. Now the interesting thing is that the market barriers here are obviously much higher, because of the FDA, than they are in Europe for this type of product. The other thing, coming back to the business case, is that the more rapid and larger markets for IVF are really outside the United States. The European community, for example, is the fastest-growing market. They do almost three or four times as many IVF cycles as we do in the U.S. The other really important part of it is that the IVF cycles in Europe, for example, are paid for by the healthcare systems in those countries. So we have a lot of business case reasons why we wanted to market outside of the U.S. before we entered into the U.S. market, which is unusual for a U.S. company. We hope to be launched in the U.S. next year and in the meantime we’ll be building a lot of sales and experience with the instrumentation with other countries. I think it’s going to be an interesting dynamic that our own docs here in this country will be among the last to see the product, which is unfortunate.
MassDevice: How will the healthcare reform act affect Molecular Biometrics?
JP: Probably negligibly. Based on what little I know about this healthcare act — I probably know as little as anyone in Congress at this point — if it follows suit with the Clinton reforms, IVF isn’t even on the radar. What happens is that the IVF market is a relatively small market, so if you compare that with the bigger healthcare issues of the country it really doesn’t get much attention. It will probably be a neutral event at the end of the day.
In this country most of the IVF is paid for out of pocket. We don’t have very good insurance at all for IVF, and the only two states that really have any meaningful requirements for insurance coverage are Massachusetts and Illinois. And then Connecticut and new Jersey have some pretty good legislation, and the rest of the few states that have any legislation to support IVF or fertility treatments are very small and modest reimbursement schemes. People still pay the lion’s share of IVF out-of-pocket. Government’s not going to change that paradigm. It will have to be private insurance groups that find a value and a rationale for doing that.
MassDevice:So how much effort went into investigating the reimbursement landscape during the planning stages?
JP: In this country, very little. Of course, we looked at it very deeply in the sense that we understand it, the paradigm for reimbursement for IVF in this country is very well-established and because it’s a private pay modality, patients as you can imagine are a very highly motivated group of individuals trying to get pregnant. They do things like mortgage their houses and do without just to pay for one cycle. When there’s a new treatment, such as what we’re providing, we historically have seen in this field patients will demand that new technology to help them conceive a baby. They’re very alert, very well-educated, higher-income-bracket individuals. They seek out information and they know about these technologies, often before they come to the marketplace, and will often demand them from physicians. So it’s a consumer-driven or patient-driven initiative that helps us become prominent with this product in the marketplace. In Europe or Israel or Australia, for example, where the government pays for a whole bunch of cycles, you can have as many babies as you want by IVF in Israel and I think you can have up to six IVF cycles in Australia. It goes down from there in terms of different European countries.
In those scenarios, reimbursement is really a very important factor, because there the government’s paying for IVF so more people get to participate in it. The challenge is, when you come down toward the end of the IVF procedure when the embryologist and the doctor have to make a decision on which embryos they’re going to transfer. Right now the only way that decision is made is by looking at these embryos under a microscope and, based on their morphological appearance, trying to judge which one might be more healthy or more viable than the next one. Of course, visual acuity is not an indication of biological function, and that’s one of the reasons why our success rates in IVF are very low. What we’ve been able to provide is another biologically based metric to help docs make that decision. As an objective, biological measurement, they can use that information from our test, combine it with morphological examination of the embryo, and do a much better job at picking the best embryo. Our data very clearly show improved pregnancy rates as a result of this procedure.
MassDevice: Are there any ethical issues involved with the ability to determine the viability of embryos? Are we ready, ethically speaking, to have access to this ability?
JP: That’s a really good question. We get fragments of that, in different formats, a lot of times. I think it’s important to first make a distinction between genomics testing and our testing, which is a metabolomics platform. If you think of this scientifically, metabolomics is sort of the terminal downstream event of gene expression. In other words, the gene expresses a certain effect or cellular activity, and in response to that gene expression, the cells will undergo certain metabolic processes. The results are what we’re measuring. We’re not measuring the gene.
So we get what we call an assessment of the phenotype, or the living cells or the person, at that point in time. The gene sort of assumes that when you understand the human genome, you can get a picture of the relative health of that organism or its susceptibility to maybe being a carrier of a disease, or that person’s propensity for developing testicular cancer or breast cancer, what have you. So the genomic work is very different than our work, and it’s the genomic work that gets people more scared. Because the genomic work is where you can alter things, or select — which is the more scary event — one desired genetic trait over another, whether it’s blue eyes or good IQ. Those are things where you get, I think, a little into the shady side or the ethically questionable side.
What we measure in metabolomics is so far downstream from the gene that we can’t alter that. We’re not going to alter anything in the cells, the cells are already created, their genomes already made up by the parents. We’re not interfering at that level at all.
We rarely have an indication that an embryo is non-viable. What we’re able to say is that there are embryos within a group of embryos that are much more viable than their sister embryos. In other words, when IVF is conducted a woman can produce anywhere from six to 12 good-looking embryos, called a cohort of embryos. Looked at under a microscope they all look very similar, but they don’t all have the same reproductive potential. Figuring out which ones have the greater reproductive potential in terms of producing a baby is really a challenge. What we’re doing is saying, within that cohort of embryos, regardless of how many embryos there are, we’re trying to identify the top two or three that would be the best candidates to transfer. Ultimately it’s not very different from what’s done today, in fact it’s not different at all. That same assessment is done by morphological examination.
I can tell you right now we want to, as most companies do, avoid even the hint of controversy, because that’s not what we’re trying to achieve here. What we’re trying to do is help couples make a better-informed choice and help their doctors make a better-informed choice on which embryos to transfer and therefore increase the treatment outcome.
The other important thing here is that in this country we have a long history of transferring many embryos in an IVF cycle. This has led to this problem of multiple gestations and multiple births. The “Octomom” is the poster child for that. One of the things we expect to be able to do with this technology is to reduce the number of embryos that have to be transferred in an IVF cycle to produce a pregnancy. The goal in that is to reduce the incidence of multiple gestation. Right now the reason more embryos are transferred than need to be is because the docs just don’t know which one is good and which one is not good.
What we hope to be able to show is that one can reduce the number of embryos transferred without compromising the pregnancy rate and therefore we begin reducing the multiple pregnancy rate in this country. Pre-term birth is a $24 billion healthcare cost to the country. Most of the pre-term deliveries come from IVF. Bringing babies into the world prematurely is not good and, unfortunately, that’s a higher incidence among IVF babies than among the general population. In fact, more than 50 percent of all IVF births are multiple gestations. But in Europe for example, what the government said is, “Look, you guys are doing IVF. You’re having all these premature babies being born, and we can’t afford that. So if you want our government to pay for your IVF cycle, you can only have one embryo transferred.”
As soon as these laws were passed and IVF centers were doing single-embryo transfer, literally the next year the healthcare costs in those countries — led by the Scandinavian countries — the healthcare costs in those countries dropped dramatically because they weren’t paying for neonatal intensive care units, they weren’t paying for young babies becoming older babies and children with healthcare problems and then adults with healthcare problems. So the legislation was really powerful and good legislation in terms of controlling healthcare costs. In this country, we don’t have that. We just won’t pass those laws in this country, so its up to the doctors to decide how many embryos to transfer.
In our FDA clinical trial, the FDA really identified with our recommendation, which was to do our clinical study in single embryo transfer IVF cycles. Because of that, all but two of our IVF centers involved in our FDA study are outside the United States, because nobody’s doing single embryo transfers in this country. When we developed our technology, through the proof of pilot and proof of principle studies up the FDA trial, we gathered more than 3,000 IVF cycle samples and most of those came from outside the U.S. again. In this country, I hate to say it, but we’re way behind the curve.