Business

Introduction

Our aim is to improve the design of our device by determining the societal impact of our circulating tumour cell (CTC) detection device. Our device is able to detect CTCs of various cancer types from blood samples, which we foresee as being an integral part of cancer diagnosis in the future worth investing in.

To get his views on this issue and to determine if our test can be scaled up to allow it to be deployed at hospitals, we interviewed Dr. Ralph Schiess, whose answers were greatly beneficial in helping us improve the design of MicroBeacon and setting our outlook and business plan. Ralph is the co-founder of ProteoMediX, a company developing a tool for detection of prostate cancer. We also asked him about his company's history and the procedure he went through to found it.

Talk with Dr. Ralph Schiess from ProteoMediX

Founding a company

The first phase in commercializing a product is research, demonstrating a proof of principle and the concept, which takes about 3 years. Then, you specify your product precisely and test it extensively, which can take about 5 years and is expensive. Ralph roughly estimated the amount of money we would possibly need to bring our test to the market to be 15 to 25 million Swiss francs, equivalent to $16 to $26 million.

A proof of concept device does not necessarily have to be simple or elegant, it only has to work. Once the validation phase is reached, the product has to be developed to the point that it can be demonstrated on a much larger sample of patients. In the last phase of development, the product takes its final form and applications for a CE certificate and FDA approval are submitted.

Food and Drug Administration and CE marking

From here, we discussed the procedure for getting approval from the Food and Drug Administration (FDA), Swissmedic, and other authorities. Ralph explained that two differing procedures exist, one for Europe and one for the USA.

To commercialize a product in Switzerland you need a CE mark, which is easy to obtain for low risk tests such as ours. A test is defined as being “low risk” if a false negative result carries a low risk for the patient/user. Cancer diagnosis is still low risk, whereas tests for HIV and other infectious diseases pose a high risk. The requirements and workflow to get CE approval are roughly as follows: you have to first present a reliable, reproducible test, then go to a notified body and fill out several forms. When CE approval has been granted, you are allowed to market your product. For the test to be marketable, however, it must undergo clinical testing in addition to the tests required to get CE approval.

In contrast to the CE, the FDA has tighter regulations for diagnostics and showing clinical validation is required. Once FDA approval is granted, however, the test is marketable. In order to get FDA approval and market a test in the USA, in most cases, it is beneficial to incorporate a daughter company in the USA before starting the process. The procedure is also more costly than getting a CE. However, having FDA approval greatly expands your market, so it pays off eventually. Different labels exist for a given diagnostic test according to the stage of development, which includes RUO (research use only), IUO (investigational use only, that means it can only be uses for clinical studies), and IVD (in vitro diagnostic test).

Scale up and industrial production

Ralph also explained to us how it would work if we would like to scale up our project and have it produced industrially. “When you want to get access to the market you could either do it by partnering with one of the big companies to get on their machines. Or you go directly with your own tests.” The procedures for the two paths are slightly different.

Find a clear medical question to answer

Talking about how to sell a test well, Ralph also said that we should think about a clear medical question to answer with our test. For example, the test from ProteoMediX gives a clear answer for prostate cancer and has a defined goal: avoiding unnecessary biopsies. At the moment, with our test, we just check if the patient has CTCs. However, “the doctors will ask, what type of cancer?” For medical doctors, a test is useful only if it has medical consequences (actionable results) such as a more personalized treatment, a better survival rate for the patient, etc. For cancer treatment, “there are now markers needed to differentiate which [type of] chemotherapy, [what] kind of treatment, which drug [to use].”

We then went on to discuss some specific applications of our MicroBeacon product. With MicroBeacon, we will distinguish cancer cells from normal cells from a blood sample. Our system can then be used for two potential applications. The first one would be early diagnosis of cancer. For instance, it was demonstrated that lung cancer is discovered often really late. However, patients often produce CTCs before the cancer can be diagnosed by current methods. Unfortunately, our system in its current state cannot determine if a CTC is from blood, lung, prostate, or any other kind of cancer. Further characterization would require some additional sequencing steps. The second potential application would be for patients in the remission state of a previous cancer. Our system can be included in the routine of periodic cancer screening tests that patients have to undergo. If CTCs are found one or two years before the emergence of metastasis, it would improve the survival rates of those patients. Furthermore, we will already have an idea of where the cancer originally came from and treatment can be better targeted towards the patient.

Answer questions with a test – do not produce more questions

In general, a diagnostic test that leads to further questions should be avoided. “A medical doctor will use a test only if it can answer a very clear question and have an actionable result. If you think about a business idea in diagnostics, your test needs to have a clear, actionable result.” So as a business idea, our MicroBeacon test could be applied in the following way: someone has a localized cancer, the localized cancer gets removed, and while waiting to see if the tumor comes back, our test can be used for monitoring/testing for reccurrence to help initiate early testing and improve the patient's chance of survival.

Many circulating tumour cells vanish when the tumour they originate from is removed. However, some tumour cells can survive up to several years in the blood stream, waiting for a good opportunity to settle and initiate a metastatic tumour. That’s why many people come back to the clinic every year or even more often to do a test. So routine tests are done anyway, but our test would be cheaper than conventional tests.

Sensitivity and specificity

Ralph later asked us about our test's sensitivity and specificity. Conventional tests are highly sensitive, but not as specific, so you get a higher false positive rate to avoid false negatives. With our approach, ideally, we want very high sensitivity to allow our test to diagnose early. If our test does get deployed at hospitals, it would be developed to sort the target cells, capture the cancerous ones, and then sequence them to determine which mutations they carry. In this context, false positive are acceptable, “because then you find out [if detected positives are true positives] at a later stage”. However, Ralph Schiess suggested that we should try to limit the number of false positives in our design, which is why we decided to include two sequential filtering steps to increase our specificity.

Never lose the business view – elevator pitch

When trying to develop a business plan, when explaining an idea to someone, it is important to never lose the business view of a project; it helps a lot to explain things in an easy understandable way, focus on the really important matters, and shape an idea. “For marketing it is important they can associate a clear idea with your business case, so they remember you. Its good for marketing, but it also helps you to shape your idea. You can get easily lost in writing all the technical aspects.”

Ralph also explained to us the concept of the “elevator pitch”: “you should be able to explain an idea in 90 seconds in an elevator...so you take out really the essentials. It can be like shells: you can always further explain it. The title and first two sentences should be really good!”

Faster, always faster

Answering our question about what he would do differently if he were to found another company, he said: “Nothing. But I would try to make it faster, always faster. If you do it the first time, you try to avoid stuff, to think twice. In the very beginning, it is hard to take the full risk, because you still think about opportunities/your academic career, it all takes time. One could do things quicker. Nevertheless, we avoided a lot of mistakes by doing things properly.”