Positive Bioscience is a leading provider of advanced cancer testing for Indian cancer patients. Their flagship product, PositiveSelect is a testing range based on next-generation sequencing (NGS). In this fascinating interview, Founder and CEO Samarth Jain describes the benefits that NGS brings to cancer patients, and the challenges it needs to overcome in order to be standardized into our healthcare systems.
Please describe the story behind the company: What sparked the idea, and how has it evolved so far?
I started Positive Bioscience in 2012 with the intent to bring the latest next-generation sequencing technologies to India. My background is not in medical sciences. I studied economics at the University of Illinois at Urbana Champaign. After that, I worked at a McKinsey, one of the largest management consulting companies out there, until I decided to do something on my own, with some help from my aunt in America, who is a scientist. She advised me that, especially for cancer patients, there was no next-generation sequencing testing available in India.
It took us two years to build, validate, and launch our service commercially, and we were the first to do next-generation sequencing-based testing in India. No one had done it before us and even as we met with doctors, none of them had ever got to use such technologies, so it was quite exciting for them to see the market evolve, from literally being at the start to where it is today. It’s a developing market, so every year we improve our testing and update our testing.
In 2015, we partnered with an American company called Myriad Genetics, which is one of the largest cancer testing providers in the world. We’ve been their exclusive partner in India since then. It’s been really exciting for us to bring a leading American testing provider and represent them in India, while seeing the processes they follow and the high quality they bring to the market, allowing Indian patients to get access to those tests for the first time.
We all know that India typically lags a couple of years behind the Western world in terms of having the latest medical technology. We’re excited to be one of those companies that try to bridge that gap and bring the latest testing for cancer patients.
Many Western markets are purely insurance-driven. In the US, for example, insurance usually covers next-generation sequencing-based testing for cancer patients. In India, it’s more of a self-pay market, which means that patients have to be able to afford such testing.
When we first launched this service, a patient had to pay about $3,500 per test. Now, for an equivalent test, you only pay about $700. So the prices have dropped a lot over the years, and that’s both driven by technology and by volume.
We are happy to be one of the oldest and most reputable providers on the market. We’ve carved a niche for ourselves as being the highest quality testing provider in India. We will never be the cheapest, but people come to us because they trust our high-quality testing, and they are willing to pay a little extra to get that differential, as compared with other labs.
As an example of that, one of the important things with testing is coverage, meaning the number of times a test is repeated in a next-generation sequencing machine. Obviously, the more times you do the test, the more accurate the results would get. We’re the only company in India that offers it at 1000 max coverage. The next companies after us offer 500 tests, and most other companies offer 250 or less.
If you read the research articles out there, doing under 500 tests already makes doctors a bit skeptical, questioning whether they can trust that report. Of course, taking fewer tests is cheaper, and the people who are paying for it obviously want the lowest possible price, but then it becomes an issue of trust. As a doctor, the question is can you really trust this report when making critical decisions about patients. Many doctors get into this ethical dilemma when their patients show up with some tests, but they can’t be sure whether they can rely on the results.
We were the first company in India to partner with a leading hospital to open a personal genomics clinic. For the first time, people in India could go into a hospital, get a genetic test done to see if they’re prone to certain diseases and have a counselor right there in the hospital who can set up further appointments with specialists. That was a really exciting moment for us because until then, even if you could get tested, which was very rare, it was always done in the fringes and shadows but never in a proper institution.
How can genetic testing shed light on the treatment of cancer?
Genetics and cancer testing as a research field has been around for decades. The reason people test cancer patients is that certain drugs, medications, and treatments that you can give to cancer patients respond when a particular gene is positive or negative.
For example, if you look up lung cancer in the American NCCN guidelines, which set the tone for the rest of the world, you’ll see nine genes are recommended to be tested before treating a lung cancer patient.
For breast cancer, there are famously three genes that almost every breast cancer patient will get tested: Her-2, ER, and PR, and that guides the treatment.
What we’ve discovered a long time ago is that certain genes being positive or negative can greatly influence how a patient responds to a particular treatment. Previously, they were testing one gene at a time. What’s changed over the years is our ability to test many genes at the same time.
With cancer, you usually test the tumor block, which is pretty small, especially in lung cancers where you have very little to test with. But with the advent of next-generation sequencing, you can test hundreds of genes at the same time. You no longer need to conduct hundreds of tests, you can do one test that gives you information on hundreds of genes. This had been a game-changer in cancer treatment.
NCCN, as well as EU guidelines, have started to recommend more genes being tested in different cancer types, because it’s now technologically feasible and the price keeps coming down, leading to the release of more cancer drugs that target specific genes. This is called a driver mutation; a mutation in a gene that causes cancerous cells to grow or accelerate. It has a big role to play.
As more of these genes are identified as drivers for cancer, more pharmaceutical companies build treatments to target these driver genes. Once the gene is targeted, then obviously, you have to test that gene before you give any treatment. There are some drugs out there, especially around immunotherapies, where you have to test hundreds of genes to see, for example, the tumor mutation burden of a patient. If it’s high, you’re more inclined to use immunotherapy, whereas if it’s low, you may want to take another option besides immunotherapy. To do that, we have to test at least a couple of hundred genes and get an accurate count.
More information about this can be found in this video by Positive BioScience:
What other medical fields is this being applied to?
Other diseases are also on the rise for genetics-based treatment. While cancer is clearly the leader, neurological diseases are not too far behind. They’re testing more and more genes now before treating patients. I think that soon, this will be the standard testing for almost any kind of chronic disease.
The reason that cancer took the lead on this is that people found more immediate success in it, compared with other diseases, but many more diseases are following this path and many drug companies have already put out genetics-based drug efficacy testing against particular diseases. I know of several companies that are doing this for neurological diseases and heart diseases.
Infectious diseases like COVID are a whole different ball game, so I’m not going to go down that road right now, but for chronic diseases like heart diseases, diabetes, neurological disorders, and arthritis, it’s going to come in slowly but surely. One by one, all medical fields will embrace genetic testing.
Right now, unfortunately, the medical system relies on trial and error. They just have to give everyone the same treatment, see what happens, and then go from that. Of course, when it comes to medicine, one size does not fit all. If you give aspirin to 100 people suffering from a headache, you’d get a small percentage with a negative reaction, and another small percentage which showed no impact at all. The whole idea of gene-based testing is to figure out what treatment the patient will respond best to, and what treatment they are less likely to respond well to.
I think that in the future, as with cancer, it will become a standard procedure to first test a patient’s genes and then figure out what treatment they should get.
Keeping cancer aside, this is a once in a lifetime test. You can map out one’s whole genome at birth, and give access to their health care providers. It’s a very good investment to make for a newborn child, that will be paying itself back for the rest of their life.
As researchers get more insights into which treatments will work better if a certain gene is positive or negative, the correlation between treatment and genes becomes more widely known and accepted.
How can DNA data be standardized into our healthcare systems?
If we look at it on a more micro level, we see that there are already certain hospitals that insist on running the entire genetic profile of a patient before treating prostate cancer. But to standardize it in a healthcare system, you’d need a lot of different components to work together.
Firstly, you need good government regulations around when exactly to use this, and when not to use it.
Then you need a lot of education at the doctor level about when you should follow reports and when you should think twice before following a particular report.
One example we often encounter is when a report might put out an aggressive drug for treatment, but if the patient is a 90-year-old woman, chances are that drug would harm her. Obviously, even if the report said that genetically, she might be more prone to get benefit from this particular drug, a doctor would not do that, because other factors would rule that treatment out.
Doctors need to be guided in applying reports on a case by case basis because you can’t just take a test and start treatment based on that without looking at other clinical factors.
Then, I think that insurance will have to play a large role in this, by reimbursing these tests. In the US, insurance has started reimbursing most genetic tests for cancer patients. I think the reason for that is they’ve realized that by getting patients on better treatment more quickly, they can cut down their costs. Especially in America, where hospitalization is very expensive, it’s in the insurance company’s best interest to get the patient out of the hospital as quickly as possible. That needs to be thought through as well.
Of course, governments have to ensure that insurance companies don’t take advantage of their access to people’s DNA data in order to overcharge them. You might be more prone to X or Y, but that shouldn’t be a reason to raise your coverage, so that has to be balanced as well.
We also need patient education. One of the things that we see with many cancer patients is that once they get diagnosed, they want to get treated right away. That often gets in the way of running tests, waiting for a week, getting some results back, and then starting a better treatment based on that. We have to educate the patients that sometimes, the right thing to do is not to pull the trigger right away, but to understand a bit more before you do it.
The last thing is that before we can start applying genetic testing vigorously to everyone, the price needs to come down. I’m using India as an example because I’m most familiar with it. In a developing country like India, where the income per capita is low, most people will not want to take a test that costs 10 times their monthly medical expenses unless they understand the benefits. Of course, if someone’s life is in danger, that always changes the equation, because they want to get on the better treatment right away.
The cost of tests has been coming down a lot. Some companies, like Illumina for example, have invested a lot of money in research and development and built machines that continue to pull the cost down. Ultimately, they should aim to make it economic for everyone, not just in first world countries.
How do you use the data that you collect, and what are you hoping to achieve from it?
A lot of the tests we run require us to collect data. Before testing anything, we need to know the patient’s age, gender, the type of cancer they have, and other related information.
For example, we have a test called EndoPredict which tells women with breast cancer how likely they are to relapse in the next decade. In that case, we need to know the pathology of a patient’s tumor, it’s nodal status and size, just to run the test. That is the kind of information we collect.
We have been very prominent in publishing data, anonymized of course, so you cannot trace it back to an individual patient. We have many international publications in many prestigious venues. For example, a couple of years ago we published data on 300 Indian lung cancer patients where we shared their genetic profile with the world.
Very few studies have been done on Indian patients, compared to other countries, and if you pick it per capita, then it’s significantly lower. So we as a company definitely believe it is our duty to publish as much anonymized data which is collected ethically and with the consent of both the patient and the doctor. We would never publish anything identifiable, but publishing such anonymized datasets is not only helpful for our company’s good name, but also for researchers and other Indian patients whose doctors may read the publications or were involved in writing them.
How do you envision the future of your industry?
Even though cancer testing in India is a huge market, next-generation sequencing-based testing is horribly underrepresented. Even with us and all our competitors combined, we are not doing nearly the amount of testing that should be done. It has been growing, but it hasn’t even reached 1% of Indian cancer patients, whereas in more developed countries, about 50-70% of people with advanced cases will be getting such tests.
India has a long way to go but it is ramping up. Even the Indian government has understood that this is an area of support and has been investing in different technology applications for the last five or six years.
One of the surprising things about the Indian market is that very little consolidation that has taken place. In other countries, like the US, there’s a plethora of deals happening where bigger companies acquire smaller companies. In India, we just haven’t seen that business consolidation happening around diagnostics and health. I think consolidation would be a positive driving factor in India because it would give companies more scale, and allow them to lower the prices further down. In our market, which is not purely insurance-driven and very price-sensitive, that’s a big deal. Cutting the price by 25% or 30% in a two-year span would increase the affordability to many patients.
As a company, we continue to invest in R&D. We continue to update our gene panels and invest making our reports more accurate, and to make sure that we have the latest information presented by guidelines and other places into our databases so that every patient can get the most up to date report possible at that given point of time. We invest a lot of money making sure that we’re doing a good job for patients.
In the short term, as more publications come out and as more cases are discussed in the medical community, doctors are more inclined to recommend next-generation sequencing testing to their patients.
In the long term, it’s even more exciting because we have a technology called CRISPR, which has been actively tested in many different parts of the globe and is potentially a game-changer. We’ve never seen anything like that in all of human history; we’ve never had the ability to play God and edit someone’s DNA until now.
These days, if you have a particular gene that is known to be causing your cancer, we can’t stop that gene. The best we can do is give you treatment to balance it out. But in the future, with CRISPR technology, you’d be able to completely turn that gene off. That’s a once in a generation technology that’s going to change medical care forever.
Of course, I’m not advocating that every patient should get their genes modified or that doing so is even responsible unless they have a dire need for it. Editing genes is very risky because we don’t yet understand the consequences. Once we manage to improve the technology and the consequences, and once we make sure we’re not polluting the gene pool of future generations, then we can do it safely and ethically and it will change everything.
