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Name:
OC-2020-002
Description:
Overcoming the challenges of precision medicine: an interview with Emily Leproust
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T00H14M32S
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https://asa1cadmoremedia.blob.core.windows.net/asset-14a7d85d-6392-451f-ad78-6ea169ecbcb9/Emily Leproust Twist Bioscience interview.mp4
Upload Date:
2020-07-14T08:53:43.4770000Z
Transcript:
Language: EN.
Segment:0 .
[MUSIC PLAYING]
EMILY LEPROUST: I am Emily Leproust. I am the CEO and co-founder of Twist Bioscience. Twist was founded seven years ago, now. And the purpose of Twist was to build a platform to write DNA using silicon technology and, from the platform, be able to develop tools to help in synthetic biology, in next-generation sequencing, in drug discovery, as well as in storing data in DNA.
EMILY LEPROUST: [MUSIC PLAYING] So if we step back, in the past, the study of cancer used to be done by pathology studies that were looking at the growth morphology of cells and/or with the tumor stainings. And those technologies are still important in the fight of cancer, but I think what we've seen over the last five, 10 years is a shift towards diagnostics using molecular techniques.
EMILY LEPROUST: And with some, those molecular techniques, we can look at the DNA, at the RNA. You can look even at the snips, at methylation state, at copy number, at induction, fusion. And groups have been able to start to associate those mutations with cancer states. And so that has been, really, the big change, is being able to go and leverage the power of next-generation sequencing to look at the molecular makeup of not only a cancer, but at individual cells of cancer in order to get the best outcome, the best knowledge from the diseases and pair that with the best medication or therapies in order to achieve a better outcome.
EMILY LEPROUST: And I think that the goal, ultimately, is to turn cancer into a chronic disease, where you may start with a set of mutations. You'll be able to suppress some mutations. Some also will take over, and when you have recurrence, again, you can detect those recurrences and get a different therapy that's associated to that mutation state. [MUSIC PLAYING] So, at Twist, we built a platform where we can write DNA.
EMILY LEPROUST: And that DNA can be used in a number of ways. And so, here, I'll go through a few of those. So, first, we have kits to do targeted sequencing of samples. And so the idea is, instead of sequencing the entire genome of the cells of the patient tumor, you can focus on a subsection of the genes.
EMILY LEPROUST: And the benefit there is that you can read much more deeply and be more cost-effective. So, for instance, you can sequence a tumor sample up to 500x coverage or a liquid biopsy sample all the way to 50,000x coverage and get very precise, a very sensitive measurement of which mutations are available or are present in those samples.
EMILY LEPROUST: So that's on the sequencing side. rDNA are used as probes, as bait, to help in the reading of-- reading and molecular understanding of the sample. Then we also have libraries of genes. So in our silicon chip, we're able to synthesize DNA and then assemble them into longer pieces. And so one of the things that we can do, which is quite powerful, is the synthesis of paired alpha-beta TCR libraries.
EMILY LEPROUST: And so if you-- some researchers are able to sequence all the T Cell Receptors from a patient, and now they have a list of many millions of TCRs, and if they want to study some of those, we're able to synthesize those TCRs from scratch, in paired alpha-beta chaining, and make thousands of them in the same tube. And then they're able to, from that population of 10,000 or more, find which is the one that could be a therapy.
EMILY LEPROUST: And then we can, instead of making a pool of just one-- or making a pool of thousands of alpha-beta TCR chains, we can also synthesize from scratch individual gene-length DNA fragments that can be used in the optimization of either TCR or CAR T therapies or even more classical antibodies to be against cancer.
EMILY LEPROUST: So we have that spectrum of product from the reading of tumor samples to the being able to make libraries of T Cell Receptors to being able to make single genes. And because of our silicon chip, those can be made at scale at the very low cost. [MUSIC PLAYING] Well, when they-- to me, I see two challenges.
EMILY LEPROUST: The first is a challenge of precision. You never have a cancer sample. It's always a mixture of cells. And some of the cells may have the same mutations. Some may not have. It may be different mutations. Sometimes, you don't-- you only have a very small amount of sample. So if you have an FFP sample, for instance, it's a very small amount.
EMILY LEPROUST: It may be a degraded amount. Or, in a liquid biopsy, you're really trying to look for the one-in-a-million fragment of DNA. So that, first, all of that combined is a challenge of precision to me. And so we need tools that will be able to very precisely detect the genetic makeup of that sample. It could be an old, degraded, a very small-dose sample.
EMILY LEPROUST: We still want to know what are the-- on the RNA side, for instance, what are the isoforms? On the DNA side, what are the snips? What are the copy numbers? What are the methylation states of some regions? And so that's why, at Twist, we're developing tools to be able to very precisely give those answers. The second challenge, maybe, is the challenge of cost.
EMILY LEPROUST: You can always, oh, you can sequence more, and you'll get what you want. Well, sequencing is still very expensive when you want to look at millions of cells or at a lot of-- at many samples, and reimbursement is still not perfect. And so that's the other angle that we are doing at Twist is not only provide great precision, but do it at the lowest cost possible in order to enable researchers to do as many tests as possible.
EMILY LEPROUST: We get as many patients possible to really provide patient access to the best diagnostics and the best therapies. [MUSIC PLAYING] Yeah, so at Twist, what we're trying to do is to build a platform that writes DNA. And so we can make a lot of different DNA sequences very quickly, very affordably.
EMILY LEPROUST: And so what that means is that, in the context of personalized medicine, maybe if you're looking maybe at minimal residual disease detection, yeah, you could look at all the genes possible for-- that you may expect for a population of patients. But then, that, you are sequencing a lot of different regions that may not be applicable to that one patient.
EMILY LEPROUST: And so in the context of personalized medicine, instead of making one big batch of a panel that you have to use for everybody, with Twist, you may be able to do a very small panel just for that patient without breaking the bank. And so, in the end, you would be able to design patient-specific panels that truly are less expensive than if you were to use a common panel.
EMILY LEPROUST: So that's the first thing. On the cost side, we believe that we can really drive the custom. And then on the precision side, we have developed our products to have very high uniformity of capture. And what that means is that with that very high uniformity, you don't have to have a sequence because you won't have a region that's covered at 5000x coverage and a region that's covered at 500.
EMILY LEPROUST: And so you will have to over-sequence to bring that 500 to 5,000. At Twist, everything with Twist products, everything is uniformly captured, which means that the cost of sequencing goes down and which means that you would be able to get more precision for the same cost. And so, really, those are the two angles that we think through in our product lines.
EMILY LEPROUST: It's how can we increase with precision while, at the same time, lowering cost? [MUSIC PLAYING] Yeah, so I think our view is that, in the next decade, personalized medicine will actually happen. I think, right now, we are still in the mode of the promise of personalized medicine.
EMILY LEPROUST: I think, however, we haven't totally made the transition. We are still actually in precision medicine. So at least we've gone away from blockbuster medicine. Now, we are more in precision medicine, where at least you can find out what is the mutation that the patient may have so that you can get a treatment that's more appropriate. But I think the next 10 years, by reducing the cost, by improving the precision of diagnostic assays, we'll be able to increase the access of patients to those tools and move truly towards precision medicine.
EMILY LEPROUST: And I think what will happen is patients will be sequenced. In the case of immuno-oncology, for instance, a patient will be sequenced. Libraries of TCRs will be identified. They will be resynthesized at Twist, and they'll be screened to find the one that does-- that is the right therapy to use. Then, they'll be amplified and then given to the patient.
EMILY LEPROUST: And that entire continuum, from the reading, from the recent disease, from the synthesis, we would be able to enable, at Twist, with our genes, our libraries, and our diagnostic tests. And so not only that would be possible but, in addition, the cost is going to drop. As more and more patients participate in that workflow, we'll able to achieve economies of scale, which will enable more people to have access.
EMILY LEPROUST: And we look forward to contributing to that great fight. [MUSIC PLAYING]
Segment:0 .
[MUSIC PLAYING]
EMILY LEPROUST: I am Emily Leproust. I am the CEO and co-founder of Twist Bioscience. Twist was founded seven years ago, now. And the purpose of Twist was to build a platform to write DNA using silicon technology and, from the platform, be able to develop tools to help in synthetic biology, in next-generation sequencing, in drug discovery, as well as in storing data in DNA.
EMILY LEPROUST: [MUSIC PLAYING] So if we step back, in the past, the study of cancer used to be done by pathology studies that were looking at the growth morphology of cells and/or with the tumor stainings. And those technologies are still important in the fight of cancer, but I think what we've seen over the last five, 10 years is a shift towards diagnostics using molecular techniques.
EMILY LEPROUST: And with some, those molecular techniques, we can look at the DNA, at the RNA. You can look even at the snips, at methylation state, at copy number, at induction, fusion. And groups have been able to start to associate those mutations with cancer states. And so that has been, really, the big change, is being able to go and leverage the power of next-generation sequencing to look at the molecular makeup of not only a cancer, but at individual cells of cancer in order to get the best outcome, the best knowledge from the diseases and pair that with the best medication or therapies in order to achieve a better outcome.
EMILY LEPROUST: And I think that the goal, ultimately, is to turn cancer into a chronic disease, where you may start with a set of mutations. You'll be able to suppress some mutations. Some also will take over, and when you have recurrence, again, you can detect those recurrences and get a different therapy that's associated to that mutation state. [MUSIC PLAYING] So, at Twist, we built a platform where we can write DNA.
EMILY LEPROUST: And that DNA can be used in a number of ways. And so, here, I'll go through a few of those. So, first, we have kits to do targeted sequencing of samples. And so the idea is, instead of sequencing the entire genome of the cells of the patient tumor, you can focus on a subsection of the genes.
EMILY LEPROUST: And the benefit there is that you can read much more deeply and be more cost-effective. So, for instance, you can sequence a tumor sample up to 500x coverage or a liquid biopsy sample all the way to 50,000x coverage and get very precise, a very sensitive measurement of which mutations are available or are present in those samples.
EMILY LEPROUST: So that's on the sequencing side. rDNA are used as probes, as bait, to help in the reading of-- reading and molecular understanding of the sample. Then we also have libraries of genes. So in our silicon chip, we're able to synthesize DNA and then assemble them into longer pieces. And so one of the things that we can do, which is quite powerful, is the synthesis of paired alpha-beta TCR libraries.
EMILY LEPROUST: And so if you-- some researchers are able to sequence all the T Cell Receptors from a patient, and now they have a list of many millions of TCRs, and if they want to study some of those, we're able to synthesize those TCRs from scratch, in paired alpha-beta chaining, and make thousands of them in the same tube. And then they're able to, from that population of 10,000 or more, find which is the one that could be a therapy.
EMILY LEPROUST: And then we can, instead of making a pool of just one-- or making a pool of thousands of alpha-beta TCR chains, we can also synthesize from scratch individual gene-length DNA fragments that can be used in the optimization of either TCR or CAR T therapies or even more classical antibodies to be against cancer.
EMILY LEPROUST: So we have that spectrum of product from the reading of tumor samples to the being able to make libraries of T Cell Receptors to being able to make single genes. And because of our silicon chip, those can be made at scale at the very low cost. [MUSIC PLAYING] Well, when they-- to me, I see two challenges.
EMILY LEPROUST: The first is a challenge of precision. You never have a cancer sample. It's always a mixture of cells. And some of the cells may have the same mutations. Some may not have. It may be different mutations. Sometimes, you don't-- you only have a very small amount of sample. So if you have an FFP sample, for instance, it's a very small amount.
EMILY LEPROUST: It may be a degraded amount. Or, in a liquid biopsy, you're really trying to look for the one-in-a-million fragment of DNA. So that, first, all of that combined is a challenge of precision to me. And so we need tools that will be able to very precisely detect the genetic makeup of that sample. It could be an old, degraded, a very small-dose sample.
EMILY LEPROUST: We still want to know what are the-- on the RNA side, for instance, what are the isoforms? On the DNA side, what are the snips? What are the copy numbers? What are the methylation states of some regions? And so that's why, at Twist, we're developing tools to be able to very precisely give those answers. The second challenge, maybe, is the challenge of cost.
EMILY LEPROUST: You can always, oh, you can sequence more, and you'll get what you want. Well, sequencing is still very expensive when you want to look at millions of cells or at a lot of-- at many samples, and reimbursement is still not perfect. And so that's the other angle that we are doing at Twist is not only provide great precision, but do it at the lowest cost possible in order to enable researchers to do as many tests as possible.
EMILY LEPROUST: We get as many patients possible to really provide patient access to the best diagnostics and the best therapies. [MUSIC PLAYING] Yeah, so at Twist, what we're trying to do is to build a platform that writes DNA. And so we can make a lot of different DNA sequences very quickly, very affordably.
EMILY LEPROUST: And so what that means is that, in the context of personalized medicine, maybe if you're looking maybe at minimal residual disease detection, yeah, you could look at all the genes possible for-- that you may expect for a population of patients. But then, that, you are sequencing a lot of different regions that may not be applicable to that one patient.
EMILY LEPROUST: And so in the context of personalized medicine, instead of making one big batch of a panel that you have to use for everybody, with Twist, you may be able to do a very small panel just for that patient without breaking the bank. And so, in the end, you would be able to design patient-specific panels that truly are less expensive than if you were to use a common panel.
EMILY LEPROUST: So that's the first thing. On the cost side, we believe that we can really drive the custom. And then on the precision side, we have developed our products to have very high uniformity of capture. And what that means is that with that very high uniformity, you don't have to have a sequence because you won't have a region that's covered at 5000x coverage and a region that's covered at 500.
EMILY LEPROUST: And so you will have to over-sequence to bring that 500 to 5,000. At Twist, everything with Twist products, everything is uniformly captured, which means that the cost of sequencing goes down and which means that you would be able to get more precision for the same cost. And so, really, those are the two angles that we think through in our product lines.
EMILY LEPROUST: It's how can we increase with precision while, at the same time, lowering cost? [MUSIC PLAYING] Yeah, so I think our view is that, in the next decade, personalized medicine will actually happen. I think, right now, we are still in the mode of the promise of personalized medicine.
EMILY LEPROUST: I think, however, we haven't totally made the transition. We are still actually in precision medicine. So at least we've gone away from blockbuster medicine. Now, we are more in precision medicine, where at least you can find out what is the mutation that the patient may have so that you can get a treatment that's more appropriate. But I think the next 10 years, by reducing the cost, by improving the precision of diagnostic assays, we'll be able to increase the access of patients to those tools and move truly towards precision medicine.
EMILY LEPROUST: And I think what will happen is patients will be sequenced. In the case of immuno-oncology, for instance, a patient will be sequenced. Libraries of TCRs will be identified. They will be resynthesized at Twist, and they'll be screened to find the one that does-- that is the right therapy to use. Then, they'll be amplified and then given to the patient.
EMILY LEPROUST: And that entire continuum, from the reading, from the recent disease, from the synthesis, we would be able to enable, at Twist, with our genes, our libraries, and our diagnostic tests. And so not only that would be possible but, in addition, the cost is going to drop. As more and more patients participate in that workflow, we'll able to achieve economies of scale, which will enable more people to have access.
EMILY LEPROUST: And we look forward to contributing to that great fight. [MUSIC PLAYING]
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