Editas Medicine, Inc. — Call Transcript 2026

All righty, everyone. Good afternoon, welcome to the Jefferies Global Healthcare Conference in New York City. My name is Matthew Pecora, and I'm here with the Jefferies Healthcare Investment Banking team. It is my great pleasure to introduce you to Gilmore O'Neill, CEO of Editas Medicine. Thank you. Thanks very much, Matthew. Good afternoon, everybody. It's great to be able to tell you about Editas Medicine and update you on where we are today. I'm going to make some forward-looking statements that you can read at some point, or rather, you can read the disclosure or disclaimer at some other point. The key thing is that Editas Medicine is a company that is focused on the development of therapeutics that are actually going to be creating meaningful clinical difference over and above the standard of care for patients. That's at the core of our strategic interest. In addition, we are using CRISPR editing in a way that is rather unique in a mechanistically differentiated approach to therapeutics by essentially using it to drive the upregulation or the increase in synthesis of proteins that could actually benefit patients or mitigate disease. Because we're using CRISPR editing, we do it in a durable manner. Finally, we're formulating the CRISPR editing packages into lipid nanoparticles so that we can actually create scalable, off-the-shelf, simple-to-use, single infusion-based therapies with a cost of goods that really means that we can actually have these medicines used, not just across tissue types, but actually in healthcare systems in a maximally effective manner to reduce the burden of human disease. EDIT-401 is our lead asset, which checks all the boxes in that strategic intent, in that it has the potential to transform the hyperlipidemia treatment landscape because of its potential to be best in class with an unprecedented mean 90% reduction in LDL cholesterol and Lp(a), essentially two key atherogenic lipoprotein particles that are critical to human disease. We have demonstrated those reductions in non-human primates. What is the need for lipid-lowering in human therapeutics? The bottom line is that atherosclerotic cardiovascular disease remains the dominant and key killer and cause of morbidity in human health around the planet. I think that's a critical point. I think the second point is that lipids like LDL-C, Lp(a), are key independent risk factors for the development of cardiovascular disease. What has happened over the last 30 years and what continues to go on is that the field and the data continue to evolve and are a constant trajectory pushing the required levels of cholesterol that we should get to lower and lower. Indeed, the most recently published guidelines have actually continued that trajectory, where it really has become clear that we need to reduce LDL cholesterol and Lp(a) to levels that we really haven't targeted before, but the data are showing we must do that. That is important for many millions of patients who, notwithstanding the current standard of care, cannot get to those desired levels of cholesterol and therefore remain at very high risk. I'm just going to describe two particular groups that sit in that very high-risk category for cardiovascular disease complications but are actually highly motivated. You might say, "Well, what do you mean by highly motivated?" Well, the bottom line is that cholesterol is your stereotypical silent killer. There are many of us in this room who probably don't even know what our cholesterol levels are. There are a lot of young-looking people in this room who probably have never had cholesterol tested. However, the cholesterol is actually accumulating and creating that silent accumulation of atheroma, which creates the risk of heart attack, stroke, or renal failure, or limb loss. These patients are. When I say they're highly motivated, they actually know that they're at risk. Let me take you through them. The HeFH, or heterozygous familial hypercholesterolemia patient, is a patient who has an inherited lesion of the LDLR receptor and has very high levels of LDL cholesterol from a very young age. Their motivation is that they've actually seen a close family relative have a heart attack or a major cardiovascular event. They may indeed have had one themselves. The vignette on the left of your screen is an example of just one type of patient. There's another patient population that sits in that very high-risk category, and those are patients who have established cardiovascular disease. They don't necessarily have a history or family history of hypercholesterolemia, but they certainly have established cardiovascular disease. They have had prior cardiovascular events. They've had a heart attack or an MI. They've had a stroke. They know that this is not just a silent killer for them. This is a very real risk for them. They also can't get to goal with the current standard of care. These patients actually remain at very high risk and are very much aware of that high risk. It is clear to them that where they can't get to target, notwithstanding the standard of care, that a 60% or 40% reduction is not enough. This is where EDIT-401 actually has the potential to offer something to those patients. Those patients, by the way, and I sort of skipped over it, do number many millions of patients just in the U.S. alone. What EDIT-401 has the potential to offer is a meaningful reduction, further reduction of more than 90% in LDL cholesterol and Lp(a). It can be done in a way that reduces the need for chronic therapy because it's maybe a simple single infusion, and it actually provides intensive, durable reduction of cholesterol and therefore meaningful reduction in risk going forward. Before I take you through some of the detailed data, let me just summarize where we are with EDIT-401 and what it can offer. A single dose of EDIT-401 has achieved a mean 90% reduction in LDL cholesterol and Lp(a) across multiply dosed non-human primates. The LDL cholesterol reductions have remained durable through six months. I'll take you through that study in a moment. We have seen highly correlated reductions in LDL cholesterol and Lp(a). What they, again, do is highlight the transformative potential for LDLR upregulation to the levels that we're actually seeing with EDIT-401. Finally, we have a very promising preclinical safety profile with no adverse clinical observations at therapeutically relevant doses. Overall, the unifying mechanism of LDLR upregulation really gives us the potential to offer a meaningful risk reduction to those patients that really remain needing it, notwithstanding today's standard of care. Let me take you through the data. This is a graph from an ongoing non-human primate study. We have taken a data cut at six months. What you can see on the Y-axis on the left is the percentage change in LDL cholesterol. You can appreciate in the treatment arms that all the animals achieved mean reductions of 90%. That was robust, and it occurred, as you can see, across the X-axis, which measures time in the first 48 hours to eight days, and that has been maintained through six months. I would say that this is associated with at least a six-fold mean increase in LDLR protein upregulation or expression in the liver. That's important because that is currently more than what preclinical work has demonstrated that PCSK9 inhibitors can achieve. Again, very importantly, we're now seeing really consistent durability over six months for this reduction. That's just the LDL cholesterol. Beyond just durability, what was also very interesting was that Lp(a) is also reduced, and this is actually biologically and mechanistically plausible in that LDLR does actually take up Lp(a), even if at a lower affinity for Lp(a), and also because it massively reduces LDL Cholesterol, which is a substrate for the manufacture or synthesis of Lp(a), it actually results in this, again, very exciting mean 90% reduction in Lp(a). Again, it's rapid, as we saw for the LDL Cholesterol, and as I say, combined together, demonstrates an ability to reduce atherogenic lipoprotein particles in a way that is going to substantially, and we hope additively, reduce risk for patients. Where did this idea come from? Why did we think to actually use a very different strategy where we actually make a change in the non-coding region of the LDL receptor gene to increase the levels of LDLR synthesis directly? This came from a critical part of our strategy, which I didn't articulate at the beginning, which is the idea that we would look in human genetic databases for naturally occurring gain-of-function variants. We found one, and this is actually published data, in an Icelandic kindred of which seven members had very low LDL cholesterols. Which, by the way, they tolerated very well without adverse effects. You can appreciate in this graph that in those seven red lines to the left, they are well below the LDL levels of their peers in Iceland. This actually we felt was a very interesting target and something that we actually built on in designing and developing our EDIT-401 molecule. Beyond just its potential for efficacy, obviously the preclinical safety profile is very important as it's going to inform our ability to move into humans and the doses at which we'll actually be able to explore. The key takeaway here is that our safety observations at the therapeutically relevant doses demonstrate that it was very well tolerated with no adverse clinical observations. While we did observe transient ALT elevations, they were very similar to the vehicle control. These all resolved in less than a week. We had no liver, absolutely no liver histopathology findings. This is a summation of our clinical or non-clinical experience from our non-GLP animal experiments comprising about 45 animals. We have an ongoing GLP tox with an additional 30 or so animals, 32 animals, in fact. The chemistry, while those studies are ongoing, we do know that the liver function chemistry is consistent with what we're demonstrating here in the GLP. I think this is a lot of confidence in actually moving this compound, EDIT-401, into the clinic. We're actually in a very good position today where thanks to a very successful financing just two weeks ago, we're in a very good position, well capitalized to execute against the strategy that's outlined here. That is that we are on track to submit a CTN in the middle of this year in Australia. We will actually be dosing patients there this year, and we anticipate having early data from our first cohort by the end of the year. Then we will complete enrollment in 2027. We will complete the enrollment of the dose-finding portion, I should say, of our phase I study, and we will have top-line data results available in 2027. As I say, the nice thing is now that sitting here at the back end of a financing driven by a lot of excitement in investors having seen this data, is that we really have a potential to deliver a best-in-class therapy, which addresses the needs of a significant at-risk population and ultimately aligns with patients' needs and healthcare system needs. I say best-in-class therapy with 401, significant at risk. I think very importantly, I just want to emphasize that as we articulated in our strategy at the beginning, is that one of our goals was to make this accessible, easily usable. Driving low cost of goods and using or creating a therapeutic that can be used with a simple single infusion really reduces the burden on patients and healthcare systems as we go forward. With that, I would love to address any questions that you might have. Thanks very much.

Speaker 2: All righty, everyone. Good afternoon, welcome to the Jefferies Global Healthcare Conference in New York City. My name is Matthew Pecora, and I'm here with the Jefferies Healthcare Investment Banking team. It is my great pleasure to introduce you to Gilmore O'Neill, CEO of Editas Medicine. Thank you. All righty, everyone. all righty everyone Good afternoon, welcome to the Jefferies Global Healthcare Conference in New York City. good afternoon welcome to the jefferies global healthcare conference in new york city My name is Matthew Pecora, and I'm here with the Jefferies Healthcare Investment Banking team. my name is matthew pecora and i'm here with the jefferies healthcare investment banking team It is my great pleasure to introduce you to Gilmore O'Neill, CEO of Editas Medicine. it is my great pleasure to introduce you to gilmore o'neill ceo of editas medicine Thank you. thank you

Speaker 1: Thanks very much, Matthew. Good afternoon, everybody. It's great to be able to tell you about Editas Medicine and update you on where we are today. I'm going to make some forward-looking statements that you can read at some point, or rather, you can read the disclosure or disclaimer at some other point. The key thing is that Editas Medicine is a company that is focused on the development of therapeutics that are actually going to be creating meaningful clinical difference over and above the standard of care for patients. That's at the core of our strategic interest. In addition, we are using CRISPR editing in a way that is rather unique in a mechanistically differentiated approach to therapeutics by essentially using it to drive the upregulation or the increase in synthesis of proteins that could actually benefit patients or mitigate disease. Thanks very much, Matthew. thanks very much matthew Good afternoon, everybody. good afternoon everybody It's great to be able to tell you about Editas Medicine and update you on where we are today. it's great to be able to tell you about editas medicine and update you on where we are today I'm going to make some forward-looking statements that you can read at some point, or rather, you can read the disclosure or disclaimer at some other point. i'm going to make some forward-looking statements that you can read at some point or rather you can read the disclosure or disclaimer at some other point The key thing is that Editas Medicine is a company that is focused on the development of therapeutics that are actually going to be creating meaningful clinical difference over and above the standard of care for patients. the key thing is that editas medicine is a company that is focused on the development of therapeutics that are actually going to be creating meaningful clinical difference over and above the standard of care for patients That's at the core of our strategic interest. that's at the core of our strategic interest In addition, we are using CRISPR editing in a way that is rather unique in a mechanistically differentiated approach to therapeutics by essentially using it to drive the upregulation or the increase in synthesis of proteins that could actually benefit patients or mitigate disease. in addition we are using crispr editing in a way that is rather unique in a mechanistically differentiated approach to therapeutics by essentially using it to drive the upregulation or the increase in synthesis of proteins that could actually benefit patients or mitigate disease Because we're using CRISPR editing, we do it in a durable manner. Finally, we're formulating the CRISPR editing packages into lipid nanoparticles so that we can actually create scalable, off-the-shelf, simple-to-use, single infusion-based therapies with a cost of goods that really means that we can actually have these medicines used, not just across tissue types, but actually in healthcare systems in a maximally effective manner to reduce the burden of human disease. EDIT-401 is our lead asset, which checks all the boxes in that strategic intent, in that it has the potential to transform the hyperlipidemia treatment landscape because of its potential to be best in class with an unprecedented mean 90% reduction in LDL cholesterol and Lp(a), essentially two key atherogenic lipoprotein particles that are critical to human disease. We have demonstrated those reductions in non-human primates. Because we're using CRISPR editing, we do it in a durable manner. because we're using crispr editing we do it in a durable manner Finally, we're formulating the CRISPR editing packages into lipid nanoparticles so that we can actually create scalable, off-the-shelf, simple-to-use, single infusion-based therapies with a cost of goods that really means that we can actually have these medicines used, not just across tissue types, but actually in healthcare systems in a maximally effective manner to reduce the burden of human disease. finally we're formulating the crispr editing packages into lipid nanoparticles so that we can actually create scalable off-the-shelf simple-to-use single infusion-based therapies with a cost of goods that really means that we can actually have these medicines used not just across tissue types but actually in healthcare systems in a maximally effective manner to reduce the burden of human disease EDIT-401 is our lead asset, which checks all the boxes in that strategic intent, in that it has the potential to transform the hyperlipidemia treatment landscape because of its potential to be best in class with an unprecedented mean 90% reduction in LDL cholesterol and Lp(a), essentially two key atherogenic lipoprotein particles that are critical to human disease. edit-401 is our lead asset which checks all the boxes in that strategic intent in that it has the potential to transform the hyperlipidemia treatment landscape because of its potential to be best in class with an unprecedented mean 90% reduction in ldl cholesterol and lp(a) essentially two key atherogenic lipoprotein particles that are critical to human disease We have demonstrated those reductions in non-human primates. we have demonstrated those reductions in non-human primates What is the need for lipid-lowering in human therapeutics? The bottom line is that atherosclerotic cardiovascular disease remains the dominant and key killer and cause of morbidity in human health around the planet. I think that's a critical point. I think the second point is that lipids like LDL-C, Lp(a), are key independent risk factors for the development of cardiovascular disease. What has happened over the last 30 years and what continues to go on is that the field and the data continue to evolve and are a constant trajectory pushing the required levels of cholesterol that we should get to lower and lower. What is the need for lipid-lowering in human therapeutics? what is the need for lipid-lowering in human therapeutics The bottom line is that atherosclerotic cardiovascular disease remains the dominant and key killer and cause of morbidity in human health around the planet. the bottom line is that atherosclerotic cardiovascular disease remains the dominant and key killer and cause of morbidity in human health around the planet I think that's a critical point. i think that's a critical point I think the second point is that lipids like LDL-C, Lp(a), are key independent risk factors for the development of cardiovascular disease. i think the second point is that lipids like ldl-c lp(a) are key independent risk factors for the development of cardiovascular disease What has happened over the last 30 years and what continues to go on is that the field and the data continue to evolve and are a constant trajectory pushing the required levels of cholesterol that we should get to lower and lower. what has happened over the last 30 years and what continues to go on is that the field and the data continue to evolve and are a constant trajectory pushing the required levels of cholesterol that we should get to lower and lower Indeed, the most recently published guidelines have actually continued that trajectory, where it really has become clear that we need to reduce LDL cholesterol and Lp(a) to levels that we really haven't targeted before, but the data are showing we must do that. That is important for many millions of patients who, notwithstanding the current standard of care, cannot get to those desired levels of cholesterol and therefore remain at very high risk. I'm just going to describe two particular groups that sit in that very high-risk category for cardiovascular disease complications but are actually highly motivated. You might say, "Well, what do you mean by highly motivated?" Well, the bottom line is that cholesterol is your stereotypical silent killer. There are many of us in this room who probably don't even know what our cholesterol levels are. Indeed, the most recently published guidelines have actually continued that trajectory, where it really has become clear that we need to reduce LDL cholesterol and Lp(a) to levels that we really haven't targeted before, but the data are showing we must do that. indeed the most recently published guidelines have actually continued that trajectory where it really has become clear that we need to reduce ldl cholesterol and lp(a) to levels that we really haven't targeted before but the data are showing we must do that That is important for many millions of patients who, notwithstanding the current standard of care, cannot get to those desired levels of cholesterol and therefore remain at very high risk. that is important for many millions of patients who notwithstanding the current standard of care cannot get to those desired levels of cholesterol and therefore remain at very high risk I'm just going to describe two particular groups that sit in that very high-risk category for cardiovascular disease complications but are actually highly motivated. i'm just going to describe two particular groups that sit in that very high-risk category for cardiovascular disease complications but are actually highly motivated You might say, "Well, what do you mean by highly motivated?" Well, the bottom line is that cholesterol is your stereotypical silent killer. you might say "well what do you mean by highly motivated?" well the bottom line is that cholesterol is your stereotypical silent killer There are many of us in this room who probably don't even know what our cholesterol levels are. there are many of us in this room who probably don't even know what our cholesterol levels are There are a lot of young-looking people in this room who probably have never had cholesterol tested. However, the cholesterol is actually accumulating and creating that silent accumulation of atheroma, which creates the risk of heart attack, stroke, or renal failure, or limb loss. These patients are. When I say they're highly motivated, they actually know that they're at risk. Let me take you through them. The HeFH, or heterozygous familial hypercholesterolemia patient, is a patient who has an inherited lesion of the LDLR receptor and has very high levels of LDL cholesterol from a very young age. Their motivation is that they've actually seen a close family relative have a heart attack or a major cardiovascular event. They may indeed have had one themselves. The vignette on the left of your screen is an example of just one type of patient. There are a lot of young-looking people in this room who probably have never had cholesterol tested. there are a lot of young-looking people in this room who probably have never had cholesterol tested However, the cholesterol is actually accumulating and creating that silent accumulation of atheroma, which creates the risk of heart attack, stroke, or renal failure, or limb loss. however the cholesterol is actually accumulating and creating that silent accumulation of atheroma which creates the risk of heart attack stroke or renal failure or limb loss These patients are. these patients are When I say they're highly motivated, they actually know that they're at risk. when i say they're highly motivated they actually know that they're at risk Let me take you through them. let me take you through them The HeFH, or heterozygous familial hypercholesterolemia patient, is a patient who has an inherited lesion of the LDLR receptor and has very high levels of LDL cholesterol from a very young age. the hefh or heterozygous familial hypercholesterolemia patient is a patient who has an inherited lesion of the ldlr receptor and has very high levels of ldl cholesterol from a very young age Their motivation is that they've actually seen a close family relative have a heart attack or a major cardiovascular event. their motivation is that they've actually seen a close family relative have a heart attack or a major cardiovascular event They may indeed have had one themselves. they may indeed have had one themselves The vignette on the left of your screen is an example of just one type of patient. the vignette on the left of your screen is an example of just one type of patient There's another patient population that sits in that very high-risk category, and those are patients who have established cardiovascular disease. They don't necessarily have a history or family history of hypercholesterolemia, but they certainly have established cardiovascular disease. They have had prior cardiovascular events. They've had a heart attack or an MI. They've had a stroke. They know that this is not just a silent killer for them. This is a very real risk for them. They also can't get to goal with the current standard of care. These patients actually remain at very high risk and are very much aware of that high risk. It is clear to them that where they can't get to target, notwithstanding the standard of care, that a 60% or 40% reduction is not enough. This is where EDIT-401 actually has the potential to offer something to those patients. There's another patient population that sits in that very high-risk category, and those are patients who have established cardiovascular disease. there's another patient population that sits in that very high-risk category and those are patients who have established cardiovascular disease They don't necessarily have a history or family history of hypercholesterolemia, but they certainly have established cardiovascular disease. they don't necessarily have a history or family history of hypercholesterolemia but they certainly have established cardiovascular disease They have had prior cardiovascular events. they have had prior cardiovascular events They've had a heart attack or an MI. they've had a heart attack or an mi They've had a stroke. they've had a stroke They know that this is not just a silent killer for them. they know that this is not just a silent killer for them This is a very real risk for them. this is a very real risk for them They also can't get to goal with the current standard of care. they also can't get to goal with the current standard of care These patients actually remain at very high risk and are very much aware of that high risk. these patients actually remain at very high risk and are very much aware of that high risk It is clear to them that where they can't get to target, notwithstanding the standard of care, that a 60% or 40% reduction is not enough. it is clear to them that where they can't get to target notwithstanding the standard of care that a 60% or 40% reduction is not enough This is where EDIT-401 actually has the potential to offer something to those patients. this is where edit-401 actually has the potential to offer something to those patients Those patients, by the way, and I sort of skipped over it, do number many millions of patients just in the U.S. alone. What EDIT-401 has the potential to offer is a meaningful reduction, further reduction of more than 90% in LDL cholesterol and Lp(a). It can be done in a way that reduces the need for chronic therapy because it's maybe a simple single infusion, and it actually provides intensive, durable reduction of cholesterol and therefore meaningful reduction in risk going forward. Before I take you through some of the detailed data, let me just summarize where we are with EDIT-401 and what it can offer. A single dose of EDIT-401 has achieved a mean 90% reduction in LDL cholesterol and Lp(a) across multiply dosed non-human primates. Those patients, by the way, and I sort of skipped over it, do number many millions of patients just in the U.S. alone. those patients by the way and i sort of skipped over it do number many millions of patients just in the u.s alone What EDIT-401 has the potential to offer is a meaningful reduction, further reduction of more than 90% in LDL cholesterol and Lp(a). what edit-401 has the potential to offer is a meaningful reduction further reduction of more than 90% in ldl cholesterol and lp(a) It can be done in a way that reduces the need for chronic therapy because it's maybe a simple single infusion, and it actually provides intensive, durable reduction of cholesterol and therefore meaningful reduction in risk going forward. it can be done in a way that reduces the need for chronic therapy because it's maybe a simple single infusion and it actually provides intensive durable reduction of cholesterol and therefore meaningful reduction in risk going forward Before I take you through some of the detailed data, let me just summarize where we are with EDIT-401 and what it can offer. before i take you through some of the detailed data let me just summarize where we are with edit-401 and what it can offer A single dose of EDIT-401 has achieved a mean 90% reduction in LDL cholesterol and Lp(a) across multiply dosed non-human primates. a single dose of edit-401 has achieved a mean 90% reduction in ldl cholesterol and lp(a) across multiply dosed non-human primates The LDL cholesterol reductions have remained durable through six months. I'll take you through that study in a moment. We have seen highly correlated reductions in LDL cholesterol and Lp(a). What they, again, do is highlight the transformative potential for LDLR upregulation to the levels that we're actually seeing with EDIT-401. Finally, we have a very promising preclinical safety profile with no adverse clinical observations at therapeutically relevant doses. Overall, the unifying mechanism of LDLR upregulation really gives us the potential to offer a meaningful risk reduction to those patients that really remain needing it, notwithstanding today's standard of care. Let me take you through the data. This is a graph from an ongoing non-human primate study. We have taken a data cut at six months. The LDL cholesterol reductions have remained durable through six months. the ldl cholesterol reductions have remained durable through six months I'll take you through that study in a moment. i'll take you through that study in a moment We have seen highly correlated reductions in LDL cholesterol and Lp(a). we have seen highly correlated reductions in ldl cholesterol and lp(a) What they, again, do is highlight the transformative potential for LDLR upregulation to the levels that we're actually seeing with EDIT-401. what they again do is highlight the transformative potential for ldlr upregulation to the levels that we're actually seeing with edit-401 Finally, we have a very promising preclinical safety profile with no adverse clinical observations at therapeutically relevant doses. finally we have a very promising preclinical safety profile with no adverse clinical observations at therapeutically relevant doses Overall, the unifying mechanism of LDLR upregulation really gives us the potential to offer a meaningful risk reduction to those patients that really remain needing it, notwithstanding today's standard of care. overall the unifying mechanism of ldlr upregulation really gives us the potential to offer a meaningful risk reduction to those patients that really remain needing it notwithstanding today's standard of care Let me take you through the data. let me take you through the data This is a graph from an ongoing non-human primate study. this is a graph from an ongoing non-human primate study We have taken a data cut at six months. we have taken a data cut at six months What you can see on the Y-axis on the left is the percentage change in LDL cholesterol. You can appreciate in the treatment arms that all the animals achieved mean reductions of 90%. That was robust, and it occurred, as you can see, across the X-axis, which measures time in the first 48 hours to eight days, and that has been maintained through six months. I would say that this is associated with at least a six-fold mean increase in LDLR protein upregulation or expression in the liver. That's important because that is currently more than what preclinical work has demonstrated that PCSK9 inhibitors can achieve. Again, very importantly, we're now seeing really consistent durability over six months for this reduction. That's just the LDL cholesterol. What you can see on the Y-axis on the left is the percentage change in LDL cholesterol. what you can see on the y-axis on the left is the percentage change in ldl cholesterol You can appreciate in the treatment arms that all the animals achieved mean reductions of 90%. you can appreciate in the treatment arms that all the animals achieved mean reductions of 90% That was robust, and it occurred, as you can see, across the X-axis, which measures time in the first 48 hours to eight days, and that has been maintained through six months. that was robust and it occurred as you can see across the x-axis which measures time in the first 48 hours to eight days and that has been maintained through six months I would say that this is associated with at least a six-fold mean increase in LDLR protein upregulation or expression in the liver. i would say that this is associated with at least a six-fold mean increase in ldlr protein upregulation or expression in the liver That's important because that is currently more than what preclinical work has demonstrated that PCSK9 inhibitors can achieve. that's important because that is currently more than what preclinical work has demonstrated that pcsk9 inhibitors can achieve Again, very importantly, we're now seeing really consistent durability over six months for this reduction. again very importantly we're now seeing really consistent durability over six months for this reduction That's just the LDL cholesterol. that's just the ldl cholesterol Beyond just durability, what was also very interesting was that Lp(a) is also reduced, and this is actually biologically and mechanistically plausible in that LDLR does actually take up Lp(a), even if at a lower affinity for Lp(a), and also because it massively reduces LDL Cholesterol, which is a substrate for the manufacture or synthesis of Lp(a), it actually results in this, again, very exciting mean 90% reduction in Lp(a). Again, it's rapid, as we saw for the LDL Cholesterol, and as I say, combined together, demonstrates an ability to reduce atherogenic lipoprotein particles in a way that is going to substantially, and we hope additively, reduce risk for patients. Where did this idea come from? Beyond just durability, what was also very interesting was that Lp(a) is also reduced, and this is actually biologically and mechanistically plausible in that LDLR does actually take up Lp(a), even if at a lower affinity for Lp(a), and also because it massively reduces LDL Cholesterol, which is a substrate for the manufacture or synthesis of Lp(a), it actually results in this, again, very exciting mean 90% reduction in Lp(a). beyond just durability what was also very interesting was that lp(a) is also reduced and this is actually biologically and mechanistically plausible in that ldlr does actually take up lp(a) even if at a lower affinity for lp(a) and also because it massively reduces ldl cholesterol which is a substrate for the manufacture or synthesis of lp(a) it actually results in this again very exciting mean 90% reduction in lp(a) Again, it's rapid, as we saw for the LDL Cholesterol, and as I say, combined together, demonstrates an ability to reduce atherogenic lipoprotein particles in a way that is going to substantially, and we hope additively, reduce risk for patients. again it's rapid as we saw for the ldl cholesterol and as i say combined together demonstrates an ability to reduce atherogenic lipoprotein particles in a way that is going to substantially and we hope additively reduce risk for patients Where did this idea come from? where did this idea come from Why did we think to actually use a very different strategy where we actually make a change in the non-coding region of the LDL receptor gene to increase the levels of LDLR synthesis directly? This came from a critical part of our strategy, which I didn't articulate at the beginning, which is the idea that we would look in human genetic databases for naturally occurring gain-of-function variants. We found one, and this is actually published data, in an Icelandic kindred of which seven members had very low LDL cholesterols. Which, by the way, they tolerated very well without adverse effects. You can appreciate in this graph that in those seven red lines to the left, they are well below the LDL levels of their peers in Iceland. Why did we think to actually use a very different strategy where we actually make a change in the non-coding region of the LDL receptor gene to increase the levels of LDLR synthesis directly? why did we think to actually use a very different strategy where we actually make a change in the non-coding region of the ldl receptor gene to increase the levels of ldlr synthesis directly This came from a critical part of our strategy, which I didn't articulate at the beginning, which is the idea that we would look in human genetic databases for naturally occurring gain-of-function variants. this came from a critical part of our strategy which i didn't articulate at the beginning which is the idea that we would look in human genetic databases for naturally occurring gain-of-function variants We found one, and this is actually published data, in an Icelandic kindred of which seven members had very low LDL cholesterols. we found one and this is actually published data in an icelandic kindred of which seven members had very low ldl cholesterols Which, by the way, they tolerated very well without adverse effects. which by the way they tolerated very well without adverse effects You can appreciate in this graph that in those seven red lines to the left, they are well below the LDL levels of their peers in Iceland. you can appreciate in this graph that in those seven red lines to the left they are well below the ldl levels of their peers in iceland This actually we felt was a very interesting target and something that we actually built on in designing and developing our EDIT-401 molecule. Beyond just its potential for efficacy, obviously the preclinical safety profile is very important as it's going to inform our ability to move into humans and the doses at which we'll actually be able to explore. The key takeaway here is that our safety observations at the therapeutically relevant doses demonstrate that it was very well tolerated with no adverse clinical observations. While we did observe transient ALT elevations, they were very similar to the vehicle control. These all resolved in less than a week. We had no liver, absolutely no liver histopathology findings. This is a summation of our clinical or non-clinical experience from our non-GLP animal experiments comprising about 45 animals. This actually we felt was a very interesting target and something that we actually built on in designing and developing our EDIT-401 molecule. this actually we felt was a very interesting target and something that we actually built on in designing and developing our edit-401 molecule Beyond just its potential for efficacy, obviously the preclinical safety profile is very important as it's going to inform our ability to move into humans and the doses at which we'll actually be able to explore. beyond just its potential for efficacy obviously the preclinical safety profile is very important as it's going to inform our ability to move into humans and the doses at which we'll actually be able to explore The key takeaway here is that our safety observations at the therapeutically relevant doses demonstrate that it was very well tolerated with no adverse clinical observations. the key takeaway here is that our safety observations at the therapeutically relevant doses demonstrate that it was very well tolerated with no adverse clinical observations While we did observe transient ALT elevations, they were very similar to the vehicle control. while we did observe transient alt elevations they were very similar to the vehicle control These all resolved in less than a week. these all resolved in less than a week We had no liver, absolutely no liver histopathology findings. we had no liver absolutely no liver histopathology findings This is a summation of our clinical or non-clinical experience from our non-GLP animal experiments comprising about 45 animals. this is a summation of our clinical or non-clinical experience from our non-glp animal experiments comprising about 45 animals We have an ongoing GLP tox with an additional 30 or so animals, 32 animals, in fact. The chemistry, while those studies are ongoing, we do know that the liver function chemistry is consistent with what we're demonstrating here in the GLP. I think this is a lot of confidence in actually moving this compound, EDIT-401, into the clinic. We're actually in a very good position today where thanks to a very successful financing just two weeks ago, we're in a very good position, well capitalized to execute against the strategy that's outlined here. That is that we are on track to submit a CTN in the middle of this year in Australia. We will actually be dosing patients there this year, and we anticipate having early data from our first cohort by the end of the year. We have an ongoing GLP tox with an additional 30 or so animals, 32 animals, in fact. we have an ongoing glp tox with an additional 30 or so animals 32 animals in fact The chemistry, while those studies are ongoing, we do know that the liver function chemistry is consistent with what we're demonstrating here in the GLP. the chemistry while those studies are ongoing we do know that the liver function chemistry is consistent with what we're demonstrating here in the glp I think this is a lot of confidence in actually moving this compound, EDIT-401, into the clinic. i think this is a lot of confidence in actually moving this compound edit-401 into the clinic We're actually in a very good position today where thanks to a very successful financing just two weeks ago, we're in a very good position, well capitalized to execute against the strategy that's outlined here. we're actually in a very good position today where thanks to a very successful financing just two weeks ago we're in a very good position well capitalized to execute against the strategy that's outlined here That is that we are on track to submit a CTN in the middle of this year in Australia. that is that we are on track to submit a ctn in the middle of this year in australia We will actually be dosing patients there this year, and we anticipate having early data from our first cohort by the end of the year. we will actually be dosing patients there this year and we anticipate having early data from our first cohort by the end of the year Then we will complete enrollment in 2027. We will complete the enrollment of the dose-finding portion, I should say, of our phase I study, and we will have top-line data results available in 2027. As I say, the nice thing is now that sitting here at the back end of a financing driven by a lot of excitement in investors having seen this data, is that we really have a potential to deliver a best-in-class therapy, which addresses the needs of a significant at-risk population and ultimately aligns with patients' needs and healthcare system needs. I say best-in-class therapy with 401, significant at risk. I think very importantly, I just want to emphasize that as we articulated in our strategy at the beginning, is that one of our goals was to make this accessible, easily usable. Then we will complete enrollment in 2027. then we will complete enrollment in 2027 We will complete the enrollment of the dose-finding portion, I should say, of our phase I study, and we will have top-line data results available in 2027. we will complete the enrollment of the dose-finding portion i should say of our phase i study and we will have top-line data results available in 2027 As I say, the nice thing is now that sitting here at the back end of a financing driven by a lot of excitement in investors having seen this data, is that we really have a potential to deliver a best-in-class therapy, which addresses the needs of a significant at-risk population and ultimately aligns with patients' needs and healthcare system needs. as i say the nice thing is now that sitting here at the back end of a financing driven by a lot of excitement in investors having seen this data is that we really have a potential to deliver a best-in-class therapy which addresses the needs of a significant at-risk population and ultimately aligns with patients' needs and healthcare system needs I say best-in-class therapy with 401, significant at risk. i say best-in-class therapy with 401 significant at risk I think very importantly, I just want to emphasize that as we articulated in our strategy at the beginning, is that one of our goals was to make this accessible, easily usable. i think very importantly i just want to emphasize that as we articulated in our strategy at the beginning is that one of our goals was to make this accessible easily usable Driving low cost of goods and using or creating a therapeutic that can be used with a simple single infusion really reduces the burden on patients and healthcare systems as we go forward. With that, I would love to address any questions that you might have. Thanks very much. Driving low cost of goods and using or creating a therapeutic that can be used with a simple single infusion really reduces the burden on patients and healthcare systems as we go forward. driving low cost of goods and using or creating a therapeutic that can be used with a simple single infusion really reduces the burden on patients and healthcare systems as we go forward With that, I would love to address any questions that you might have. with that i would love to address any questions that you might have Thanks very much. thanks very much