Good morning, everyone, and thank you for joining us to take part in Novocure's 2020 Virtual Research and Development Day. In addition to today's prepared remarks, there will be two live question-and-answer sessions facilitated by Dr. Peter O'Neill, Novocure's Senior Vice President of Global Medical Affairs. Please submit any questions that you have for today's presenters via the chat function on the event platform. You can find the chat function on the right-hand side of your computer screen. The chat will be monitored throughout the event, and questions will be prioritized during the facilitated Q&A sessions. Today's presentations and a live webcast will be available on the Investor Relations page of our website, www.novocure.com, and will be available for replay for at least 14 days following the event.
Before we start, I would like to remind you that our discussions during this event will include forward-looking statements, and actual results could differ materially from those projected in these statements. These statements involve a number of risks and uncertainties, some of which are beyond our control, including those risks and uncertainties described from time to time in our SEC filings. We do not intend to update publicly any forward-looking statement except as required by law. Thank you for your interest in Novocure. We hope that you enjoy today's event.
I've always had jobs where I've tried to make a difference, but at Novocure, it's almost hard not to make a difference.
I had never thought that we could deliver a treatment without some of the more known side effects of cancer.
20 years ago, no one really believed that it would work. When we started to design the new first in humans, we were so happy about it and so proud about it. We didn't know then that it was just the beginning of the journey.
We have accomplished a lot in the last 20 years. It's only the beginning, but it is a beginning, and we should be very proud of that beginning.
Novocure's mission is so important because we start and end with the patient in mind.
I think this patient-forward mission we have of striving to extend survival in some of the most aggressive forms of cancer is foundational to kind of that drive, that focus that then fuels the kind of courage we can have to be innovative.
Innovation for Novocure, it's the third chain of our DNA. When you start something so new, it's your duty to bring it all the way through.
It takes a great deal of commitment and dedication to not accept the status quo and to continuously challenge the process.
There are many instances across the company's history where I think externally people have said, "You can't do it that way. That's not how we do it." But we have always stepped back and said, "Yes, we can."
In my early days, I equated this to an engine that could. I feel like we've turned this into an engine that can and an engine that will for the future of this organization.
What we've built is a company with almost $500 million of net revenue driven from three continents. That has enabled us to invest in our future. That's why the 20 years is only the beginning. The 20 years will enable us to realize our objectives and our ambitions for the next 20 years.
If you were with us five years ago, you made an impact then. If you were with us in 2000, you definitely made an impact then. But guess what? If you started yesterday, you will also make an impact tomorrow. And I think that's what's so exciting about Novocure and what we truly mean when we say we're only beginning.
It's the tip of the iceberg, and there's so much more to come, so many more milestones, and so many more patients served.
When I see what we already accomplished, and I look in the future and see what our future challenge, I realize that for me, it's just the beginning.
We pause, we reflect, we celebrate where we've come from, and then we kind of go heads back down and do it again.
This is not another job. It is something that I will be able to tell to my children and to my grandchildren.
Good morning. My name is Bill Doyle. I'm Novocure's Executive Chairman, and I am pleased to formally welcome you to Novocure's 2020 Virtual Research and Development Day. Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of Tumor Treating Fields. We anticipate readouts from key clinical trials over the next few years. Our plan today is to review the extensive body of Tumor Treating Fields research conducted over the past two decades. We will also introduce areas of ongoing research intended to identify optimal use of Tumor Treating Fields and to improve the predictive value of the scientific evidence generated. Additionally, we're excited to highlight growing interest in Tumor Treating Fields from across the global scientific community as we advance our collective mission to extend cancer survival.
We believe we are in a virtuous cycle of execution and innovation at Novocure. Our established commercial business treating patients with GBM and MPM continues to drive revenue growth and financial strength, which enable us to fund significant increasing investments in R&D. The clinical evidence generated informs potential opportunities to increase our addressable market through the expansion of treatable cancers and to increase efficacy through product innovation. Today, we will focus on the research and development activities intended to propel further growth in this self-reinforcing cycle. We have made incredible progress since our last R&D day in 2016. We have grown R&D investment by more than 160%, with $112 million invested in the last four quarters alone.
We have published promising Phase II pilot data in three additional solid tumor types, resulting in a Humanitarian Device Exemption, FDA approval for malignant pleural mesothelioma, and the initiation of Phase III pivotal trials in lung cancer, pancreatic cancer, and ovarian cancer. We've expanded our clinical pipeline to investigate Tumor Treating Fields in liver and gastric cancers.
We have seen a steady increase in publications citing Tumor Treating Fields, and we believe we are at the point where Optune has clearly established its central role in the treatment of GBM. As proud as we are of the scientific progress made over the last 20 years, and as clearly as we understand the ability of Tumor Treating Fields to disrupt cancer cell division, we believe we're only beginning our potential to impact oncology. Ongoing research is informing the optimal use of Tumor Treating Fields and improving the predictive value of scientific evidence generated.
Our existing pipeline programs create the potential to extend the reach of Tumor Treating Fields therapy to many more cancer patients, with multiple data readouts anticipated over the next few years. Interest is growing across the global scientific community to demonstrate Tumor Treating Fields' effect in multiple solid tumor targets and in combination with radiation and additional chemotherapies and immunotherapies. All of the research and development underway, both at Novocure and across the scientific community, build upon and enrich the Tumor Treating Fields ecosystem. Translational research, clinical development, and product innovation programs drive our opportunity to expand the approved indications for Tumor Treating Fields therapy. Research grants support in vivo, in vitro, and other preclinical projects conducted by interested scientists around the globe. Investigator-sponsored trials further refine our understanding of Tumor Treating Fields' optimal use in the clinic.
All of these efforts are ultimately in service of patients as the entire ecosystem strives to extend survival in some of the most aggressive forms of cancer. Our patient-forward mission is clear. This morning's agenda will focus both on translational research and on clinical development, with two opportunities for live Q&A. We will feature six leaders from Novocure's R&D teams and five external KOLs engaged in Tumor Treating Fields research programs.
Translational research presentations will focus on how basic biology, dosimetry, and product development programs can address clinical unmet needs. Clinical presentations will highlight potential combinations with chemotherapy, immunotherapy, and radiation therapy. Throughout the event, you will have the opportunity to access a virtual exhibition hall featuring additional Tumor Treating Fields resources. We hope you leave today as confident as we are in the potential of the Tumor Treating Fields therapy platform. With that, I will hand the program to Dr. Uri Weinberg, Novocure's Chief Science Officer, who will discuss Tumor Treating Fields' mechanism of action
My name is Uri Weinberg, and I'm the Chief Science Officer at Novocure. For over a decade, I've been involved in the development of a cancer treatment called Tumor Treating Fields therapy, or TTFields for short. Let me show you a brief explanation of how this treatment works. When cancer develops, we see rapid and uncontrolled division of unhealthy cells. Electrical forces within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. This is where Tumor Treating Fields come in. TTFields are electric fields tuned to specific frequencies that disrupt the conditions necessary for cell division. Let's look at how electric fields interact with cells. All cells are surrounded by a lipid bilayer membrane, which separates the interior of the cell, the cytoplasm, from the space around it. This membrane prevents low-frequency electric fields from entering the cell.
TTFields, however, have a unique frequency range between 100 kHz-500 kHz, enabling the electric fields to be generated through the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry, and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected. Whether cells are healthy or cancerous, cell division or mitosis is the same. When mitosis starts, charged proteins within the cell, the microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts, and the two daughter cells separate.
Now let's look at the same dividing cell and see how TTFields interfere with these conditions. When TTFields are generated in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electric forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death. To deliver TTFields therapy, a portable medical device with two primary components is used: an electric field generator and arrays that are placed on the skin covering the region around the tumor. When the device is turned on, TTFields are continuously generated within this specific region of the body covered by the arrays.
Healthy tissues located outside of this region remain unaffected by the treatment. Ongoing research around the world expands our knowledge on TTFields and will hopefully continue to impact the lives of cancer patients and their families.
Hello and welcome. My name is Moshe Giladi. I joined Novocure 15 years ago, and for the past 10 years, I lead our internal preclinical research activities as well as our research collaboration with many leading institutes worldwide. I feel fortunate to study TTFields engineers' invention of Professor Yoram Palti and take part in expanding the knowledge of this novel electric field-based therapy. While there are multiple other modalities in medicine which utilize electric fields, TTFields are unique in their frequencies, intensities, and their mode of delivery. By tuning the frequency to several hundred kilohertz, we now have the ability to continuously generate an electric field within the cell. By doing so, we mainly affect processes which need to be carried in a very precise and orchestrated manner and that have a detrimental effect on cell fate.
Probably the best example is mitosis, a process where a single cell divides into two identical daughter cells, as you saw in the movie. From the very early days, we noticed that TTFields disrupt key structural elements of mitosis, thus leading to mitotic cell death or to the formation of compromised daughter cells. With that knowledge, we and others, as you will hear from Dr. Hagemann, started testing the combination of TTFields and anti-mitotic agents, discovering synergistic interaction in many of these cases. Three of Novocure Phase III studies in non-small cell lung cancer, ovarian cancer, and pancreatic cancer combined TTFields with anti-mitotic agents. TTFields anti-mitotic effect is only the starting point for multiple other downstream outcomes. Those cells which did not die during mitosis are compromised. They divide slowly, their ability to form colonies is reduced, and many of them will die shortly afterwards.
Not only that, these compromised cells also demonstrate various forms of stress, such as induction of autophagy and stress. These are the key drivers for immunogenic cell death, the kind of cell death which primes the immune system to go after the dying tumor cells. Realizing that TTFields could kickstart the cancer immunity cycle, we started combining TTFields with immune checkpoint inhibitors. Novocure's LUNAR Phase III study in non-small cell lung cancer and our recent study with Merck test the combination of TTFields and immune checkpoint inhibitors. It doesn't end there, as TTFields could prime the immune system in other ways, as you will learn later from Dr. David Tran. In recent years, multiple publications demonstrated that TTFields interfere with DNA damage repair, which, like mitosis, need to be performed in a very accurate manner and have a detrimental effect on cell fate.
Indeed, the combination of treatment which induces DNA damage, such as radiation therapy with TTF ields, or better yet, with irradiation and PARP inhibitors, proved to be highly synergistic in preclinical models. Novocure's recent Phase III study in GBM, TRIDENT, and our studies in mesothelioma, pancreatic cancer, and gastric cancer combined TTFields with modalities which induce DNA damage. Through the understanding of the underlying mechanism of action, we now have a better understanding of why some cells are more susceptible to the effect of TTFields. Based on this, we are exploring combination strategies to sensitize the less susceptible cells and enhance TTF ields efficacy. The story of TTFields continues to evolve all the time. In the past two years, we learned that TTFields could affect cell membrane permeability and could also affect the blood-brain barrier integrity. Of this, you will hear more from Dr. Hagemann.
Novocure's ability to make breakthroughs in some of the most aggressive types of solid tumors is the result of continuous investment in R&D and in the science of TTFields. We are developing preclinical research tools which are offered to our many excellent collaborators worldwide. In my years in Novocure, the number of our preclinical research scientists had multiplied by 20. This year marks our highest investment in R&D to date. We now have a grant mechanism to support TTFields research together with the American Association for Cancer Research, AACR. I strongly believe that in the upcoming years, TTFields research will reveal many new outcomes of this therapy and will allow us to further improve treatment efficacy. I'm now going to turn it over to my colleague, Dr. Carsten Hagemann.
Thank you, Moshe. Dear ladies and gentlemen, for the first time, I heard about TTFields in 2014 at the EANO meeting, and honestly, this was very interesting because we just had published our data on synergistic effects of spindle checkpoint inhibition in combination with the spindle poison vincristine. The inhibited protein kinase, MPS1, is a key regulator of the mitotic spindle checkpoint. It detects upper end spindle fiber attachment to the sister chromatids during mitosis, as they are caused by vincristine, regulates multiple protein complexes, and thereby leads to a mitotic cell cycle arrest. This provides time for the cell to repair the damage so the cell might divide normally, even with initial spindle damage.
Since the effects of TTFields on spindle fibers seem to be very similar to those of vincristine, we wondered whether a combination of spindle checkpoint inhibition and TTFields would synergistically augment the TTFields' effects. We reproduced the known effect of TTFields at 200 kHz for our glioblastoma cell lines and treated these cells with TTFields in combination with MPS1 inhibition. While the single treatments led to a reduction in cell proliferation, the combination resulted in reduced cell numbers compared to the start of the experiment. This was due to increased cell death resulting from aberrant mitosis. The upper panel shows normal mitosis and on the right, normal nuclei of the cells, while the lower panel highlights the combination treatment leading to mitotic catastrophe indicated by the highly aberrant shape of the nucleus. We published these data in 2018.
At this time, a colleague approached me with a plan to investigate drug treatment of the blood-brain barrier to better treat glioblastoma. The blood-brain barrier protects the brain from harmful substances, including drugs transported by the blood, and is a special composition of the brain's blood vessels. The vessels are formed by astrocytes, pericytes, and endothelial cells. The latter are connected by tight junctions which densely seal the vessels and are the major structure of the blood-brain barrier. They prevent that many effective drugs can reach the targets inside the brain. Since any new drugs must be used in conjunction with the standard therapy, we tested the endothelial cells with TTFields. We grew these cells as monolayer, stained the tight junctions at the cell-cell boundaries shown in green, and treated them with different frequencies of TTFields.
I did not expect to see any effect because TTFields had not been described to affect normal non-malignant cells. Therefore, I was very surprised to see such major delocalization of the tight junction proteins when using TTFields at 100 kHz. Transendothelial electrical resistance was reduced, indicating opening of the blood-brain barrier and allowing blood-brain barrier impermeable molecules to pass through. Most striking was that these effects were reversible so that the blood-brain barrier recovered within 72 hours after TTFields were switched off. The team of Dr. Giladi performed animal experiments for us. Mice received the contrast agent gadolinium, which does not pass an intact blood-brain barrier, and MRIs were taken before, directly after, and 96 hours after the end of TTFields treatment. The contrast agent only passed the blood-brain barrier and accumulated inside the brain in case of TTFields application.
96 hours after the end of TTFields treatment, the blood-brain barrier recovered, confirming our in vitro data. We even have first results that the TTFields induced opening allows blood-brain barrier impermeable drugs to pass through for an effective treatment of glioblastoma. This research of the last blood-brain barrier opening through TTFields and its subsequent recovery could lead to possible clinical strategies for enhanced and more effective drug delivery for the treatment of brain tumors and other diseases of the CNS. Thank you for your attention.
Hello. My name is Ze'ev Bomzon, Director of Science at Novocure. I joined Novocure over seven years ago, and since then, I have had the privilege to be part of a scientific and technological spearhead advancing the science of TTFields dosimetry and treatment planning. This spearhead has involved extensive collaborations with clinicians, physicists, and engineers around the globe and at Novocure, the establishment of prolific physics and algorithms teams dedicated to this field. It is the story of this journey that I would like to tell you today. Let me begin by defining TTFields dosimetry and treatment planning.
To me, this is the scientific area concerned with: A, understanding how to define TTFields dose in a clinically meaningful manner. B, understanding how TTFields dose distribution influences patient outcome. And C, utilizing our understanding on TTFields dose to better plan treatment, for instance, plan an array placement on the skin to maximize dose distribution of the tumor. The real breakthrough in this field came at the end of last year, 2019, when a collaborative effort including Dr. Matthew Ballo, who will speak after me, was published in the Red Journal. This publication showed a correlation between TTFields dose of the tumor and overall survival in GBM patients.
In this study, we utilized a combination of numerical simulations and mining of clinical data to provide a clinically meaningful definition for TTFields dose and show that within the EF-14 trial, higher TTFields dose of the tumor bed was associated with prolonged survival. The modeling methods we developed for this study, as well as our understanding on how to define TTFields dose in a clinically meaningful manner, have enabled us to develop MAXPOINT. MAXPOINT is a software system built to enable physicians to perform TTFields treatment planning in a patient-specific manner, utilizing computational simulations. The platform provides clinicians with tools for creating patient-specific computational models, optimizing TTFields array layouts to maximize dose in target regions, as well as graphic aids for visualization of TTFields dose distributions within the patient-specific models.
The platform was designed in collaboration with clinicians, including Dr. Ballo, and has a touch and feel similar to that of radiation planning software. It brings advanced treatment planning options into the clinic in a user-friendly manner. So how did we get here, and where are we going next? The most fundamental cornerstone for treatment planning is the ability to create computational models.
This is because computational models are the only practical tool for estimating field distributions and predicting how the field will distribute in response to a series of treatment plans. First simulations of delivery of TTFields to the brain were published in 2007. Here you can see an excerpt from the publication showing delivery of TTFields to a rat brain. Obviously, in this case, the model is highly simplified, yet it was sufficient to establish that TTFields could be delivered at therapeutic intensities of above 1 V per centimeter to small rodents.
Interestingly, the first simulations of TTFields delivery to a human brain were performed outside of Novocure by Pedro Miranda and colleagues. These results were published just before I joined Novocure. They were sufficient to settle the author's skepticism about TTFields being able to be generated through the relatively insulating skull so that therapeutic intensities were obtained within the brain. This study was the first of many establishing techniques for simulating TTFields delivery in realistic human models. However, the techniques for developing realistic head models developed by Miranda and his colleagues, as well as others, were labor-intensive and required hours to days to create a single head model. Hence, such techniques were not suitable for rapidly creating head models on a scale compatible with that required for personalized treatment planning.
To overcome this problem, we developed a new model creation technique, the schematic of which you can see on this slide. This technique was utilized for the Red Paper study, and an improved version is used in MAXPOINT. We are now moving ahead, developing methods for creating personalized torsion models, improved methods for tumor segmentation, and using deep learning and continuing our study on the effect of TTFields distribution on progression patterns. Combining physics with computer vision, deep learning, and data mining, we hope to improve our understanding about how TTFields influence disease and are aiming to develop methods that may enable prediction of patient outcomes in response to TTFields therapy. So what research activities make up the field of TTFields dosimetry and treatment planning? This slide shows the various topics we are interested in.
These topics include a better understanding on how to define TTFields dose and its clinical implications, understanding the biophysics of TTFields at a cellular level, improving our methods for modeling TTFields and optimizing treatment, experimental work to better characterize tissue properties and TTFields distributions, and QA, the art of understanding all uncertainties associated with a treatment plan and integrating these uncertainties in order to improve treatment plans and manage patients in an effective and realistic manner. And what is the vision for the future? To get a hang of this, it is worth looking at radiation therapy. Years ago, radiation was planned for single field using X-rays. Computational capabilities and technological breakthroughs have brought about advances such as IMRT that enables accurate delivery of radiation to small tumors.
I believe we are just at the beginning for TTFields therapy, at the phase just one step above the equivalent of single field radiation therapy. By pushing the activities I described above, you can imagine the following schematic for TTFields treatment. We will likely have advanced hardware for delivering TTFields, which we could personalize so that delivery of TTFields is optimal. Physicians would be able to perform this optimization using future versions of treatment planning software. Over time, as disease patterns change, physicians could utilize the treatment planning software to replan treatment for the patient. When replanning is performed, all historical medical data, as well as recent MRI and CT, might be incorporated into algorithms that not only suggest optimal plans based on dose distributions, but also based on models and algorithms that predict how the tumor will grow in response to a given plan.
I feel privileged to have played a part in this development and am excited about the potential that lies ahead, and now I'd like to hand it over to my friend and colleague, Dr. Matthew Ballo, to let him talk a little bit more about treatment planning.
Thanks, Ze'ev, for that introduction. I've been asked to provide some thoughts on the research and development of tumor treating fields and the management of patients with solid malignancies. I'm Matthew Ballo, a radiation oncologist at the West Cancer Center located in Memphis, Tennessee. I first became interested in tumor treating fields research in late 2015 when the preliminary results of EF-14 became available. I remember hearing the results presented at the Society for Neuro-Oncology meeting and immediately thinking that these results were going to be very important, not just for my patients with glioblastoma, but also potentially for my patients with other solid malignancies. It seemed that tumor treating fields' mechanism of action was sufficiently high up in cellular pathways that it was going to be very difficult for cells to develop a means of resistance.
After reviewing the literature and familiarizing myself with the basic science research, I concluded that this technology would not only benefit my patients, but it would be an opportunity for our multidisciplinary group at the West Cancer Center, and it would be an opportunity for radiation oncologists to engage in the development of a new and exciting anti-mitotic therapy. Our neuro-oncology program was newly established, and we were looking for ways to bring the multidisciplinary team closer together. Tumor Treating Fields, clinical research, and clinical implementation fit our needs perfectly. The surgeon introduces the need for multidisciplinary care, including Tumor Treating Fields, at the time of diagnosis. The neuro-oncologist writes the order for Optune, and the radiation oncologist, that's me, does the array layout mapping. We've even created an institutional database for our patients where we track our outcomes, patient adherence, and their views towards this novel therapy.
In many ways, Tumor Treating Fields served as the nidus for the advancement of our multidisciplinary activities. It was equally apparent that within the multidisciplinary team, the radiation oncologist would become the primary driver for Tumor Treating Fields' acceptance. Radiation oncologists regularly visualize the spatial distribution of ionizing radiation, and we're accustomed to manipulating this distribution to maximize the dose delivered to the tumor volume. That's what we do all day long. Research I performed with the physicists at Novocure proved that just like in radiation therapy, the dose of Tumor Treating Fields is important because a higher dose translates into better tumor control. MAXPOINT, the software developed for visualizing the spatial distribution of Tumor Treating Fields, will allow radiation oncologists to manipulate the dose delivered to the tumor, and it also creates a framework for managing our patients' device usage.
Novocure has gone a long way to engage radiation oncologists from around the country to help develop this software, and I'm really quite honored to be involved as one of the test sites. This software represents a potential leap forward because physician engagement leads to patient engagement. And remember, our research proves that the more patients use the device, the better their outcome. In summary, from a clinician's perspective, Novocure has done everything right, from patient and physician engagement to device and software development, all of this with an eye towards our shared goal of improving quality of life and ultimately improving patient survival. Thank you.
Hello, and good morning. It is a privilege to be here today to present our product development programs. My career prior to Novocure was in venture and growth equity investments. I was fortunate to be on the team executing the first VC investment in Novocure in 2004, and I am as excited today about the future of Novocure as I was then. I'm confident that we can continue to build on the innovation of our founder, Professor Yoram Palti. I will start with some background on our innovation today and then take a look forward to our next major initiatives. As a reminder, we believe that two key factors have the potential to increase patient survival. The first is the field intensity at the tumor location. The second is the patient's time on therapy. Accordingly, we prioritize development in terms of increasing dose and making our product easier to use.
We think about our product in terms of the device, the arrays, and software applications. We have organized our development teams to deliver innovation in each area. As you may know, we introduced product innovation as a corporate objective in 2020, and I'm happy to report that we have made tremendous progress this year. First, we advanced a new high-intensity array to a clinical trial in Q3. This new array is designed to increase the field intensity delivered to the patient's tumor. The EF-33 trial is expected to enroll 25 patients and will test the safety and effectiveness of the new array for patients with recurrent glioblastoma. Once we have the results, we will compare the safety and efficacy of the new arrays to the control data from the EF-11 study and determine the appropriate regulatory pathway. Final data from the study is expected in 2022.
In addition, as you heard earlier, the MAXPOINT system has advanced into a beta test phase. We are now actively collaborating with our beta sites to refine the software to maximize the end-user experience. We believe that MAXPOINT will be an important step forward, allowing physicians to create patient-specific treatment plans to increase the delivered dose for their glioblastoma patients. We also continue to make progress on a new, more flexible torso array and on the introduction of our Gen2 device for torso applications. Both programs have the potential to improve ease of use for our patients in our clinical trials, as well as for our commercial MPM patients. I also want to spend some time talking about MyLink. As a reminder, the MyLink tool allows patients to transmit data from their device directly to our support teams.
MyLink eliminates the need for our device specialists to visit the patient and connect to the device. We commenced the pilot launch of MyLink in the United States in Q2. We're happy to report that the pilot launch of MyLink was successful, and we are now rapidly expanding access to MyLink in the United States and will make MyLink available in Europe next month. As a reminder, we expedited the release of MyLink in response to the pandemic. MyLink helps protect our patients from potential exposure to COVID-19 by eliminating face-to-face support visits to download device data. But importantly, we also believe in the long-term potential for MyLink to help improve our patient support function. We have always known patient training and support in the first month of device use are critical.
GBM is among the most aggressive cancers, and we must help the patient maximize the time on therapy right away. I will share one story that shows the potential impact of MyLink. Earlier this month, we completed a virtual patient start, providing remote training for both Optune and MyLink. This was our first virtual start with MyLink. With the MyLink tool in place, we began receiving patient compliance data within the first 24 hours following the virtual start. Normally, we would not have access to this data for at least a week. Our support teams immediately noticed gaps in treatment that indicated the patient needed additional training. Our device specialist was able to work with the caregiver to customize the support plan, and over the coming week, the patient achieved the targeted compliance rate.
So overall, we believe that MyLink has the potential to improve patient safety and improve device use. While we are excited about the success this year, we know that we have much more to do in product development. As I mentioned at the beginning, our product development teams are focused on maximizing dose and increasing ease of use. We also believe that we can increase the adoption of our products by making the devices more comfortable and easier to use. So to prepare for 2021 and beyond, we have taken a fresh look at how we prioritize product development. We started by plotting our existing programs against our design priorities to understand where we can best invest. As we went through this exercise, we've found that our programs to date have often focused on a single priority of either dose or usability.
Now, to be clear, we believe that each existing project represents an important advance for patients, but the real imperative for our team is to focus on the projects that maximize both dose and ease of use, so today, we are happy to introduce three concepts for product development over the coming years. First, we are now focused on designing a next generation of arrays that are both more flexible and can deliver higher intensities. We are referring to this design as our next gen array concept. We are currently in the design feasibility stage, testing multiple potential concepts. Second, we are looking at how software applications can support our patients and physicians. Specifically, we are thinking through how to launch in multiple additional indications that have much larger patient populations than those we serve today. We are referring to this effort as our patient-centered software application initiative.
Within this program, we are focused on leveraging the unique role that Novocure plays within oncology, as we have a direct connection to the patient. We believe that we can build a series of software applications and related services that enable real-time device support interventions, both by Novocure and the physicians. Lastly, we are going to work towards a Generation 3.0 of our Tumor Treating Fields generator. We believe, as you heard today, that we can optimize and expand the ways in which we use electric fields to treat tumors. We plan to complete design feasibility testing on several new device concepts in 2021. With all of our next generation programs, we will provide updates once the program exits the design feasibility stage and is placed in the product development pipeline.
As I close out, I want to highlight that Novocure has aligned product development and business development under the same umbrella. We believe that tumor treating fields will become a backbone therapy for solid tumor cancers, adding to surgery, radiation, and systemic therapies. We recognize the need to collaborate with our industry peers to maximize patient outcomes. To that end, we were very happy in Q3 to announce our clinical collaboration with MSD, a subsidiary of Merck. Our collaboration on the KEYNOTE-B36 trial will enable us to gain critical insights on the combination of tumor treating fields with an anti-PD-1 agent. We at Novocure are excited about the potential to extend patient survival through product innovation, and we appreciate our investors and recognize the vital role that all of you play in helping us to serve our mission. Thank you.
I'll now turn the session over to my colleague, Dr. Pete O'Neill, for a live Q&A.
Great. Good morning, Frank. What a great start of the day and so much excitement around this R&D convention this morning with our investors. So lots of questions, so let us dive right in. And the first two questions come from Larry Biegelsen at Wells Fargo. The first one is for our internal Chief Scientific Officer, Uri Weinberg. Uri, when it comes down to the intensity delivered, is there a limit to the amount of energy that you can deliver to the tumor, or is there at some point a side effect to be expected? Uri?
Thank you, Pete. Hello, everybody. I would like to start by saying that it is great to share these presentations and messages with you despite the forced social distancing. To me, looking at this, it truly gives a sense of accomplishment considering what Novocure managed to achieve based on Professor Yoram Palti's groundbreaking invention. I would like to refer to the question and to say that to date, we have not identified dose-limiting toxicity that would limit our delivery of higher field intensities to the different regions where tumors are located in humans. Since we saw throughout our extensive clinical experience to date that the only frequent adverse event is mild to moderate skin toxicity, but there are no systemic toxicities when we deliver treatment tumor treating fields to multiple cancers.
We believe that we are able to deliver higher intensities of TTFields through engineering development that Frank covered earlier and achieve greater efficacy, and that follows what Dr. Ballo demonstrated earlier and our understanding that higher intensities of TTFields would hopefully translate into greater efficacy and greater overall survival for patients.
Great. Terrific, Uri. The next question also from Mr. Biegelsen is directed to Frank, our Chief Development Officer. Frank, Mr. Biegelsen is curious about the Gen2 torso device. It wasn't clear to him what exactly the benefits will be from this new version.
Thank you, Pete, and thank you, Larry, for the question. As some of you may know from several years ago, we had moved from a Gen1 device for our CNS applications to a Gen2 device for the CNS applications that was roughly half the weight, half the size. Our Gen2 torso device will replicate that for the MPM indication, helping our patients to improve their ease of use, which, as we've talked about several times, is one of our key priorities in terms of product innovation.
Great. Great. Thank you, Frank. The next question comes from Jason Bednar at Piper Sandler. Thank you for the question, and it goes to Uri. And Uri, what will be the next steps to evaluate drug delivery bypassing blood-brain barrier? Are there any specific primary or metastatic tumors that make the most sense for the initial clinical work for the blood-brain barrier application of Tumor Treating Fields?
Thank you for the question. The findings that were presented by Dr. Hagemann earlier on and were reproduced also by our research team here in Israel are very exciting and basically suggest that we can create a blood-brain barrier disruption in a temporary manner, meaning that it is entirely reversible, allowing us to potentially deliver drugs at higher intensities and even potentially drugs that have not been able to be delivered to the brain in the past, and doing all of this without compromising patients' safety profile, meaning that the blood-brain barrier will become intact once we discontinue the delivery of TTFields at the relevant frequency, which is 100 kHz.
We believe that following the development of this technology through our preclinical testing, we will be able to open a clinical study focusing on the blood-brain barrier relevant to our applications in oncology, focusing primarily in GBM initially, although obviously there are implications that may go beyond this application, and we are intending to explore them as well.
Great. Great. Uri, thanks for that. And as it was such a great presentation by Dr. Hagemann, Dr. Hagemann, any perspective from your side on where to, what's the next step, and what potential applications you're thinking of first in your lab and research field?
Yeah. We have, of course, first to check whether we really can treat the glioblastoma in the animal model. That's the next step we are going in our cooperation with Moshe Giladi in Israel, and other applications, of course, would be other brain tumors. I'm working in the neurosurgery department, so that's our main focus, maybe some metastatic tumors, things like that, and what we are doing in the preclinical research now is also to translate these findings, which were done on murine cells and in the murine model with human cells so that we can be sure that we can reproduce our findings also in human blood-brain barrier cell culture models.
Great. Great. Thank you, Dr. Hagemann. The next question for Uri comes from Vijay Kumar at Evercore ISI. Thank you very much for the question. Uri, Mr. Kumar states that the anti-mitotic cancer drugs have shown effect on different cancer cell lines similar to Tumor Treating Fields, but they've not worked on all cancers. What gives us at Novocure the confidence that the Tumor Treating Fields platform is a platform with a broad applicability across multiple tumors?
The answer to this question is very simple. What gives us the confidence that Tumor Treating Fields is applicable in multiple different cancer indications is the data. We explored the efficacy of TTFields in multiple preclinical and clinical models throughout 20 years of extensive research and development and realized that what we perhaps anticipated ahead of time is indeed that what we see in the petri dish and then in humans, the fact that TTFields targets the basic building blocks of every cell division process, and with the right parameter modifications and the right fine-tuning and adjustments, we are able to deliver it effectively to multiple different tumors. Right now, we have a rich pipeline covering tumors that go beyond our late-phase clinical trial program, and we intend to continue and bring those cancers to clinical trials in the near future.
Great. Great. Bill, I think you'd like to add something to that.
I want to underline what Uri said. I think what we are attempting to communicate is while we are at the beginning of our journey with Tumor Treating Fields, and we see tremendous opportunity to optimize the way it's delivered to patients and the combinations with other therapies that can be used. In our 20 years of research, we've never found an instance in either the preclinical research, in the animal models, or in our clinical program where it has not been effective. This is, of course, across multiple tumor types in multiple conditions and in multiple models. If anything, our confidence continues to build that with the research that's ongoing, we can further improve the efficacy, but we've never seen an indication in any tumor model where the fundamental modality does not work.
Great. Thank you, Bill. Next question, I'll direct to Moshe first. Moshe, so if Tumor Treating Fields increase cell permeability when used in combination with drugs, any risk that the opening of the blood-brain barrier, that now these chemo agents could be harmful to normal cells?
Thank you very much for the question. So the change in cell membrane permeability, as was demonstrated by our bright colleagues from Stanford, demonstrated that the increase in permeability was only seen in cancer cells. And they checked very carefully whether this effect was also seen on normal cells, and they could not see that. And this is, of course, very assuring for us that we can continue to apply TTFields in a safe manner, as was reported in previous studies. With regard to the blood-brain barrier, we also expect that the main effect to be delivered is around the tumor. So again, based on what we have seen so far, we are very confident that the safety profile of TTFields will be maintained even in the future studies.
Okay. Uri, did you want to add anything to that?
I think our philosophy has always been to work step by step and very thoroughly investigate any new development and any new finding that is reported to us or is found by our own research teams. And this is going to continue to be the way we work. And that gives us so far the credibility that what we take into the clinic and what we do is only after reassuring with the highest level of confidence patients' safety and collecting enough preclinical efficacy data to see that there is a very good rationale for this to be translated in the clinic.
Great. Great. Great. The next question comes from Cory Kasimov at JP Morgan, and it's directed to Frank. Frank, would you be able to comment on what you see as a potential future innovation around the battery used in the Tumor Treating Fields system?
Thank you, Pete. Thank you, Cory. What we introduced today and talked quite a bit about is that we view that there's the two key parameters to improve our product, one being maximizing the field intensity that we're delivering at the tumor location, and the second being the overall ease of use of the product, and there's a series of innovations that I would categorize as the evolutions of the electronics and battery industry that will just naturally carry over into our product, becoming smaller, lighter, easier to use. Battery technology is certainly one of those, and so we are, as we look forward to this Generation 3.0 of the device, looking to see how the evolving battery tech can be brought into the device to help us further reduce the weight, just make it easier to use and smaller overall.
But importantly, as we move ahead and taking in some of the new science even introduced here today, we're also looking at this next generation of our device as an opportunity to further improve how we deliver the field intensities and to increase the field intensities. So we think as we move ahead, you'll be hearing, number one, a sustained cadence of innovation from us across the device array and software and services platforms. But specific to the Generation 3 device, you're going to hear us speaking both about improvements in battery technologies and in general advances in making a device smaller, but also in how the device can deliver a higher field intensity.
Great. Thank you, Frank. And let me just have a quick look at the next question that has come in from Difei Yang at Mizuho. And it goes to Dr. Ze'ev Bomzon, and then I'll also turn it to Dr. Ballo. Ze'ev, for the MAXPOINT software, have you got thoughts about how it's used in the torso-based indications in mesothelioma, malignant pleural mesothelioma, for example? And how much of the torso would you need to model to plan treatment? And does a change in treatment depth affect the complexity of the planning model?
Thank you very much for this question. It's a very technical question, and I'll try to be a little bit short on this. Based on what we already know about modeling in the torso and where we're going and results that, in fact, I even showed in the presentation out here. Let's start with the first part of the question. We know from simulations when we published various posters and work at conferences regarding delivery of TTFields to the torso. So we know that when we deliver to the torso, we're able to get very good coverage of the lungs. And we've shown that in multiple publications. In fact, theoretically, at least based on the simulations we have, we're able to deliver high field intensities to the lungs and to the entire lungs with the correct layout.
The area we need to model the torso is essentially we have to go probably from, I would say, middle of the abdomen up to about the neck in order to get reliable models, and that's based on sensitivity analysis we've done within the lab. Looking forward at MAXPOINT and the future, we are looking at developing MAXPOINT for the torso in the future, and it will come out hopefully in years to come as we develop on it, and I showed you some of the first work we've done on this and on modeling, curating patient-specific torso models in the presentation.
Thank you, Ze'ev. So how much would you be able to lift and shift from the GBM work to the torso application, or would it require new code?
As I said, it will require us to make models of the patient torso, and that's something that's ongoing research, and we've made considerable developments in that area.
Understood. Okay. Dr. Ballo, was there anything you wanted to add to Ze'ev's answer?
Yes. The only thing I really want to add is I think Novocure is recognizing through the research that we've been doing with Ze'ev and the other physicists is that the limitation is not a device limitation. One of the things I'm most interested in is really engaging the physicians and engaging the patients and using the software to show the physicians that the dose can be manipulated and the dose is important. And then if it's important to the physicians, it's going to be important to the patients. So I think that, and Novocure is recognizing that, that the limitation is not with the device.
Absolutely. Thank you for that. And yes, the patient remains the North Star, and the outcomes is what ultimately matters. Next question comes from Gregg Gilbert at Truist. And the question goes to Bill. Bill, based on Tumor Treating Fields being able to open the blood-brain barrier, are you thinking about studying a combination of Tumor Treating Fields with drugs that may have previously failed GBM trials in themselves?
Thanks, Gregg. While in these scientific presentations, we try not to get too overexcited. I think Dr. Hagemann's research is really incredibly interesting for all of us. I mean, just conceptually, if we can prove we have the ability to turn on and turn off the blood-brain barrier, it will. That opens up all sorts of additional clinical strategies for oncology, tumors of the brain, and of course, other CNS potential indications. Again, Dr. Hagemann mentioned that we have work to do to verify the initial findings. But absolutely, all of us who work on our clinical plans can see specific strategies for using drugs that are very effective or have proven to be very effective systemically, but have not been able to benefit patients with brain malignancies because they simply couldn't get to the tumors. So it's very, very interesting for all of us.
Great. I could not agree more. Next question is another one on MAXPOINT, and it will be for Dr. Ballo. Coming from Jason Wittes at Northland Securities. Dr. Ballo, what parameters will get altered with the patient-specific monitoring, and will this require a greater physician involvement and possibly the use of the need for a dosimetrist or a physicist in that application?
Yes, absolutely. So that's a great question. I mean, there are two factors that are important. It's the intensity of the tumor treating field that's delivered to the tumor bed, and then you have the usage of the device. And both of those are manipulated through MAXPOINT. So my plan would be to engage both our physicists and our dosimetrists to allow for the manipulation of the dose distribution through the tumor bed on a regular basis. The way we're doing it right now is we'll plan upfront, and we may replan down the road. But right now, we don't quite have that connection between the visual dose distribution and patient outcome. And that's what MAXPOINT will allow us to do, to actually manipulate the dose distribution on a week-to-week or month-to-month basis, like we could do with radiation therapy now.
Great. And I think you've said it, but then the ultimate benefit for the patient would be?
I mean, ultimately, what we're seeing is that the higher intensity, the better the outcome, and the more the usage of the device, the better the outcome.
Yep. That makes sense.
That will really improve overall survival.
Great. Thank you, Dr. Ballo. The next question is from Jack Shearus, and it is for Uri. There are several genetic syndromes with increased cancer risk, such as chromosome-breaking syndromes, some of them having specific cancer types, such as leukemias, lymphomas. Uri, do you think that cell lines from such patients might facilitate the recognition of the effects of tumor treating fields and lead to faster results?
That is a very interesting question. Thank you for this. We're actually utilizing this in both facets. The first one is through genetic genomic research, attempting to better understand the downstream mechanisms of TTFields in order to facilitate better application of TTFields and select combinations that will be optimal for achieving a better effect for an individual patient. That is one part and one side of this. At the same time, we're trying to identify patients with specific genetic subtypes that will have tumors that are extremely or especially susceptible to Tumor Treating Fields and will benefit from this even more, certain cancers or certain subpopulations.
While we see efficacy through our Phase III experience to date in the overall population of patients, especially when we talk about glioblastoma, for example, we continue the research in these particular directions, and we will be very happy to share more results and data from our ongoing research when it is mature enough, and we can share that.
Excellent. Thank you, Uri, and thank you, everyone, for this great first session. Let's have a break now for five minutes approximately. We will resume after the break at 8:40 A.M. sharp, so we will look forward to see you in the next session of this Novocure R&D Day. Thank you very much.
Good morning. My name is Ely Benaim. I am the Chief Medical Officer at Novocure and lead all medical-related activities with a focus on our clinical trials. As a Chief Medical Officer, I feel very much inspired, of course, by our patient-forward mission. We cannot remind ourselves enough of the significant unmet needs that still exist for patients diagnosed with some of the most aggressive solid tumor cancers that we are treating and researching today. In our Phase III trial in newly diagnosed GBM, EF-14, Optune plus temozolomide showed superior efficacy and no significant increase in serious adverse events versus temozolomide alone. Tumor Treating Fields is now part of the NCCN Category 1 recommendation for newly diagnosed GBM and is also endorsed in the consensus guidelines in 2020 by the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
Real-world evidence plays an increasingly important role in how we evaluate the safety and efficacy of drugs and devices to assess how they really perform in current-day practice. So I want to highlight two important analyses for you today. First, with respect to safety, this publication in the Journal of Neuro-Oncology by Dr. Wenyin Shi, who will present later today, underscores Optune's safety profile with extensive real-world evidence. The investigators gathered safety data in over 11,000 patients and corroborated the overall tolerability of Optune therapy. No differences were observed between the total cohorts across regions, diagnosis, or age. This speaks to the treatment's broad applicability in multiple GBM subpopulations, including the elderly. Here is a second important example of recently published real-world evidence. The authors of this publication analyzed data from the SEER database from 2005 to 2016.
Their trained analysis showed that there was a significant increase in median survival for GBM patients and a significant time-dependent downward trend in hazard ratio. Interestingly, we see the trend break with a clear, observable increase in GBM survival in 2015 and 2016, the early years of the introduction of Optune, commercially with no other significant changes in the standard of care for GBM. And proud as I am of the compelling evidence we have generated in GBM and more than 17,000 patients that we have treated today, we still have work to do to extend the reach of TTFields to many more cancer patients. Now, I'd like to shift attention to the other cancer indications currently in development. The numbers speak for themselves.
When looking at the five-year relative survival rate for some of the cancers that Novocure is actively studying, the task ahead of us is still very real. Despite recent advances, the unmet needs persist. We have principally set out to combine Tumor Treating Fields and have designed our trials to demonstrate clinical benefit of the existing standard of care, pursuing significantly improved overall survival as the primary endpoint in most of our clinical trials. You heard earlier today about the exciting preclinical work on Tumor Treating Fields, but I'd like to take a moment to highlight the promising Phase II data that we have generated in the indications currently in development in our Phase III pivotal trials. Across all of these Phase II pilot studies, Tumor Treating Fields demonstrated an extension in overall survival when compared to historical controls without adding any systemic toxicity.
Let me begin with our lung cancer program. The LUNAR study was designed to generate data that incorporates the evolving standard of care of patients with non-small cell lung cancer. The trial is testing the safety and effectiveness of Tumor Treating Fields with physicians' choice of immune checkpoint inhibitors or docetaxel for second-line treatment in patients who progress while on or after platinum-based therapy. The study is powered to measure an extension of survival by approximately four months, and we anticipate final data in 2023. In addition, we're also investigating the potential impact of Tumor Treating Fields in non-small cell lung cancer that has metastasized to the brain, building on our deep expertise in delivering Tumor Treating Fields to brain tumors. The METIS trial is testing the safety and effectiveness of stereotactic radiosurgery plus Tumor Treating Fields for patients with 1-10 brain metastases from non-small cell lung cancer.
Because this trial focuses on a secondary tumor, METIS aims to extend time to intracranial progression by approximately six months. More recently, we entered into a clinical collaboration with a subsidiary of Merck, a global leader in oncology, to study Tumor Treating Fields in a Phase II pilot trial with Keytruda in stage 3 first-line non-small cell lung cancer. This study represents the important expansion of Tumor Treating Fields' clinical development into first-line, stage 3 non-small cell lung cancer in comparison to second-line, stage 4 treatment being studied in LUNAR. We're also running an abdominal cancer clinical program. I will leave most of the discussion on our pancreatic cancer trial to Dr. Babiker. We'll be speaking after me. Allow me simply to highlight that the PANOVA-3 trial is powered to measure an extension in overall survival by approximately five months, and we anticipate final data in 2023.
The INNOVATE-3 trial is testing the safety and effectiveness of Tumor Treating Fields with paclitaxel in patients with platinum-resistant recurrent ovarian cancer. Nearly all patients with recurrent ovarian cancer develop platinum-resistant, and the prognosis for this population remains poor. The study is powered to measure an extension of overall survival by approximately four months, and we anticipate final data in 2023. In addition to these Phase III pivotal trials, we're also investigating the safety and efficacy of Tumor Treating Fields in two other very aggressive abdominal cancers, hepatocellular carcinoma and gastric adenocarcinoma. We have completed recruitment in our Phase II HEPANOVA trial in liver cancer with data readout expected in Q1 2021. And the Phase II trial in gastric cancer is currently enrolling patients in China in partnership with Zai Lab.
We have established TTFields for the treatment of GBM, but we continue to push the boundaries of these GBM patients by exploring the potential impact of adding TTFields therapy earlier in the treatment paradigm. To do so, I am glad to announce that we have made significant progress towards opening the TRIDENT study, which Dr. Shi will talk to you more about shortly. We plan to enroll 950 patients in TRIDENT, making it one of the largest prospective trials in the field of glioblastoma ever to be undertaken. We expect first patient enrollment before the end of this year. Beyond our work in brain cancer, the thoracic and abdominal cancer programs are comprised of robust Phase II and III clinical trials, broadening the potential scope of tumor treating fields application in the near future.
I would like to state that the continued progress we make at Novocure to better understand these aggressive cancers and the many ways we can target them is only possible because of the company's unrelenting commitment to research. We see the map illustrate the many places where Novocure has partnerships and where independent research takes place to deepen our understanding of the potential of tumor treating fields to extend survival across multiple solid tumor cancers. Scientific progress cannot happen in isolation, and I believe that this day is a great tribute to our commitment to these invaluable external partnerships. It is now a great honor for me to introduce the next three speakers. Dr. Babiker from the University of Arizona will talk about how tumor treating fields can be combined with chemotherapy in the treatment of pancreatic cancer.
Dr. Tran from the University of Florida will share his exciting investigational work on the combination of tumor treating fields and immune checkpoint inhibitors. And to conclude, Dr. Shi from Jefferson University in Philadelphia will talk about the potential synergistic effects of tumor treating fields with radiotherapy. Thank you.
My name is Dr. Hani Babiker. I'm the Director of the Early Phase Clinical Trials Program at the University of Arizona, and I am a Phase I oncologist, and I'm also a GI oncologist with a focus in pancreatic cancer. For me, starting my career really earlier on, my interest was not only biology and medicine, but also physics. After my hematology oncology fellowship years ago, I had the opportunity to become a drug development scholar and work hand in hand with scientists and physicians that had a strong imprint in the treatment to fight cancer, including Dr. Von Hoff. I remember a meeting where he discussed a new treatment modality that was exciting, which was Tumor Treating Fields, and that immediately grabbed my attention given my strong interest in medicine and, as I mentioned previously, in physics.
Hearing about this treatment modality, you know, immediately captured my interest when you have Tumor Treating Fields that affect cancer cell division. It's almost like I remember the word that uses paclitaxel on a belt, meaning a treatment that is non-invasive and uses Tumor Treating Fields to affect cancer cell division. And then you can, as you can see in that image in front of you, is TTF affecting septins and microtubules and hence leading to cancer cell death and apoptosis. Now, fast forward now, TTF is approved in GBM and malignant mesothelioma. What really now it's actually coming back home is because I'm a GI oncologist with specific interest in pancreatic cancer. That interest actually accumulated to a project where we studied all the data outlined in TTF and led to a publication on Clinical Cancer Research.
You know, per the Surveillance, Epidemiology, and End Results, you know, currently the five-year survival in pancreatic cancer is 10%. The PANOVA-2 trial was a trial that looked at a cohort of patients who were treated with gemcitabine and antimetabolite chemotherapy plus TTF, but also patients who had an Abraxane or gemcitabine nab-paclitaxel. The PANOVA-2 trial revealed a marked improvement in progression-free survival to the combination of TTF, gemcitabine, and nab-paclitaxel with improvement in median PFS and median overall survival. In the one-year survival for locally advanced pancreatic cancer of 87.5% and metastatic of 62.5%.
So this really, you know, actually, hit home where combining medicine with physics, a new treatment modality that is outside chemotherapy, surgery, and radiation, even immunotherapy, that is really non-invasive and now not only in GBM and malignant mesothelioma showing some efficacy in a cancer that has really poor survival and is aggressive and is really an unmet need in the world of oncology. This obviously was very exciting to GI oncologists, and that led to a randomized Phase III international trial that is currently ongoing looking at patients being treated with either standard of care gemcitabine and Abraxane versus TTF and gemcitabine and Abraxane. We're very excited about this trial. You know, I look forward to seeing the results of this trial. Again, this is a treatment modality that is non-invasive.
You know, you know, I'm an oncologist and we give chemotherapy and we see how patients have responses, but that chemotherapy also had some side effects. 80%-85% of our patients present with either locally advanced and resectable or metastatic disease. There's no surgery, there's no option for surgery. So, you know, the conclusion I have from this is that looking back, I mean, I'm very excited. I was involved in 2015 and now moving forward five years, you know, it's, I'm still very interested. I think it's a modality that for me captures my interest, like I mentioned in medicine, physics, and now pancreatic cancer. And I really look forward to some of the results of the PANOVA-3 trials. We've dubbed in our manuscript the TTF as the fourth treatment modality to fight cancer, and it's non-invasive and tolerable. I really look forward to future results in this field.
Hello, my name is David Tran. I'm the Chief of Neuro-Oncology at the University of Florida. First, thank you so much for having me today. I'm happy to share with you some of the very, very exciting work that we have done with TTFields in the areas of cancer immunotherapy. I have been involved with TTFields now for the last 10 years since 2010, the very early day of the technology. And what we have observed over the years is that many patients who respond remarkably well to this technology tend to go through a phase where their tumor appears to swell up, look like it's progressing, but the patient continues to do very well.
In this patient, over time, this inflammation is beginning to subside, as shown here in the very typical appearance of a patient who goes through this phase we call pseudoprogression because of TTFields. So the antimitotic MOA of TTFields, which is based mostly on apoptosis, which is a relatively inert mode of cell death, cannot explain this phenomenon completely. So we hypothesize that TTFields must have induced tumor inflammation, perhaps by causing immunogenic cell death through a novel mechanism. Over the last five years, Novocure has supported our independent research. We are given complete independence in our pursuit of this mechanism, and it's proven this exciting hypothesis will have a far-reaching impact in the future cancer immunotherapy, not only in GBM, but for many other solid cancers that TTFields are being tested on.
We and others have observed that the antimitotic activity of TTFields can generate a large amount of abnormal chromosomes or DNAs in the cytoplasm. It's also been known for a long time that abnormal accumulation of DNA in the cytoplasm is highly inflammatory. Nature has created multiple mechanisms to sense and eliminate these types of abnormal DNA since the presence of this DNA tends to signal the presence of a viral infection. Two very well-known DNA sensor systems are called cGAS and AIM2. You can see here that cGAS activates the STING pathway, which then in turn activates and produces a large amount of pro-inflammatory cytokines and type I interferon response genes, which are very critical in producing adaptive immunity.
On the other hand, AIM2 activates a completely different pathway cascade leading to the phenomenon called immunogenic cell death, where the entire contents of the cells spill out into the environment, creating a highly inflammatory phenomenon. What we have shown is that TTFields can activate very robustly both of these pathways, creating a highly inflammatory environment inside the cells. In essence, TTFields is an agonist, a dual agonist for both STING and AIM2. Because of that, we hypothesize that TTFields may be used to immunize patients against their own GBM. First, we will successfully demonstrate that TTFields can produce anti-tumor immunity in animal models of GBM, as shown here in the diagram. Because of this observation, we hypothesize that if we combine TTFields with immune checkpoint inhibitors, that we would achieve a very robust therapeutic synergy.
Over the last several years, we have conducted clinical trials testing this very concept in patients with newly diagnosed GBM, as shown here in the diagrams, where we combine the standard treatment for these patients with TTFields in addition to Keytruda, which is an immune checkpoint inhibitor. As of today, 20 of the 24 planned enrollments have been completed. We have observed a clinically significant response. We are investigating the tumor-specific immune activation in these patients, and if the data confirm our hypothesis, it will have a paradigm shift in how we approach therapy for these patients. Thank you very much for your attention. I'd be happy to answer any questions you may have in the Q&A session.
Thank you very much for this opportunity to present here. It is my great pleasure to discuss combining TTFields with radiation treatment. TTFields is the most recent FDA-approved therapeutic option for patients with GBM. There are many strong rationales to support a combination of TTFields with radiation treatment, and this led to our initial investigation of this combination strategy, and we all know multidisciplinary approach is the most important and the most successful anti-cancer strategy. As a matter of fact, this strategy has been perfectly demonstrated in the management of GBM. Initially, surgery alone was the treatment used before. The 1970s, it has abysmal outcome. The overall survival is less than six months. Adding radiation treatment after surgery almost doubled overall survival.
And as we all know, in the early 2000s, clinical trials demonstrated adding temozolomide with radiation treatment can further improve overall survival for over two months. Most recently, after chemoradiation treatment, combining TTFields with maintenance temozolomide makes an even bigger stride in overall survival. Besides this, there's also from the EF-11 and EF-14 clinical trials, as real-world experience, we know that earlier initiation of TTFields can lead to better survival benefits. And the longer use of TTFields can also improve overall survival. So combining radiation treatment with TTFields not only allows us to initiate the TTFields treatment sooner, but also will increase usage time by at least three more months. Moreover, and probably most interesting and importantly, is there's substantial data indicating combining radiation treatment and TTFields can lead to synergistic effects.
So based on this, combining TTFields and radiation treatment holds very great promises in improving outcomes. The key issue we need to address for successful combination therapy is to avoid overlapping or dose-limiting toxicity. As we all know, the most significant toxicity from TTFields is skin irritation. Radiation treatment can also cause some skin irritation. So we need to come up with a strategy to address and avoid excessive skin toxicity. Fortunately, modern radiation treatment is precise and accurate, and we are able to protect the scalp as avoidance structure to use advanced radiation technology to minimize the skin radiation dose. And this approach is very feasible, as demonstrated in the result from our early clinical trial. As you can see, even though the tumor is getting 60 gray of radiation treatment, the scalp dose actually can be kept very low.
This will minimize or eliminate the radiation-induced skin irritation and make the combination therapy feasible. Currently, we already have clinical evidence to support the feasibility and the tolerability of such combination therapy. There are two published clinical trials reporting early safety data. Both have very consistent findings. There are common but very mild skin irritation, and this is not significant enough to result in radiation treatment interruption. Here are some of the pictures of one of our clinical trial patients who received radiation treatment while wearing the TTFields arrays. As you can see, the radiation setup is perfect, and the patient can get radiation treatment without any issue while still wearing the TTFields arrays. Currently, both trials have only reported early survival data of 10 patients each, and these two studies were not designed to compare outcomes.
However, we do see a signal of favorable results when comparing to historical benchmarks. As a clinician, each patient is an individual person to us. It is particularly meaningful for us to see the positive impact we have on any patient. So please allow me to share a case to highlight this combination therapy. This is a 64-year-old previously healthy African American male with newly diagnosed GBM. Unfortunately, as you can see on the right-hand panel, he has very infiltrated diffuse disease involving almost the entire body. This is a phenomenon referred to as gliomatosis. It is associated with particularly bad outcomes. He's highly motivated and would like to have the most aggressive treatment approach. So we enrolled him in our clinical trial.
He started TTFields treatment at the beginning of radiation treatment, and he has perfect compliance to TTFields treatment, as you can see from the treatment log, and he also encountered minimal or no toxicity. When he returned one month after finishing radiation treatment, the MRI scan showed a very definitive treatment response. As you can see, the previous diffuse involvement of the brain has resolved significantly with only a very small area of residual abnormality. More importantly, he continues to have a perfect performance status and leads a very normal life, and the recent follow-up continues to show excellent clinical response, and this is a case that demonstrates the favorable clinical outcome, which is not expected from conventional treatment, and it provides great encouragement for patients as well as clinicians. Ultimately, clinical trial is the foundation of modern evidence-based medicine.
Currently, we are very excited that the combination of TTFields with radiation treatment approach is being tested in a large international Phase III randomized trial, EF-32. This trial is recently activated in the U.S. This trial will further open in a total of about 150 sites internationally. This is a superiority trial designed to test overall survival benefit of such combination strategy, and its result will provide the highest level of evidence. We are very eager to support this trial and look forward to its results. Thank you very much.
Great. Thank you, everybody, for bringing that perspective on the busy work that's going on in the clinical development department and then the external perspective of our great physicians on the call here. Let's dive into the questions for this session. The first one comes from Vijay Kumar at Evercore ISI and is directed to Uri. Uri, the question relates to LUNAR, the non-small cell lung cancer study. The question goes as follows: The LUNAR hazard ratio of 0.75 or a survival benefit of four months, what is the exact power of the trial? And is the trial powered to show a 0.75 difference in both the chemotherapy as well as in the immunotherapy arm? And is the trial powered to show a 0.75 difference in both arms?
The question then continues: If the trial hits the overall primary endpoint of 0.75 hazard ratio for the drug chemo and IO versus device, but fails to meet the hazard ratio for the IO subarm, what does that mean for adoption?
Thank you very much for the question. I'll start with a quick reminder and say that the LUNAR trial in non-small cell lung cancer is one of our four ongoing Phase III studies in brain metastasis, in ovarian cancer, in pancreatic cancer, and of course, in non-small cell lung cancer. The LUNAR trial itself is a Phase III trial pivotal study for 534 patients utilizing TTFields at 150 kHz with physicians' choice of either PD-1 inhibitors, immune checkpoint inhibitors basically, or docetaxel as the backbone in combination with tumor treating fields, TTFields. The trial intends to treat patients following progression after receiving the platinum agent. The primary endpoint, as mentioned in the question itself, is indeed overall survival for the entire population of patients treated with tumor treating fields plus one of the systemic therapies versus the control arm of patients receiving the systemic therapies alone.
The study is indeed powered as needed in order to demonstrate and detect the hazard ratio of 0.75. And that will translate to a median overall survival advantage of four months in patients treated with Tumor Treating Fields in addition to the systemic therapy. But interestingly, we included secondary endpoints to look into those two populations of patients separately: TTFields plus immune checkpoint inhibitors and TTFields plus docetaxel alone. We are hopeful, and based on our preclinical data and the clinical experience that we had on our pilot study in non-small cell lung cancer, that we will be able to demonstrate efficacy when TTFields are combined with each of these systemic therapies. And that demonstrates again the broad applicability of TTFields.
Regarding hypothetical outcomes of the study, we would like to stick to what we know, to the data, and wait until the end of the study and hopefully have a successful trial and good news to share once it is completed. Thank you.
Awesome. Thank you, Uri. The next question goes to Dr. Tran, and it comes from Jason Bednar at Piper Sandler. And the question goes as follows, Dr. Tran: So for your study, 2-THE-TOP study evaluating Optune with Keytruda in newly diagnosed GBM patients, I think you said that you've seen a clinically significant response in the enrolled patients thus far. Would you mind expanding any further on the clinically significant response you've seen and when we would be able to expect your clinical data to be announced and published?
Thank you so much for the questions. When we set out to do these clinical trials, the primary purpose was to demonstrate that TTFields can generate an immune reaction in the line of the STING and AIM2 pathways. That was the main purpose. We allow all patients who have resection, patients who have biopsy alone, we're allowed to enroll in the trial. We have about 50% of patients who have biopsy alone, who have tumors that are in a very critical part of the brain, for example, the thalamus, the splenium in the back of the brain. These are the patients who historically have been sort of the poor actor in terms of survival. We actually observe a significant response rate, effective response rate measured by MR scan in many of these patients who have biopsy alone.
So as of today, we have 22 patients enrolled now out of the 24. 18 of them have been followed at least nine months. We observed 50% response in these 18 patients. And half of these responding patients actually have objective response. We actually measure shrinkage greater than 50% of the tumor before and after treatment. So from the therapeutic standpoint, a 50% response rate and half of them are objective response rate is almost unheard of in these types of tumor. So we're very excited. We expect that the last patient will be enrolled by the end of the year, 24 patients. And we built in survival, the progression-free survival of at least seven to eight months. So we expect that the data will be mature sometime in mid-2021. By the SNO meeting next year, hopefully, we'll have sort of the semi-final data to share with all of you.
Okay. Thank you, Professor Tran. That definitely sounds very promising. To our Chairman, Bill Doyle, Bill, what would prevent us, provided that the Phase II data reads out well in 2021, would there be anything preventing Novocure from running a Phase III trial on this concept?
No, absolutely not. I think it's consistent with our mission. It's consistent with our practice. And I think it's something that we would move toward as quickly as we can.
Great. Thank you, Bill. The next question comes from Difei Yang at Mizuho, and it's directed to Dr. Shi. Dr. Shi, do you think that the higher intensity arrays will have an elevated risk of skin toxicity if used concomitantly with radiation therapy? And in that scenario, would you look to lower Tumor Treating Fields intensity or the radiation dose?
That's a very good question. We already explained we have done a tremendous amount of preclinical work as well as some early clinical investigation regarding minimizing the radiation dose to the skin. And we have done that very successfully. And our clinical data suggesting we can reduce the skin dose by radiation by at least 60% or more. That's eliminated, pretty much reduced or eliminated the risk of radiation-induced skin toxicity. We're not quite as concerned of added toxicity. Regarding the TTFields arrays, as we have heard from previous discussion, we know that the 200 kHz TTFields really have not much impact on the normal cells. It really has anti-metabolic effects on the cancer cells. The increased intensity is really not anticipated to cause more skin toxicity because the mechanical action does not really directly impact the normal cell effects at all.
Thank you, Dr. Shi. Next question comes from Cory Kasimov at JP Morgan. Thank you for the question. It goes to our Chief Science Officer, Uri Weinberg. Uri, regarding LUNAR again, would you mind commenting on the power and the alpha of the interim analysis this time anticipated in 2021? And what would be the hurdle to potentially stop the trial early?
Thank you for the question. So despite the fact that we're not sharing, unfortunately, very specific details regarding our planned interim analysis. So by the way, a side note, thanks to our financial strength, we are building a new department here. I don't know if you can hear the beats of the hammers of the workers here. I asked them to stop that, but it keeps going. So apologies for that. But I will go back to my answer and say that I can certainly share that our interim analysis considerations and statistical design for that has been, on all of the studies, very, very ambitious. We are designing our studies to complete their enrollment to completion and to enroll the last patient in the designated time that we determined and updated you about.
And therefore, we do not expect anything major or any surprise following the interim analysis, which will focus on reviewing safety and efficacy data. Of course, we are always ready for any great news and any unexpected news. Nevertheless, we are planning and we have built our resources based on the assumption then that we will continue and complete enrollment on all of the studies until the last patient, 534 patients on LUNAR.
Great. Great. Thank you, Uri. And next question for our Chief Medical Officer from Larry Biegelsen at Wells Fargo. Ely, of the four ongoing Phase III trials, which one do you feel most confident about in terms of a positive clinical outcome? And if so, would you like to speculate why that would be?
Hello, everybody. And thank you, Larry, for that call. This is a little bit like, which child do you love the most? So you love them all the same. And I would say that right now, after being in the company for a little over a year and a half, I still cannot decide which one I love the most. I think our strength of over 20 years of, I would say, confidence on the Tumor Treating Fields benefit on patients, I would not be able to provide, I would say, guidance on any of this. I think we are very enthusiastic about all these trials. And as Uri just mentioned, we are prepared to have anytime, any great news and move forward.
Great. Maybe while we have the question about which one we feel very bullish about, maybe our external physicians on the call may want to comment. Dr. Babiker, any favorites?
Being a GI oncologist with a focus in pancreatic cancer, I'm obviously going to say the PANOVA-3 trial. But having to say that, I do think that all the trials are exciting. The world of anti-regimens and molecules and devices to fight cancer is growing. And it's very exciting to see an emerging new treatment modality that is non-invasive, I guess, is very exciting. I can say that data speaks for itself, just like was mentioned previously by some of my colleagues and Dr. Weinberg, that from the patients that we're currently treating in the PANOVA-3 trial, we are currently seeing exciting results. I was very excited last week to discuss a patient in tumor board who had locally advanced unresectable cancer, who had the cancer wrapped up around an important artery, which is the superior mesenteric artery and celiac artery, who after several treatments became resectable.
And we're sitting in the tumor board and there are multiple physicians with different specialties. And to get surgeons excited is always great. So I do think that it's an exciting treatment modality. We're seeing patients go on treatment longer than was published previously on trials. And I look forward to the results of the PANOVA-3 trial.
Great. Great. Thank you for your insight. And thank you for sharing a very motivating story with you on that patient. We hope the patient does really well. Dr. Shi, would you like to comment on any favorite you have of the four Phase III trials?
I'm actually excited about all trials. I think all these Phase III trials are built on very solid preclinical and early clinical investigations. So we have very good evidence to support the design and the hypothesis of those studies. And as a matter of fact, I think we actually looking at the implication of TTFields in different cancers is really going to be a strong evidence to convince the communities and both on the scientific committee as well as the patient to welcome and adopt this new therapy. As you know, because it's a brand new mechanism of action, there are a learning phase for the physicians and the adopting phase for the patient. Even we have Phase III data for GBM, but when we have the early data for pancreatic cancer, mesothelioma data, it's really strengthened the confidence for the physician to adopt this treatment for our patients.
I'm really excited to see all four trials. Hopefully, we have the ability to bring solid data in multiple solid tumor treatments for our patients.
Thank you. Thank you. And time allows us one more question. And this one is for Bill Doyle. Bill, you mentioned studying Tumor Treating Fields in other large populations. And which additional tumors are you guys considering at Novocure?
I think, as has been described by our internal colleagues and our external colleagues today, the fundamental mechanism of action of Tumor Treating Fields is very high, if you will, division process. It's applicable to any cancer cell type that we can expose to Tumor Treating Fields. That means that, in essence, all of the tumors of the head, neck, chest, and abdomen are our potential targets. We don't go into Phase III programs lightly, as has been underlined. Each Phase III program is built on a foundation of preclinical and then pilot evidence. You can sort of follow our progress. Our Phase II program next, hepatocellular carcinoma, gastric cancer are next in line, if you will. One cancer type that hasn't been mentioned where we have very strong first in this case, first-in-human data is breast cancer.
Another very large unmet need that we haven't discussed today but is very amenable to Tumor Treating Fields therapy that I want to mention. I guess finally, I've mentioned because of our toxicity profile and because of the preclinical work that we've done, it's been hypothesized that Tumor Treating Fields can be used very early in the treatment paradigm. So as early diagnostic techniques become more available, we talk about blood-based diagnostics where tumors can be, or at least potential cancers can be identified before tumors can be imaged. The question becomes now, what does one do? Tumor Treating Fields is particularly amenable to these very early potential diagnoses and even prophylactic use. So we have a very interesting range of applications in front of us.
And then, of course, the work that was emphasized this morning, because we can work in combination with immunotherapy, in combination with radiation therapy, in combination with chemotherapy, it just further expands the potential to contribute to oncology.
Great. Thank you, Bill. And before I allow you to close this wonderful session, I would like to share a video now of a patient's experience with life on Optune. And after that, Bill, we will be ready to close this session.
I had my daughter. Now she is 19 months, and she's a little human that we created, so we pretty much watched her grow up.
Can you say hi to the phone?
Hi, Blue.
Here we are at our turnaround point.
And you say I'm totally alone.
Aha. We found him. He's a shade seeker.
Sunday and down in Long, Gregory and Tormented Goat School.
We didn't know that we would have the opportunity to sit there in the audience and hold hands. Well, they recited the Hippocratic Oath. So that was pretty special.
I've got a daughter, and I've got some grandkids and a husband. And every time we get to celebrate one of their birthdays, it's just one more time that I'm here for it. And I'm so thankful for that.
Happy birthday, dear Pierre.
I gave Pierre a really special 60th birthday party last year, which also happened to fall on the day of his diagnosis anniversary one year. There were 55 people there, and they came from all over. Friends came from Texas, from Chicago, from Oregon, from Washington, and it was really special for him because it was all his friends really celebrating his life.
My wife and I were able to go to Ireland this year and we spent eight days there and it was a great time. It's been called Five Peaks Challenge. You basically do the five highest peaks in San Diego in one day. I'd been training for that before and I kind of took a break because I was going to have surgery and I built myself back up. I accomplished the Five Peaks Challenge, which was a big feat for me.
Pierre is a major football fan, being from Texas. So I bought tickets to a Chiefs game at Arrowhead Stadium in Kansas City and flew us out there for a game. During the halftime, the cheerleaders came and found us and gave him a signed ball by Chris Jones. So that was really amazing.
I'm an avid guitar player. So I got back into doing that. And I played a couple live gigs and just doing that with Optune on. So I wasn't going to let cancer or the thought of cancer and the diagnosis kind of take away from living my life.
Each year on my brain anniversary, I send a note to my surgeon and to my doctor and just tell them how appreciative I am that I'm still here to be able to send that note.
So when Professor Palti handed the reins to Asaf and me to commercialize his invention, he emphasized two things. First and foremost was that this was for patients and that we were to do everything that we could to bring this new therapeutic modality to cancer patients. The second thing he emphasized was that if we were going to be successful, we had to build on a foundation of science. He knew, and I think we've all seen, that bringing something brand new, unexpected into medical practice is not easy. And the only way to do that is through science, research, and data. And we've maintained that commitment from day one with Professor Palti. And we've continued to take all the resources that we've been able to generate and to put it into further research, further development, and further expansion to help patients.
I'm going to end today thanking all of my internal colleagues. This seems like you just snap your fingers and something like this comes together. But it's the result of a tremendous amount of work internally. And I also want to thank all of our colleagues external to Novocure from around the world. This is not a single company activity. As we mentioned, it's an ecosystem. And we're thankful for all of your efforts, again, focused on the patient to bring our therapy to those in need. There is an expo hall that's also available. It'll be available until 5:00 P.M. today. So I would encourage everyone to visit that for further information. And with that, I will say have a good day. And we will see you all soon.