BioTech Showcase 2015, January 12, 2015 Transcript
Transcription of Presentation by Linda Powers
Well thanks everybody for coming. I know it’s the end of a long day that’s been a zoo for everybody with back to back meetings so I really appreciate everybody coming… and anyone that’s listening on the webcast, thank you, especially on the East Coast where it’s kinda late. So let’s… first of all, the obligatory disclaimer, I am going to talk about forward looking and anticipated events for 2015 and beyond so there’ll be an obligatory disclaimer there.
Okay, let me start by going over an overview of the company and the highlights. 2014 was a really strong year for us, and it was a really strong year for the whole immune-oncology space. It continued to become hotter than ever, and busier than ever with companies of all sorts and sizes jumping in. We are at the forefront of this exciting space from every measure that you might look at.
First of all, the stage of our programs. Our lead product is far along in Phase three trials, international Phase three trials which we have the finish line in sight. We’re coming along very well on that. We are now embarking on our second product entering two simultaneous Phase two trials in two different cancers, and we expect those to be enrolling over the course of this year, and delivering data in the first half of next year… so around the same time as the Phase three trial.. so having a Phase three trial and two Phase two trials in three different cancers with two different products reading out relatively soon within the next five or six calendar quarters, so that’s very exciting.
Secondly, if you look at the breadth of our addressable markets, our lead product is for all types of operable solid tumors… that’s a tumor in any tissue in the body. Our second product is for all types of inoperable solid tumors. If you think about the scope of those markets — solid tumors, any tissue in the body, those markets are enormous, and I’ll show you just some examples of the numbers later on.
And a big advantage, a key differentiator of our technology is we are not limited by tumor characteristics, we are not limited by patient characteristics. We can treat all of those patients in these markets. Additionally, a major advantage that we have from a regulatory pathway standpoint is once we have an approval of our product for the first type of cancer, each one of those other cancers is just a label extension. Much simpler and faster regulatory pathway.
Third area, clinical results to date. Both in terms of safety and in terms of what we’ve seen as far as efficacy in the clinical trials to date, I would say it puts us right at the forefront of the space as well. First of all, in terms of the toxicity, we have been in clinical trials for ten years with our lead product with over 1200 treatment cycles of multi-hundred patients, nearly 300 patients; in that whole time, the grand total of serious adverse events is… three. And those were things like seizures in patients that have brain cancer, who have seizures as part of their disease. It is a non-toxic product.
We now have 18 months of experience with our second product, the Direct injection product, and we’ve had patients have a similar experience. Patients get fevers, the fevers don’t last more than two days, they don’t go up more that 2 degrees centigrade. You ask a patient if that’s okay, that’s okay. Compare that to chemotherapy and even compared to other immune therapies, where a significant percentage of patients are ending up in the hospital for in-patients stays, sometimes in the intensive care unit, just to survive the treatment. Those are exciting treatments, they’re I think going to have a great future, but they have some serious challenges on their safety profile that we do not have.
In terms of efficacy, again, we are still in clinical trials, we have to see how the further trials read out, there’s no guarantees, but we’ve seen up ’til now has been quite encouraging. These are extensions of the time to disease progression, progression free survival, and extensions of overall survival in the realm of years… not weeks or months… but years, and I’ll show you the data later in the slide there.
Another aspect of our leadership and being at the forefront of this space is regulatory validations and early approvals that are unparalleled. No other company in our peer group has anything of this sort. Both in Germany and in the UK, two of the toughest regulators on the planet, particularly for cell therapy products, we have gotten unique, regulatory approvals. In Germany, we have a Hospital Exemption that is an early approval. It gives us five years to actually sell our product. The scope is much broader than even our clinical program… it’s all glioma brain cancers. There is no limit on the number of patients. There is no other company that the German regulator has given an approval like that to, certainly no other immune therapy company.
We’ve also been determined eligible for reimbursement on an extraordinary basis at the request of ten major hospital centers all across Germany who applied on our behalf to their health system, and that is obviously extraordinary to be eligible for reimbursement while you’re even still in clinical trials.
A similar situation is in the UK… the national health system which constantly surveys the landscape looking for better technologies about a year and a half ago adopted our lead product technology as a nationwide priority for the UK, and last year, when the UK government launched a brand new program called the Early Access to Medicine Scheme or EAMS, we were the first company to receive the first designation as a Promising Innovative Medicine. The UK government considered this such a significant thing that the UK government Department of Health put out its own press release about granting this approval to us, and that announcement was at the Minister level, the UK government has placed a great priority on this program, and its a great validation for our technology.
Again, these are validations, very important regulatory validations from the same regulators who will be looking at our products for the full approval when the time comes, and they are unparalleled in our peer group.
Lastly, and super importantly, are the practical aspects of our product.
We’ve all seen a very disappointing situation with Dendreon where practicalities were really not what they needed to be. Right now, there is tremendous excitement around some other immune therapies such as the CAR-T cells, but there are a host of practicality issues that lie ahead… those are very exciting technologies, I think they’ll have a very exciting future, but we already passed all those practicality issues. We’ve been working on those for ten years. What do I mean by that? I mean the manufacturing at a level that is sufficiently rigorous and consistent and safe and reliable and potent, that the regulators feel we’re ready for prime time, ready to be rolled out commercially. I mean making the processes so efficient that today we can make three to five years worth of doses for one patient in eight days in a single manufacturing run. Unlike Dendreon who had to do a manufacturing run for each one month of treatment, we do one manufacture for each patient… that’s it. One time.
We validated the frozen shelf life, it’s a frozen product. We’ve validated the frozen shelf life for more than three years to the satisfaction of regulators in three different countries. These are just examples of the practicalities that make an exciting technology a real world commercial product. And all of this work lies ahead for some of the other exciting technologies today. But it lies behind for us.
Now some of the highlights of 2014 — 2014 was a very big year of progress for our company. In our DCVax-Direct program, we completed the enrollment in the Phase one trial. We treated seven different kinds of cancers, we tested three different dose levels, we tested two different methods for activating the dendritic cells, and so on and so on. It was a very intensive program over the course of that year, which has now positioned us to embark rapidly on multiple parallel Phase two trials during 2015, this calendar year.
In our lead program, DCVax-L, I’ve already mentioned a lot of the highlights, major expansions of the clinical trial program. Interim analysis was done for safety, the safety profile as I said is excellent; and we’ve had these major regulatory approvals.
So now let me focus on the year ahead.
What can all of you be looking for as we look through 2015? Well, we have three major activity areas. We have an enormous number of milestones and catalysts coming. Nearly a dozen milestones and catalysts here, and these are just the highlights. Additionally, as I’ll show you on the next slide, there is a further area, a fourth area, that we will be… exploring.
So, first off… the DCVax-L Phase three program, we will continue expanding that program. You can look for announcements during this Q1 in that regard. We will be sometime this year conducting the first interim analysis for efficacy. That will be conducted by the Data Monitoring Committee. Up to now, the assessments have only been safety, so this will be the first assessment for efficacy. We do expect to complete patient recruitment, as I said. We will have ongoing follow-up of the 55 patient (Info Arm). Last September, we released information on 55 patients who were too sick to meet the eligibility criteria to enroll in the Phase three trial. But we had already manufactured product for them so on a compassionate use basis so we allowed them to be treated with the same DCVax product at the same medical centers as the clinical trials using the same treatment regimen as the clinical trials with the data collected by the same CRO that is conducting the clinical trial. The data was not collected by us.
The results were quite striking. We published those in September. Patients who have such rapid progression that their tumor is already regrowing by the time they finish their six weeks of radiation and chemo after removing the tumor in the first place — which is a really aggressive version of the cancer — those patients typically live seven to ten months. And in our group there, they were at the time, in the 18 month range.
We will continue to follow those patients, and continue to see how they do. That will be over the course of this year as well. And of course we’ll accumulate events towards the primary endpoint of the trial.
So one major activity track is the lead program Phase three.
Second major activity track will be the two Phase two trials in two different cancers with the Direct injection trial.
Third activity area will be continuation of all of the preparation and program building and ramp up of our early commercialization, if you want to call it that, in other words, the early roll out of our product, and collection of payment for it, under the early access program approvals that we’ve gotten in Germany, and… hopefully, we’ll receive in the UK.
We will pursue that special approval stage two, the actual decision under the EAMS program in the UK, the second and final stage of that process. We’ll do that this year. We will continue the negotiations, which have so far been ongoing for months with the health insurance funds in Germany for the pricing and the reimbursement of our product. We are not going to rush that process. That process can very often take a full year of negotiation, sometimes longer. We want to make sure we come out with good reimbursement levels, and we are working on that. We are encouraged so far.
And last, and very importantly, we’ve recently announced major initiatives in major capital investments to expand our manufacturing greatly in the UK for Europe, to supply Europe. And we’ll also be expanding our manufacturing in the US. Also getting all the distribution and logistical arrangements… handling living cell product requires a different distribution network, and biologics or small molecules. All of this is pioneering, all of it has to be built. Once it’s built, it’s a proprietary competitive advantage over those who come behind and have to build it likewise. So we are right in the thick of that right now thanks to these early approvals, and we’ll be doing a lot of that work over this calendar year as well. It essentially allows us to practice for commercialization before we reach full commercialization. So those are our three major activities with our three major programs.
Now I mentioned a fourth area that we’ll be exploring.
Checkpoint inhibitors are one of the two super hot exciting areas of immune therapy for cancer. The immune system has built into it certain off switches so that you don’t have a run away immune reaction. You have an over reaction of your immune system and you get auto immune disease. And your own immune system can kill you. It’s a very important thing that your immune system has these built in “off switches”. Unfortunately, what happens is tumors highjack those off switches and they turn the immune response off. The off switches are called “checkpoints”. Checkpoint inhibitor drugs get in the way and prevent the tumor from highjacking the off switch. That’s a really good thing. It’s really exciting. You’ve seen the first of these drugs getting approved for Big Pharma. Big Pharma is in a massive foot race with each other… BMS, Merck, Astra Zeneca, Pfizer, everybody. Now where do we fit into that? Well each of these receptors that you see here — these are all checkpoints. One checkpoint inhibitor drug only deals with one of these. Dendritic cells, which is what this middle cell is here, are built by nature to deal with all of them. Additionally, dendritic cells mobilize the whole immune system, including T-Cells. Now today, not only are there a large number of checkpoints, and so far most of the checkpoint inhibitor drugs are all going after just one or two of those out of all of these, but importantly, the response rates to these checkpoint inhibitors drugs right now are only about 30% of the patients who take them. That means 70% of the patients are non-responders.
Nobody in the research community yet knows entirely why are the non-responders… non-responders. A strong possibility is that these patients don’t have enough activated T-Cells in the first place for checkpoint inhibitor drugs to do any good. If you don’t have the immune system activated and mobilized, the off-switches are not mobilized, and there is nothing for a checkpoint inhibitor drug to do. Well what does our technology DCVax do? It activates and mobilizes T-Cells. And it does so in a very big way. And it does so in a non-toxic way, as we’ve already talked about. And not only does it do it in a big way and a non-toxic way, it does it in a broad spectrum way. Each of these other elements, these checkpoints, are all rifle shots; and if you’ve noticed the combination treatment regimens that have been tried so far are combinations of rifle shots with rifle shots. As far as we’re aware, nobody has yet combined a rifle shot with a broad spectrum treatment, which is what our DCVax is. So we see a great opportunity for mutual benefit to at least test the concept of whether DCVax can mobilize T-cells and turn some of those non-responders into responders. That would obviously be very valuable for Big Pharma.
On the flip side of the coin, if the check-point inhibitors can help perpetuate an immune response that our DCVax has already mobilized, that’s good for adding to the long tail of survivors with year’s long responses that we’re already getting. So it’s potentially very attractive for both parties. This is something that we’re going to be exploring this year… that’s all I can say, is that we’re going to be exploring it.
(Someone asks a question and Linda asks, “Can we do the Q&A at the end?”)
So that’s something that we’re going to be exploring this year, right?
So we have these three major areas filled with milestones and catalysts, and we have this exploratory area. And just in regard to this exploratory area, and to remind you about the biology that underlies our technology, the active ingredient of our technology is dendritic cells. The dendritic cells’ role in life is to mobilize the whole immune system. Everything — including, as you see down here on the right, the T-cells, but also the B-cells, the natural killer cells, and others, right? And that role is so important… that’s why the dendritic cells were the subject of the Nobel Prize in 2011. They mobilize the whole immune system.
Additionally, as I said, they mobilize the T-cells in a big way… well each, each dendritic cell will mobilize hundreds of T-cells. That’s a great ratio. With a dose size of two and a half million dendritic cells multiplied by multi-hundred T-cells… and the T-cells are only part of what gets mobilized… that’s what I mean by a broad spectrum mobilization with our technology.
Now again, the key differentiators of our technology versus other immune therapies that you may look at… and look, there’s room for lots and lots of winners… just because our technology has the strengths that I’m going to describe, doesn’t mean the other immune therapies… I’m not criticizing them… but these are real strengths and differentiators of our technology.
First off, as we just showed you, you’re mobilizing the whole immune system, which means you have many active agents hitting the tumor, not just one active agent.
Secondly, and this is the biggest differentiator of all for us, is that we use the whole set of targets on the tumor. We don’t pre-select one target, or a handful of targets. Small molecule drugs, biologics, and even checkpoint inhibitors and CAR-T cells are all pre-selecting one or a couple of targets. We believe that the reason we are getting such durable, multi-year long clinical responses, extensions in survival and delay in tumor progression, is because when you have many active agents hitting many targets on the cancer, that makes it much harder for the tumor to escape, then if you have just one agent hitting one target, or a couple targets. That’s the key differentiation of our technology.
The other differentiation is our technology is personalized, so we know that not only are we using the full set of tumor targets, we’re using the right set, the relevant set. When you pre-select one or a couple of targets, you have inevitably… Russian Roulette. That patient may, or may not express some, or all, of those pre-selected handfull of targets… and that’s where you get Russian Roulette, and that’s where you get limited a percentage of patients responding.
Now, in the last period here, I just want to quickly run through a little bit of the clinical data, and then finish so we have some time for Q&A.
Our technology is embodied in two product lines that I described at the beginning. DCVax-L, which is for all types of operable solid tumors; and DCVax Direct, which is for all types of inoperable tumors. Each of these two products has the same two key ingredients: the immune cells themselves, which are the dendritic cells, and the targets on the tumor, the biomarkers which are called antigens. With the operable tumors, we capture the tumor tissue in the operating room, just drop it into a kit, and they send the kit to us. It literally takes five minutes in the operating room. For inoperable tumors, we directly inject into those inoperable tumors; and we can reach any location in the body with image guidance. Any form of image guidance, it’s physician’s choice, ultrasound, CT, MRI, they all work just fine.
I mentioned earlier I’d give you just a glimpse of the breadth of the markets for a product like this that can apply across the board. These are just five examples. These are just five of the seven cancers that we dealt with in Phase one with our DCVax-Direct: Sarcoma… in fact it’s one type of Sarcoma…, Ovarian, Pancreatic, Colo-Rectal, Lung. As you see, new cases a year in the US, new cases a year in Europe, and… what people often forget is… existing, accumulated cases. Prevalence. The numbers are… enormous. And these are just a few of the examples of the cancer we’ve treated. And I’m going to show you quickly, now, in five minutes. Five minutes, five case studies with some of these cancers.
Just as a preface, with our DC-VAx Direct injection… what we are looking for, in terms of the clinical response in the patient is first, a local effect, which is tumor cell death in the tumor that is injected. Secondly, in a longer time frame, because it takes longer, we look for systemic effect… meaning tumor shrinkage, or elimination in the tumors that were not injected reflecting that the whole immune system has been immobilized throughout the whole patient’s body. And third, and very importantly, immune memory. That’s one of the key attributes of all these immune therapies.
Okay… couple of key things about what did we learn from the Phase one trial that I’m going to show these handful of five or so case studies. Well again, we treated more than seven different cancers, three different dose levels, two different methods of activating the dendritic cells, the feasibility of different methods of image guidance to get to the interior body. Very importantly, we did both imaging and biopsies and we correlated them because on the imaging, the tumor may look like it’s getting bigger… it may actually be getting bigger. But you don’t know if it’s a good bulge, or a bad bulge. A good bulge is… what the bulge consists of is immune cells that have come to the site of the tumor and infiltrated the tumor, attacking the tumor, doing their job. That’s a good bulge. A bad bulge is… more tumor cells. Well, the biopsy will tell us whether it’s a good bulge or a bad bulge. And we have done both, and we have correlated them, and we have correlated them with clinical outcomes. And we’ve evaluated both the local response in the tumors that were injected; and the systemic responses in the tumors that were not injected. So this has been a tremendously information-rich trial. We are very grateful that the FDA let us do such a concentrated trial. It shaved at least a year off the development time, maybe longer. And now we’re going into Phase two with that information shaping the design of the Phase two.
For shortness of time, let’s just dive right into the case studies.
First off, I think a lot of folks now are familiar with the pancreatic case study. This gentleman works for National Geographic. He’s been very generous in being very public with his case. He had five tumors… this is very typical of the patients. The patients in this trial had all failed all existing treatments. They had actively progressing disease. They typically had four or five tumors because the most common reason tumors are inoperable is because there is too many of them. And these patients were basically on the doorstep of hospice.
So this gentleman had five tumors including one in his liver and abdomen. He’d failed at least seven cycles of two different chemotherapies. He had nothing left to try. When he went on DCVax-Direct injection, he reached stable disease, meaning no more growth of tumors or appearance of new tumors by the fourth treatment. Suffice it to say, he’s actually now more than twenty two months out. He’s looking very good. I encourage everybody to watch his two minute, three minute video. It’s really encouraging. He looks terrific. He’s living his life. He’s working. He’s going onwards.
Ovarian - a real silent killer and a very big problem. Eighty percent of patients are diagnosed when they’re already at stage 3 or 4. It’s a really bad cancer situation. Similar situation with this patient. This patient had failed all the prior treatments, and you see hear on the imaging… this was her primary tumor… and this was at the fourth treatment. And it continued to shrink. There’s also one small one that started up new. One of the things about the treatment regimen in the Phase one trial is that the treatments were spaced as much as a couple of months apart… with no treatment in between. And we only injected one [tumor] out of the tumors that they had. Why? Because this was a first in man study. You have to be super conservative… you have to be really conservative. So suffice it to say, in Phase two, we will be injecting multiple tumors, and we’ll be injecting every couple weeks, not every couple months, right? But these are the results you are seeing with even only injecting one out of the tumors, and with the treatments spaced as much as a couple months apart. So that’s ovarian.
Sarcoma - a lot of people aren’t really aware of sarcoma. It’s a pretty bad cancer, actually, and this was a gigantic one. The patient’s primary tumor was 15 by 19 by 17 centimeters. Centimeters are almost half an inch… You can visualize the size of that. It was where… Sarcomas are connective tissues… so it was where the patient’s arm joined his torso… and he had lung metastases. What these holes are showing you is literally the tumor is being eaten away by the immune cells. This tumor became “swiss cheese” and it ultimately collapsed. The primary tumor collapsed, and his lung metastases, one of them started shrinking, and the other stabilized and stopped growing. Again, this is with very limited treatment in the Phase one trial.
Another Sarcoma, a different kind of Sarcoma, the patient had five tumors. Only the purple one was injected [referring to 5 lines in diagram], and you see the typical curve of the response of the other tumors. It takes a little while for the immune therapy to be responded to, and then all his tumors start shrinking. And the bottom [of the slide] gives you a few images just to see what we see when we see through the microscope looking at it. The brown dots are immune cells. The more brown dots, the better. We love brown dots. Brown dots mean that it, the immune cells are infiltrating the tumor, and they are eating away at it and making it collapse like I showed you.
Last case study, Lung cancer… we just reported on this for the first time at a conference last month, right before Christmas. The patient had Lung cancer, non-small cell Lung cancer, which is the kind you get from smoking, and comprises the majority of Lung cancer world-wide, of which there are 1.8 million new cases a year, world-wide. The patient was first diagnosed at stage four. Her tumor was ten centimeters. That’s the size of a grapefruit. She couldn’t even breathe… She had no chemotherapy, she was past all that. The only systemic treatment she’d received was DCVax. As you see, we received an email from her physician…
[Ono slide: “… was the pt with radiation as the only therapy! no chemotherapy. She presented w Stage 4 lung cancer - DC fax is the only systemic therapy. Interesting pt - she has recovered and has great QOL.”]
Suffice it to say, before she even finished the treatment regimen with DCVax-Direct injection, she was back to her full life. She was breathing, she was swimming for exercise.
So Phase two plans, injections in multiple tumors, more frequent injections, we’ll use the better of the two activation methods, and so forth.
So I think that we’re out of time, or we’re slightly over time, so I’ll skip over the rest and just say the manufacturing, it’s an eight day process, as I said, it’s very practical, the manufacturing is already well established in both the US and Europe, and has been validated to the satisfaction of regulators on both continents. That’s years of work to accomplish that.
Huge intellectual property portfolio, over one hundred and eight issued and pending patents worldwide, management team… everybody has twenty plus years of experience in their role, and finances, very strong. We raised 79 million dollars last year, 35 million of it was just not that long ago in November, and so we expect to be accelerating our programs this year, and having a very strong year. So thank you very much for your attention.