Thanks for sticking around, everyone. That is impressive in itself. These are my disclosures. BioInvent, we are a company dedicated to the discovery and development of antibody-based drugs for cancer immunotherapy. We have four ongoing clinical programs, a world-class scientific team in-house, GMP manufacturing, and clinical development capabilities. We are fortunate to be backed up by some of the strongest international shareholders. Our operations are funded until the first quarter of 2017. Why therapeutic antibodies and in particular immunomodulatory antibodies? The reason is, of course, that immunomodulatory antibodies have transformed cancer survival, and they are continuing to do so as reflected in these graphs. Antibodies like those targeting PD-1 or CTLA-4 shown on this left-hand graph induce long-term survival and even cure in cancer patients that previously had no hopes of surviving.
It is known that these drugs work by activating a patient's own CD8-positive T cells, in particular, those that are specific to different tumor antigens. As a consequence, those drugs can be used to treat many different types of cancers. They are currently approved for more than 30 different indications. As great as these drugs are, and while they work in patients whose tumors are infiltrated by these critical CD8-positive T cells, they do not work in patients whose tumors are not infiltrated by these CD8-positive T cells. That is unless, and as shown recently, you combine them with something else. Shown to the right-hand side is the survival curve of the combination of a PD-1 targeting antibody with the immunomodulatory small molecule compound paclitaxel.
You can see that the anti PD-1 antibody, actually at the far end of the curve, brings with it the increased long-term survival that is exemplary for this class of drugs, albeit in a very small fraction of patients. There is a huge unmet need to improve on this. It does show that maybe if we combine the existing antibodies with new drugs, with new mechanisms of action, maybe we can elevate that survival curve and make the majority of patients with cold tumors respond too. What should those mechanisms be, and what should those drugs be doing? Anyone?
You do not need to be a rocket scientist to come up with the hypothesis that if I have a drug that can bring the CD8-positive T cells into the cold tumor, then maybe that is a good thing, and maybe I can then use the old drugs to unleash their potential even further. Oh, we are missing a table here. These shown down here in the square are some types of cancers that do not respond to the immunotherapies. On the way top, you see that half of patients respond to the immunotherapy, and this follows as a direct correlation of how well their tumors are infiltrated by these CD8-positive T cells. Again, bringing in the CD8-positive T cells seems to be a good thing if you want to improve cancer survival. This is exactly what we do at BioInvent.
We specialize in understanding the tumor microenvironment and coming out with new targets and new antibody mechanisms of action that can help overcome resistance. As I will tell you with our lead clinical BI-1808 antibody targeting the immunoreceptor TNFR2, see activity also in those cold types of tumors. In the interest of time, I will focus on this program. We have another program, which is also really interesting, but that will be saved for next time I come and speak. What is it that is so different about our BI-1808 antibody? Why should this work when there are so many compounds that have been claimed to be immunomodulatory and have not really panned out? Well, for one, our antibody seems to be doing exactly that which we had all agreed seemed to be a good thing in the previous slide.
It brings in those CD8-positive T cells, and that seems perhaps to be a really trivial thing to do, but actually has not been previously observed in any meaningful manner. It does this by triggering initially two different events. One is by binding to immunosuppressive myeloid cells that can constitute up to 50% of a tumor. They are really abundant. When it does so, it activates the myeloid cell to release factors to call for the CD8-positive T cells. These are validated biologies. The molecules that are being produced are known to call for CD8-positive T cells that then come to the tumor. The second thing the antibody does is it binds to T regulatory cells. Not only those, but the most immunosuppressive T regulatory cells that are positive for our target TNFR2 and CCR8, and it deletes them.
This is also good news because invariably, if you get influx of these good guy CD8-positive T cells, the immunosuppressors will follow to try and counterbalance activation in a normal human being, inappropriate activation and destruction of tissue. Of course, here we want to destroy the cancerous tissue. You will appreciate that this mechanism is quite different to the validated immunomodulators like PD-1, which act directly on the recruited CD8-positive T cells. The drugs should be complementary and work well together. I will show you how well they work together soon. Before I do that, I just want to show you that our mechanism is active in those types of cancer patients that are known to very infrequently respond to any type of immunotherapy. Shown here is a patient with a cancer called gastrointestinal stromal tumor. These do not typically respond to anti-PD-1 at all.
You can see prior to treatment with our antibody, this is a picture of the tumor. T cells are shown in green. Well, you see very few green cells. Activated T cells are indicated by red. Again, this is kind of a desert. It does not have many immune cells, consistent with a patient having a type of cancer that is non-immune infiltrated. A few weeks after treatment with our antibody, we are seeing abundant infiltration of the CD8-positive T cells, and not only those, again, as highlighted by the red dots here, activated CD8-positive T cells. A bit later, we are seeing this is the size of tumors of this particular patient. All of the four identified target lesions have started shrinking. Actually, at the end of the journey of this patient, we biopsied tumor lesions, but we are unable to find tumors in this patient.
So again, a patient that shouldn't have responded to immunotherapy, but very abundantly and vigorously responding to therapy. There are some further data which really support that our mechanism is what we're saying and seeing in animals, and that is that we're expanding in blood also the CD8- positive effector T- cells that are known to precede a response to the validated immunotherapies. In other words, this is activating CD8-positive T cell anti-tumor immunity, a good and well validated type of biology. How about PD-1 combinations then? It should work really well, and does it. We've done a lot of preclinical experiments on this. Recently published a paper in Cancer Research. You can go and have a look at that. But looking at the most resistant models that, again, don't respond to anti-PD-1 or anti-CTLA4, the validated therapies, even if you give full therapeutic doses.
We see that when we combine PD-1 with BI-1808, we can get cures in a majority of the animals. Really, again, consistent with our antibody's mechanism being complementary to that of PD-1 and being relevant to the cold tumor model setting. Based on those really strong human clinical data and also supportive preclinical mechanistic data, we have then moved into combination studies with our drug and anti-PD-1 in one of the prototypically cold types of cancers, which would be ovarian cancer. While it's early days, we've dosed, well, at least at the last reported time point, some 25 of the 40 patients that we plan to dose. We're seeing some really compelling activities. Again, if you treat with anti-PD-1 alone, and there's been a large study looking at this, less than one patient in 10 will respond.
Here at the first readout, well, more than two, approximately a quarter of patients had responded to the combination therapy. That's all nice, but what really matters is, of course, how long is that response ongoing? A patient wants to live longer. Here we have even stronger indicative data by looking at the progression-free survival of patients, which again, with our combination, was estimated to 10 months at this first readout, compared with just a bit north of two months for the single agent treatment with anti-PD-1. I think it's fair to say, again, while early days, this is really compelling data that strongly suggests that our antibody's doing something above and beyond what the state of the art can provide. Importantly, ovarian cancer is not one type of cancer. It comes in many different variants.
We're seeing activity both in, for example, clear cell ovarian cancer, shown in the orange lines, but also in high-grade serous adenocarcinomas . Right. That by itself indicates that our drug, when combined with PD-1, could be really interesting and of great value to patients. But the really interesting piece comes with this newly approved combination of drugs, PD-1 and paclitaxel. Because we're seeing that our antibody shown to the right, actually, this is a preclinical model. This is the human data. If we add our antibody on top of the two reagents here, we very significantly, in the purple line, improve survival of the animals with the potential for actually curative effects. Very importantly, our antibody seems to be very well tolerated. We have no greater than two adverse events in the single agent dose escalation study.
Upon combination with PD-1, we're seeing very similar activities to what you'd find with PD-1 administration alone. Am I running over a minute?
No.
Oh, yeah. Well, no time for questions, ladies and gentlemen. Well, needless to say, we think this has blockbuster potential, not only in ovarian cancer, but also beyond. Apologies for that, and thanks for staying awake during that lengthy presentation of mine.
That's all right. That's fine. We have time. If there are some questions in the room, I'm happy to take them. What we'll do then is you have Yeah, that's a little bit after. Say you have about a minute. What did you not get to say that you really want to say?
Yeah. Well, thank you. A very kind offer after having—
Thank you. After cutting you off.
—taken up so much time. Yeah, no. Fundamentally, I think there is a great unmet need in these patients that cannot be treated with any drug, not only immunotherapy, but not with targeted or cell therapy or anything.
As a field, if we can do anything to help those, that would be fantastic. So I feel that we're on the track of something that could be hugely valuable. I hope you're seeing that and you want to be part of our journey.
Thank you so much, Björn.