NorthWest Biotherapeutics Inc (NWBO)

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Lifespan WPRI News Conference, Jan 6, 2022 Transcript

https://www.youtube.com/watch?v=cU_-1ECBMAU

Video begins with Dr. Steven Toms, Dr. Heinrich Elinzano, and Dr. Wafik Aldiri at the dias

0:02
Dr. Elinzano: Good morning everybody, thanks for coming to this press conference. We called this press conference to share with the community this breakthrough study that came out a couple of months ago for which we were part of. It's a study on the most common malignant tumor that primarily involves the brain. It is called glioblastoma. Just to put things in perspective, glioblastoma has a survival of probably an average of one to two years – there's not a lot of good treatment options.

So this study came up with this treatment approach that really improved the outcome of these patients. To break down the results I'll simplify it. First off it improved the Overall Survival (OS) by several months compared to the standard treatment of radiation and oral chemotherapy. Two, it also almost doubled the proportion of patients surviving over five years which is a long time for this tumor. Then three, for those patients whose tumor came back, or recurred, it improved their survival more than twice what would be what we'd expect for someone whose tumor came back. It's also a novel approach, and Dr. Toms next to me will describe this design.

1:21
We used a vaccine approach in addition to the standard treatment, like I said, of radiation and oral chemotherapy and it's a big study. It included 94 sites, one of which is Rhode Island Hospital and Geisinger is the other, in about four countries. Studies like this are quite rare in this tumor because they're not too many of these tumors, although they are the most common malignant brain tumor, and conducting a study with different sites also has its own set of problems. I'd like to turn over now to Steve Toms who will describe the design of the study and then after him, I'll turn over to Dr. Aldiri to kind of give us an idea of where cancer care is heading in our state of Rhode Island.

Dr. Toms: Thank you Dr. Elinzano. I want to welcome everybody who's come to talk about this exciting development and, you know, highlight some of the local flavor of it. the lead investigator on this study was Linda Liau, she was class of ‘87 here at Brown and a year behind me. Her daughter is currently a student here at Brown, and Dr Liau is currently chairperson at UCLA. She’s been studying these immune techniques in cancer over about the last 35 years.

2:41
The study was designed initially as a randomized control study, which is the standard in cancer therapy, and a randomized trials – but unfortunately due to some changes in the care of glioblastoma of the 20 years and some design elements that the FDA mandated, including crossover such that the patients who did not get the vaccine up front got vaccine later on, the data is a little tough to interpret in some ways. As Dr. Elinzano pointed out, the data suggests about a three-month survival increase in the patients who got this vaccine in overall survival, but
the thing that really stood out in this was the tail – the number of long-term survivors.

In communications with Dr. Liau, she has a few patients who are 17 and 18 years out under this treatment, which is longer than any survivors I or Dr. Elinzano have. I have a couple of 12 year survivors at this point.

Let's talk a little bit about how this complex study went. So as Dr. Elinzano mentioned, the standard of care for glioblastoma is that, you know, a barber such as myself, a surgeon does a bad haircut, goes ahead and does an operation to try and take out the maximum safe amount of the tumor you can. In some patients it's as small as a needle biopsy because it's in such an eloquent area of the brain, but our goal is to try to have those surgeons such as myself get out as much as we can. Then we follow that typically with six months of radiation with concurrent oral chemotherapy, the temozolomide.

4:22
What made this study unique is that we took each of the patient’s cancers and we put those essentially on ice and shipped them down to a place for processing. The tumor samples are then processed by lysing the tumor cells, which exposes some of their proteins, including the
proteins that are on the cell surface. The body can then recognize and attack. These things are called neoantigens, or new proteins, that come out in the cancer during the cancer evolution. So once that is done the patient then had to undergo a special type of procedure called a leukapheresis where their blood is drawn out and monocytes, which are a type of immune cell in the body, are taken from the patient. Those are then again put on ice and shipped down to a processing center centrally in the U.S, turned in the petri dish to these specialized cells called dendritic cells. Dendritic cells are a type of immune system that's involved in that antigen processing which is taking proteins in the body, whether it's from a
bacteria, a virus, or new proteins from the cancer and processing them such that other immune cells can recognize and then attack them. So essentially what was done is in the petri dish or in the laboratory the lysate or the proteins from the tumor were then mixed with the patient's own immune cells, and those immune cells were processed the tumor themselves, and then were used to re-inject into the body as a vaccine.

Each of the injections included about two and a half million dendritic cells and they were done about three times the first month and then every other month for about six months up to a maximum of 10 to 12 vaccine inoculations. Each of those inoculations is very similar to the vaccines we're all familiar with for the flu and COVID and what not.

6:04
So where we are with this process right now is that the study is out and has been reported, the data is looking quite promising but as we said it is a little bit messy because we don't have an internal control because of changes that were mandated by the FDA. But there's
certainly signal there that I have seen myself. Dr. Elinzano, an oncologist who have been involved in this study has seen, and in fact Dr. Liau has been continuing to work on these processes and combining her vaccine with some things called immune checkpoint blockade that rev up the immune system as well and are used in many other cancers such as kidney cancer, and melanoma lung cancer very commonly. In early studies that she has done with 10 to 20 patients she is seeing some survivals of five years, up to 40 to 50% vs the 4 to 5% we used to see in our traditional treatments and the 13.5/14% we saw in this study of using the vaccine alone. So I think there's a lot more promise in this type of technique. It's the first personalized cellular therapy that's been designed for cancer and we're hoping that the FDA will act on this within the next year or so.

7:25
The thing that's important for all of our patients to remember is if they or a family member have someone with glioblastoma it is important to be seen at a specialized cancer center that deals with brain tumor. Here at Lifespan we have a multi-disciplinary brain tumor clinic; we'll have our brain tumor board, in fact, in this very room in about an hour where we meet weekly to go over complex cases and then every week we have our neuro-oncology team along with our radiation oncology team, social workers and our neurosurgeons all come together to see patients together to give Optimal Care. We hope and expect and certainly I advocate now that if you or a family member has glioblastoma you think about coming to a cancer center that will not only give you that type of treatment but have access to clinical trials, and I personally advocate for our patients to freeze their tumors at this point because if this becomes FDA approved there is a way where we can unfreeze the tumor and make the vaccine if we get to the point where we have this therapy available widespread in the next year or so for our patients.

So I I want to thank everyone for being here, to thank Dr. Elinzano for pioneering the study here. It's good to be back to the old alma mater. Yes?

8:36
Reporter: This is a quick question. Would you consider this a breakthrough?

Dr. Elinzano: I would. We would, I think. One, because right now, prior to this study there's probably just two standard treatments, with the oral chemotherapy and radiation therapy and there's a device that is approved for use for this type of tumor, but this vaccine approach is kind of a novel, a breakthrough in the sense that the results are pretty impressive compared to a standard that's already in use, it's a very innovative approach in managing this tumor.

Dr. Toms: I would echo what Dr. Elinzano is saying. In the in the past, since we had the improvements in early 2000s with what's called the Stupp protocol – combining the radiation and chemotherapy to improve survival from about 12 months to 14 months, we have not seen
much progress. There have been over 400 clinical trials in glioblastoma in that time and only two have been positive. One was for an electrical device called Tumor Treating Fields (TTF), which has increased survival somewhat and is relatively non-toxic, but patients find it hard to comply with that. This is a very easy protocol, has very limited toxicity that we've seen thus far – minimal immune reaction problems that we sometimes get with the immune checkpoint blockade drugs. So I think this is potentially a huge breakthrough for patients with glioblastoma and potentially with other solid cancers down the road once these techniques are applied to other cancers.

10:01
Dr. E: It's actually an important point which Dr. Toms highlighted, the quality of life aspect of it. Whenever you have a treatment approach you always want to balance out benefits you're deriving from the treatment and the risk or side effects that patients may experience with the treatment. In this particular study we didn't really see a lot of those. Although it wasn't highlighted in the study itself we have people who pretty much enjoy their day-to-day living without a lot of assistance with other folks and up to the point where their tumors sort of, progressed they were still kind of functioning as usual.

10:39
Reporter: How many people involved in the study?

Dr. E: So they're about 331 patients enrolled in the study, and so that included 94 sites, one of the sites is us here in Rhode Island. (inaudible question) It's done already, it's completed already and that's why it was published a couple of months ago.

Reporter: When did it start?

Dr. Toms: 2005/6, it was almost a 20-year long study.

Reporter: So that’s how you've been able to measure just how effective – you said some people still alive 12 year later?

Dr. Toms: Dr. Liau and some of her early studies, before this phase three trial, she's got some survivors who are 18 years out.

Reporter: This was Phase III? (nodding affirmative) So you expect, it is possible that the FDA could approve this within a year?

Dr. Toms: When I spoke to the CEO at our investigators meeting at Society for Neuro-Oncology (SNO) they said they are in the process of the application. They put together I believe she said three quarters of a million pages of documentation for the FDA thus far – it will obviously take some time to go through the application. but given that glioblastoma is in many ways an orphan disease with very few options. I feel like the 35 years I've spent doing research on this has been mostly an exercise in futility in that we've had so many failed trials. I get that even though the data is not perfect we would love that, you know, we had perfect data, but this is real world data. Given the mandates of the FDA that there was crossover and people were allowed to get the vaccine even if they were in the control group once they progressed because they had to undergo surgery, because they had to undergo an invasive procedure called leukapheresis, the FDA demanded that, the data is not as pristine as some would like. People have used that to try and tear down the data and say that this data is not effective, but I am somewhat biased as having been involved and having known the primary investigator since we were teens and knowing what a moral, wonderful person this is who's been doing this for years.

12:57
Reporter: The incidence rate for glioblastoma is what?

Dr. E: So the incidence rate according to the central brain tumor registry of the United States is about three per 100,000. We have a relatively high incidence here in Rhode Island so if you calculate about a million people in Rhode Island three per 100 000 that's probably about 30 cases per year but we see about 60 to 70 cases per year here in Rhode Island Hospital alone and that doesn't include other hospitals in Rhode Island.

Reporter: About 60 to 70 cases – why you think that's the case (next part of transcript not relevant to $NWBO)

14:35
Reporter: Which entity would be seeking FDA approval?

Dr. Toms: That would be the company that is trying to commercialize this, a company called Northwest Biotherapeutics and it's up to them to commercialize. They are a publicly traded company.

Reporter: Can you explain the difficulty in treating glioblastoma? It has these like little tentacles? So you can’t really get to everything and that’s why it tends to come back?

Dr. E: Exactly that's uh that's correct. As I often tell patients like plumbing a pudding that you just scoop out and be done with – there are microscopic cells left behind even if you're able to take out most if not the bulk of the tumor safely. And then we're dealing with a tumor that
involves the brain. The brain itself is a very delicate organ and so you encounter a lot of issues with treatment. And then there's still a number things unknown about this tumor, although we've come so far in terms of understanding the tumor, I think that there's still a lot of unknowns that we need to explore and do research on.

Host: Dr. Aldiri, would you like to provide a little bit of a comment and then afterwards we can just go to questions?

15:49
Dr. Aldiri: Thank you I'd like to thank everyone and in particular congratulate this amazing team for the tremendous progress that's been made in the treatment of brain tumors that's really affecting people's lives – this is very important for us in Rhode Island. (Non-relevant Rhode Island discussion)

18:09
Reporter: I have a question. If somebody comes in with a glioblastoma now do they have access to this vaccine or not until or if it is approved by the FDA? The clinical trials are done, right?

Dr. Toms: Correct the clinical trials are done. Right now the only access to this vaccine is through a Specials program in the United Kingdom, so unfortunately right now the only way to do it is to pay for it out of pocket, for us to take the tumor out and send the lysate over to the United Kingdom, have their leukapheresis done there, and the vaccine made there, and then the injections done there. So it's a very time and cost prohibitive thing. I believe the cost is somewhere near $200,000.

Reporter: So that’s why it’s so important to get it FDA approved…

Dr. E: Exactly. Yeah exactly. And it's not just an urgency because we need to take care of this tumor right away but really need to have options for them.

Reporter: Where is the funding coming from, where did the funding come from for the clinical trials and how much did that cost?

Dr. E: I don't know much about the exact amount but funding came from the sponsor which is Northwest Biotherapeutics.

19:20
Reporter: Did they get an NIH Grant or or anything like that?

Dr. Toms: So Dr. Liau has had multiple NIH grants to do her small studies at UCLA. She has had both R01 grants and what are called Spore grants and they have a small what's called a GMP facility at UCLA to make vaccine themselves. But they're an academic center, they can only make one or two vaccines per month and they cannot scale it. Northwest Biotherapeutics was the funding mechanism for this they've been a publicly traded company for many many
years.

Reporter: So when and where will the results of this come and be published?

Dr. E: They’re published already in November of last year in JAMA which is a big oncology journal.

Dr. Toms: Journal of the American Medical Association Oncology or JAMA oncology

Reporter: Really basic question. If the results were published in November why are you holding this news conference today?

Dr. E: Actually we wanted to do this much earlier on but there were a lot of issues. In December there was a weather issue that kind of affected the conference.

Reporter: So currently there are no vaccine treatments for glioblastoma?

Dr. E: There are vaccine treatments but they're investigational. So you may see clinical trials done by different centers, different approaches using vaccine or vaccine therapy, but none has been shown to be as effective as this one in a big large-scale study.

20:50
Reporter: This is an important thing? (nodding) You would regard it as a breakthrough?

Dr. Toms and E: Yes

(non-relevant Rhode Island research discussion)