NovoCure Limited (NVCR) Earnings Call Transcript & Summary

And Bill last year, when we were getting close to LUNAR, the interim analysis, you gave color on approximately when the interim analysis is going to happen, which was at the time, late 2020, I believe. When we -- as we get closer to 2021, are you going to give us a sense of when those 3 interim analysis will be done, whether it's first half, second half of the year? Right now, we have no idea what part of 2021 that will occur?

Yes. When we get into the year, and we have a better sense, we will narrow down the timing.

Okay. And I wanted to get your take and the audience's take on which of these 4 Phase III studies you have ongoing, that you feel most confident about in terms of the positive clinical outcome? I mean it's a little bit ironic to me, the non-small cell lung cancer, LUNAR trial, seems to get the most attention. It's probably the largest patient population that you're studying. It was also kind of the first interim analysis we were going to see. But when we look at the Phase II data for pancreatic and ovarian, they were quite strong and the unmet clinical need is arguably higher for some of the other tumors that you're pursuing. I guess do you have a favorite, Uri or Bill, do you have a favorite child?

I'll start, and then I'll let Uri talk about that. The one thing that I remind everyone of when asked this question is that our mechanism of action is a fundamental interruption of cell division. We've seen it work on every single cell type that we have exposed to Tumor Treating Fields. We've seen it work in every animal model with every type of cancer. We've seen it in every Phase I and in every Phase II and in every Phase III. So it's not a mechanism where a certain expression of a factor weighs on the outcome or certain genotype ways. It really is dependent on whether we can get our fields to the region of the cancer. And all of the cancers that we are treating, we know we can get the fields to the region of the tumor. So from that perspective, I don't have a favorite where I think it's going to work a little better in ovarian and a little -- I think it's going to work in all of them. In terms of the markets themselves, I think these are all markets with tremendous unmet medical needs. Even non-small cell lung cancer, where there's been quite a bit of progress, virtually, everyone who's diagnosed with non-small cell lung cancer is going to die of non-small cell lung cancer. And so I think we have the opportunity to contribute in all these areas. I will say -- and maybe this is what you were getting at, the unmet needs in terms of patient suffering and maybe speed in pancreatic, of course, is extreme, very little progress has been made there, and I think we can make tremendous progress. Again, based on our Phase II response data, ovarian similarly. So I'm -- I could wax poetic about each one of these brain metastasis as we get better and better at controlling the solid tumors in their location, more and more patients are dying of the spread of brain mets. But Uri, maybe you have a favorite child?

I don't know -- yes. I would actually echo Bill and Larry you compared or gave an analogy to children. And similar to how I feel regarding my sons, I would sincerely say that I don't have any particular favorite. I would like to share that also from what I hear from investigators actively working on our studies, there is a lot of enthusiasm shared regarding them. And this is certainly based on the primary signal that we received from our Phase II completed studies, and also the strong scientific rationale and unmet need in those areas. And I can expand on any study as needed if this is of interest. But in general, I think that we have also been, as a company, very selective with -- going for the Phase III trials on indications that we feel very high confidence regarding the solid data that we generated in preclinical and early clinical programs. Since indeed, the TTFields could be a therapy potentially targeting other solid tumors, but we decided to select those tumors first as we continue to expand our program.

That's helpful. Let's try polling question here. It's the first one. So our technician, [ Zach, ] I think your name is. I apologize if I got that wrong, but -- [ Josh ], sorry. Because you put the first polling question up, and we'll give the audience a couple of seconds. So Novocure's 4 ongoing Phase III studies, which do you think is the highest probability of clinical success in its Phase III trial? And I list the 4 here, METIS, for brain metastasis. So you if could try to click on this, and we'll see what comes up, we'll give everyone about 30 seconds. [Voting]

[ Josh ], still have...

Everyone's voting on it now.

Why don't we -- all right. Brain metastasis number one, interesting, then pancreatic cancer, okay. Bill or Uri, any reaction? It's helpful to get your reactions. Maybe there's nothing to add, but useful to see what investors think.

Uri?

I think it potentially recognizes the very strong conviction that there is an unmet need there and TTFields is a therapy that has already demonstrated efficacy in brain cancer and technical feasibility and demonstrated that patients can stay on the therapy for a significant amount of time, it makes a lot of sense. This is a very high population, very high incidents that we're talking about. Of course, if we speak about METIS, we are targeting non-small cell lung cancer brain metastasis. But if the study is successful, it could be a starting point for plenty of other tumors that frequently metastasize into the brain. And with the existing therapies, whole brain radiation therapy on one hand, which treat those lesions well in the brain, but leads to neurocognitive decline, quality of life decline. And stereotactic radiosurgery, on the other hand, which treats the tumor well prevents some adverse events, but recurrence rate is high. I think that maintenance treatment with TTFields has the potential to be a great modality to treat those brain metastases effectively, and this is what we would like to see through the METIS study.

All right. Super. So Uri, maybe we'll stick with you. We have 2 Phase II studies coming next year, HEPANOVA and your gastric cancer study, I can't remember the name of that trial. But in the past, we've seen Phase II studies. When you guys have presented Phase II studies like with the pancreatic trial a few years ago, the data were quite strong, but it didn't seem to resonate a lot with investors at the time, from my memory. So why HEPANOVA and the gastric cancer trial, what's important about those Phase II readouts? And why should people care about that data, assuming it's [indiscernible]?

Yes. So I'm not 100% sure that I mean full agreement with your comment regarding our previously conducted Phase II studies. Because it was actually mostly the reaction from the communities side from those physicians and investigators who work on those malignancies that led us and encouraged us to open Phase III clinical studies in those indications. I think that the intention of every Phase II trial that we conduct is to provide us with the safety data and the initial efficacy data that would support us in developing a Phase III trial, and we are hopeful that the currently ongoing HEPANOVA and the EF-31 trial in gastric cancer, will be the first stage towards a Phase III trial in those indications. Hepatocellular cancer, the PANOVA study is a malignancy that progresses mostly locally. And is treated quite well with local therapies, but at some point, unfortunately, for the vast majority of the patients, the tumor progresses to a stage where those treatments are no longer effective and cannot be applied due to toxicities. And then patients have to receive systemic therapies, such as sorafenib, a chemotherapy, which is used as part of the HEPANOVA study. And we would like to see TTFields treating this malignancy locally and in a safe way, maintaining patient well-being and improving their response rate. This is a primary endpoint of the HEPANOVA study. And the same goes for gastric cancer. Patients usually are treated with toxic chemotherapies. Also on the study, we treat unresectable gastric cancer patients locally with Tumor Treating Fields in an attempt to improve the current response rates that we see in this malignancy. And both of them follow very strong preclinical evidence that Tumor Treating Fields are effective in those malignancies.

Please, Bill.

I was going to just add from an investor perspective. I think in some respects, investors have been conditioned a little bit to discount Phase II data in drug trials because it doesn't necessarily lead to success in Phase III for various reasons. In our case, I want to emphasize just a couple of things. One, why do drugs fail in Phase III? One reason is because a safety signal that they didn't see in small populations manifests in the large population. We really don't have any reason to believe that there's going to be any safety signal in Tumor Treating Fields for reasons that we've described at length. Another reason that they fail is that for some reason, you've been fooled in Phase II, you actually don't have a drug. Maybe there's been a placebo effect or something like that. We know we have a drug, if you want to think of it that way. The mechanism of action is very clear. It's worked again and again. And so I would hope perhaps that assuming success in these trials that it will just add to the totality of evidence with respect to Tumor Treating Fields. And our ability to treat tumors, not only in the head but in the abdomen. So I think they're both important readouts.

We've got 3 minutes left, and I've got 2 questions I wanted to hit. But maybe I'll just ask them right now, and Bill or Uri, you guys can both tackle them. So the KEYTRUDA agreement, collaboration with Merck. Do you think that the Merck agreement validates the technology or in some way, Merck is kind of look at your Tumor Treating Fields mechanism of action and agreed to that collaboration because they thought it had some merit? And second, on EF-33, the high-density arrays. Just remind us of the status there and the importance? And hopefully, we can get those two in the next 3 minutes.

Uri, you take EF-33 first, and then I'll do Merck.

Okay, very good. So the EF-33 intends to test a new type of hardware. A new transducer array that incorporates additional electrodes into the existing array. This increase in electrodes from 9 to 14 increases the surface through which we deliver our alternating electric fields, ultimately, translating this into potentially increased TTFields, increased dose and the intensity of Tumor Treating Fields in the treated area. And we have seen that in preclinical methods. And we are now testing this for the first time in a recurrent GBM in an attempt to extend the progression-free survival of such patients using this new hardware, the new array. And this is a very exciting development coming from the engineering side because we are convinced that we are seeing the tip of the iceberg when it comes to the efficacy that we can potentially generate from TTFields through such engineering development and also from combination that are synergistic with TTFields and other agents. And at this point, I would like to transition this to Bill to discuss the collaboration with Merck.

Yes. And Larry, very quickly, I think this is -- you used the word validation. I think this is just another indicator of the importance of Tumor Treating Fields in the broader oncology landscape. There's no question that Merck is the dominant player in non-small cell lung cancer. They have, by far, the leading franchise. But as I said earlier, most patients who are diagnosed with non-small cell lung cancer will, in fact, still die of non-small cell lung cancer. And so they're very interested in expanding the therapies they have in combination with others to improve outcomes. Importantly, this trial was designed in collaboration with the Merck non-small cell lung cancer team to address a subpopulation, a very large subpopulation where they believe there's the potential to benefit from the combination. We are delighted to be working with the leader in this area. And we see this expansion because our Phase III trial today is focused on second line patients. This is a trial in first line patients, and it also complements our work in mesothelioma. So it adds to our non-small cell lung cancer franchise, if you will. Because, ultimately, we believe we have the potential to add to the therapy across stages, across lines with a whole variety of pharmacological combinations. Whatever the pharmacologists come up with as the best pharmacological standard of care, across all the solid tumors that we're treating, we would then expect to add Tumor Treating Fields to that to maximize the benefit to patients.

Perfect. Bill and Uri, we're out of time. Thank you so much for being here, and have a great rest of the year.

Thanks, guys. Thanks for inviting us.

Thank you, everybody. Thank you, Larry. Goodbye.