Genocea Biosciences, Inc.
Q4 2020 Earnings Call Transcript

Published: 11 Feb 2021

[Operator:]

Good morning and welcome to Genocea Fourth Quarter 2020 Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will begin the call up for your questions. Please be advised that the call is being recorded at the Company's request. At this time, I would like to turn the call over to Dan Ferry, of LifeSci Advisors. Please proceed.

[Dan Ferry:]

Thank you, Operator, and good morning, everyone. Earlier today, we issued a press release that outlines the topics we plan to discuss today. This release is available at genocea.com, under the Investors tab. During the call today, Chip Clark, President and CEO, who will provide a brief corporate update and the Company's Chief Financial Officer, Diantha Duvall will review the financial results. After the prepared remarks, we will open up the call for Q&A and Chip, Diantha, Tom Davis, Genocea's Chief Medical Officer; and Jessica Flechtner, Genocea's Chief Scientific Officer, will then be available to answer your questions.

[Chip Clark:]

Thanks, Dan. And thank you all for joining us today. We're pleased to provide updates on several important efforts. I'll start with our two clinical programs GEN-009 and GEN-011. As a reminder, GEN-011 is Genocea's neoantigen targeted peripheral T cell therapy, or NPT therapy, which we're testing initially in checkpoints inhibitor refractory patients. Our TITAN study is a Phase 1/2a study evaluating safety, biomarkers of activity and clinical efficacy in patients with a range of tumor types across two dosing cohorts. One with a single GEN-011 dose, and the other with GEN-011 administered as multiple low doses. We have initiated two clinical sites and have begun accruing patients. We will provide updates throughout the year and expect to report initial efficacy data from a patient subset late in the fourth quarter of this year, or the first quarter of 2022. Next let me update you on GEN-009, our adjuvanted peptide neoantigen vaccine. In November, we presented expanded clinical and immunogenicity findings for the ongoing Phase 1/2a trial at the 2020 Society for immunotherapy of cancer or SITC Annual Meeting. We were pleased to find evidence of GEN-009 clinical activity on top of checkpoints inhibitor responses. Among the nine CPI sensitive patients dosed with GEN-009, three patients experienced a novel reduction in tumor volume and achieved independent resist responses, post-GEN-009 dosing, including two PRs and one CR. Five additional CPI sensitive patients have shown disease control post-vaccination for up to 11 months. Within the CPI resistant population, five of seven patients appear to have stabilized the disease lasting up to seven months. And these results could become even more compelling with additional follow up. GEN-009 elicited strong anti-tumor CD4+ and CD8+ T cell responses. We look forward to providing additional clinical and immunogenicity data from these patients in Q2.

[Diantha Duvall:]

Thank you, Chip and good morning everyone. We ended the quarter with $79.8 million of cash and cash equivalents compared with $40.1 million at December 31, 2019. Our operating results for the quarter ended December 31, 2020 are as follows

[Operator:]

Your first question comes from the line of Ben Burnet. Your line is open.

[Ben Burnet:]

Great, thank you very much and congratulations on the update this morning. I want to ask a question first about the GEN-011 clinical program. I guess have you started manufacturing clinical material for GEN-011? And are you able to say anything about the manufacturing experience thus far?

[Chip Clark:]

Hi Ben, thanks for the question. We are in the middle of our needle-to-needle process, as you might call it for GEN-011. It's a little bit too early to comment specifically on the patient experience. But based on the 15 plus development and engineering runs we conducted with the GEN-011 process. We have a high degree of confidence in the processes overall robustness. And as I said, you know, we intend to provide an update, updates rather throughout the year. So we'll certainly manufacturing success is one of those things we expect to be able to report on.

[Ben Burnet:]

Okay, excellent. And then just one other question about the SARS-CoV-2 program and just Genocea’s role in the collaboration with Dr. Finberg I guess what kind of data could we see from this collaboration? And when might we get this? And also just from a cash perspective, what sort of impact is this - as the SARS-CoV-2 antigen discovery program have on cash burn?

[Chip Clark:]

So thanks Ben, for the question. I’ll have Jess speak to the scientific nature of your question. And then I'll ask afterward Diantha to speak to the cash impact.

[Jess Flechtner:]

Thanks, Ben. So as you know and as Chip laid out, T cells help antibodies do their jobs, and they persist when the antibodies are gone. And so our role with this collaboration with UMass is to use ATLAS to help us identify the right targets of T cell responses to include in a vaccine a next generation vaccine against this virus. So, you know we published many years ago, that antibody targets change, right, that's what's happening right now with spike. That because of antibodies, they all bind to essentially the same region of the protein the virus mutates the way to try to evade the antibody response. T cells, the targets of T cells don't do that. They don't change. They are not under selective pressure in the virus, because everybody presents a different piece of the same protein to their immune system to make a response to. So what we are trying to find are those conserved antigens that are targets of T cells. That are associated with protective immunity and not enhanced disease, which is where the Inhibigen may come into play. And that are going to help target any variant of the virus and not just, you know, a particular strain. So, we're really excited to see the continued data from this collaboration. We have certainly begun already looking. And we find very interesting results with our ATLAS screens. Diantha?

[Diantha Duvall:]

Thanks Jess. So Ben, as far as sort of a cash impact or investment, the investment relatively modest I mean, obviously, our focus is on our two clinical programs. And this is a preclinical. So this is a relatively modest investment at this stage.

[Ben Burnet:]

Okay, that's fantastic, great. Thank you so much for the color.

[Chip Clark:]

Thanks Ben.

[Operator:]

Your next question comes from the line of Daina Graybosch from SVB Leerink. Your line is open.

[Daina Graybosch:]

Hi, thank you all for the question. I wonder we could get into GEN-011 and the 60 data that you guys presented last year. I think you said again, that you had a response, in immunogenicity response to 89% of the targeted neoantigens. And I also noted that you have an increase in polyclonality of TCR. Wonder if you can help us understand, specifically, patient-by-patient, sort of how many TCR are dominating the product? You're getting one dominant, five non-dominant and average of two dominant. I just wonder patient-by-patient how consistent it is, and how spread the dominance is for the GEN-011 that you actually stimulated ex-vivo. And then also how much there is the sort of antigen spread polyclonality afterwards?

[Chip Clark:]

Thanks, Daina a bunch of related questions and I heard that I think we kept track of them all. But I'll of course have Jess, speak to them.

[Jess Flechtner:]

Hi Daina, thanks for the question. So I think that there was a few pieces in there. One yes, we said that in our manufacturing process, we maintain responses to about 90% of the targets that we want the T cells to be responding against. And so if we are growing that patient's T cells against 30 neoantigens, what it means is that at the end of our manufacturing process, we have responses still to 27 of those neoantigen. Now, we also presented that the product is polyfunctional, that analysis was not related to the TCRs that was related to the characteristics of the T cells that were responding. And it meant that they were secreting multiple cytokines that we would believe to be very good once we transfer those cells into the body to help them and graft to help them kill the tumor. So that's where the polyclonality came from. Your last question was – on TCR, and how to know, the clonality or how many TCRs emerge and if there's a dominant one. We have looked at some of our development runs TCR profile overall. And what I can tell you is that there is not an outgrowth of, a dominant TCR. So that 97% of the product is all one T cell type. In fact, what we just see is that there's an enrichment of TCR, specific for the antigens that we want to target with our product. And this is exactly what we imagined that we would want to have, as we go through our process. So in the peripheral blood, you're going to have millions of different TCRs. And as we hone in on the antigen specific ones, you should see a reduction in the overall number of TCR that you find and outgrowth of specific TCRs for your product, which is what we want. Your last question was on antigen spread, we won't see that until we transfer the product into the patients and look at immune responses or engraftment after the transfer. And that's what will happen in our clinical trial as we start treating our patients.

[Daina Graybosch:]

Perfect. And thank you for taking my meandering question and making it more specific. Let me just make sure I understand. So in the product, you're getting 90% of the T cells that you want, and you're not seeing dominance in that product, you're seeing pretty even spread across, let's say, in your example the 27?

[Jess Flechtner:]

Just to put a finer point on it, you're correct. We see that 96% of the T cells in our product are specific for neoantigens. And then if we look at the breadth of the responses, what we're seeing is that we wanted them to respond to 30 things. And at the end of the process, they're still responding to 27 of the 30 things that we targeted. So I just – I know it's a really nuanced argument.

[Operator:]

Your next question comes from the line of . Your line is open.

[Unidentified Analyst:]

Hi, this is for Mike, thanks for taking our questions and congrats on the progress. On the GEN-011 study, can you talk about kind of how many more additional sites you're looking to add throughout the year and any sort of initial feedback on if there's any interest in one dosing regimen over the other?

[Chip Clark:]

Thanks for the question, . Tom, would you handle that, please?

[Tom Davis:]

Sure, certainly good question. As you know, the protocol has two cohorts an initial one that serves as a dose escalation step for safety. What's important from that perspective is that we'll be able to tell what the product itself does when we infuse it into patients. It's not going to be – the patients will not be giving lymphodepletion, but they will be given low dose IL-2 so this would be a very patient friendly regimen. That we then can rapidly dose escalate to the TIL type regimen that uses food lymphodepletion, as well as high dose IL-2. I think your question focus on how many patients will be putting in each arm. But in reality, we'll see what happens as the protocol progresses, but we'll be focused on the high dose regimen since that's the one that's most likely to be effective. That said, we certainly think that the low dose could be effective and could be very appropriate for patients who can't tolerate TIL type of therapies. So we'll basically be assigning patients to either arm dependent on what's appropriate for that patient.

[Unidentified Analyst:]

Great thank you, that's really helpful. And then on – congrats on the multiple collaborations announced, to on the T cells targeted proprietary shared neoantigens program. I think a little bit more about where you are in the process and if there's any clarity on when we might see an update from that program?

[Chip Clark:]

Yes Colleen, maybe Jess could you answer that first by speaking to, what we have found in terms of shared neoantigen thus far and then report on the progress?

[Jess Flechtner:]

Yes, so it's a really good question. What we have found so far is quite interesting. So while we find common mutations, in people that we have screened over the past several years that we have been doing our ATLAS screening of Newton ohms. Just because they are common mutation does not mean that they are a common antigen, that people can actually make a T cell response to them. And in fact, some of the common mutations that we have found across subjects are not never antigen. In some cases, some of the common mutations are dominant Inhibigen that anytime we find a T cell response to them, they are inhibitory responses, which we would want to necessarily avoid. And then there are some that are actually very good T cell targets they’re every time that we have screened them. They are indeed neoantigens for the patients who we have screened. And so there's, the first one is the one that we are working on with the University of Minnesota. And this common new antigen is quite interesting, because we found it in about 10% of the subjects that we screen across multiple different solid tumor types, which means that we're not limited in our ability to target different cancers with the same product. And so we are currently cloning this TCRs and showing that we can create a TCRT against this common mutation, and then we have others in the queue that we will pursue next.

[Operator:]

Your next question comes from the line of Gil Blum from Needham and Company. Your line is open.

[Gil Blum:]

Good morning, everyone. And thank you for taking our questions. So maybe kind of a simple one, could you set our expectations for the data update coming out of the GEN-009 in the second quarter? Are we going to look at longer time here, and is there potential for some of these disease control patients to improve?

[Chip Clark:]

Thanks, Gil for the question. Tom, could you speak to that?

[Tom Davis:]

Sure. At this point following these patients for outcome as you suggested, so the data that we're generating at this point in time is long-term follow-up. So we'll be able to talk about the patients that we have presented, but what has happened to them over time. And in all these patients, of course, with a broad retargeted drug like GEN-009, we would hope that we can not only shrink tumors, but also that we can stop them from growing. So at this point, the follow-up is going to focus primarily on the durability of these responses and particularly in the refractory patients where they are expected to grow quite quickly, if we see stability there, particularly if it's durable that would be a clear sign that we have helped these patients. You really don't see refractory patients develop stable disease that lasts for 6 to 12 months. And those are the kinds of follow-ups that we will have. Of course, we'll also be looking at the correlative science, still a significant amount of data to still come out showing really the connection between the vaccination and what has happened to the patients.

[Gil Blum:]

Excellent. Maybe a bit of a follow on to Daina’s question just to make sure that I also understand what you guys talked about. So, once you give the therapy even if there is different T cells responding to different antigens. Overtime, you would expect less clonality as the immune system is focusing on the right targets, is that the right way to think about it?

[Chip Clark:]

So I’ll have Jess take that question please.

[Jess Flechtner:]

I think that's a very difficult question to answer, especially without data. So what we will do is we will track the dominant clonotypes present in our product and our cell therapy product, after we transfer them into the patient to identify if some of those clones persist and grow, if some disappear altogether. And we will of course look for them infiltrating the tumor. That is the best that I can answer your question at this point in time.

[Gil Blum:]

Okay, that makes sense. Data will help clarify things and kind of…

[Jess Flechtner:]

Exactly.

[Gil Blum:]

…maybe a last theoretical one here. Do you guys think of making a role for Inhibigens and no infectious disease? Could you find an Inhibigens for COVID? Is that possibility?

[Chip Clark:]

Yes, absolutely. Jess?

[Jess Flechtner:]

Absolutely. So I can give you the anecdote from our Epstein-Barr virus program that we have reported publicly on - maybe it was in 2017. Inhibigens are very much in play in infectious disease. And what's very interesting is that - they have the opportunity to serve either as something bad and dangerous, as we've seen in cancer, or potentially protective, as we saw in Epstein-Barr virus. And so in the case of Epstein-Barr virus, we showed that people who had Inhibigens specific T cell responses did not develop mononucleosis, after EBV infection, which is a lymphoproliferative disorder basically the immune system grows out of control. And those that did not develop these Inhibigens specific responses did develop on us. And so it's exactly this question or this type of question that we can answer in the context of COVID with ATLAS, and it's possible that Inhibigens may - it could be good, that they protect the patients from getting that really severe syndrome that occurs in response to infection, or conversely it could be driving the wrong kind of immune response that is driving this pathology. And we will be answering that question with our screen.

[Gil Blum:]

Really interesting stuff. Thanks for taking our questions and congrats on the progress.

[Chip Clark:]

Thanks, Gil.

[Operator:]

And I am showing no further questions at this time. I would like to turn it back to the speakers for further comments.

[End of Q&A:]

[Chip Clark:]

Thank you, Operator. And thanks again everyone for joining us today.

[Operator:]

Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.