Genocea Biosciences, Inc.

Good morning and welcome to Genosha 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'd like to turn the call over to Dan Ferry of LifeSci Advisors. Please proceed.

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 Genosha.com under the Investors tab. During the call today, Chip Clark, President and CEO, 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, Genosha's Chief Medical Officer, and Jessica Fleckner, Genosha's Chief Scientific Officer, will then be available to answer your questions. Before we begin, I would like to remind everyone that statements made during this conference call relating to Genosha's expected future performance, future business prospects, or future events or plans may include forward-looking statements, as defined under the Private Securities Litigation Reform Act of 1995. All such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. Actual outcomes and results could differ materially from those forecasts due to the impact of many factors beyond the control of Genosha. Genosha expressly disclaims any duty to provide updates to its forward-looking statements, whether as a result of new information, future events, or otherwise. Participants are directed to the risk factors set forth in Genosha's 2019 Annual Report on Form 10-K and other periodic reports filed with the Securities and Exchange Commission. It is now my pleasure to pass the call over to Chip.

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, GEN9 and GEN11. As a reminder, Gen 11 is Genosha's neoantigen-targeted peripheral T-cell therapy, or NPT therapy, which we're testing initially in checkpoint inhibitor refractory patients. Our Titan study is a Phase I-IIa 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 11 dose and the other with Gen 11 administered as multiple low doses. We have initiated two clinical sites and have begun accruing patients. We'll 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 GEN9, our adjuvanted peptide neoantigen vaccine. In November, we presented expanded clinical and immunogenicity findings for the ongoing Phase I-IIa trial at the 2020 Society for Immunotherapy of Cancer, or CITC, annual meeting. We were pleased to find evidence of GEN9 clinical activity on top of checkpoint inhibitor responses. Among the nine CPI-sensitive patients dosed with Gen 9, three patients experienced a novel reduction in tumor volume and achieved independent resist responses post-Gen 9 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 disease lasting up to seven months. And these results could become even more compelling with additional follow-up. Gen 9 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. Now let me move on to some other news. A few weeks ago, we announced a milestone publication in Cancer Discovery, which shares preclinical and clinical research confirming that ATLAS is the only antigen selection platform able to identify the tumor surface-presented antigens that induce T-cell responses, whether they are neoantigens of anti-tumor T-cell responses or, uniquely to ATLAS, inhibitory antigens, which we call inhibigens, of pro-tumor CD8, and CD4 T-cell responses. We also demonstrated in the B16F10 mouse melanoma model that including an ATLAS-identified inhibigen in an otherwise protective cancer vaccine can completely abrogate such protection and showed that inhibigen-mediated suppression of anti-tumor T-cell responses cannot be overcome by checkpoint inhibitor therapy. Finally, bringing it back to Part A of the Gen 9 clinical trial, we showed that by selecting the right antigens with ATLAS, we were able to elicit T-cell responses to 99% of the vaccine antigens. Collectively, these findings further validate our unique ATLAS platform and highlight the potential importance not just of targeting the right neoantigens, but also of identifying and excluding inhibigens as cancer immunotherapy targets to maximize patient clinical efficacy benefits. As part of our efforts to investigate inhibitions further, we are excited to report a research collaboration with Dr. Ingen Strome's laboratory at the University of Minnesota, a leading group in cancer immunotherapy and T-cell engineering methods. Together, we will also develop T cell receptors targeting proprietary shared neoantigens identified via ATLAS. Now, like everyone, we've been deeply affected by the global pandemic. And we believe we may be able to help enable a next generation COVID vaccine with the potential to protect universally against SARS-CoV-2. And so we're pleased to unveil our ongoing effort to identify novel T cell antigens of the virus. As part of this effort, we have initiated a collaboration with Dr. Robert Finberg, Chair of the Department of Medicine at the University of Massachusetts, to identify conserved antigens of protective T cell responses to SARS-CoV-2. Pairing ATLAS's antigen selection capabilities with Dr. Finberg's expertise may lead to a better understanding around the role of T cells and inhibitions in the severity and duration of SARS-CoV-2 symptoms. In addition to this operational progress, we recently strengthened our executive leadership team, appointing Dr. Raymond Stapleton as Executive Vice President of Pharmaceutical Sciences and Manufacturing. Ray brings 20 plus years of industry experience leading technical quality control and manufacturing operations at commercial and clinical stage biopharmaceutical companies. I have no doubt that his leadership and expertise will prove essential to our plans to scale and commercialize our cancer immunotherapies. We are pleased at our progress on multiple fronts, not only this quarter, but throughout a very challenging 2020. We believe this momentum has set us up well for success in 2021. I'm now going to pass the call over to Diantha to summarize our financials from this quarter before opening the call up to questions. Diantha?

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 31st, 2019. Our operating results for the quarter ended December 31st, 2020 are as follows. R&D expenses were $7.8 million compared to $6.8 million for the same period in 2019. G&A expenses were $3.9 million compared to $3 million for the same period in 2019. And our net loss was $15 million compared to $9.4 million for the same period in 2019. Genosha's operating plan extends its cash runway to the end of 2022. With that, Let's now open the call up for questions.

Operator? At this time, please press star and then the number one on your telephone. If your question has been answered or you wish to remove yourself from the queue, please press the found key. We'll pause for a moment to compile the roster.

Great. Thank you very much, and congratulations on the update this morning. I want to ask a question first about the Gen 11 clinical program. I guess, have you started manufacturing clinical material for Gen 11, and are you able to say anything about the manufacturing experience thus far?

Hi, Ben. Thanks for the question. We are in the middle of our needle-to-needle process, as you might call it, for Gen 11. 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 11 process, we have a high degree of confidence in the process's overall robustness. And as I said, You know, we intend to provide updates throughout the year. So certainly manufacturing success is one of those things we expect to be able to report on.

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

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.

Thanks, Ben. 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 away 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 inhibitions 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 screen. Diantha?

Thanks, Jess. So then as far as sort of a cash impact or investment, the investment is 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.

Okay. That's fantastic. Great. Thank you so much for the call.

Thanks, Ben.

Your next question comes from the line of Diana Grace Bosch from SBV Living. Your line is open.

Hi, thank you all for the question. I wonder if we could get into Jan 11 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. I wonder if you could help us understand specifically patient by patient sort of how many TCRs are dominating the product. Are you getting one dominant, five non-dominants, an average of two dominant? I just wonder, patient by patient, how consistent it is and how spread the dominance is for the Gen 11 that you actually stimulated ex vivo, and then also how much there is a sort of antigen spread polyclinality afterwards.

Thanks, Dana. A bunch of related questions in there that I think we kept track of them, but I'll, of course, have Jess speak to them.

Hi, Dana. Thanks for the questions. 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 neoantigens. 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 engraft, to help them kill the tumor. So that's where the polyclonality came from. Your last question was on, you know, 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, you know, 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 TCRs that you find and an 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.

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.

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, but the point is that nearly every single T cell in the product is specific for the cancer. which is different than what has been reported for TIL therapies, for example, where there are a lot of bystander cells that get grown up alongside the tumor-specific cells. And so the T cell product is not purely targeting cancer antigens. That's very helpful.

Thank you.

Thank you, Dana.

Your next question comes from the line of Michael. From there, your line is open.

Hi, this is Colleen Cousin for Mike. Thanks for taking our questions and congrats on all the progress. On the Gen 11 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?

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

Sure. Certainly a 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 given lymphococcin but they will be given low-dose IL-2. So this would be a very patient-friendly regimen. But we then can rapidly dose escalate to the TIL-type regimen that uses full lymphodepletion as well as high-dose IL-2. I know your question is focused on how many patients we'll 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.

Great. Thank you. That's really helpful. And then on... Congrats on the multiple collaborations announced, too. On the T cell targeted proprietary shared neoantigens program, can you talk 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?

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

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 mutinomes, just because they are a 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 never antigens. In some cases, some of the common mutations are dominant inhibigens that any time 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. 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 percent 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 those 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.

Thanks so much.

Thanks, Holly.

Again, if you have a question at this time, please press star 1 on your touchtone telephone. Your next question comes from the line of from Needham and Company. Your line is open.

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-controlled patients to improve?

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

Sure. We're 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 of these patients, of course, with a broadly targeted drug like GEN9, 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 six to 12 months, and those are the kind of follow-ups that we will have. Of course, we'll also be looking at the correlative science. There's a significant amount of data that's still come out showing really the connection between the vaccination and what has happened to the patients.

Excellent. Maybe a bit of a follow-up to Dana'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, over time, you'd expect less clonality as the immune system is focusing on Is that the right way to think about it?

I'll have Jess take that question, please.

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, in 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.

Okay. That makes sense. Data will help clarify things. Exactly. And kind of a last theoretical one here. Do you guys think there might be a role for inhibitions and, you know, infectious disease? Could you find an inhibition for COVID? Is that a possibility?

Absolutely. So I can give you the anecdote from our Epstein-Barr virus program that we have reported publicly on in maybe it was in 2017. Inhibigins 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 inhibigen-specific T cell responses did not develop mononucleosis after EDV infection, which is a lymphoproliferative disorder. Basically, the immune system grows out of control. And those that did not develop these inhibigen-specific responses did develop mono. 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 inhibogens 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.

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

Thanks, Gail.

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

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

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