HOOKIPA Pharma Inc (HOOK) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to HOOKIPA's full-year 2020 financial and corporate update call. (Operator Instructions) I must advise you that this conference is being recorded today, Thursday, March 18, 2021.

I would like to hand the conference over to your speaker today, Matt Beck. Please go ahead, sir.

Good morning. This is Matthew Beck, the Head of Investor Relations for HOOKIPA. A slide deck accompanying today's call is available in the Events section of the HOOKIPA website. Please manually advance the slides as we prompt you through them.

Turning to slide 2, the HOOKIPA executive team is here with me today, including Chief Executive Officer, Joern Aldaq; Chief Financial Officer, Reinhard Kandera; Chief Medical Officer and Head of Global Research and Development, Igor Matushansky; Chief Business Officer, Christine Baker; and Chief Technology Officer, Roman Necina.

Turning to slide 3, our safe harbor slide. During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of investigational agents, our clinical and nonclinical plans, our plans to present or report additional data, the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development, and possible intended use of cash and investments.

These forward-looking statements are based on current information, assumptions and expectations that are subject to change and involve risks and uncertainties that may cause the actual results to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Securities and Exchange Commission, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements which are only made as of today's date. The company disclaims any obligation to update such statements.

For today's call, Joern will provide opening remarks. Reinhard will offer high-level comments on our financials, and then we'll open up the call to Q&A. With that, I'll pass the call to Joern.

Hey, good morning, everyone. Nice to talk to you. Very welcome to HOOKIPA's earnings call. Please turn to slide 4.

We had a strong year in 2020, culminating with promising clinical data in both our oncology and our infectious disease spaces, and a follow-on offering that has secured our cash runway through to the end of 2022. The data we presented make us proud. Early clinical proof-of-concept in HPV-positive cancers in checkpoint inhibitor refractory patients in a monotherapy setting. And secondly, immunogenicity and signs of efficacy in the CMV prophylactic setting.

In addition, we raised $81 million and extended our runway to year-end 2022. We're expecting a lot more data this year in both programs, beginning at AACR next month, where we will disclose early clinical translational data supporting our mechanism of antigen-specific T-cell generation.

We hope to show you at AACR for the first time that patients with cancer who were injected systemically with HB-201 or HB-202 at dose level two will have had an increase in key systemic pro-inflammatory cytokines and chemokine levels, which would suggest a virus-induced immune activation and a strong and persistent induction of HPV16 E7/E6-specific T-cells.

At ASCO, we hope to show initial data from our alternating dual vector treatments in patients, hopefully boosting T-cell responses even more. Data from higher doses will be explored and demonstrated in the second half of 2021. Also, antibody T-cell and efficacy data from more CMV patients will be shown publicly in the second half of 2021.

Please turn to slide 5. Despite the COVID pandemic, our oncology accrual dynamics are very positive and faster than expected. As a reminder, our initial oncology therapies built from our replicating technology and expressing the E7/E6 fusion protein from HPV16 are being tested in an ongoing Phase 1/2 trial. Worth repeating, HB-201 is currently tested as a monotherapy or standalone treatment, no checkpoint inhibitors, targeting advanced metastatic patients who have progressed on checkpoint inhibitors or platinum-based therapy or both. I'm sure you'll agree with me that showing an effect in such a setting is a great result.

In June 2020, we also filed our IND submission for our HB-202 program, and in October, we dosed the first patient in our HB-201/HB-202 alternating two-vector program. We know from preclinical testing that by combining HB-202 and HB-201 in an alternating sequence, we generate stronger immune responses than using a single vector. HB-202 carries the same E7/E6 antigen as HB-201, but it's based on a different vector backbone. Like HB-201 alone, our HB-201/HB-202 is being tested in a dose escalation Phase 1 trial of late-stage HPV16-positive metastatic patients who have progressed on checkpoint inhibitors and/or platinum-containing regimens.

Please turn to slide 6. The initial clinical data from our HB-201 Phase 1 trial, which included patients on the first two dose levels, showed a favorable tolerability profile. In terms of efficacy, in the 15 evaluable patients, we saw one complete response, one partial response, and numerous stable disease patients. The efficacy for the first two doses in the Phase 1 escalation shows a remarkable trend, a 73% disease control rate and 18% response rate from the head and neck squamous cell carcinoma HPV16-positive subgroup are comparable or better than response rates from studies of PD-1 inhibitors in earlier line head and neck cancer patients. So specifically we've compared to nivolumab and pembrolizumab.

The December interim analysis data were generated with our initial two dose levels. We're continuing to explore additional dose regimens and levels as we optimize for the recommended Phase 2 dose. In that data set, we highlighted one patient who after progressing twice on prior rounds of pembrol clinically progressed on HB-201 monotherapy. The investigator asked to keep the patient on his HB-201 regimen while adding pembrolizumab in combination. As of the data cutoff, the patient had begun to respond with visible and radiological signs of tumor shrinkage.

With the off-protocol addition of pembrol, the patient is no longer included in our recorded HB-201 data. However, it is encouraging sign to see a synergistic response with the combination of HB-201 and a checkpoint inhibitor and see that this is safe. We plan to explore the simultaneous HB-201 or HB-201/202 combination and checkpoint inhibitor combination in the Phase 2 portion of the trial.

Two weeks ago, we announced that the preclinical data on our HB-201/202 alternating two-vector program was published in Cell Reports Medicine. These preclinical data showed that alternating IV administration of two replicating arenaviral vectors induce tumor-specific responses exceeding 50% of the circulating CD8 T-cells, which resulted in tumor cures and long-term immunity against tumor rechallenge.

Please turn to slide 7. As I mentioned earlier, we're currently analyzing and we'll report early translational data on our HB-201 and HB-202 vectors at the upcoming virtual AACR conference in April. The abstract title of preliminary analysis of immunogenicity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy in patients with advanced HPV16-positive cancers was released last week. We will report on in vivo CD8 T-cell proliferation and biomarker data from patients treated with single HB-201 or HB-202 vectors.

We also plan to update clinical data from the HB-201 program and report initial safety, tolerability, and efficacy data from the HB-201/HB-202 program at the ASCO conference in June. This might be the first time that we show patients' data which demonstrates the superiority of the alternating two-vector approach over the single vector approach with regards to T-cell induction and efficacy. We expect to identify the recommended Phase 2 dose in Q4 of 2021.

Please turn to slide 8. Switching gears now to CMV, HB-101 is a preventative vaccine based on our nonreplicating technology designed to stimulate the immune system against cytomegalovirus infection or reactivation in organ transplant situations. From the ongoing Phase 2 trial in kidney transplantations, we reported late last year positive safety, immunogenicity, and preliminary efficacy data that exhibited reductions in CMV viremia, the use of antivirals, and CMV disease in post-transplant patients and in line with our expectations. Also, we have confirmed our mechanism of action of driving T-cell and antibody responses.

Enrollment in this Phase 2 trial continues slower than expected. COVID is the primary driver of the difficult accrual. Many transplant sites either shut down or drastically slowed their transplant schedules for many months to avoid immunosuppressing patients during the intense outbreak periods. We plan to wind down accrual no later than the third quarter of this year, by which time we will have recruited approximately 100 patients against an original target of 150. As you may recall, our trial protocol includes monitoring patients and their outcomes for 12 months post transplant.

The next data release planned for the second half of this year will provide further efficacy data to inform about the path forward for this program. We're in the process of analyzing the opportunities in the CMV space beyond kidney transplant, looking at liver transplant, hematopoietic stem cell transplants and prophylaxis of congenital CMV infections.

Our collaboration with Gilead in which we're seeking therapeutic cures for chronic hepatitis B and HIV continues to progress and is further approaching the clinic. We anticipate reaching select milestones, including one request for development for the HIV program, in 2021. We believe we're progressing to the satisfaction of Gilead; however, are unable to provide development timelines as Gilead is controlling those.

With that, I will turn over to Reinhard for comments on our financials. Go to slide 9, please.

Thank you, Joern. Good morning, everyone. On the financial side of our business as well, we are looking back to a very successful year 2020. Despite the progress that we made in our clinical studies, our loss increased only marginally and our operating cash flow even slightly decreased compared to 2019. Most importantly, with our successful $81 million follow-on financing in December, we are advancing to the next development phase with a solid cash balance.

Slide 9 summarizes our fourth-quarter and full-year 2020 financial results, and I will focus on the full-year results. As you can see there, we had an increase in revenues by more than 60% to almost $20 million, which is proof of the progress that we are making in our collaboration with Gilead, which is currently our only source of revenue. These revenues include cost reimbursements of $13 million and more than $6 million from recognition of upfront and milestone payments. Our R&D expenses increased by 18% to approximately $55 million. And the main cost driver in 2020 was our HPV16-positive cancer program, followed by the costs and our Gilead collaboration and the CMV program. We expect our R&D costs to continue to grow in 2021 as we continue to progress on these programs.

Our G&A expenses grew as we continued to expand our operations. The main driver of the increase were personnel expenses, including non-cash stock compensation expense. Our other income of more than $9 million includes approximately $6.5 million in grants, as well as exchange rates and currency translation gains.

Bottom line, we show the net loss of $44 million in 2020, slightly up from $43 million in 2019. Our 2020 operating cash outflow was $39.3 million, which compares to $41.7 million in 2019. Our year-end cash balance was $143.2 million at the end of 2020, which gives us a solid financial footing to further grow our spending as we progress our R&D programs.

With that, I'd like to pass back to Joern.

Yes, thank you. Before I end with the milestones you can expect over the next 15 months or so, I'd like to comment on the coronavirus pandemic and how it's affecting HOOKIPA. Our top priority is the health and safety of our employees, followed by business continuity. We continue to operate from home in the US at 100% productivity level, while Vienna's labs are open full-time and other staff are working part-time from home. Here also, I would say the productivity is very high.

Travel is reduced to an absolute minimum. Our employees quickly adapted to the new circumstances. We maintain close contact with our trial-side CROs, CMOs, and development partners and have adapted to the situation, hoping that with vaccinations now, things will change relatively soon back to more normal.

I'm indeed very proud of our people and their drive to support the company's and our shareholders' objectives throughout this unusual period. And I'm very proud that in summary, we're maintaining our clinical milestones throughout 2021. We will present translational oncology data at AACR in April, and this will contain a whole series of T-cell data and other translational data as I've mentioned earlier in the talk. We plan to present additional HB-201 and initial HB-201/HB-202 two-vector data at ASCO in June. And this will be clinical data and also translational data. We will report additional CMV data from the Phase 2 trial in the second half of this year.

I'm very pleased with HOOKIPA's corporate and promising clinical progress in 2020 and early 2021. We're laser-focused on execution to produce compelling proof-of-concept data with our proprietary arenaviral-based products and intend to do so with our clinical data readouts later this year.

With this, I would like to end the introduction and we'll open up the line for Q&A. Operator?

Thank you, sir. Ladies and gentlemen, we will now begin the question-and-answer session. (Operator Instructions)

Stephen Mallon, RBC Capital Markets.

Good morning. This is Steve on for Brian, and thanks for taking our question. In light of the possible synergy between checkpoint inhibitors and 201, can you share any updates on your thinking as to how 201 and 202 or the platform in general may combine with additional systemic cytotoxic therapies like [IR] and chemo?

Yes. I'll pass this on to Igor.

Thanks for the question. Of course, as we think about moving up our therapies from monotherapy in the advanced settings to earlier settings, we are beginning to strategize how that would combine with other therapies that are still more commonly used in the first line, including chemotherapy and radiation therapy. We are doing preclinical work to see how the various chemotherapies interact with our 200 therapies. And we are also speaking with various academic groups about doing some exploratory investigator-initiated and/or exploratory biomarker studies to assess the preliminary nature of these interactions.

As you know probably, checkpoint inhibitors and other immunotherapies have for the most part interacted favorably with chemotherapies in terms of improving response rates and survival in those patients. And we believe the same will hold true for our approach as well. We will of course tread cautiously by doing some investigator-initiated exploratory biomarker studies as a prelude to advancing our therapies in combination with the more standard ones you mentioned in the first-line settings.

Thank you.

Chris Liu, SVB Leerink.

Hey, guys, this is Chris on for Andy. So just thinking about the AACR presentation, I know the focus is on immunogenicity and safety for the alternating dose regimen. But just wondering if there could be any potential preliminary efficacy data, like a case study or something small like that?

Igor?

At AACR, we will be focusing exclusively on updating our translational datasets. At ASCO, we will, of course, be doing a more formal clinical update, in which case we would expect to see additional clinical data, including safety, efficacy, and of course, any additional anecdotal data we will share as of the cutoff date for that presentation. But at AACR formally, we will not be doing any clinical updates, just translational data. But the translational data will be coming from more recent patients. But the efficacy data will have to wait for ASCO.

Sure. And is there a way we should think about the potential read-through from the immunogenicity data to potential efficacy?

Well, if you follow our preclinical story, we have continuously stated and published that our efficacy always correlates to our mechanism of action. And so we have shown preclinically multiple times that the better our induction of antigen-specific CD8 T-cells, the better our tumor control in the preclinical setting.

And clearly, that is, I would say, the whole goal of trying to go to higher dose levels using two vectors in alternating manner. And everything else you're trying to do during a dose escalation phase in order to improve our immunogenicity, because clearly based on our preclinical data set, we believe that translates to improved efficacy.

We are getting the data out as fast as we can. And so, clearly the translational data, we can generate a little bit faster than our clinical efficacy data. And we will get that out for AACR. But again, it's just the timing of the clinical efficacy data. We'll have to wait until ASCO.

Got it. And just one final question, if I may. It sounded like we're having multiple potential clinical updates for the alternating dose regimen. Is that correct?

No. Well, no. I mean, again, we will update at AACR. We will focus again on translational data. That translational data will come both from 201 and from 202/201.

[And as going here] --. Yeah, go ahead, Igor.

At ASCO, we will update the clinical efficacy for both 201 and for 202/201. Clearly later on in the year at other conferences, we'll continue to update it in both the translational and the clinical efficacy. But for the next several months, translational data will come at AACR and clinical update data will come at ASCO, and probably at ASCO we'll clearly try to make some correlations between the two.

Got it. Thanks.

Alec Stranahan, Bank of America.

Hey, guys. Thanks for taking our questions. Two from me. First on the HB-101 program. We're certainly looking forward to the data updates from the kidney transplant study in the second half of this year. But I guess at what point or what additional data would you guys need to see to feel comfortable to expand the program into congenital or other transplant settings, like you mentioned. And then, I wanted to dig a little bit more into the translational data.

So, looking at your recent publication in Cell Reports, I guess as you're looking at the percent of anticancer T-cells produced by either HB-201 alone or the HB-201/202 combo, is there a certain amount of T-cell education that needs to be surpassed to achieve clinical responses to [FPR or CR]? Or does this really vary from patient to patient? So I guess said slightly differently, how would you frame the 50% tumor-specific T-cells generated with the combo versus the anticipated clinical responses? Thank you.

And so let me quickly answer on 101. We have shown in the 101 trial that when we have the ability to administer three doses to patients, we're actually getting a full proof-of-concept, if you want, of our hypothesis, which is that we're driving antibody and T-cell responses and that we're controlling CMV viremia to a significant extent, the use of antivirals. And we're controlling to 100% CMV disease. These are the key endpoints and things that you would want to control. And the data we've shown publicly earlier was on the basis of fewer patients, relatively few patients. But we think that this is a confirmation of our proof-of-concept.

Going forward, we're trying to get as many patients possible in which we are confirming the data that we have seen earlier. And if we're confirming it, I think that would give us a very strong signal for moving the program forward. At this point in time, we have chosen solid organ transplant as a relatively fast and low patient way to get to proof-of-concept of our technology.

At this point in time we're looking at will we be taking it forward in solid organ transplant? Could we also take it forward in hematopoietic stem cells transplant or potentially even find a way to get it financed for congenital trial in which you're trying to prevent CMV disease in a congenital setting. These things are being analyzed. And as we're seeing more patients coming in, as I'm saying, if we're confirming the data that we've seen before, we would feel comfortable to progress the trial.

Igor, maybe you take the second question?

So -- and this was a great question. And I wish I or anyone else had an easy answer to what a number would correlate and guarantee a response. I think that, in general, if you look at, you know, the works of others specifically, I would say most comparably in the TCR space, the more we can get antigen-specific CD8 T-cells into the blood of the patients, the quote-unquote, it's a better correlation to response.

However, there has been, I would say, no magical number, no kind of a hard--line percentage that could be identified or guarantees a response either. A lot of it has to do with not just the quantity, but I certainly do believe the quality of the CD8 T-cells, how many of them are activated and how many of them are not exhausted.

So there is no straightforward number. I will say that if you look at -- putting everything we know together, I would say if you could generate a response that gives you a high single-digit percent CD8 T-cell from an active immunotherapy like ours, that would be very, very remarkable and probably has not been demonstrated with a direct [Eliza] in the past. And if we could demonstrate something like this, there, I would say, would be a good chance that it will correlate two responses, and it would lead to improved efficacy.

So I would say, what number would we be very, very excited, the kind of number that no one in this kind of space has been able to demonstrate before as a measure directly from patients' blood without any kind of artificial expansion, I would say, a minimum of high single-digit percentages.

Great. Thanks again.

Ingrid Gafanhao, Kempen.

Hello, good morning, good afternoon. Thank you for taking the question. (multiple speakers)

I was glad to see some progress also in the Gilead partnership (inaudible). We were just wondering is there any significant milestones that we could expect for this year?

Yes. You should expect a milestone in the HIV program. And that milestone is linked to what is called request for development in Gilead language. Request for development is the moment where they commit to bringing a program forward to clinical trial, and with a committed biodistribution tox studies and also to manufacturing for the clinics. We've passed this milestone for HPV. This is to come for HIV, and we're expecting it sometime in the middle of the year. Apart from that, we're unable to talk about timelines. We would expect the HPV program, looking at standard timelines in the industry or specifically in HOOKIPA, we'd expect that to be late this year or early next year to be moved in the clinic.

That is great. Thank you very much.

Roy Buchanan, JMP Security

Great. Thanks for taking the questions. And appreciate the clarity on the CMV program. So for the update in the second half from the Phase 2 for HB-101, what post-transplant durations are you going to report for viremia and antiviral efficacy? I know you mentioned that the primary endpoints or the efficacy endpoints are 12 months. But are you going to report any earlier data points? And then do you have any information on how the follow-up has been for the trial, especially considering COVID? And I have a follow-up.

Igor, do you want to take that?

No, thanks for the question. So I think you're right. The overall follow-up for the program is designed to be 12 months following transplant. The overall efficacy points will, of course, be given, you know, not only as the viremia in terms of percentage and the number of viremic events in a 12-month period, but also, of course, I would say, all the sub-categories of that: duration of viremia, intensity of viremia, et cetera, et cetera. And of course, the kind of commitments used with antivirals. So again, were they used, how long they were used, et cetera.

So all of that will be reported in the endpoint of a 12-month time point and all that information will be followed. We are going to be updating the program. We have, I think, stated previously in the second half of this year. But probably not any sooner.

And in terms of how the follow-up has been, I think the majority of impact that we've had from COVID, as Joern indicated earlier, has been on, I would say, accrual. In other words, because pay -- because at sites are, I would say, not being able to perform as many elective procedures and while it is a live donor kidney transplant serious procedure, it's still an elective. And many of them, of course, are stopping elective procedures. But even more so, they are stopping clinical trials that are related with elective procedures due to simply administrative efforts that require most of the hospitals to focus on COVID-related issues.

Now, while this has affected new accrual and of course continual accruals, it has naturally affected follow-up. The patients are followed routinely as per standard of care. And we do not really -- our clinical trial does not have any additional, I would say, hardships in order for follow-up. And so follow-up for these patients has not been affected.

Okay. That makes sense. Kind of a more general question. I guess you guys haven't seen any safety, tolerability issues with the arenavirus vectors to date. Have you thought about using the replicating technology for infectious disease, particularly for hard-to-treat viruses like hepatitis C? And if Gilead thought this was a good idea, that should be possible under the existing agreement? And would that require a new request for development from them?

The answer to both those questions is yes, we have thought about it. And I would say that conversation is on the table for discussion with Gilead. No final decisions have been made whether we will be using our replication-defective programs there or not], and the contract is completely open from that point of view.

Okay. Thank you.

Asthika Goonewardene, Truist Securities

Hi, good afternoon, Joern and Reinhard. And good morning to Igor and Matt. Good to speak to you guys. I'd like to focus back on AACR, please. Igor, can I ask, about how many patients' worth of translational data will you have? And maybe can we get a little more color on the kind of analyses, specifically whether you will have some of that data that tell us what percentage of antigen-specific T-cells are of the total CD8 complex. Then I got a follow-up on that.

Sure. So AACR data will present, I would say, single-digit number of patients coming from our first analysis. It will be, I would say, a combination of 201 patients as well as 202/201, but more skewed towards the 201, clearly because we've had more patients and analyzed more of them in our first batch.

The data will be focused mainly on using direct Eliza as a readout for the first readout. And as a direct Eliza, it's not reported as a percentage. That percentage could be [back] calculated, of course, but the data is primarily not reported as a percentage because it's coming out of a direct Eliza analysis.

The analysis that translates into, I would say, percentages is based on a different analysis called an intracellular staining analysis, and that data, we have not performed as much of it. We'll probably not be releasing at AACR. We will probably be releasing it at (inaudible).

Great. And then I know COVID hampers sample collection. But I'm just wondering, would you also happen to have any serial biopsy data or maybe any data on T-cell fitness at AACR?

T-cell fitness? Is that the question?

Yes. (multiple speakers)

Yeah. So we will not be showing any T-cell fitness data at AASR. We will be showing basically, as Joern said earlier, interferon gamma cytokine signature data. The biopsy data that we will -- our R&D is collecting. That data will be available most likely at [Oscient] conference. And as part of that data, we will of course be looking at tumor-infiltrating lymphocytes and actually looking at the exhaustion state of those CD8 T-cells as well. As you know, the Oscient conference is about a month after the AACR and a month before ASCO.

Great. Excellent. Thank you so much for taking my questions.

(Operator Instructions)

Arthur He, HC Wainwright.

Hi, everyone. This is Arthur for RK and thanks for taking my question. I have two. One is regarding the HB-101. So I know we could expect the Phase 2 data at the second half of this year. Could we also expect some -- any feedback from -- for your interaction with the FDA in this year?

For the 101 program, I would say that currently the way we are looking at the program is that somewhere towards the second half of this year, we will be basically doing an analysis and putting together a package for the FDA. If that package, I would say, is -- if we get a response from the FDA within a reasonable amount of time, the answer could be yes. But I think if you want me to give you a ballpark -- a general ballpark figure for when FDA feedback might be expected, it could be either late this year or early next year.

Okay, that's great. And also regarding the 301 program, I'm just curious. Could you guys give us more color on the general strategy for the clinical development? Would that be more like 201/202? My question is like, could we also expect some alternating dosing strategy for this program?

I think what we're currently thinking about this program is to basically go in directly with the alternating approach as our primary approach. So I think we are going to go directly with kind of what we call the alternating LCMV [switching] approach into patients. And we are going to use three antigens as we previously spoke about, TAP, PSA and PSMA. And we are probably going to go into similar to the 200 program in the advanced setting in a monotherapy setting. In the advanced mode of therapy in patients who progressed on standard of care.

So maybe I had a follow-up on that. So also, so you will be testing the ITIV in both -- in also as well as the (multiple speakers)?

No, no. For prostate cancer, it's a little bit different, as I'm sure you know. A lot of prostate cancer is bone -- metastatic bone lesions. And because of the propensity for bone, fully intratumoral injection is not the better strategy. And so for the prostate cancer program, just due to the pattern of metastases, which the majority of those patients present, we're probably only going to pursue the intravenous approach.

I see. Thank you. Thank you very much for the update.

There are no more question at this moment. Please continue.

Well, I think in that case, we're done for today. I'm very pleased that you participated in this call. And I would like to just say that we're all very, very excited at HOOKIPA about the multitude of different readouts that we have in front of us in both programs. Very rich on the first half as we've just discussed for cancer and interesting data coming out for 101 in the second half. So overall, we think at this point in time, we're rich in new data, and we're really curious to seeing it and presenting it to you.

Thanks a lot for participating in this call. And if there are any further questions from folks, please let us know directly as well. Thanks a lot.

That concludes our conference for today. Thank you for participating. You may now all disconnect.