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spk01: I'm Matthew Beck, Executive Director, Investor Relations. A slide deck accompanying today's call is available through the webcast and in the events section of the Huquipa website. Please manually advance the slides as we prompt you through them. Looking at slide two, the Huquipa executive team is here with me today, including Chief Executive Officer, Jern Aldag, Chief Financial Officer, Reinhard Kandera, Chief Medical Officer and Global Head of Research and Development, Igor Medeshansky, Chief Scientific Officer Klaus Orlinger, Chief Business Officer Christine Baker, and Chief Technology Officer Roman Nesina. Slide three. 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 non-clinical 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 events to differ materially from those contained in the forward-looking statements. These and other risks are described in our periodic filings made with the Security 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, Yearn will provide opening remarks. Reinhart will offer high-level comments on our financials, and then we'll open the call to the Q&A. With that, I'll pass the call to Yearn.
spk03: Thank you for joining us today in this conference call. 2021 was a year of impressive continuous progress for Huquipa. It was a year in which we have successfully navigated tumultuous financial markets and delivered on the need to drive scientific progress and a financing strategy that supports continued company growth into 2024. We delivered on our claim that we can drive unprecedented levels of antigen-specific T cells in humans. We continue to expand the evidence that our technology applied as a monotherapy helps control the disease in advanced line head and neck cancer patients, motivating us to invest in broadening our pipeline with new oncology indications. Beyond virally driven cancers, we demonstrated the ability to break tolerance in animals, opening to the wide space of self-antigens and driver mutation-based cancers. We see incredible potential for this platform. especially in combination with other oncology modalities, to overcome challenges of many immunotherapies and many different cancer types by providing the missing but essential T-cell induction. We're pushing two high-value programs towards the clinic, prostate cancer candidate HP300 and HP700, targeting the most frequent KRAS mutations. Our science is continuously validated through partnerships with leading pharma organizations. We progressed markedly on the partnering front by, one, renewing our collaboration with Gilead, I'll come back to this, by taking responsibility for the clinical phase 1B of an HIV Q project, and two, signing a supply agreement with Merck for testing Keytruda with HP200. The FDA granted us fast-track designation for this combination trial of HB200 with femoralizumab in the first-line setting. We also advanced partnering discussions in oncology with other prospective collaboration partners. As I mentioned earlier, Gilead, faced with bottlenecks in their development area and knowing the T-cell data of our HIV development candidates and non-human primate models, asked us to take responsibility for the development up to the end of phase 1b of our HIV functional cure collaboration. They wanted an option to take the program back after this phase 1b. And in exchange, we received a non-refundable $15 million upfront in addition to $4 million milestone payment and took down the first $5 million of a $35 million equity facility Gilead provided to us. This transaction helped us execute a well-prepared financing in early 2022, securing $75 million, and a follow-on offering extending our cash runway significantly with high-quality existing and new investors. Our December 31st cash position plus the Gilead and follow-on proceeds give us a performer cash position of $157 million, and adding the additional $30 million from the drawdown facility by Gilead provides us a runway into mid-2024. We believe that these accomplishments speak to the strength of our data and investor faith in our ability to execute in 2022 and beyond. So what's in store for 2022? Slide five. Next month, At AACR, we will share four poster presentations that provide further preclinical, translational, and clinical evidence of the broad potential of our arena viral platform to address unmet needs in various types of cancer, either alone or in combination with other modalities. In mid-year, we will update our Phase I HP200 monotherapy data. We will give a comprehensive overview of the HB200 Phase I dose escalation program, including safety, anti-tumor activity, and additional translational data of HB201 and HB202-201. We will update the status of all patients in the Phase I program and present our selected Phase II dose for the HB202-HB201 alternating two-vector therapy. And we will discuss the clinical path for HB200 in the advanced setting known as third line or post standard of care. To be clear, we will not provide at this time nor comment on any initial phase two data in combination with Fembrolizumab during the phase one update. We will, however, report initial safety and efficacy data results of the HB200 phase two combination trial which combines HP200 and pembrolizumab in the first and second line settings in the second half of this year. We aim to present an initial data set on 10 to 20 patients in total and seek to approximately double the current pembrolizumab monotherapy response rates in first line and second line head and neck cancers. We're also on schedule to file the IND for a prostate cancer program known as HP300, in the third quarter of this year. Current immunotherapy's target PAP, a key tumor agent, provide modest efficacy for people with castrate-resistant prostate cancer. With our versatile arena virus platform, we're exploring incorporating additional tumor targets, PSA and PSMA, to help address the unmet needs and improve the standard of care for these patients. We aim to dose the first patient in the late fourth quarter of this year or early 2023. Last but not least, we have started a KRAS program targeting the main KRAS mutations relevant in several large tumor indications. This program has attracted significant interest from pharma companies. Finally, in our infectious disease programs, we're committed to filing our HIV IND in 2023 And Gilead tells us that they're on schedule to file the HB and the hepatitis B virus functional cure IND by the end of 2022. Though Huquipa is not in control of their timelines, we expect that this is what we can expect. I reiterate that Huquipa is now funded through all of these milestones and beyond. We have bold promises for 2022, and the Huquipa team is invigorated to deliver. Now I'd like to pass the call to Reinhard for some brief comments on our financials. Reinhard.
spk02: Thank you, Jörn. Good morning, ladies and gentlemen. I want to give you a few highlights of our financial results for the year 2021, which actually reflect the clinical progress that we have made in that past year. Our revenue line includes milestones and cost reimbursement from our Gilead collaboration. And the continued high level of revenue is evidence of the good progress that we have been making under this collaboration, as both partnered preclinical programs are now moving towards phase one clinical trials. Looking at our operating expenses, we increased our investments in the oncology pipeline and internal research and development resources based on the encouraging early antitumor effects seen in our HP200 trial. The increased spending in these areas was the main driver of the overall increase of our R&D expenses from $55 million in 2020 to $83 million in 2021. A significant portion of the 2021 R&D spending already relates to the 2022 activities for HP200 and HP300 So we expect to be able to maintain this spending level in the coming quarters while executing on those programs. In terms of general and administrative costs, we were able to keep this well under control in 2021 and even to slightly decrease our G&A expense year over year. Other operating income net, which mainly consists of grants and subsidies, was partially offset by currency effects, mainly in the fourth quarter of the year 2021, and is therefore below 2020 levels. Our net loss for the year 2021 was $76 million compared to $44 million in 2020, with this 2021 increase being driven by R&D spending as a result of our clinical progress. Our cash outflow from operations in 2021 was $66 million, and in addition, we made investments of $12 million in property, plant, and equipment, mainly to prepare ourselves for GMP manufacturing requirements in our next growth phase. Our year-end cash was $67 million, and we were able to significantly strengthen this cash position in the first quarter of 2022 by a $75 million follow-on offering and cash inflows from our Gilead transaction. This proceeds leads to a pro forma cash position of $157 million when added to our year-end cash. With that, we see ourselves well-funded through the coming catalysts, but I would want to add that in a difficult funding environment as we see it today, we are putting greater emphasis on non-dilutive funding sources as well and are making good progress in seeking collaborations to potentially increase our revenues. With that short overview, I would like to pass the call back to Jörn for some closing remarks.
spk03: Slide seven, I'm indeed very proud of our people and their drive to support the companies and our shareholders' objectives throughout this difficult market period. And we're laser focused to produce and present to you our clinical data updates throughout the year, as we said earlier. Thanks a lot for listening. And with this, I would like to open up for Q&A. Operator?
spk04: Thank you. As a reminder, to ask a question, you will need to press star one on your telephone. To withdraw your question, press the pound hash key. Once again, if you'd like to ask a question, please press star and 1. Your first question today comes from the line of Alex Stranahan from Bank of America. Please go ahead. Your line is open.
spk07: Hey, good morning, everyone. This is John on for Alex, and thanks for taking our question. So I think my question is just one question, but that kind of has two parts to it. And it's about the Gilead partnership. Since you basically be running one, running the Phase 1B trial for the H1B yourselves, it would be cool to get some outlook about what you're focusing on specifically for the Phase 1B and what kind of Phase 1 you're contemplating for the H1B trial. And more specifically, also, could you also shed some light on what would Gilead specifically be looking for if there's any specific metrics that they're interested in? Thank you.
spk06: Thanks for the question. So the first part of that question is we will be running a Phase 1b safety immunogenicity trial. The endpoints will be clearly to assure that we have safety and, as I said before, reactogenicity, and immunogenicity. The patient inclusion criteria, as we have previously stated, will include HIV-positive individuals who are well-controlled on antiviral therapies. The patients will receive a planned limited number of doses, followed by approximately six months of observation or therapy to assess how long the post-dose immunogenicity lasts. We are currently planning two doses and with a total number of patients somewhere in the 30 or 40 range. That are the current plans, but have not yet been finalized. In terms of your second question, what might Gilead be looking for, we don't have specific clarifications on that, but again, as you can see from the way the trial is designed, what they will be looking for in general is A, safety, and B, immunogenicity that actually is lasting at the end point of six months after our last dose.
spk07: Alright, thank you.
spk04: Thank you. Your next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead. Your line is open.
spk00: Thanks and good morning. This is Steve on for Brian. Congrats on all the progress and thanks for taking our questions. As you think about HB300 targeting the tumor-associated antigens, how much of the learnings from the HB200 on dose, vector combination, and checkpoint inhibitors will translate to the prostate program? Do you expect similar T cell responses and infiltration there? Do you think there are kind of unique challenges with that antigen that might require some additional clinical testing? Thanks.
spk06: Thanks for the question. So I'd say there is a fair amount of learnings from the 200 program that are being translated to the 300 program. First of all, we have discussed with the FDA about whether or not we need extensive pre-IND studies, or whether or not we can use the pre-IND, specifically GLP toxicology, from the 200 program to apply to 300 program, and they do believe that is appropriate, and are looking at our technology as a platform technology where we don't have to repeat all of the, or the majority of the pre-IND studies, and use the 200 to actually support the 300 filing. In the clinic itself, we actually do believe that we will actually see similar immunogenicity in terms of T cells induced for the 300 as we did for the 200. Why do we believe this? Preclinically, when we looked at our technology comparing viral vector antigens to mouse self-antigens, we are actually able to induce equivalent amount of tumor antigen-specific CDAT cells, regardless of whether that antigen comes from a virus or a mouse self-antigen. Since our data for the viral program is translated so nicely from the clinic, from the preclinical to the clinical, we anticipate that the data will translate similarly from mouse self-antigens to human self-antigens. So we do expect that The kinds of CD8 T cell tumor engine-specific responses we observed for the 200 program will be seen for the 300 program as well. There is, I would say, no rational way it would not because the technology that drives these T cells is the same. And we have shown that preclinically it doesn't matter whether it's viral or self-antigen. The questions on dosing, we do believe we actually know what is the appropriate dosing regimen. as well as the appropriate, I would say, dose level that we will be starting at and escalating with. And we know the dosing schedule of Q3 week is the preferred schedule, and intravenous is the preferred administration. So we do anticipate that these things, which we have learned from the dose escalation of the 200 program, will be applied to the 300 program. And so the dose escalation of that program, we anticipate, should be significantly higher.
spk04: shorter does that answer your question yes it is yeah thanks for all that color i appreciate it thank you your next question comes from the line of andrew barrett from svb warring please go ahead your line is open hi thanks um
spk08: Just a couple for me. It sounds like for the checkpoint combo, I just want to clarify that there'll be no more efficacy from the phase one portion. And it didn't sound like there was going to be any efficacy from the phase two. It sounded mostly safety, probability, and PK. And then you threw out a benchmark of doubling head and neck cancer responses versus checkpoint alone. Can you just give us, you know, what that number would be? And how does that compare to some of the, I know it's obviously a targeted opportunity, but some of the specific data we've seen, like, say, from Marist and LGR5, EGFR activity so far in a small number of patients.
spk06: Hi, Andrew. Maybe I can just comment on a couple of things that were said. Let me just clarify the 2022 update. that we have previously commented on, just to be clear. In the middle of the year, we will be updating the kind of motor therapy or the advanced cancer patient population, focusing on updates on 201 as well as 202.201. This will update the November presentation that we gave, where at that time we had several patients that were still either ongoing or had not yet been on therapy long enough where efficacy scans were yet attained. So at the middle of the year, we would anticipate that there would be approximately an additional 10 patients in total that were not yet ready for efficacy determination because they have not been on therapy long enough or had since gone on therapy since our November update. So in middle of this year, there will be approximately 10 patients that we will talk about that are new or have not yet, data has not yet been presented because it was not yet available at some of our last presentation. The combinations with pembrolizumab in the first and or second line setting, that data will be updated at the end of 2022. Okay. In terms of the expected response rates that we are hoping to attain, we have stated before that we would like to double the response rate of checkpoint inhibitor-like pembrolizumab in the frontline data. We believe that the reason why a checkpoint inhibitor-like pembrolizumab has approximately a 23% response rate, even in a pre-selected CPS or PD-L1 high patient population, why it is only 23% is because the other 77% that are not responding are missing significant tumor antigen-specific CDAT cells that would allow them to have a response. So we do believe that by providing tumor antigen-specific CDAT cells on top of pembrolizumab, we should be able to double the 23% response rate, and so we have constantly thrown out a number that are somewhere in the 45 to 50% range, based on a doubling of the 23% in the first line. In the second line, pembrolizumab has an approximately mid-teen response rate, somewhere in the probably 15%, depending on which study you quote. So we would like, for similar reasons, to believe that the 85% that are not responding, concurrent with our understanding of biology, is that They're missing tumor antigen-specific CDAT cells. And again, we would like to bring those in and believe we can double that response rate. And so in the second line, we'd like to get us somewhere in the 30% response rate.
spk08: Okay. Now, that would definitely be very compelling. But just to clarify, you'll have enough patients and enough data by the end of the year to give us response rates in both lines of therapy?
spk06: We are anticipating that in totality we might have somewhere between 10 to 20 patients in total to support these assertions.
spk08: OK. Great. Thanks for the call, Igor.
spk04: Thank you. Your next question comes from the line of RK from HC Wainwright. Please go ahead. Your line is open.
spk09: Thank you. Good morning and good afternoon, folks. Hi, Arcee. At the AICL conference coming up in a couple of weeks, can you give us an idea of what to expect there, since you have four different presentations?
spk06: Right. So, as you already commented on, they will focus predominantly on our preclinical, translational, and some biomarker data from our ongoing studies. We'll focus on updating on some of our prostate cancer work and some of our 20221 work as well as additional biomarker work from our ongoing clinical trial with 201.
spk09: Thank you for that. And then for the HP 700 program, two questions. One, what needs to be done? And two, How are you going to kind of stage this program in the sense, do you need to get to a certain level of development with that 200 and 300 before you start putting 700 into clinic? Or is it going to get started much sooner in the sense maybe late 22 or early 23?
spk06: So let me answer the second question first, only because I didn't get to hear the first question well. The program, the KRAS 700 program, is not dependent on any additional clinical data from those programs. That program will start as soon as we are actually ready to manufacture that product and move that forward. We believe we have sufficient data from the 200 program, a sufficient read-through, and sufficient preclinical data with our KRAS constructs, then we are convinced that that program will have activity in the clinic. We do not need way to further clinical data or additional clinical reason from the other programs to initiate that program.
spk03: So the only point regarding your timeline, it's not going to be 22 for the IND. It's going to be more like 23 or beyond.
spk09: Perfect. Thank you very much for taking my questions, gentlemen.
spk04: Thank you. Ladies and gentlemen, as a reminder, if you would like to ask a question, please press star 1 on your telephone keypad, star 1 to ask a question. Your next question comes from the line of Roy Buchanan from JMP Securities. Please go ahead. Your line is open. Hi.
spk05: Thanks for taking the questions. I guess to start, maybe follow up on the 700 program so you mentioned in the prepared remarks that it's attracted significant interest from pharma are you guys planning to partner this out um or maybe just x us or what are you thinking about there i know it's early and then igor you just said that once you have sufficient you're able to manufacture it i guess is it dependent on your capacity to manufacture at this point or is it just the standard time it takes to ramp up the program thanks
spk06: I'll answer the second question first. I mean, it's a question of standard timelines to ramp up the program combined with CRO slots. You know, CROs for viral vector manufacturing are always at a premium, you know, and a lot of them are currently booked up with vaccine for COVID and others. So I think it's a matter of standard ramp-up times and when we can get a time slot.
spk03: And the first part of the question, obviously, KRAS is a very interesting target if you want. We have looked at the possibility to put together a string of beads incorporating the most common mutation, mutations actually five that play a role in the context of KRAS-induced cancers. And combined with the strong T cell responses that we're seeing, we do have pharma companies interested actually in the approach. I cannot say more. It's clearly something that we're progressing internally and think is a high-value program.
spk05: Okay, great. And I just had a quick one on the CMV program. I know you guys... are not focused on infectious disease, but are you actively seeking out partners for that program, and are you seeing any inbound interest? Thanks.
spk03: It's early stages partnering. We have committed to not investing our dollars into infectious disease programs, and we're progressing through an outreach to pharma companies to see the level of interest in the HB101 program.
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