Q4 2022 HOOKIPA Pharma Inc Earnings Call
Speaker 1: And.
Speaker 2: Good morning and thank you for joining the Hukipa Pharma fourth quarter and full year 2022 earnings and 2023 outlook conference call. All lines have been placed on mute to prevent any background noise.
Speaker 2: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press the star key, followed by the number 1 on your telephone keypad. If you would like to withdraw your question, press star 1 again.
Speaker 2: I will now pass the call over to Matthew Beck, Executive Director of Investor Relations.
Speaker 2: I will now pass the call over to Matthew Beck, Executive Director of Investor Relations. Please go ahead. Matthew Beck Thank you,
Speaker 3: Thank you. A slide deck accompanying today's call is available through the webcast and in the events section of the WhoKeeper website. Please manually advance the slides as we prompt you through them.
Speaker 3: Joining me today are Chief Executive Officer Jeroen Aldag, Chief Financial Officer Reinhard Candera, and Chief Medical Officer Katya Schlanger.
Speaker 3: 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, or plans to present or report additional data.
Speaker 3: the anticipated conduct and the source of future clinical trials, regulatory plans, future research and development, and possible intended use of cash and investments.
Speaker 3: 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 statement.
Speaker 3: These and other risks are described in our periodic filings made with the SEC, 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 dates. The company disclaims any obligation to update such statements.
Speaker 3: For today's call, yearn will provide opening remarks. Reinhard will offer high-level comments on our financials, and then we'll open the call to Q&A. With that, I'll pass the call to yearn.
Speaker 4: Okay, good morning, everyone. I'd like to focus first on our accomplishments in 2022.
Speaker 4: And second, highlight what's coming in 2023.
Speaker 4: At UTPIBA, we're leveraging our arena viral platform to create therapies that deliver unprecedented antigen-specific CD8 T cells to combat disease.
Speaker 4: In 2022, we saw progress both in and toward the clinic across four different programs in areas of considerable unmet need.
Speaker 4: Please go to slide three, which is our petroleum slide.
Speaker 4: Key developments in 22 were the progress of our HPV-positive cancer drug, HB200, in a phase 2 single-arm cohort in combination with vembrolizumab.
Speaker 4: The acceptance of an IND for 300, or prostate cancer therapeutic targeting self-antigens.
Speaker 4: A material collaboration with Roche for a novel approach to target shared new antigens and cancers for lung, pancreas, and colon cancers with KRAS mutations.
Speaker 4: and achieving phase 1 readiness for our Gilead-partnered hepatitis B therapeutic vaccine.
Speaker 4: Let me give you a bit more background on these major achievements.
Speaker 4: Our phase 1 dose escalation study showed that HP 200 was generally well tolerated, rapidly induced a high magnitude of tumor specific T cells.
Speaker 4: and showed early anti-tumor activity and difficult to treat patients as a monotherapy.
Speaker 4: We progress to testing HPV200 and HPV16 positive head and neck squamous cell carcinoma patients in phase 2.
Speaker 4: For currently enrolling patients,
Speaker 4: in three-dose expansion cohorts.
Speaker 4: A cohort in the non-randomized first line setting in combination with PAMBRA.
Speaker 4: a cohort in the non-randomized second line setting and second line plus setting in combination with Vembro, and a cohort of patients in the post-standard of care setting at the recommended phase 2 dose. This Oo Allied series of videos has been traded to charity or by FFG and others among other cause the send most entertaining bits.
Speaker 4: Regarding the HP 200 trial, I reaffirm our Q2 data guidance.
Speaker 4: We will disclose data from 10 to 20 patients each.
Speaker 4: in the first and second line settings in combination with PEMBL, and we will provide an update on our monotherapy dose escalation cohort.
Speaker 4: We will present an update on this trial and all three cohorts in a press release and an investor call in the second quarter and inform about the likely path forward.
Speaker 4: As a reminder, our HP 200 trial which targets an oncoviral antigen supports the first of all three-part strategy in oncology.
Speaker 4: The second pillar in our oncology strategy is targeting self-antigens, which we are pursuing with our HB300-Pro1 prostate cancer.
Speaker 4: The trial is now open for enrollment as per our guidance to start the trial in Q1 2023. Targeting neoantigens is the third pillar of our oncology strategy. In October , we announced a collaboration in this field with BROSH to advance our HP 700 logets to googleORP solution for AGI and R
Speaker 4: targeting KRAS mutations in multiple indications, and an option to develop a second undisclosed candidate. We're pleased by the progress across our oncology portfolio, as well as the acceptance by the FDA last July of our Drug Master File.
Speaker 4: The information from that master file can be used to support new IND filings using our platform, leading to reduced preclinical cycle times.
Speaker 4: Regarding our Gilead collaboration, much progress has been made. After restarting the HIV program, HPV500, under our control to bring it to the end of Phase 1b, we're working with our academic collaborators in plan and IND filing in 2023.
Speaker 4: The Hepatitis B program progressed well. As planned, we completed the OKEPA contributions for IND preparations in 2022, triggering a $35 million milestone payment.
Speaker 4: Gleb guided to a start of the trial on the SHBV program in 2023.
Speaker 4: So what's in our plans for 23?
Speaker 4: The readout of all three HP 200 Phase II expansion cords in the second quarter of 2023 shall guide our decision to move into a randomized HP 200 trial in combination with PEMBRO versus PEMBRO alone.
Speaker 4: We have fast-track designation for such a trial and a supply agreement for Pembrole with Merck, US. In our HP 300 phase one trial targeting prostate cancer, we're recruiting now and we'll start those in patience.
Speaker 4: Expect initial data in the first half of 2024.
Speaker 4: We had a good start in 2020-23 with two significant milestone payments reflecting significant progress in our collaborations.
Speaker 4: First one, $5 million from Gilead for the completion and delivery of a regulatory support package for their Phase 1 clinical trial of a therapeutic cure for chronic hepatitis B using HB400. And the second, a $10 million payment from Roche for starting the NP manufacturing of the QS therapeutic.
Speaker 4: an important step before fighting the IND, which we expect to happen in the first half of 2024.
Speaker 4: Expect to file our HP 500 HIV therapeutic cure candidate, IND in 2023.
Speaker 4: We will continue our work for Roche, both on the KRAS therapeutic as well as on the option package for an additional target, which Roche may decide to exercise in in 2024.
Speaker 4: In summary, we've made significant progress in 2022 and we have positioned for an exciting 2023 with material useful to come from our key programs.
Speaker 4: Finally, I'd like to highlight that we have significantly strengthened our attach balance.
Speaker 4: with $113 million at year-end 2022, who are well-funded for many major data readouts.
Speaker 4: With that, I will turn the call over to our CFO for more financial details. Thanks, Jeroen. Good morning, everyone. I want to give you a few highlights of our financial results for the fourth quarter and the full year 2022.
Speaker 4: As shown on slide four of our presentation, we ended the year with a strong water in revenues, which amounted to $7.8 million and included the milestone payment from Gilead and the start of the recognition of the $25 million upfront payment received under the Roche Collaboration.
Speaker 4: Our Q4 spending was very much in line with the average of the previous quarters, leading to a quarterly net loss of 12.3 million for Q4.
Speaker 4: For the 2022 results, I want to start by pointing out our significantly strengthened cash position, which we achieved through our $75 million capital raise in the first quarter and cash inflows from partnering.
Speaker 4: including $19 million from Gillert and $25 million from Rosh.
Speaker 4: I'm also proud to report that we were able to achieve a significant 2022 R&D progress that Jörn has just detailed at a 17% lower spend compared to 2021. Our G&A expenses moderately increased.
Speaker 4: but the increase was more than offset by higher grant and interest income. Bottom line, we reported a full year 2022 net loss of slightly less than $65 million, which is 14% below 2021. We continue to manage our burn rate tightly and to rely on partnerships to support the growth of our businesses.
Speaker 4: in milestone payments.
Speaker 4: With a cash balance of $113.4 million at the end of 2022, plus the $15 million in partner milestone income already achieved in 2023, we consider ourselves well-funded to reach beyond important upcoming pipeline catalysts.
Speaker 4: With that, I'd like to hand back to Jörn for some closing remarks.
Speaker 4: Thanks, Reinhard. We're coming to the end of this call. I'm indeed very proud of our talent at PIPA and their drive to support the companies and our shareholders' objectives as well as this difficult capital market environment.
Speaker 4: We're laser focused to produce and present to you our clinical data updates throughout the year.
Speaker 4: With that, I'd like to reopen the line for QLA operator.
Speaker 2: Thank you. At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad.
Speaker 3: We'll go first to Brian Abram at RBC Capital Markets. Hi guys, thanks. It's Leo, on for Brian and congrats on another quarter and thanks for taking our question.
Speaker 3: How are you thinking about the bar for HB200 and what's achievable? If the response rates fall in the 25 to 35% range, how are you thinking about next steps for the program? And what's your sense of where standard of care is for each line and what docs would find meaningful? I mean, would you add more patients to tease out a response or would you pivot?
Speaker 3: and look to modify the program depending on what you see. And maybe I'll have a follow up after that. Thanks.
Speaker 4: I'll let Kathy give you more specifics to it, but in general, we know that the Standard of Care's pambrolism up.
Speaker 4: And in the second line how the response rate objective response rate of 15%
Speaker 4: And in the first line, an objective response rate of 20%.
Speaker 4: And we consider success if we're able to double these, meaning that we reach around 40% objective response with the combination of HB200 together with standard care pamprolizumab.
Speaker 5: Yes, and adding a little bit to that, you know, we will look at the totality of the data. So if we are in the gray zone, if it's not clearly yeah or nay, you know, we would look at other markers of efficacy. We would look also at the immunogenicity.
Speaker 5: and we will then decide if we want to start the trailer map.
Speaker 4: So in brief, if we make 40% objective response rate, there's a clear go ahead signal. But we will be looking at the totality of the data in making that final decision, because you know that this is going to be a phase three trial with a very significant investment.
Speaker 3: Got it. Thanks. And then maybe just a quick follow-up on that. Have you talked about how much follow-up you'll be expecting for the patients that you present at the upcoming data cut? Is it going to be only patients with more than two scans? And you mentioned you'll be presenting the data now.
Speaker 6: press release? Are you still looking at a medical meeting submission around that same time? Thanks. I'll hop back in the queue. Yeah, we intended this point in time to have a press release and also an investor event. So we'll substantially detail the data.
Speaker 6: and be at a medical conference some point after the summer.
Speaker 6: some point after the summer.
Speaker 5: Yes, no, nothing more to add to that, exactly that.
Speaker 5: Of course, we will present our data to scientific conference afterwards.
Speaker 2: We'll go next to Vikram Pirohit at Morgan Stanley .
Speaker 7: Hi everyone, this is Will on Per Vicrum. Thanks for taking our questions and congrats on the quarter.
Speaker 7: Just kind of the same vein as Leo's question, how would you frame expectations for the initial data expected for HPE 300 in the first half? Can you just give us a sense of what we can expect to see in terms of the data points and what you would consider a win?
Speaker 6: We're looking at a self-antigen.
Speaker 6: Clearly, establishing immunogenicity against the antigens that we've chosen would be a significant win in the first half of 2024.
Speaker 6: antigenicity against the antigens that we've chosen would be a significant win in the first half of 2024. Katja?
Speaker 5: No, exactly that. I think it's our first readout as well as the German safety profile. We don't expect a lot of surprise based on the excellent safety profiles that we have demonstrated with the 200 program using exactly the same.
Speaker 7: So all this information will come in 2024. Okay, great. And is that going to be just a press release or is that going to be associated with medical conference as well?
Speaker 6: It depends on the timing of the data availability versus a major conference at which we could present.
Speaker 7: It's not decided yet. Okay. Well, thanks for the color. Appreciate it. Congrats again.
Speaker 1: Welcome.
Speaker 2: We'll move next to Alex Stranahan at Bank of America.
Speaker 8: Hey guys, thanks for taking our questions. Hey, just a couple from us.
Appreciate the additional color on the 2Q updates for the 200 program.
You know as we're thinking through the historical controls obviously those are in a broader head and neck population is there any reason to think that Keytruda monotherapy would perform better or worse in a HPV 16 positive population just trying to think
if that's an apples to apples and then
just on the capital allocation priorities next 12 months, starting a few new studies. Obviously, you've got some partner funding as well. So I guess where does that sort of put you guys in terms of Runway and where is sort of your main focus in terms of capital allocation?
Thanks.
Katia, will you take the Kishuda monotherapy question? Yes. Yes, absolutely. So in Tino048, which is a randomized phase 3 trial that led to bambolism and approval in first line for patients with head and neck squamous cell carcinoma, there was no known difference between those patients and patients with Tino048. And then there was a lot of difference between those patients and patients
with HPV positive or HPV negative head and neck.
So that's to answer the first question. Were you thinking of something specific around that question?
No, I think that's helpful.
No, I think that's helpful. And just on the capital analysis. All right.
Yeah, okay, so on the capital allocation clearly the the key priority at this point is moving HP 200 along
HP300 from a strategic perspective is important because we're targeting in cell antigen. And if we're able to generate significant T cell immune responses against cell antigens, and by that breaking tolerance, we're clearly in a pretty good comp.
So that is our priority number two, strategically important. Clearly also important from a capital allocation perspective are HB 500, which is the HIV program which we are running until after the end of Phase 1B, where Gilead has an option to take it in.
and the very interesting KRAS program that we're running with Roche. But both these programs are basically funded through payments that we're receiving from Gilead and Roche. So your question actually addresses the key spend and that's obviously HB200 and its progression.
and where we have various avenues to take it forward, including the H-200-04 randomized trial and an HB-300. Regarding the cash runway, I would like to have Rainer answer that question.
Yeah, given the uncertainty of the business and the dependence on R&D outcomes, we don't give specific numbers, but I can give you some orientation. I've mentioned that our R&D cost is going to increase moderately. On the other hand, we have two big partnerships with Roshan and Gilead.
that provide increasing support from partnership revenue to cover that cost. So by and large, expect our net loss in the current year to be similar than in the previous year around around 65 million dollars.
As I mentioned, we have more than 113 million in cash at year-end. There is another 15 million that already came in from partnerships in the first quarter. I'll let you know where this takes us in terms of cash runway.
Great. Thank you. Looking forward to the updates. Thanks for that.
We'll take our next question from Arthur He at H.C. Wainwright.
Hi everyone and thanks for taking my question. For the HB200 program, regarding the randomized study,
Could you give us a more specific regarding the study initiation, and when could we expect the data from the randomized phase two study for the first line patient? Well, the first point, obviously, a lot of preparation has been done. We have manufactured HP 200 product. Then we also have Pawinn.
We have a clinical protocol in place that we can apply. We have had discussions with the relevant CROs that would support the clinical trial. We have to make the decision and inform folks that we would make that decision based on information that is available.
be a flavor on initial data from the 200 program to randomize trial when it gets started.
Yes, and just as a reminder, we have a fast track deviation of the G's that we obtained from the NDA for that study. We have this supply agreement with Merck. We have already discussed the design of our trial with NDA, and we just, you know, would like to have an evaluation of the Eyes- forgive, outside the DNA,
a deep look into our data from the H201 data is a single cohort to make basically the decision to move ahead.
Is that a helpful answer or should I answer something else? No, that's helpful. That makes sense.
Anyway, and so for your upcoming presentation at the AACR, it's quite interesting for the target. Could you elaborate more on that particular candidate?
We do know that a significant number of immunotherapies are suboptimally working with regard to efficacy because they're lacking T cells at the site of the tumor.
For that reason, we were claiming that we're able to drive very high levels of antigen-specific T cells.
and that this ability to drive these antigen-specific T cells towards the tumor could actually help a number of different immunotherapies to work.
You may remember that last year at ACR we demonstrated the combination with some 4,1-BB.
In this AACR presentation, you will be looking at a different and immunocereputic IL-2, which we think has a significant promise in combination with HP200 as well. And what we're trying to show, albeit preclinical for the time being,
is that with these types of combinations, we can actually significantly enhance therapeutic effect in cancer patients across many different...
many different diseases. And we're very pleased that at the AACR we have the mini symposium, so an overall presentation of that data.
that you're referring to. Great, thanks for the additional color and congrats on the progress. Have a good one.
Thank you. Thank you. And we'll go next to Asvika Gunorden at Truist Securities.
Hi, guys. Thanks for taking my question. I want to go back to the first question asked about the bar here and the tinnitus-related patients, what they did and what they're looking forward to in the second quarter. You told us the bar in response rate, but as we know, I.O. also shows that the I.O. works. You have a nice durable response. So what do you think is the bar for duration of response?
shown that with our vector as a single agent, we see some patients with stable disease from lung disease.
And so we're planning to report that as well. In terms of duration of response, you know, this will be what we will have, you know, the knowing that we have started and what is the station at the beginning of 2022. So we will put.
the maximum of data that we have at this point, we guided to 10 to 20 patients in first line and 10 to 20 patients in second line plus.
So, Clatchett, maybe I'll ask you more directly. Do you think the duration of a sponsorator will be mature enough to see a signal when you present this data in the second quarter or will you need more follow-up to really understand the center with the median duration of responses in these cohorts?
Yes, we will probably need to continue to follow up. You know, it's quite frequent that for this kind of data, there's updates on the data regularly at each of the conference. So we will continue to follow up the station no matter what. And obviously this would be a fact we need, but we will continue to follow up.
continue to follow up those patients and provide regular updates at scientific conference.
So, I think it is important to note... Oh, yeah, sorry. No, no, no. Go ahead, Jörn. Yeah, it's important to note that the median progression for survival, for example, for PEMBA alone is very short. So, I think it's important to note that the median progression for survival is very short.
And while we will not have data that has fully matured across the entire data set of patients, you will be able to see how we compare against the median progression-free survival of femoral lung.
Okay. And then when you're looking at this at the more longer term follow up, hopefully later this year or maybe early next year, what is the bar then for progression-free survival or duration of response that you would like to see given that you said that you're looking for double the ORR?
Would you want to see double the median PFS or double the duration? So, I can think that we know that for immuno-oncology, PFS is not necessarily the best primary endpoint. We know that for PAM-related maps, for example.
It's three months in first line and two months in second line class, and that does not reflect the huge risk advantage that is provided in first line and second line for the patient.
So, I would like just to question that, yes, we will provide all that we have, but PFS is not the setting, the right measure for immuno-oncology projects.
In terms of duration of response, so this is measuring the time on treatment with a progression in patients who are responding. This will take several months to assess. And we will probably provide an update later on through scientific conference, abstract and presentation. The ps sorry folks, s.
Got it. Okay. And then just lastly, just bigger pages here. Previously in our discussions, and we felt this too, the really strong immunogenic response that you were generating with HP 200 in the platform does really attractive and it kind of makes sense that...
adding something like PD-1 was a logical step to making this work. Given what you know today, and the emergence of other data, preclinical and otherwise, how do you feel about that? And if there is anything that you would like to add to a combo, what would that be?
I'm not here about what you specifically want to find out here, but could you just specify your question a bit more?
Yeah, yeah, I mean, I'm just wondering, like, do you need to, you know, you're getting the immunogenic response with the C-200. You're getting checkpoints, blockade with the PD-1. Is there anything else from an immunological perspective that you think would be useful to add to this combination? Do you think getting more danger signals with chemotherapy?
What do you think is the next logical component that you might want to add to this type of therapy here? It may be interesting to look at the data that we will present at ECR.
But I let Katia answer the question. Yes, so certainly, like we know, what we saw in monotherapy, we saw that we were able to see clinical response and stable using some patients.
We saw huge immunogenicity induction with very high levels of CBAT cells specific to the tumor antigen in the circulation. We saw that those T cells are poly-functional and that they do infiltrate the tumor.
So we would like to continue to develop those data in monotherapy and in combination with pangolinumab over the next months. To tell you exactly what we will show and what it means, you know, I think Jeremy the shield is looking for a general correlation between the immunogenicity and efficacy, and we will look at that and report what we find.
Awesome guys. Thanks. I look forward to it and look forward to your updates with ASER coming out, as well.
Awesome guys. Thanks. I look forward to it and look forward to your updates at AICI as well. Great. Thank you.
We will take our next question from Roy Buchanan at J&P Securities. Thanks for taking the questions. Just a few quick ones. The first one is for Reinhardt. Can you just remind me if Gilead has a timeframe they need to make the purchase of stock? I think there is 30 million still eligible to purchase. Is there a certain timeframe on that?
Yes, there is a time frame. We have actually the choice to draw that additional equity and it is until end of 2023.
Okay, great, thank you. And then has Gilead said if the phase one in hepatitis B is going to be in patients or healthy volunteers?
We have to close that yet and I don't think we can. We have to leave that to be.
Okay fair enough. And then just the last one can partners use the drug master file like can Roche use it for the KRAS program?
Yeah, we can use it as we're preparing the Phase 1B, and we're doing the IND work, and we can use that. Unknown State practice Or even if you can move your foot around better.
drug master file from the HP 200 and 300 in that context as well. Okay, great. What about partners that are doing the phase one themselves? Can they use it?
master file from the HP 200 and 300 in that context as well. OK, great. What about partners that are doing the phase one themselves? Can they use it? OK, can you answer this?
Yes, they can certainly use it, you know, like when they use our project. This could be something that they can use when they find an IMV in projects that are related to those.
you know, the ones that you are using really are a bit different than the ones that you are using in oncology. So that our BESTA file was done for the two vector replicating, which is different from the 400 technology.
So it's depending on what our partner will use. So for example for ROSH absolutely This will be used for the IED submission as well. Great. Okay. So I had it just very very briefly. Yes, they can use it at this point in time No one is doing a phase one with our program.
on what our partner will use. So for example, for ROSH, absolutely, this will be used for the IMU submission as well. Great, okay. So just very, very briefly, yes, they can use it. At this point in time, no one is doing a phase one with our program. Got it, thank you. With the Reaniverse.
Great. And our next question comes from Suzanne Van Boerthusen at Campen.
Hi, good afternoon. Thanks for taking my question. I just wanted to circle back to the Q2 update on the HP 200 program. I'm not sure I heard it right. So can you clarify what you will include in terms of duration data in the press release?
Will it include both duration of response and PFS? What conference in the later half of the year are you targeting to get the data presentation? Then I'll have to follow up as well.
Yes, so in terms of duration of response, you know, it's
The challenge would be to obtain a median for all patients. Probably we will not have a median at that time, but I'm just speculating. The duration of response for Pamboli is 22 months.
So we, you know, it's difficult to know if we will be able to reach a meeting at that time. We will disclose on what we have in terms of the object response rate, in this control rate and associated efficacy end point. We will disclose also the safety profile and the immunogenicity data.
that we will have at the time.
Is that helpful? Yes, for sure, thank you. And what conference in the latter half year are you targeting for presentation?
So we did not decide yet and we will leave it when we are ready.
A follow-up is on a different topic with now Gilead and the addition of Roche as partners for Hoogba. How are you looking at potential further BD? We would like to hear your considerations and preferences. These reports aregrounded organization is simply available from street to wherever businesses
in terms of type of deals, on quality or infectious diseases, development stage or platform deals. Just some thoughts that you can share there.
Yeah, so any collaboration is actually quite a complex undertaking. Working with bigger pharma companies like Elliot and Walsh does trigger a lot of activity, organizational and otherwise, within an organization. And adding business development activities.
It has to take account of that. So we at this point in time would like to retain value in our programs and not partner them away. So we at the end of time would like to retain value in our programs and not partner them away.
Having said that, we have a technology platform and we know that there are many different antigens that we are currently not tackling, which we could.
if a pharma company was interested in it. And clearly the development of capital markets
the way we're seeing them today may also trigger one or the other thought about interesting deal structures that would provide funding capital to the company. So you're asking a complex question. At this point in time, we're very happy about our collaborations with Rosh and Gilead.
know that retaining value in the company is important and therefore we would have to look at it at the moment that such partnership discussions come up.
retaining value in the company is important. And therefore, we would have to look at it at the moment that such partnership discussions come up. Got it. Thanks a lot.
And there are no further questions at this time. I would like to turn the conference back over to management for any additional or closing remarks. Thank you very much.
Very briefly, I think we've had a great year 2022. We're gearing up to some important value inflection points and milestones and looking forward and curious to see the outcome of all of this and would basically tell our shareholders that we're doing our utmost.
to keep our burn low up until better times in the markets, to really progress the company to big value infection points that will change its valuation and end with that the future. Thanks a lot.
and talk to you soon.
to you soon. Bye bye.
And that does conclude today's conference. Thank you for your participation. You may now disconnect.
We C.
I have you.
Thank you. A slide deck accompanying today's call is available through the webcast and in the events section of the WhoKeeper website. Please manually advance the slides as we prompt you through them.
Joining me today are Chief Executive Officer Jeroen Aldag, Chief Financial Officer Reinhard Candera, and Chief Medical Officer Katya Schlinger.
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.
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 statement.
These and other risks are described in our periodic filings made with the SEC, 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, Yern will provide opening remarks.
Reinhard will offer high-level comments on our financials, and then we'll open the call to Q&A. With that, I'll pass the call to Jeroen. Okay. Good morning, everyone.
I'd like to focus first on our accomplishments in 2022, and second, highlight what's coming in 2023.
At Opepa, we're leveraging our arena viral platform to create therapies that deliver unprecedented antigen-specific CD8 T cells to combat disease.
In 2022, we saw progress both in and toward the clinic across four different programs in areas of considerable unmet need.
Please go to slide 3, which is our portfolio slide. Key developments in 22 were the progress of our HPV-positive cancer drug, HB200, in a Phase II single-arm cohort in combination with fimbrolizumab.
The acceptance of an IND for 300, prostate cancer therapeutic targeting self-antigens.
A material collaboration with Roche for a novel approach to target shared new antigens in cancers for lung, pancreas, and colon cancers with KRAS mutations.
and achieving phase 1 readiness for our Gilead-partnered hepatitis B therapeutic vaccine. Let me give you a bit more background on these major achievements.
Our phase 1 dose escalation study showed that HP 200 was generally well tolerated, rapidly induced a high magnitude of tumor specific T cells.
and showed early anti-tumor activity and difficult to treat patients as a monotherapy. We progress to testing HPV200 and HPV16 positive head and neck squamous cell carcinoma patients in Phase 2.
anti-tumor activity and difficult to treat patients as a monotherapy. We progress to testing HP-200 and HPV-16 positive head and neck squamous cell carcinoma patients in phase 2. For currently enrolling patients,
in three-dose expansion cohorts, a cohort in the nonrandomized first-line setting in combination with PEMBRO, a cohort in the nonrandomized second-line setting and second-line plus setting in combination with PEMBRO, and a cohort of patients in the post-standard-of-care setting at the recommended phase 2 dose.
Regarding the HP 200 trial, I reaffirm our Q2 data guidance. We will disclose data from 10 to 20 patients each in the first and second line settings in combination with PEMBL, and we will provide an update on our monotherapy dose escalation cohort. We will present an update on this trial and all three cohorts.
in a press release and an investor call in the second quarter and inform about the likely path forward. As a reminder, our HP 200 trial, which targets an oncoviral antigen, supports the first pillar of our three-part strategy in oncology.
The second pillar in our oncology strategy is targeting self-antigens, which we are pursuing with our HB300-Pro1 prostate cancer.
The trial is now open for enrollment as per our guidance to start the trial in Q1 2023. Targeting neoantigens is the third pillar of our oncology strategy. In October , we announced a collaboration in this field with Roche to advance our HP 700 unit.
targeting KRAS mutations in multiple indications, and an option to develop a second undisclosed candidate. We're pleased by the progress across our oncology portfolio, as well as the acceptance by the FDA last July of our drug master file. The information from that master file is available to you.
can be used to support new IND filings using our platform, leading to reduced preclinical cycle times. Regarding our Gilead collaboration, much progress has been made. After restarting the HIV program, HV500, under our control, to bring it to the end of Phase 1b.
We're working with our academic collaborators and plan and IND filing in 2023. The Hepatitis B program progressed well. As planned, we completed the OKEPA contributions for IND preparations in 2022, triggering a bearish capability todiarr Advanced N
We have guided to the start of the trial of the HPV program in 2023. So what's in our plans for 2023?
The readout of all three HP 200 Phase II expansion cohorts in the second quarter of 2023 shall guide our decision to move into a randomized HP 200 trial in combination with PEMBRO versus PEMBRO alone. We have fast track designation for such a trial and a supply agreement for PEMBRO with Merck US.
In our HB300 Phase 1 trial targeting prostate cancer, we're recruiting now and we'll start dosing patients. Expect initial data in the first half of 2024.
We had a good start into 2023 with two significant milestone payments reflecting significant progress in our collaborations. First one, $5 million from Gilead for the completion and delivery of a regulatory support package for the Phase 1 clinical trial of a therapeutic cure.
for chronic hepatitis B using HB400. And the second, a $10 million payment from Roche for starting JNP manufacturing of the KOS therapeutic, an important step before fighting the IND, which we expect to happen in the first half of 2024. We expect to file our HB500 HIV therapy
We've made significant progress in 2022 and we are positioned for an exciting 2023 with material news flow to come from our key programs. Finally, I'd like to highlight that we have significantly strengthened our cash balance with $113 million at year end 2022. We're well funded.
for many major data readouts. With that, I'll turn the call over to our CFO for more financial details. Thanks, Jeroen. Good morning, everyone. So I want to give you a few highlights of our financial results for the fourth quarter and the full year 2022. As shown on slide four of our presentation, we ended the year with a strong...
leading to a quarterly net loss of $12.3 million for Q4.
For the 2022 results, I want to start by pointing out our significantly strengthened cash position, which we achieved through our $75 million capital raise in the first quarter and cash inflows from partnering.
including $19 million from Gilead and $25 million from Roche.
I'm also proud to report that we were able to achieve a significant 2022 R&D progress that Jürgen has just detailed at a 17% lower spend compared to 2021.
Our G&A expenses moderately increased, but the increase was more than offset by higher grant and interest income. Bottom line, we reported a full year 2022 net loss of slightly less than $65 million, which is 14% below 2021. We continue to manage our burn rate tightly and to rely on partnerships.
balance of 113.4 million at the end of 2022 plus the 15 million in partner milestone income already achieved in 2023, we consider ourselves well-funded to reach beyond important upcoming pipeline catalysts. With that, I'd like to hand back to Jörn for some closing remarks.
Thanks, Reinhard. We're coming to the end of this call. I'm indeed very proud of our talented PIPA and their drive to support the companies and our shareholders' objectives as well as this difficult capital market environment.
We're laser focused to produce and present to you our clinical data updates throughout the year. With that, I'd like to reopen the line for Q&A. Operator. Thank you. At this time, I would like to remind everyone in order to ask a question, press star then the number one on your telephone keypad.
200 and what's achievable? If the response rates fall in the 25 to 35% range, how are you thinking about next steps for the program and what's your sense of where standard of care is for each line and what docs would find meaningful? I mean, would you add more patients to tease out a response or would you pivot and look to modify the program, depending on what you see? Yeah, and maybe I'll have a follow-up after that. Thanks. Yeah, I'll let Kathy give you more specifics to it, but in general, we know that the...
them up.
Yes, I'm adding a little bit to that. You know, we would look at the totality of the data. So if we are in the gray zone, if it's not clearly yay or nay, you know, we would look at other markers of efficacy. We would look at the immunogenicity.
and we will then decide if we want to cut the trial or not. So, in brief, if we make 40% objective response rate, there's a clear go-ahead signal, but we will be looking at the totality of the data in making that final decision, because you know that this is going to be a phase 3 trial.
And you mentioned you'll be presenting the data in a press release. Are you still looking at a medical meeting submission around that same time? Thanks. I'll hop back in the queue. Yeah, we would... We intend at this point in time to have a press release and also an investor event. So we'll substantially detail the data.
and be at a medical conference some point after the summer. Katja? Yes, nothing more to add to that. Of course we will present the scientific conference afterwards.
We'll go next to Vikram Pirohit at Morgan Stanley . Hi everyone. This is Will on for Vikram. Thanks for taking our questions and congrats on the quarter. Just kind of the same vein as Leo's question, how would you frame expectations for the initial data?
establishing immunogenicity against the antigens that we've chosen would be a significant win in the first half of 2024.
against the antigens that we've chosen would be a significant win in the first half of 2024. Katja?
No, exactly that. I think it's our first readout as well as the GERN safety profile. We don't expect a lot of surprise based on the excellent safety profiles that we have demonstrated with the 200 program using exactly the same vectors. So all this information will come in 2024. Okay.
Great. And is that going to be just a press release, or is that going to be associated with medical conference as well? It depends on the timing of the data availability versus a major conference at which we could present. It's not decided yet.
Okay, well thanks for the color. Appreciate it. Congrats again. Welcome. Thanks. We'll move next to Alex Stranahan at Bank of America. Hey guys, thanks for taking our questions. Okay, just a couple from us.
Appreciate the additional color on the 2Q updates for the 200 program.
You know as we're thinking through the historical controls obviously those are in a broader head and neck population Is there any reason to think that Keytruda monotherapy would perform better or worse in a HPV 16 positive population? I'm just trying to think
if that's an apples to apples. And then just on the capital allocation priorities next 12 months, starting a few new studies, obviously you've got some partner funding as well. So I guess where does that sort of put you guys in terms of runway where is sort of your main focus in terms of capital allocation?
Thanks. Katia, will you take a few more of the therapy questions? Yes. Yes, absolutely. So in Tino048, which is a randomized phase 3 trial that led to bambolism and approval in first line for patients with head and neck and excrement cell carcinoma.
There was no known difference between those patients with HPV positive or HPV negative head and neck. So, that's to answer the first question. But were you thinking of something specific around that question? No, I...
were able to generate significant T-cell immune responses against self-antigens, and by that, breaking tolerance, I'm clearly in a pretty good camp.
So that is our priority number two, strategically important. Clearly also important from a capital allocation perspective are HB500.
which is the HIV program which we are running until after the end of phase 1B, where Gilead has an option to take it in, and the very interesting KRAS program that we're running with Roche. But both these programs are basically funded through payments that we're receiving from Gilead and Roche. So your question actually addresses the key spend and that's...
That's obviously HB200 in its progression, where we have various avenues to take it forward, including the H204 randomized trial and HB300. Regarding the cash runway, I would like to have Rainer down.
On the other hand, we have two big partnerships with Roshan with Gilead that provide increasing support from partnership revenue to cover that cost. So, by and large, expect our net loss in the current year to be similar than in the previous year, around 65 million dollars.
As I mentioned, we have more than 113 million in cash at year end. There is another 15 million that already came in from partnerships in the first quarter. So I'll let you do the math of where this takes us approximately in terms of cash runway.
Great. Thank you. Looking forward to the update. Thanks for that. We'll take our next question from Arthur He at HC Wainwright.
Hello, everyone, and thanks for taking my question. Just for the HB200 program, regarding the randomized study, could you give us a more specific regarding the study initiation and when could we expect the data from the randomized phase two study for the first line patient?
Well, the first point, obviously, a lot of preparation has been done. We have manufactured the HP 200 product. We have a clinical protocol in place that we can apply. We have had discussions with the relevant CROs that would support the clinical trial.
And we have to make the decision and inform folks that we would make that decision based on information that is coming from our clinical trial, which is currently ongoing and running, which we will be reporting about in June . So more specific timelines you will hear when we do the data release. I'm catching maybe a flavor on...
initial data from the 200 program to randomize trial when it gets started? Yes, and just as a reminder, we have a fast track deviation of the data that we have seen from the NDA for that study. We have this supply agreement with Merck. We have already discussed the design of our trial with NDA. And we would like to have a deep look into our data from each...
20001 data into single cohort to make basically the decision to move ahead. So, is that a helpful answer or should I answer something else? No, that's helpful. Yeah, that makes sense. Anyway.
So for your upcoming implementation of ACR, it's quite interesting for the target. Could you elaborate more on that particular candidate? We do know that a significant number of immunotherapies are suboptimally working with regard to efficacy because they're lacking T cells at the site of the tumor.
For that reason, we were claiming that we're able to drive very high levels of antigen-specific T cells. And that this ability to drive these antigen-specific T cells towards the tumor could actually help a number of different immunotherapies to work.
You may remember that last year at ACR we demonstrated the combination with some 4,1BB.
in this ACR presentation, you will be looking at a different immunotherapeutic, IL-2, which we think has a significant promise in combination with HB200 as well. And what we're trying to show, albeit preclinical for the time being.
is that with these types of combinations, we can actually significantly enhance therapeutic effect in cancer patients across many different diseases. And we're very pleased that at the AACR, we have the mini symposium, a presentation of that data.
that you're referring to. Great, thanks for the additional color and congrats on the progress. Talk to you soon.
to. Oh great thanks for the additional color and congrats on the progress. Thank you.
Thank you. And we'll go next to Aspika Gunorden at Truist Securities. Hi, guys. Thanks for taking my questions. I want to go back to the first question asked about the bars here and the,, internet.
Tenant to greater patients, what they did, they're looking forward to in the second quarter. You told us the bar in response rate, but as we know, IO also shows that an IO works, you have a nice durable response. What do you think is the bar for duration of response in both these cohorts that you're planning on presenting? I've got a couple follow-ups on that.
Yes, absolutely. So we're planning also to look at a number of other efficacy endpoints, like disease control rates. You know, indeed, sometimes we have shown that with our vector as a single agent, we see some patients with stable disease from one side.
And so we're planning to report that as well. In terms of duration of response, this will be what we will have, knowing that we have started and will be doing station at the beginning of 2022. So we will put...
the maximum of data that we have at this point, we guided to 10 to 20 patients in first line and 10 to 20 patients in second line plus. So Clachit, maybe I'll ask this more directly. Do you think the duration of response data will be mature enough to see a signal when you present this data?
in the second quarter or would you need more follow-up to really understand what the median duration of response is in these cohorts? Yes, we will probably need to continue to follow up. You know, it's quite frequent that for this kind of data, there's updates on the data regularly at each of the conferences. So we will continue to follow up the station no matter what.
this would be a first release, but we will continue to follow up the patient and provide regular updates at scientific conference. So I think it is important to note. Oh, yeah, sorry. Sorry, pay attention to students'aine. advisor.
No, no, no. Go ahead, Jorn. Yeah, it's important to note that the median progression for survival, for example, for PEMBA alone is very short. And while we will not have data that has fully matured across the entire data set of patients, you will be able to see how we compare against the median progression for survival of PEMBA.
And then when you're looking at this at the more longer term follow up, hopefully later this year or maybe early next year, what is the bar then for progression-free survival or duration of response that you would like to see given that you said that you're looking for double the ORR?
You know, we know that for PAMB or DIMAP, for example, it's three months in first line and two months in second line plus, and that does not reflect the huge risk advantage that is provided in first line and second line for the patient.
So, I would like just to question that, yes, we will provide all that we have, but PFS is not necessarily the right measure for immuno-oncology projects.
In terms of duration of response, so this is measuring the time on treatment with a progression in patients who are responding. This will take, you know, several months to assess. And we would probably...
provide an update later on through scientific conference, abstract and presentation. Got it. Okay. And then just lastly, just bigger pages here. Previously in our discussions, and we felt this, too, the really strong immunogenic response that you were generating in the HP 200 in the platform that was really attractive, and it kind of made sense that adding something like PD-1 was a logical step to making this work.
I mean, I'm just wondering, like, do you need to...
you're getting the immunogenic response with the C200. You're getting checkpoint blockade with the PD-1. Is there anything else from an immunological perspective that you think would be useful to add to this combination? Maybe, like, do you think, like, getting more danger signals with chemotherapy? What do you think is the next logical component?
like we know. So what we saw in moment therapy, you know, we saw that we were able to see clinical response and stable disease in some patients. We saw huge immunogenicity induction with very high level of CBAT cells specific to the tumor antigen in the circulation.
We saw that those T cells are polyfunctional and that they do infiltrate the tumor. So we would like to continue to develop those data in monotherapy and in combination with pangolinumab over the next months. To tell you exactly what we will show and what it means.
I think Jeremy is looking for general correlation between immunogenicity and efficacy. And we will look at that and report what we find. Awesome, guys. Thanks. I look forward to it and look forward to your updates with ASER as well.
the field is looking for general correlation between the immunogenicity and efficacy. And we will look at that and report what we find. Awesome, guys. Thanks. I look forward to it and look forward to your updates with AHRQ as well. Great. Thank you.
We will take our next question from Roy Buchanan at JMP Securities. Thanks for taking the questions. Just a few quick ones. First one for Reinhardt. Can you just remind me if Gilead has a timeframe they need to make the purchase of stock? I think there is 30 million still eligible to purchase. Is there a certain timeframe on that? Yes, there is a timeframe. We have actually the choice to…
Okay, fair enough. And then just the last one, can partners use the drug master file? Like can Roche use it for the KRAS program?
Yeah, we can use it as we're preparing the Phase 1B and we're doing the IND work and we can use that Drugmaster file from the HP 200 and 300 in that context as well. Okay, great. What about partners that are doing the Phase 1 themselves? Can they use it? Dr. can you answer this?
Yes, they can certainly use it, you know, like when they use our project, this could be something that they can use when they find an IMV in projects that are related to those.
the ones that are using VLA-ID is a bit different than the ones that we're using in Oncology. So that our BESTA file was done for the two vector replicating, which is different from the 400 technologies. So depending on what our partner will use...
For example, for WASH, absolutely, this will be used for the IMD submission as well. Great. Okay. So, just very, very briefly, yes, they can use it. At this point in time, no one is doing a Phase I with our program.
Got it. Thank you. Great. And our next question comes from Suzanne Van Borthusen at Campen.
Hi, good afternoon. Thanks for taking my question. I just wanted to circle back to the Q2 update on the HP 200 program. I'm not sure I heard it right. So can you clarify what you will include in terms of duration data in the press release?
Will it include both duration of response and PFS? What conference in the later half of the year are you targeting to get the data presentation? Then I'll have to follow up as well.
Yes, so in terms of duration of response, you know, the challenge would be to obtain a median for orientation. Probably we will not have a median at that time, but I'm just speculating. The duration of response for PAM or UMA is 22 months. So we, you know, it's difficult to know if we will be able to reach a median at that time.
Thank you. And what conference in the latter half year are you targeting for presentation? So we did not decide yet and we will leave it when we are ready. Got it. All right. And then a follow up is on a different topic with now Gilead and the addition of Roche as partners for Hoogba. How are you looking at potential further BD?
I would like to hear your considerations and preferences in terms of type of deals, on quality or infectious diseases, development stage or platform deals. Yeah, just some thoughts that you can share there.
Yeah, so any collaboration is actually quite a complex undertaking. Working with bigger pharma companies like Elliot and Roche does trigger a lot of activity organizational and otherwise within an organization and adding business development activities.
has to take account of that. So we, at this point in time, would like to retain value in our programs and not partner them away. Having said that, we have a technology platform and we know that there are many different antigens that we're currently not tackling, which we could, if a pharma company was interested in it. And clearly, since the Daryl Act was passed, we are starting to see single- Behavioraleta
the development of capital markets, the way we're seeing them today, may also trigger one or the other thought about interesting deal structures that would provide funding capital to the company. So you're asking a complex question. At this point in time, we're very happy about our collaborations with Roche and we're very happy about that.
is important. And therefore, we would have to look at it at the moment that such partnership discussions come up. Got it. Thanks a lot.
And there are no further questions at this time. I would like to turn the conference back over to management for any additional or closing remarks. Very briefly, I think we've had a great year 2022. We're gearing up to some important value and selection points and milestones and looking forward and curious to see the future of the year 2022.
big value infection points that will change its valuation and end with that the future. Thanks a lot.
and talk to you soon. Bye-bye.