HOOKIPA Pharma Inc (HOOK) 2019 Q4 法說會逐字稿

Good morning and thank you for joining the HOOKIPA Pharma fourth quarter and full year 2019 earnings and 2020 outlook conference call. At this time, all participants in listen-only mode. (Operator Instructions) I 'll now pass the call over to Matthew Beck, Executive Director for Investor Relations. Please go ahead.

Thank you. Joining me today are Chief Executive Officer, Joern Aldag, Chief Financial Officer, Reinhard Kandera, Chief Medical Officer and Head of Global Research and Development, Igor Matushansky and Chief Technology Officer, Roman Necina. 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 plan 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. Igor will detail the progress of our clinical programs. Reinhard will offer for high-level comments on our financials, and then we'll open the call to Q&A. With that, I'll pass the call to Joern.

Thanks, Matt, and thank you, everyone, for participating in today's earnings call to keep us first, since our IPO in April of last year, and we're very happy to have this call with you today.

Please see on slide 2, our Safe Harbor statement and then switch to Slide 3. We have had a strong year and have made great progress both in terms of building our team and on the clinical front, we're now in the clinic in both the infectious disease and oncology area. On the corporate side, so you see here on this slide, we expanded our executive team by hiring Christine Baker, our Chief Business Officer, was also managing our Gilead alliance and our US headquarter office. We also added Roman Necina as Chief Technology Officer in November. Roman is responsible for key US global manufacturing operations, including analytical and process development. These key hires have rounded out our corporate needs for strategic growth and future in-house manufacturing.

Switch to the next slide please, HB-101, a program based on our non-replicating VaxWave technology designed to stimulate the immune system against cytomegalovirus infection or reactivation is in its Phase 2 trial in kidney transplant patients. Before going public, we had completed our Phase 1 healthy volunteer trial showing strong and durable T cell and antibody immunogenicity. We continue to enroll patients and plan to report safety and immunogenicity data from roughly one-third of the total patients in the first half of 2020. Igor will provide more detail shortly.

Flip over once. We also dosed our first patient in our immune-oncology trial in HPV16+ positive cancers in late December 2019. You can imagine how excited we were about this. This is a Phase 1/2 trial of TheraT-based program, HB-201, a replication competent vector technology expressing the E6/E7 fusion protein from HPV16.

That trial accrued the first dose cohort of intravenously treated patients completing accrual for intra-tumoral, the treated patients as we speak and has begun accruing patients in the second intravenous dose cohort. We expect to submit the IND for HB-202 program in the first half of 2020. This product is carrying the same antigen as HB-201, but it's based on a different vector backbone to be used in combination for stronger immune responses. Igor will again provide more detail on these programs.

Slide 6. Our collaboration with Gilead seeking therapeutic cures for chronic hepatitis B and HIV is rapidly progressing. We were proud in January of 2020, who keep agreed with Gilead to expand and accelerate the development of both programs. As a result, we'll keep us adding staff that will be solely focused on the Gilead programs. The full cost of which is borne by Gilead themselves. Gilead internally approved a what they call request for development in the HBV program, triggering a significant milestone payment. The program is now progressing towards the clinic. We couldn't be more pleased working with Gilead as a development partner.

Slide 7 is a summary of our clinical milestones. As communicated earlier, we will deliver our preliminary efficacy data for CMV for preemptive patients at the end of 2020. And importantly, how immuno-oncology program will show initial safety and efficacy data late 2020 or early 2021 as guided before. And our combination of HB-202 and HB-201 to drive the highest T cell responses, will provide important data in the middle of 2021 in our Gilead collaboration. As communicated earlier, we achieved one milestone following Gilead's decision to commit to preparations to advance the HIV and HBV vectors towards development. It is difficult to provide timelines at this point for these programs as Gilead is controlling the time.

Slide 8. Before I end my overview, I'd like to comment on the coronavirus pandemic. And how it's affecting people. Our top priority is the health and safety of our employees, followed by business continuity. We have instituted a work-from-home policy for both the US and Vienna offices for the foreseeable future and are working with our lab technicians to sustain ongoing experiments in the company, travel is reduced to zero, our employees have quickly adapted to the new circumstances and a non-lab-based colleagues are trying to continue business from home as best as they can.

We are in close contact with our trial sites that with the clinical research organizations and development partners. However, at this time, it is difficult to say with any certainty whether there will be any clinical trial disruptions or delays.

For solid organ transplants, we believe it is unlikely that transplant centers will risk voluntary immunosuppression during the coronavirus outbreak. Our HPV16+ patients are in the advanced metastatic setting and post first and second line treatments, so the risk is their ability and willingness to get to trial sites for continued treatment.

We have to assume that recruitment of our trials will be impacted though, as of today we remain on track with the disclosed milestone dates. We will communicate updates to our milestones once there is more clarity on the effects and duration of the slowdown. While we are well-funded. And this at this current point in time is critically important with a cash reach to the end of 2021. We are currently looking at the prioritization of all activities with a goal to extend the runway.

Our top priorities are the CMV program, our cancer programs, HB-201, HB-202 and new adjuvant studies that we're running and Gilead and everything else on is second priority. We will communicate the results of this effort, the moment we have more clarity both on the developments outside and the outcome of our internal discussion. I will now pass the call over to Igor for a deeper dive into our CMV and HPV16+ cancer programs. Igor.

Thank you Joern. Hello. This is Igor Matushansky, Chief Medical Officer and Global Head of Research and Development are key for us. As Joern mentioned, we're progressing through a proof of concept, infectious disease and oncology trials, both as important efficacy readouts at the end of 2020 or early 2021.

Please see slide 9, our CMV prophylaxis program, HB-101 dosed the first Phase 2 patient in December of 2018 that continues to accrue patients to review. The Phase 2 program is a randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of HB-101 by Biovail and prophylactic vaccine for cytomegalovirus. It's that a measure of virus negative patients awaiting kidney transplantation from living, CMV, positive donors based on HB-101 tolerability profile and the target patient population and to gain further insights that will inform Phase three trial design.

We recently added a new cohort of CMV positive recipients awaiting kidney transplantation from either CMV, positive or negative donors to the trial in early 2020. We believe the addition of CMV positive patients will also help to expedite trial recruitment. In the first half of 2020 as Joern mentioned, we expect to report on the safety of approximately one-third that is 50 patients of the total 150 to be enrolled.

The safety monitoring period will include the period between the first dose and the date of transplantation. Also in the first half of 2020, we expect to report an immunogenicity of approximately one-quarter that is 35 to 40 patients of the total to be enrolled. We expect both CMV specific antibody and CMV specific CD8 T cell responses for the placebo-controlled part of the trial, we expect to demonstrate an inter-patient effect that is between those patients that received placebo versus dose receiving the vaccine.

For the recipient positive group, we will measure and ensure a patient effect that is an increase over baseline in those patients that receive vaccine. We view positively if T-cell and B-cell antibody values are in line or higher than those reported in the Phase 1. Also, we expect to demonstrate no significant vector neutralizing antibody detection with repeat administration, as we have also previously demonstrated in our Phase 1. Additionally, we plan to release preliminary efficacy data from HB-101 patients late in the second half of 2020.

The data we have based on the quantity quality and number of complete data sets available. The most important focus will be on the patients treated in the preemptive antiviral therapy post-transplant arm. Since these patients are tested often and only administer antivirals when evidence of CMV viremia presents, who will provide substantially more information about this data readout later in the year.

Please see Slide 10. Moving on to our oncology programs. We were excited to have submitted our HB-201 IND in July and dosed our first patient in December of 2019. HB-201 is the Verity platform-based replication, competent vector from the coronavirus family expressing a non-oncogenic but highly antigenic E6, E7 fusion protein and HPV 16. The monotherapy Phase 1/2 trial is an open-label dose escalation and dose expansion trial in 100 patients with locally advanced and or metastatic HPV16+ cancers who have progressed on standard of care.

It is designed to evaluate the safety, tolerability and preliminary efficacy of HB-201 one as monotherapy and in combination with an immune checkpoint inhibitor. For Phase 1 dose escalation, the patient population is divided into two groups of 20 patients each. The first group is enrolling locally advanced and or metastatic HPV16+ head and neck squamous cell carcinoma patients progressing on standard of care. We will then receive intravenous administration of HB-201 every three weeks as monotherapy.

The second group is enrolling locally advanced and or metastatic HPV16 positive cancers of any site of origin with an accessible tumor who will receive one intra-tumoral administration of HB-201, followed by intravenous administration of HB-201 every three weeks as monotherapy. It is a standard three plus three dose escalation study design and doses will go up and launched scales.

Importantly, we are not trying to compare intravenous to intra-tumoral administrations, but rather to develop both approaches as therapeutic options, depending on how patients present, some patients present with cancer with numerous tiny tumors around the body with no central mass and treat them with suggests a systemic approach.

Other patients present with metastatic disease across the body with a central large tumor as well as additional systemic disease and this latter case, we provide the option for investigators to inject HB-201 one directly into the tumor, which may accelerate the response of that one tumor site while still providing an (inaudible) like effect.

You had mentioned earlier that the trial has already completed the accrual of the first dose level in the intravenous arm and now is currently already accrual of patients at the second dose Level, the intra-tumoral arm is completing accrual of the first dose level as we speak. We plan to accrue, and study backfill cohorts in between dose levels 2 and 3 to test different dosing schedules.

We anticipate dose level 3 will begin accruing patients late in the second half of this year. The primary endpoint of the Phase 1 portion of this trial will be to evaluate safety and tolerability to determine the recommended dose for the Phase 2 portion. Secondary endpoints will evaluate antitumor activity as defined by resist 1.1 and immunogenicity. We expect preliminary data to be available in late 2020 or early 2021.

Now please see Slide 11. We also expect to submit our HB-202 IND in the first half of 2020, the IDE submission will be an amendment to the current HB-201 IND not a standalone submission. The benefit of this approach is that we will be able to amend our protocols and dose patients at the same time as the currently ongoing HB-201 monotherapy trial, the HB-201/202 trial will be an alternating to that therapy using different arena viral vectors derived from potential virus and LCMV. It will follow substantially similar trial design as HB-201 monotherapy. And we are very excited to get that going in the later part of this year. With that, I'll turn it over to Reinhard for comments about financials. Reinhard. Thank you.

Thank you, Igor. Good morning, ladies and gentlemen. Let me give you a short overview on the financial results that we released this morning, and which are summarized on slide 12 of your presentation. These results and the year-on-year developments reflect the significant progress that we'll keep it has made in 2019 in advancing our clinical pipeline in delivering on our collaboration with Gilead and in the transformation from a drivers to a publicly listed company.

Since the fourth quarter results were very much in line with previous quarters. I will focus on the full year results. Let me start with revenues, which resulted exclusively from our collaboration with Gilead and increased by $4.3 million compared to 2018. Gilead revenue included $3.2 million in milestone payments, $4.4 million from the partial recognition of the upfront payments that we received in 2018 and $4.3 million from reimbursement of research and development expenses.

In early 2020, we received another milestone of $4 million triggered by Gilead's decision to move the hepatitis B program towards clinical entry. R&D expenses increased by $24.3 million in 2019 and the main cost drivers were the Phase 2 clinical trial for our HB-101 program. The preparation costs of clinical trials for HB-201 and HB-202 programs, expansion of earlier stage programs, costs in connection with securing manufacturing capacity for production of clinical trial material and the costs related to the general increase of our R&D capacities and personnel.

The increase of our G&A costs by $9.9 million was substantial, and it reflects the overall growth of our organization and the cost to operate as a public company. It was driven by an increase in personnel related expenses of $5.4 million, including stock compensation by an increase in professional and consulting fees and other expenses such as D&O insurance costs.

Our other operating income mainly includes grant income of $6.7 million from the Austrian government and interest income on our cash balances, partially offset by interest expenses. Our combined cash outflow from operating activities and investments sometimes referred to as cash burn, was USD43.7 million.

Between the February 2019 Series D financing and our IPO that closed in April 2019, we raised net proceeds of approximately USD112 million, which provided us with a strong year-end cash balance of roughly USD113 million.

Pending any coronavirus related impacts, we expect our 2020 spending to only moderately increase compared to 2019. We expect our cash reserves to fund our operations through the end of 2021, at least and most importantly, beyond our key clinical milestones. Now with that, I'd like to pass back to Joern.

In closing, I'm very pleased with two key US corporate and clinical progress in 2019 and early 2020. We remain focused on execution to produce compelling proof of concept data with our proprietary arena viral vector-based products. And I'm excited to see both our trials unfold and to keep continue to develop. We will stay in close contact with you as the pandemic unfolds and on and we'll keep communicating on if any of our plans are impacted.

I'd like to leave you with one final thought. We must ask ourselves what we as individuals and company contributors can gain from working at home during this unusual coronavirus pandemic period. In 1665, the great plague of London hit University of Cambridge caused and sent students home to continue their studies and practice today's version of social distancing.

One student had some of its greatest breakthroughs during that period without has professors who produce papers that would become the bedrock of early calculus and made his famed observations about gravity. There was indeed an apple tree outside of his bedroom window. You may have heard of him. His name was Isaac Newton. With that, I'd like to open the line for Q&A. Operator?

Andrew Berens, SVB Leerink

Well, I want to thank you for all the color and for hosting the call despite everything that's going on. I just wanted to get a little more color on the hypothetical delays to the transplant program. Is it that the transplant centers are decreasing the number of transplants are doing or these are still happening, but you think it's hard potentially hard to introduce a novel adjuvant intervention into that sequence.

Igor, would you respond?

Of course, essential for the question. I think it is too early to tell. Certainly, however, in the current environment, it is possible that surgery requiring immunosuppression will be delayed, hospital staff may be redirected to pandemic-related interventions who keep is not unique in this.

I think all clinical trials requiring hospital inpatient resources in the midst of the pandemic when hospital resources are expected to be stretched. We'll be facing similar challenges.

So I think you know, the live donor kidney transplant patients at high risk is a difficult patient to accrue but with a view of what we know today, we'll be able to deliver on the milestones. I stated it's not a question of if perhaps how many patients, but we believe we are on track to deliver the milestones as previously stated.

And Andrew, we heard that in China kidney transplants are down significantly in the context of the crisis that took place there. So it clearly document does impact things.

Okay. And just can you remind us some of your trials are not in China?

We're not in China.

Andrew Berens

Okay. And then on, are you seeing any impact of potentially on the supply of the agents, any manufacturing impact because of the pandemic?

At this point in time, no, I would like to have Roman answer this question, and we're obviously working very hard with our CROs who also have impact but are trying to keep their manufacturing sites up and running. And Roman, maybe you want to give a little bit more color here.

Hello, everyone. Roman Necina speaking, we are very close to our external partners, both to CMOs as well as to extend lives because they face similar challenges like we in our labs, they have also on to make sure that they have sufficient people to execute and achieve the relevant tasks.

And so far, we have a lot of solid business continuity plans, but of course, as the situation evolves, the need to be constantly adapted. And so we have a very close line of communication updating each other on a regular basis.

We know that CROs are actually also prioritizing and clinical trial material and GMPs seems to be very high on their priority list, whereas other things are de-prioritized and there may be impacts. But at this point in time, we're not seeing anything impacting the material for our trials.

Okay. Can you just remind us, I don't remember what you guys have publicly announced about the supply chain, but if there's anything, could you just remind us what it is?

You mean who we're working with in this high-growth area?

Right?

Yes, Roman, and just quickly. We have transferred to several CROs on all of our processes that we're using in clinical trials, and we have good relationship with these people. And I would like to have room and give a sort of brief summary on the relationships with these suppliers.

And also, with our own on manufacturing side, which we're running in Sweden, Roman, just very brief.

We have CMOs in Europe and in US. Pipe drug substance manufacturing. We have for drug product CMOs in Europe. And we have eight external labs doing our testing and release relevant activities. And we are in the process of ramping up of five drug substance capacity whenever here, we have a dedicated GMP plant for a GMP manufacturing of Phase 1/2 clinical material, and they have implemented our process most recently and they will ramp up GMP manufacturing in the second quarter of this year. Of course, everything depending on the coronavirus.

Okay. And then on, are you seeing any impact on regulatory interactions or progress with either the EMA or FDA?

Igor, please comment.

No, we have not seen any delays, or we have not received any kind of guidance that indicates that there will be delays coming as of yet. We of course, are concerned. And, you know, I would say, being very conservative in this and realizing that there, of course, might be delays as the health authorities and internal resources are devoted to deal with the current COVID-19 situation. But we have not had any communications or any indications that any kind of delays are forthcoming.

Okay. And maybe just one last question and I'll stop hogging the bandwidth. In regards to the Gilead collaboration, they obviously made the milestone payment that you highlighted. Was there any other non-financial commitment that they've made when they decided to go forward with the infectious disease program.

Yes, they request for development means that they are doing everything possible to get a program into a Phase 1 clinical trial are there is a formal stage gate when they decide to move something in Phase 1. The RFT actually sort of unlocks the commitment. And then, you know, manufacturing is a longer-term commitment which costs money and it unlocks the commitment to actually go into Phase 1 clinical trial and we interpreted on the fact that they have asked us to expand the collaboration we now have on we had 15 people working on this.

It's now 30 FTEs and accelerate on the programs towards clinical trials is a very positive sign and which tells us with the commitments they made to ready reserve capacity at our manufacturing sites at the CROs. So a very positive sign that they will take these programs into clinical trials and within the normal timeframe that you would expect for biologicals to be manufactured for bio distribution tox studies and then go through the IND process and go into clinical trials.

Okay. Thanks a lot for all the questions, guys, and good luck with everything.

Thank you, too.

Alec Stranahan, Bank of America.

Hey, guys, thanks for taking our questions. And hope you guys are staying safe and given everything that's going on, so just a couple from me and first on HB-101, could you just remind us as to the safety profile from the Phase 1, and if there are any factors that may change safety or level of immune stimulation in the Phase 2 versus what we saw in healthy volunteers? And then maybe could you talk a bit more about the rationale for expanding the study into still positive recipients, is it primarily for accelerating enrollment? And then I've got a follow-up.

Igor

Thanks, sure. So, I think in terms of mining of the safety Phase 1, what we saw in Phase 1 was most importantly through no systemic effect from the intramuscular administration. We did see mainly local reactions to the intramuscular administration such as erythema. However, interestingly enough, they were very similar to what was observed in the saline placebo.

So overall, from the healthy volunteer Phase 1 data was a very I would say, safe, and it's an interesting kind of profile. In terms of in terms of the immunogenicity and whether we will see similar immunogenicity in the Phase 2, as we saw in the Phase 1, we do believe we will, the patients that are under are being treated are being treated pre transplantation before any kind of immunosuppressants are on board. And so we do not fundamentally biologically believe that there will be a difference in the immune response that will be seen to our vaccine. It will anyway differ from what we have seen in the healthy volunteer study.

And the third part of your question was, why did we add our positive arm? It was basically in response to many of the investigators having observed and having had experience with our vaccine for over one year and not noting any concerning safety signals were more keen and much more interested on expanding this to there in the positive recipients who, of course, have a lower risk of post-transplant viremia. But still the risk is in the order of 40% and therefore, having demonstrated a very safe profile in a high-risk patient population, they were very keen to for us to expand that, too, our more lower risk population.

This of course, serve, as you know, our interests as well. It helps us clearly as a part of the accrual of the program. But I think more importantly, it allows us our data to suggest to the FDA that our vaccination strategy should be much more broadly applicable, which was, of course, our plan all along to vaccinate all comers. And this will not provide us additional data to support that argument.

Okay, great. Yes, that makes a lot of sense. And then since coronavirus is obviously at the top of most people's minds right now, and what will your plan be for data dissemination in the event that conferences continue to be postponed and due to the virus, particularly for the planned one-half '20, safety and immunogenicity updates for HB-101.

Detailed press releases on the results that describe the results and the data. Igor, do you want to say something?

No I mean, I agree with you and I will start with the press release. I think the big and more interesting data will be the efficacy data will come at the end of 2020. And I think at that point that will also follow with a press release and of course, the conference to come shortly after, as you know, most conferences now have three to four months in advance submissions. So any data that we submitted in press release by the end of 2020 will be ready for presentation at a conference three to four months later, by which point I am by being, I would say, maybe realistic that all of this will be behind us and data will be able to present on track.

Okay. Okay. And last one for me. Sort of along those same lines, you guys sort of alluded to this during your prepared remarks, but I know that you're laser focused on your core pipeline programs. But given the flexibility of your vaccine platform, have you given much thought into developing a coronavirus vaccine yourselves, perhaps could you just talk through the hypothetical strengths of such a vaccine built on your antivirus virus platform versus others such as Madonna, DonTech, et cetera?

So I think our technology is in the long term, very suited for developing a vaccine up works for something like this for the coronavirus and related strains. The only question is timing and a decision of where to prioritize. Currently, we have decided, as you have already stated, to be laser focused on our core programs. Certainly, in the future, we think we are well suited to do this, and it's simply a matter of prioritization at the moment, and currently, we're just simply prioritizing our core programs.

Okay. Thanks for taking our questions.

Brian Abrahams, RBC Capital Markets.

Thanks very much for taking my.

Hi

Can you hear me okay?

Yes, sure.

Great. Well, thanks so much for taking my questions and congrats on all the progress and appreciate all the color on the potential COVID-19 impact. I guess my first question is on HB-202. I was wondering if you could talk a little bit more about us sort of how things are going on with those initial cohorts? And then you mentioned the backfill cohorts, I'm curious what types of dosing schedules you might test there and whether those what you're going to be testing is based on any sort of efficacy or safety findings from the cohorts dose so far?

Thanks Brian. I'm assuming you mean the HB-201 program. Not the HB-202?

Yes. Sorry. I- yes, I meant to say HB-201, sorry.

No, perfect. So, our first question, what are we seeing from dose level 1, we have seen nothing from our safety concerns and escalated very smoothly to a dose level 2. And so that remains a completely on track. As I remind you, our preclinical toxicology package was completely safe and we had no dose-limiting toxicity or any kind of classes all know well, in preclinical GLP studies. Therefore, we did not and still do not anticipate that we will see any and DLTs in the human clinical trials.

Therefore, it was no surprise that we went very smoothly with no safety concerns now from dose level 1 to dose level 2. And remember, we are escalating by logs. I think we're making quite rapid progress, in terms of what do we expect the study in the backfill cohorts? We entered the trial, as you know, with the dosing schedule of every three weeks. That three weeks was somewhat of an arbitrary number based on extrapolation from what we have seen in our preclinical mouse and monkey work.

However, we would like to actually explore more aggressive schedules in man and bar by data by what I mean there is to dose more frequently such as every two weeks or every one week in order to trying to quickly much more quickly improve on our immunogenicity responses. We have seen some recent data internally that says, if you do, indeed here our products more frequently, you can actually get the CD8 T cell responses up faster so we will actually be trying more aggressive schedules in the backfill cohorts. That is the plan there.

Got it. That's really helpful. And then on HB-101, you talked a lot about the potential impact of coronavirus but assuming that there might be some disruptions there. Can you talk about any, I guess, contingency or backup plans, whether they might be shifting to different sites or any amendments to the protocol that might facilitate adequate enrollment there over the course of this outbreak, and I'll hop back into queue. Thanks.

Yes. Thank you, (inaudible). Thanks, Brian, for the question. I think you know; we need to kind of first of all comment on how does this affect to our current milestones. As you know, most of the relevant samples and other data for the analysis that will contribute to our reporting of data at both the first half of 2020 and even the efficacy endpoint at the end of the year, will be based on the on the first one-third of those of patients, the majority of those patients have already been accrued to the study and the majority of the samples off from that has already been collected. Therefore, we do not feel that the current situation will affect our ability to report on the current 2020 milestones.

Now what happens beyond that? I think you know; we need to see how the current situation evolves. As you know, the current situation is equally evolving and evolving the world. So we have we have some caveats in our protocols that allow sites, of course, to get blood from patients from the CMV trial at local sites who are seeing do not need to come into their main center. We also are putting in place a shelf life extension to make sure that we have sufficient drug product and at sufficient time in order to continue the trial if there are unexpected delays given the current situation.

That's really helpful. Thanks again.

Debjit Chattopadhyay, Wainwright.

Good afternoon, guys. Oh hi, this is Aaron on for Debjit. Good afternoon. So have you guys made any protocol amendments to screen for source code to inpatient prior to or during treatment with therapy. And I'm wondering if you might expect a change in activity of therapy in a patient with an active infection and those patients might be excluded from analysis?

Igor

Yes, great question. We specifically have not made any amendments or provisions. However, I will say, you know that I have spoken to all the investigators who are participating in our oncology program. And as you could imagine, every single hospital at this point has instituted specific guidelines for COVID-19 screening which, of course, means that anybody presenting with signs and symptoms that are suspicious for COVID-19 is undergoing specific COVID-19 testing as part of institutional guidance.

In speaking with the investigators, everybody feels that their own institutional guidelines are more than sufficient as a screening measure and therefore no additional screening measures would be required and what only complicate their already overburdened administrative staff, if we were to on top of their own institutional guidelines, start putting in amendments that require processing that their sites, everyone was quite comfortable high at a recent [PI] call that them their own institutional guidelines are more than sufficient to cover the screening of COVID-19 patients.

Now to the second part of your question, how do we feel that a COVID-19 infection affects the ability of the patients to go on a therapy program? Standard oncology protocols cover these kinds of provisions. And I would say no COVID-19, it is perhaps somewhat no different than patients who have advanced pneumonia or advanced flu, and they're being actively treated in that regard.

And therefore, our investigators have to make sort of a specific decision as to whether or not the patients are, quote unquote have other medical conditions that prevent them from either going on trial or from being treated so we are all comfortable. And again, in a recent conversation with investigators that meet a standard oncology guideline for concomitant medical issues, how it has built into protocol are more than sufficient to cover the current situation.

Okay. Thank you. That's interesting. So are there any threshold levels of CD8 T cell proliferation that you're targeting or any ratio of CD4 CD8 T cells that you have internally goals for?

I think we would like to see in terms of CD8 T cells as extrapolated from other studies that I've actually looked at the impact of CD8 T cells on the control of cancer. And this is data that mainly comes from adaptive T cell therapies. You think you can get a general pattern that number somewhere in the single digits, somewhere between 5% to 10% could actually demonstrate a peripheral CD8 T response and antigen-specific manner.

There is indeed showing a correlation with efficacy. So ideally, what we'd like to see is somewhere in the single digits, 5% to 10% response rate. We know from preclinical data that our therapy program, even as monotherapy is about a tenfold more potent than our VaxWave program. We know that our website program and the healthy volunteer study demonstrated we see it as a specific CD T cell levels that were on the order of about 0.3%, therefore, and that was after two or three administrations.

Therefore, we feel that two to three administrations for the therapy products should at least demonstrate a 3% peripheral CD8 T cell response. And of course, we will be giving more than two three administrations. And we know that since we do not get back to neutralizing antibodies that our immunogenicity should increase with each administration. Therefore, we believe that we should be able to get into the high single digits for HB-201 alone. And of course, the heterologous should be even a significant increase upon that.

You're right. And so last question, do you know of any correlation between CD8 T cell expansion in peripheral blood and petitioning to the tumor or localizing into the tumor site?

It's a great question. I think again, the majority of the data for this comes from adaptive T cell therapies ratio or your TCR like approaches with initially looked at the all the ratio between peripheral and tumor-infiltrating lymphocytes and the best we could say right now is that clearly there is a correlation between the more you have in the periphery, the more you will have in the infiltrating the tumor.

But certainly, there has not been enough studies to give kind of a standard correlation. All we can say is more correlates with more. But more than that, I don't think anybody can say at this point.

Okay, great. Thank you, Igor.

Suzan van Voorthuziren, Kempen.

Hi yes, this is Suzanne. Good afternoon or good morning. Thanks a lot for the color on the potential coronavirus impact. That's very helpful. I have just one question left on the CMC program. So circling back to that third arm of lower risk patients that was added. And since you have communicated clear goals for the other arms, what do you wish to see? I'm wondering if you have set some benchmarks of what would you like to see in this arm specifically?

Thanks for your question, I think you know, as commented in our 10-K, you know, as we've hired, I think I mentioned earlier, what we are looking for in our positive arm is kind of the intra patient variation. Otherwise, we would like to see is that the additional of the vaccine in that pool significantly increases the CMV specific antibody and CMV specific CD8 T cell responses above the baseline of those patients.

As to what is the right level to correlate to we believe that it is an improvement of two to three fold over the baseline on those patients would be good barometer for success. Okay. That's very clear. Thanks a lot.

There are no more questions at this time. Please continue.

No more questions.

No sir, no more questions.

I think we can close the call. I would like to thank everyone for participating in this call. I hope we made it very clear that we will keep up because of its financial strategy in the past is in a very strong financial position to overcome this current problematic period, and we're doing whatever we can in order to deliver in the middle of this year. And in particular at the end of this year, efficacy data from our CMV and from our first immuno-oncology trials. So thank you very much. Stay tuned, and we'll be in touch on as this crisis continues with our many news. If there are any that are impacting our programs, stay healthy, everyone, and take care. Bye-bye.