Thanks for joining this morning's HOOKIPA call. This teleconference will refer to the accompanying slide deck that can be found on our website at hookipapharma.com on the Investors tab in the Events section. You will need to manually advance the slides, and we will prompt you to do so. We will be discussing forward-looking statements today, so please refer to the safe harbor disclosures on slide two of the presentation. Joining me this morning are Chief Executive Officer, Jörn Aldag, Chief Financial Officer, Reinhard Kandera, Chief Medical Officer and Head of Global Research and Development, Igor Matushansky, and Chief Business Officer, Christine Baker. I'll now turn the call over to Jörn.
Go to slide three. Welcome everyone to this conference call. After some great news last week, we're excited to share initial data from our HB-201 cancer program with you today. HB-201 is a monotherapy using our single vector therapy in advanced metastatic HPV16+ patients, most of whom have progressed on checkpoint inhibitors. The safety, tolerability, and early efficacy data are very encouraging and establish an early proof of concept in this very difficult to treat patient population. Today, we're presenting data from the first two dose levels. The study will continue and explore higher doses and alternating dosing frequencies. Also, we have started dosing patients with our alternating two-vector therapy, results of which will be released in the middle of 2021. In the phase II part of the trial, we will explore the recommended phase II dose in combination with PD-1 inhibitors. Slide four.
We have developed three different approaches to treating patients with our arenavirus technology. Firstly, non-replicating single vectors in prophylactic applications. We presented early proof of concept data using this technology in our phase II CMV data release last week. In brief, we showed that HB-101, which is using our non-replicating technology, is safe, immunogenic for T cells and B cells, and efficacious. Secondly, replicating single vector technology, which in preclinical experiments have proven to be significantly more immunogenic. The data which are the subject of our call today are based on this approach. Thirdly, we recognize that using a replicating two-vector approach with two different arenaviruses encoding the same antigen can give us up to 10-fold higher immune responses compared to the single vector approach. We started dosing HPV16+ cancer patients with this approach.
Data will be available in the middle of 2021 and is not part of today's presentation. Turning now to the replicating single vector rationale and data. Slide five. In preclinical experiments, we have demonstrated that by increasing the dose, we increased tumor control. In other words, there is a direct relationship between increasing the dose to increasing T cell responses to enhancing tumor control. Slide six. The data we're presenting today are data from the replicating single vector HB-201 monotherapy in HPV 16+ metastatic patients who have failed on average three prior cycles of treatment, and most of whom have progressed on checkpoint inhibitors. Slide seven. HB-201 as said is a replicating single vector encoding E6, E7, highly relevant targets in HPV16+ cancers. Our approach is to establish a fast path to a third line approval.
With our HB-201/HB-202 dual vector approach, our intent is to develop a best-in-class treatment with potential for application in first line metastatic HPV16+ cancers. With this, I will turn over to Igor Matushansky, our Global Head of Research and Development.
Thank you, Jörn. On slide eight, I will remind all of us about our ongoing phase I, II program in HPV16+ metastatic advanced cancers. The program is a phase I, II design. Group one in the phase I focuses on HPV16+ head and neck squamous cell carcinoma patients in the advanced metastatic setting who have progressed on platinum and checkpoint inhibitors. We are delivering our therapy with intravenous dosing initially every three weeks. The first patient on this group one was accrued on December 27th of 2019, almost one year ago. Group two is treating advanced metastatic HPV16+ cancers of any tissue of origin, including head and neck squamous cell carcinoma, cervical, anal, penile, vaginal, vulvar.
The only difference between the way we are dosing group two versus group one is that in group two, the patients must have at least one tumor lesion that is amenable for intratumoral delivery. Subsequent administrations are intravenous. We are not trying to compare intravenous to intratumoral administrations. We are simply trying to develop both approaches as options depending for how the patients present. Group three and group four, not shown here, are for our two-vector alternating therapy, which Jörn just spoke about, which actually started dosing its first patients a few weeks ago and will not be the subject of this presentation. The overall point of the phase I/II program is, of course, part of the phase I is to determine the recommended phase II dose. Secondary endpoints include efficacy measured in multiple parameters as well as additional safety and tolerability information's. Next slide.
Today, we're happy to update you on the 22 patients that have been accrued to date in the ongoing HB-201 monotherapy. This is, of course, the heavily pre-treated patient population, all of them having progressed on standard of care and at least who had an head and neck squamous cell carcinoma that by definition includes platinum and a checkpoint inhibitor. Of the 22 patients that we have enrolled to date, seven patients are not evaluable for efficacy. The reason they're not evaluable for efficacy is because five of the seven patients have been recently accrued on trial and have not been on trial long enough to have a first scan performed. One additional patient withdrew consent after receiving the first dose, but before a scan could be obtained, and another patient was taken off trial for clinical progression prior to the first scan.
While five are still ongoing, they're not yet available, and that leaves us with 15 patients evaluable with the first scan for efficacy. Of these 15 patients, 11 patients are your classical head and neck squamous cell carcinoma patients. Four are considered other, including two cervical, one anal, and one vaginal. Next slide. Turning to safety first, overall, our immunotherapy HB-201 has a very favorable safety profile. Many of the patients reported AEs, but only nine out of 22 patients had treatment-related AEs, and the AEs were mostly grade one and grade two. We saw some fatigue as well as some viremia-like signs and symptoms, including low-grade fevers and chills. For the intratumoral administrations, we did see some local site injection swelling as well as some pruritus at the skin. Overall, we only had one grade three fatigue AE in a VasCell cohort patient.
This was a patient that was wheelchair-bound at baseline and perhaps was not unexpected. Otherwise, we are still continuing to dose escalate. We have had no DLTs to date. Overall, we believe we have a fairly favorable tolerability profile moving forward. Next slide. Turning to efficacy, we believe that HB-201 monotherapy is demonstrating promising efficacy, especially in advanced third line and more HPV16+ patients. Specifically focusing on the head and neck squamous cell carcinoma, the 11 patients, all of which we've progressed on a checkpoint inhibitor, we have observed one patient with an unconfirmed complete response, one patient with unconfirmed partial response who is still ongoing, six patients with stable disease, for an unconfirmed response rate of 18% and a disease control rate of 73%.
A note on the vocabulary, the term unconfirmed has to do with RECIST or specific radiological criteria that requires the scan to be repeated at least four weeks later in order to confirm what a previous scan has shown. While these are the response rates, they are by definition of the radiological criteria RECIST used in this trial are have to be classified as unconfirmed until they can be subsequently confirmed with additional scans. As the patients continue on our trial, those scans will be obtained. Again, one patient with unconfirmed complete response, one patient with unconfirmed partial response, six patients with stable disease, an unconfirmed response rate of 18%, disease control rate of 73%. Perhaps to put those numbers into context, it is perhaps important to take a look at what was the data for a checkpoint inhibitor in an earlier or second-line setting.
As we know, checkpoint inhibitors were approved with a 13% overall response rate and a 48% disease control rate in the second line setting. Of course, we are in the third line and more advanced setting, and we would therefore believe the numbers we are seeing in this more advanced setting is even more telling of the potential efficacy of this therapy. If you then look overall at the 15 evaluable patients, that include the four additional non-head and neck patients, the numbers are fairly similar, 13% for unconfirmed response rate and 67% for disease control rate. Next slide. Looking a little bit more carefully at the data and looking specifically at the 22 patients that we are discussing, what you're seeing here is a swimmer's plot that shows how long patients have stayed on therapy as well as their best response indicated.
You see a couple of things. The data that I showed you before is now shown in terms of durability. Second of all, you see perhaps most obviously that the pink colors are longer than the blue colors, and the pink represents dose level two, while the blue represents dose level one. You begin to see the trend for a dose response curve, something that is very important, especially as we talk about dose escalating. Not only dose escalating, but also making dose-dense schedules, so we attempt to deliver more therapy but in a more tighter schedule. Next slide. Focusing in a little bit more on the 15 evaluable patients. Again, the data becomes to look a little more cleaner. Again, a clear improvement in the time on therapy for the pink colored patients. Again, dose level two as compared to dose level one.
Also as important, you begin to actually see the spider curve plots. We have now plotted each of the individual patients on the left, on the right, and what you're clearly seeing are, yes, we have five progressors. Those are the patients that are kind of going straight up from baseline. You have a fair amount of patients that are stable disease. Those are the patients that are sort of in between the two dashed gray lines at + 20% and -30%, respectively. As important, we begin to see some responders. Those are the patients who have downward trending lines. You see, we'll be talking about some of these patients shortly. Next slide. Focusing in specifically now on the 11 head and neck squamous cell carcinoma patients. You see again, a very nice dose response curve. The pinks definitively now show longer responses than the blues.
On the right, you see a very clear spider curve plot for this. You again see now three progressors. You see two clear responders. Now you can clearly see there's a third patient at the first scan that only has one scan, but they just had it. They're still ongoing, showing a downward trend as well. That patient, we are optimistic, will also cross the -30% dashed line, making that person a partial response with the next scan. You can see we have several patients that have clearly crossed that threshold, and we'll be talking about them shortly. Overall, in these advanced, pre-treated patient populations, 18% response rate, 73% disease control. Next slide. Focusing a little bit more on the durability of the response. We took a look at the ongoing median progression-free survival.
Technically, half of our patients are still on trial, so the median technically is not yet reached because patients are still ongoing. As it is today, in terms of a snapshot analysis, we know that the median PFS is 72 days. Again, comparing that number to a previous benchmark data set from checkpoint inhibitors, nivolumab, in an earlier line of setting, we saw there was 60 days median progression-free survival for nivo in the second line, where we are showing 72 days and ongoing in patients who failed nivo in the more advanced line. Again, further adding support to the fact that we are indeed seeing promising efficacy data all around. Next slide. As the old saying goes, pictures are sometimes worth thousands of words. Let's take a look at a couple of our patients in order to better understand what we're looking at.
This patient, profile number one, is a 68-year-old male with head and neck squamous cell carcinoma who has a complete response. The patient is heavily pre-treated, having actually received multiple chemotherapy, including a checkpoint inhibitor, twice on two separate occasions during their long treatment history, and who subsequently has progressed. You can see at the CT scans at the bottom, and allow me to orient you. What you're looking at basically is a cross-section through the chest right above the heart, and that's a mediastinal lymph node being circled there. You can see from pre-baseline to baseline, that nodule, that metastatic lymph node, gets larger. When they come to us at baseline, we start treating with our monotherapy HB-201. You can see immediately that tumor begins to shrink. Following the first treatments at the first scan, the tumor is 25% smaller as compared to baseline.
We need 30% shrinkage to qualify for PR. Even though it appears smaller radiologically, it is still technically considered as stable disease. Subsequent treatments, you can see the tumor shrinks even further to about a 50% overall reduction, now breaking the 30% partial response criteria and is therefore classified as a partial response. Subsequently, a third scan is performed, you can see the tumor almost completely goes away, and technically speaking, this is a lymph node that we are discussing. When lymph nodes become less than 10 mm or less than their normal allowable size, they are considered complete response for that lesion. This patient is a complete response. In order to have qualified this patient for confirmed versus an unconfirmed, we would have needed to have repeated this current third scan at a later time point.
Unfortunately, this particular patient passes away at this point of time from bleeding into the lungs, likely resulting from the fact that this particular lesion was eroding into the pulmonary vein. When the lesion receded, unfortunately the tumor went away, but opening up the erosion in the heart. In the pulmonary vessel resulting in bleeding. While clearly demonstrating the efficacy of this treatment, it clearly also highlights the fact that the rapid response to this did not allow us to perform a subsequent scan. Next slide. This patient here is another patient with facial follicular lymphoma, who similarly presented with mediastinal, again, lymph nodes. You can see them in the high-resolution images, and you can see clearly with treatment from baseline to first scan, the tumor begins to shrink. Again, it shrinks at about 25%, just missing the classification for a partial response.
With additional therapies, you can clearly see it almost disappears completely. Clearly now showing at about 40% overall response rates are clearly a very nice partial response, and this patient is still ongoing. Next slide. This is a patient seen at the University of Chicago who is a 69-year-old male with head and neck squamous cell, this time with metastases to the neck. You could see at baseline, this patient presents with a large mass in his neck that he goes on therapy, and you can actually see the patient progresses on therapy and that the tumor actually gets larger.
When you talk about immunotherapies, there's a commonly described pseudo progression or false progression, where due to the immunotherapy treatment itself, a lot of immune cells will rush into the tumor and engorge it, resulting in a radiological appearance of progression, even though this is clearly a beneficial response. To allow for the immunotherapy to work, patients are allowed to stay on therapy following progression in order to see if the tumor will respond and radiologically regress despite initially progressing. That's what happened here. You'll basically see that after the first scan, although radiologically progressing, the patient stays on therapy, and you clearly see with the second scan the tumor is indeed resolving both visually as well as radiologically. The patient stays on therapy, and this classic kind of pseudo progression followed by response is a very classic immunotherapy effect. Next slide.
Our last case profile here today has to do with a 68-year-old male who also had head and neck squamous cell carcinoma. You can see in these photographs, there are very large metastases also to his neck. This patient, again, heavily pretreated, also having received checkpoint inhibitors twice before, their treatment history had progressed both times on a checkpoint inhibitor, subsequently went on our trial. You can see when he started our trial from baseline to the first scan, the patient was clinically progressing. You can see that quite clearly by the fact that the tumor began to break through the skin more than it did so before. The investigator images the patient. As you can see by the imaging, the tumor itself is relatively radiologically stable.
Because the investigator suspects clinical progression based on this visual presentation, pembrolizumab is added back yet for a third time, even though it has failed twice before. This time, when he adds pembrolizumab on top of our therapy, you can clearly see what happens. There is immediate clinical improvement. This photograph was taken three weeks later, and we just received the radiological confirmation that actually shows that the previous large mass in that neck has now actually deconvoluted into two independent, much smaller masses. That is exactly what you're seeing in that red line that begins to slope down. A very nice response in terms of showing synergy with our drug in a situation where pembrolizumab independently failed twice before. Next slide. All right, so putting things in some perspective.
The initial phase I cohorts from our ongoing HB-201 monotherapy in the advanced HPV16+ cancer patients suggest a very favorable tolerability profile. We show promising evidence of efficacy in heavily pretreated patients with HPV16+ cancers. Again, 18% unconfirmed response rates, 73% disease control rates in the valuable head and neck squamous cell carcinoma patients. Many of those patients are ongoing and will have their scans repeated in four to six weeks. We specifically showed you evidence of one patient with unconfirmed complete response. We've shown you one patient with unconfirmed partial response, a case of pseudo progression and response, and a case of synergy in combination with a checkpoint inhibitor. In addition, of course, six patients with stable disease. The median progression-free survival is currently 72 days and ongoing.
To the degree that benchmarks could be done in the third line, in which there are no independent studies, but our ability to benchmark to second-line nivo shows that these numbers are quite impressive in the advanced setting when you think about what checkpoint inhibitors are showing in earlier lines in comparison. We continue to enroll patients on this trial. We continue to not only dose expand by doing more tighter dose schedules, not only dosing every three weeks, but we are beginning to dose every two weeks and even every one week to see if we can actually get responses sooner rather than later. We have additionally spoken about how we have begun doing our two-vector replicating therapy of HB-201 and HB-202. Two patients were treated on this several weeks ago, and we are eagerly anticipating the efficacy data from that shortly.
Data will be updated regarding that program in approximately mid-2021. As we have told you, the phase II is coming in 2021 as well for the monotherapy as we identify the recommended phase II dose and schedules. Of course, as part of that, we plan on combining with a checkpoint inhibitor. In short, very excited by our preliminary data in terms of both safety and efficacy to date. Now I may hand this back over to Jörn for some additional thoughts. Jörn?
Last slide, 21. Thank you, Igor. You can see how excited we are. We showed last week the results from the non-replicating single vector, which is a potent but least potent technology that we are using in prophylactic vaccinations. That data showed a strong safety profile, immunogenicity, both with regard to antibodies and T cells, and efficacy. Today, we have shared with you the replicating single vector technology results. Again, a strong safety profile, immunogenicity, and very promising and encouraging signs of efficacy in this heavily pre-treated and difficult to treat population. The replicating two-vector system has started. Initial patients have been dosed, and we are even more excited to see the results from this, which visually you can see could potentially be driving still significantly higher T cell responses and with that potency for the benefit of our patients.
We're looking forward to those results that will be coming from HB-202, HB-201 combinations. We'll be looking at confirming and strengthening the results that we have discussed today. Thank you very much. Let me open the session now for Q&A.
Thank you. Your first question comes from Brian Abrahams from SVB Leerink. Please go ahead.
Hello, can you hear me?
Yes.
Yes.
How are you?
Hi. A couple of questions on the efficacy. Congrats on the data. I guess from the case studies, it seems that the CR won't confirm because the patient died from a hemorrhage. The PR, the confirmation is still pending, is that correct?
Yes. Patient is still on study, doing really well, and we expect repeated scans probably in mid-January.
Okay. Is that something that we'll be updated with when it happens?
Will there be a PR update?
No, we'll update-
Yeah. Please, Jörn.
We'll update on further data in the first half of next year.
Okay. If I understand correctly, there were head and neck patients that could have gotten systemic therapy plus or minus intratumoral injections. It doesn't appear, at least from what I could see on the slides and the presentation, that you saw as much efficacy than those that got intratumoral injection. Is that correct?
No, that is absolutely correct. We went into this program exploring both intravenous and the intratumoral to actually determine whether or not there was any benefit doing intratumoral at all. Some of our preclinical data did suggest that intratumoral was able to both control the tumor that was injected sooner rather than seeing a systemic effect. We have not seen that in the clinic to date. All our responses to date have been in the intravenous group. We continue to explore.
Okay
both to see if higher doses will result in this. The preliminary data presented to date, you are correct, all of our responses have been in the intravenous groups, perhaps supporting our hypothesis that we are a systemic therapy.
Okay. You are still planning to keep testing intratumoral as part of the program?
Yeah, we are. This is still a phase I early study, still in the research phase. We will continue to do this. I think, if as we get towards the end of dose escalation, we do not see signs of efficacy of intratumoral over the intravenous, we will probably enter the intravenous only. Sorry, the phase II only with intravenous. Time will tell on that.
Okay. You gave us some benchmarks for the patients that responded, and appreciate it. If we wanted to put the stable disease into perspective, what would be the typical progression of these patients clinically? Is it chronically indolent, or is it an aggressive disease?
These patients are advanced metastatic patients with advanced disease. If you look at the, I can only refer you to the checkpoint inhibitor phase II data, which included a significant portion of those patients who were indeed HPV positive. If you actually broke out their progression-free survival data set and other indicators, they were not significantly different than non-HPV positive. This is not an indolent disease by far. It is seen clearly by some of the other examples of our patients that progress rather rapidly.
Right. Okay. Well, thanks for that, and congrats again on the data.
Sorry, that was Andrew Barrons from SVB. We now have Brian Abrahams from RBC. Please go ahead.
Hey, guys. Thanks so much for taking my questions. Congratulations on the data. I guess first one from me, can you speak to any correlation between T cells, antigen-specific T cells, and response in these patients? Is that something that you looked at? Have you also looked at any changes in the tumor microenvironment in terms of cytokine signals, T cell penetration, or inflammatory indicators?
We are collecting both PBMCs at various time points during this trial as well as this protocol has multiple de-escalation cohorts and options to obtain paired biopsies. I will say that all of those efforts are in progress. We are, at this point, collecting both blood samples and tissue for the analysis itself, but we have not performed the analysis, and so I have no specific information to state regarding that. Other than the fact that we have samples and tissue to do that analysis, and we are simply waiting for it to batch it.
Got it.
We'll be hopefully getting that data early next year and updating it in mid-2021 at our next update.
Got it. Great. We'll look forward to that. I'm wondering, did you see any predictors of either response or disease control, I guess, beyond IV administration or dose, any patient-level characteristics that you noted?
The short answer is no. We have not observed any additional things that predict why some patients are potentially responding versus others. You hit on a couple, including are we seeing CD8 T cells in the blood? Are we seeing CD8 T cells in the tumor screen? Those, of course, respond to responses. There are additional, perhaps, how "good" is the viremic take? Is the viremic take in some patients better than others? This is an active replicating virus therapy. You could clearly imagine that if it doesn't, for one reason or other, replicate as well in some patients versus others, although I have no reason to believe that would be the case. That might explain some of this, and we are looking at all of these parameters.
No, as I've shown you in the case studies, we've had patients who were actively progressing on therapy that responded very nicely. I have no answer at this point, other than to say we are collecting that kind of data and hoping to better identify to predict which patients might predict. Of course, as seen by the dose response curve, I think, as we continue to both dose escalate as well as do tighter dose schedules, we will simply be getting many more responders.
Great, then one last one from me. As we look towards the next data set, I know it's early days in enrollment, but do you have any broad sense as to how much data in terms of number of patients and follow-up we might see from the HB-201/HB-202 combination mid-next year? When we could look for the next cut of this HB-201 data with the tighter dosing schedule and some of the higher doses. Thanks again.
Yeah. No, it's okay. Again, I would agree with Jörn's earlier guidance. We're looking probably at mid-HB-201 as an update. I would simply say, we are accruing aggressively and basically this year, despite the COVID situation, we have put on 24 patients on this trial. It's a 3+3 cohort design. The HB-202/HB-201 combination is using the exact same schedule, and I would assume the same kind of accrual pace as we had for the monotherapy. With that, I think we'll probably come up with a reasonable number of patients to expect come middle of next year.
Great. Thanks again.
Your next question comes from Alex Hanahan from Bank of America. Please go ahead.
Hey, guys. Thanks for taking our questions and congrats on the rapid succession of clinical data here. Definitely looks like you're keeping busy. My first question is, in patients who received a PD-1 previously, could you give us a sense of the median time between discontinuation of PD-1 therapy and the first injection of HB-201? Was this greater than four weeks? I guess, from the data so far, do you see any particular tumor types as being more amenable to HB-201? Obviously acknowledging it's still early days, particularly for the non-head and neck patients, or did you have any preferences to specific tumors heading into the study? Then I have a follow-up.
Sorry, I didn't quite catch that second question. Let me answer your first one first, and then you can repeat your second one for me. If you look at the slides on slide 16, 17, 18, and 19, at least for the four cases, the time from the previous checkpoint inhibitor is listed. On slide 16, you can actually see it's 84 days since last dose. Under the prior treatment category for patient 17, it's 21 days. For patient on slide 18, it's 42 days. For patient number 19, I have a patient on slide 19, it's 38 days. I've shown you four of the 11 patients. I would say we've seen quite a spread, from the minimal washout of around 21 days to anywhere over a year.
I think these four patients are fairly good indicators. Perhaps to your question, the underlying point to your question is, do we know whether or not there's a lingering checkpoint inhibitor effect? If it's a better way to ask that question, do we know why these patients ever responded to a checkpoint inhibitor in the first place? We definitely know, especially for patients who've gone and who have tried this twice before, that we have several patients who are literally primary progressors on checkpoint inhibitors that have now responded to our therapy.
Okay, perfect. just to repeat the second question.
Yes, please.
Just to try to get a sense of what you're thinking about in terms of specific tumor types for maybe? The phase II-
Yeah.
... obviously it's early days.
Yes. No. I think at this point, we are encouraged by that the majority of our responders have been in head and neck squamous cell carcinoma patients. I think that makes it, I would say, an obvious path forward. We designed this study in such a way in order to really prioritize having group one focus on head and neck. We are, I think, encouraged by the fact that all of our responders have been there for the moment. I think head and neck remains a high priority and a high target area for us. We are, of course, exploring other indications. We haven't had as many patients with the others. We only had, I think, one anal patient. We've had only two cervicals and one vaginal, although we have not seen responses there as of yet.
I think to date they are early, so I think part of the phase I program is indeed to first clinically identify which are the categories that also might be clinically beneficial, in addition to head and neck. From a biological perspective, there should be really no reason why head and neck should respond differently than other HPV-positive cancer subtypes, but I think we don't have enough information to really answer which of those categories that would be. We are accruing patients. We're open to accrue all HPV 16+ cancer patients, and we will look for additional signs of efficacy in other indications.
Okay, great. That makes sense. My last question. It's definitely encouraging to see the tumor scans, but I was wondering, have you seen any distal effects in patients with visible metastatic lesions, or were the tumor reductions primarily in the target lesion? I'm wondering if you'd expect this to differ between the intratumoral and IV routes of administration.
I'm sorry, I didn't catch the first part of the question. Come up again. Is it difference between what and what?
I'm just wondering if you're seeing distal effects on the metastatic lesions, or if the effect is primary on the target lesion?
Oh, I see.
This is expected to differ between the routes of administration.
Right. For the intravenous routes, we've seen effects on the target lesions, and so those are, of course, not intratumorally injected. For the intratumoral patients, we have not observed any decrease on either the tumor being injected or non-injected lesions. We have observed no responses to either the intratumoral injection to the tumor injected or otherwise. We are specifically going to be opening up some biopsy-driven translational programs next year, where we'll be injecting a small group of patients with tumors and doing biopsies of both injected and non-injected lesions to find out if there is indeed evidence for a abscopal-like effect. We have not seen responses to date in either injected or uninjected lesions following intratumoral administration.
Okay, thanks. Congrats again on the data.
Your next question comes from Asthika Goonewardene from Truist Securities. Please go ahead.
Hi. Good morning, guys, and thanks for taking my questions and offer my congrats as well to you, for this very neat update. I was wondering with patient 12 and 14, the ones that, Igor, that you mentioned maybe had pseudo progression. I'm sorry if I missed this. Did you obtain biopsies to verify T-cell infiltration?
We have not obtained biopsies from this patient. We have done paired biopsies in multiple other patients. We have not, however, performed the histological analysis. We are still batching those patients. Hopefully, we will have that data in multiple patients next year.
Got it. Okay. I'm going to ask the prior checkpoint question in a different way. Of those three to four profiles that had prior checkpoints in, I think, 21 days ago, 42 days ago, 38 days ago, Igor, what's your thoughts about the residual receptor occupancy of PD-1 having a synergistic effect with HB-201? Also related, did you have any other patients that had checkpoints in the last six months that didn't have an SD?
Yes. We've had patients both who were progressing on a checkpoint inhibitor within 21 days and went on our therapy and responded. We had those patients. That's an example of the patient shown on slide 17. This patient was on a checkpoint inhibitor and had lesions that were progressing on the checkpoint inhibitor, and then started our therapy and is beginning to show response. We have also had patients that have been off a checkpoint inhibitor for a long time. They came on our therapy, and either stabilized or responded. We've also had patients who were on the checkpoint inhibitor, they recently started our therapy and progressed. In short, we don't have any direct data at this point from the clinic that suggests that there is a relationship to the checkpoint inhibitor and the response.
What I can tell you is that the one, perhaps the strongest evidence we have, for synergy, comes from the patient shown on slide 19, where the administration of our drug first, followed by the reintroduction of a checkpoint inhibitor in a patient who failed, now all of a sudden resulted in massive improvement. This, of course, I would say, underlies the mechanism of disease. If you can imagine our therapy bringing massive antigen specific CD8 T-cells and then a checkpoint inhibitor suddenly coming off and taking quote unquote, a fuse, the lace, and the foot off the brakes, letting all those CD8 T-cells do their job. This is what you would expect. The real test would be is not whether the checkpoint inhibitor was on first, but perhaps whether our therapy comes first, followed by a checkpoint inhibitor.
That's just me putting everything together from the small amount of clinical data I have and some of our early preclinical work.
Okay. That's all very encouraging. Thanks for taking my questions, guys.
Your next question comes from Roy Buchanan from JMP Securities. Please go ahead.
Hi. Great, thanks for taking the questions. Just a couple quick ones. Back to the intratumoral injections. It looked, from a non-expert view, patients three and four looked like they might've been suitable for intratumoral injection. Is there some reason they didn't get that approach, or was that a decision made after you saw the initial clinical data? I have a follow-up.
No. For head and neck cancer patients, it is up to the investigators to simply make the decision whether or not they want to do intratumoral or intravenous. You are right. Looking at some patients who have obvious head and neck masses, they can make a decision. They are amenable to it. It's up to the investigator, the other thing is, just keep in mind, to do an intratumoral injection usually requires interventional radiology guidance. For that, some sites are, let's just say, better equipped than others to do it. It's not only investigators decision as for head and neck, but also whether the site can be set up to do it.
Okay. That's helpful. Thanks. For the phase II part of the trial you guys are going to start next year with and without the checkpoint inhibitor. Are those groups going to enroll in parallel at the same sites? I guess, are we going to get a stratified look between the two groups with and without checkpoint inhibitor?
The answer is yes, but there's no concern about whether they're at the same site, but they're different lines of treatment, right? To enroll concurrently with a checkpoint inhibitor would be now these days, first-line patients. Patients who progressed on a checkpoint inhibitor would be second-line patients for the monotherapy. The two groups can enroll at the same time because they don't actually compete with each other.
Got it. Okay. Thank you.
Thank you. There are no further questions at the moment, but once again, it's star and one if you would like to ask a question. We still receive no further questions. Jörn, I'd like to hand the call back to you.
Yes. Hi, this is Jörn again. Thanks a lot for participating in this call. We're hugely excited and are looking forward to what's coming next. The first quarter, second quarter of 2022 will be great moments again to update and see the progression of this great data. Thanks a lot. Bye-bye.