Thanks for joining this morning to keep up call. This teleconference will refer that can be found on our website at hokeepapharma.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 2 of the presentation. Joining me this morning are Chief Executive Officer, Yaron Aldag Chief Financial Officer, Reinhardt Candera Chief Medical Officer and Head of Global Research And Development, Igor Matashansky and Chief Business Officer, Christine Baker.
I'll now turn the call over to Yaron.
Welcome everyone to this conference call. After some great news last week, we're excited to share initial data from our HB-two zero one cancer program with you today. HV-two zero one is a monotherapy using our single vector therapy in advanced metastatic human papilloma 16 positive 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 2 vector therapy, results of which will be released in the middle of 2021. In the phase 2 part of the trial, we will explore the recommended phase 2 dose in combination with PD-one inhibitors. Slide 4. We have developed 3 different approaches to treating patients with our Arena virus technology.
Firstly, non replicating single vectors in prophylactic applications. We presented early proof of concept data using this technology in our phase, 2 CMV data released last week. In brief, we showed that HB-one hundred and one, which is using our non replicating technology as 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 2 vector approach with 2 different arena viruses encoding the same antigen, can give us up 16 positive 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 5, 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 6.
The data we're presenting today our data from the replicating single vector HB-two zero one monotherapy in HBV16 positive metastatic patients who have failed on average 3 prior cycles of treatments, and most of whom have progressed on checkpoint inhibitors. Slide 7. HB-two zero one, as said, is a replicating single vector encoding E-sixty seven, highly relevant targets in HBV16 positive cancers. Our approach is to establish a fast path to a 3rd line approval. With our HP201202 dual vector approach, our intent is to develop a best in class treatment with potential for application in 1st line metastatic HBV16 positive cancers.
With this, I will turn over to Igor, Matuszanski, our Global Head of Research And Development.
Thank you, Jorne. On Slide 8, I will remind all of us about our ongoing Phase III program in HBV16 positive metastatic advanced cancers. The program is a phase 1two design. Group 1 in the phase 1 focuses on HBV16 positive head and neck squamous cell carcinoma patients in the advanced metastatic setting who have progressed on platinum and checkpoint inhibitors. We are delivering our The first patient on this group 1 was accrued on December 27 2019, almost 1 year ago.
Group 2 is treating advanced metastatic HBV16 positive cancers of any tissue of origin, including had an ex squamous cell carcinoma cervical anal, penile, vaginal vaginal vulvar. And the only difference between the way we are dosing will 2 versus group 1, is that in group 2, they must, the patients must have at least 1 tumor lesion that is amenable for intratumoral delivery. Subsequent administrations are intravenous. We are not trying to compare intravenous to intramural administrations We are simply trying to develop both approaches as options depending for how the patients present. Group 3 and group 4 not shown here are for our 2 vector alternating therapy, which Johan just spoke about, which actually started dosing its first patients a few weeks ago, and will not be the subject of this presentation.
Two programs, of course, part of the phase 1 is to determine the recommended phase 2 dose. Secondary endpoints include efficacy measured in multiple parameters as well as additional safety and tolerability informations. Next slide. Today, we're happy to update you on the that have been approved to date in the ongoing HB-two zero one monotherapy. This is, of course, the heavily pretreated patient population, all of them having progressed on standard of care, and at least we had an ex squamous cell carcinoma that, by definition, includes platinum and the checkpoint inhibitor.
Of the 22 patients that we have enrolled to date, 7 patients are not evaluable for efficacy. The reason they're not evaluable for efficacy is because 5 of the 7 patients have been recently accrued on trial and have not been on trial long enough to have a first scan performed. 1 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. So while 5 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, had an explain the cell carcinoma patients, 4 are considered other, including 2 cervical, 1 anal and 1 vaginal.
Next slide. So turning to safety first, overall, the our immunotherapy 2.0 on has a very favorable safety profile. Many of the patients reported AEs, but only 9 out of 22 patients had treatment related AEs. And the AEs were mostly grade 1 and grade 2. 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 great 3 fatigue ae in a back cell cohort patients, and this was a patient that was wheelchair bound at baseline and perhaps is not unexpected. Otherwise, we are still continuing to dose F escalate, we have had non No DLTs to date. And overall, we believe we have a fairly favorable tolerability profile. Moving forward. Next slide.
Turning to efficacy. We believe that HB-two zero one monotherapy is demonstrating promising efficacy, especially in advanced third line and more HBV16 positive patients. Specifically focusing on the head and neck play myself carcinoma 11 patients, all of which we progressed on a checkpoint inhibitor. We have observed one patient with an unconfirmed complete response, one patient with unconfirmed partial response is still ongoing 6 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 resist or specific radiological criteria that requires the scan to be repeated at least 4 weeks later in order to confirm what a previous scan has shown.
So while these are the response rates there, by definition of the radiologic criteria resist used in this trial are have to be classified as unconfirmed until they can be subsequently confirmed with additional scans. And as the patients continue on our trial, those scans will be obtained. So again, one patient will unconfirm complete response, one patient will unconfirm partial response, 6 patients with stable disease and unconfirmed response rate of 18%. Use control rate of 73% and perhaps to put those numbers into context, it is perhaps important to take a look at what was the data for, I checkpoint inhibitors were approved, with a 13% overall sponsor rate and a 48% disease control rate in the 2nd line setting. Now of course, we are in the 3rd line and more advanced setting, And I believe 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 4 additional non head and neck patients The numbers are fairly similar, 13% for unconfirmed response rate and 67 were 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 splice that shows how long patients have stayed on therapy as well as their the data that I showed you before is now shown in terms of durability. And second of all, you see perhaps most obviously that the pink colors are longer than the blue colors and the pink represents dose level 2, while the blue represents dose level 1. And so you begin to see the trend for a dose response curve, something that is very important, especially as we talk about dose escalating, but not only dose escalating, but also, making dose dense schedules, so we attempt to deliver more therapy but in a more tighter Focusing in a little bit more on the 15 evaluable patients, you, 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 2 is compared to dose level 1, but 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 5 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 patients that are sort of in between the 2 dashed gray lines of plus 20 and minus 30% respectively.
And as important, you begin to see some responders. Those are the patients who have downward trending lines. You see and we will be talking about some of these spaces shortly. Focusing in specifically now on the 11 head and neck, splay miscell carcinoma patients, You see, again, a very nice dose response curve, the blue, the pings definitively show longer responses than the blues. And on the right, you see a very clear Spider Curve plot for this.
You again see now 3 progressors. You see 2 clear responders. And 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. But showing a downward trend as well.
That patient, we are optimistic will also cost the negative 30 dash line, making that person a partial bonds with the next scan. And you can see we have several patients in your clinic cost, that threshold, we'll be talking about them shortly. But overall, in these advanced pre accretive patient population, 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 and the technically, many half of our patients are still on trial So the median technically is not yet reached because patients are still ongoing.
But 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, being followed up in an earlier line of setting, We saw that over 60 days median progression free survival for nivo in the second line where we are showing 72 days ongoing in patients who failed nivo in the more advanced line. Again, further adding, support to the fact that we are indeed seeing a promising efficacy data all around. Next slide. And so as the old saying goes, pictures.
So something's worth thousands of words. Let's take a look at a couple of, of our patients in order to better understand, what they're looking at. This patient, profile number 1 is a sixty eight year old male that had an ex squamous cell carcinoma who has a complete response. The patient is heavily pretreated, having actually received multiple chemotherapy, including a checkpoint inhibitor twice or 2 separate occasions during their long treatment history and was subsequently as progressed. And you could 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 the mediastinal lymph node being circled there, right, And you can see from 3 baseline to baseline that nodule that metastatic lymph node gets larger. When they come to us at baseline, we start treating with our monotherapy 201, you could see immediately that tumor begins to showing following the first, treatments at the first scan tumor is 25% smallest compared to baseline. We need 30% shortage to qualify for PR even though it appears small or radiologically, they're still technically considered as stable disease. Subsequent treatments, you could see the tumor insurance even further to about a 50% overall reduction now breaking the 30%. We a partial response criteria and is therefore classified as a partial response.
Subsequently a third scan is performed and could see the tumor almost completely goes away. And technically speaking, this is a lymph node that we are discussing and when lymph nodes become less than 10 millimeters or less than their normal allowable size. They are considered complete response for that lesion. So this patient is a complete response. And in order to have qualified this patient, for complete versus or confirmed versus unconfirmed, we would have needed to have repeated this current 3rd 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. And when the lesion receded unfortunately, the tumor went away, but opening up the erosion in the, hard soil. So in the pulmonary vessel, resulting in bleeding. So while clearly demonstrating of the efficacy of this treatment, it clearly also highlights the fact that the rapid response to this, does not allow us to perform a subsequent Next slide. This patient here is another patient patients are more or so oncatter.
And you similarly presented that media's final, again, lymph nodes. You can see them kind of in the high resolution images and you can see clearly with treatment from baseline to first scan of tumor begins to shrink. Again, just the insurance say about 25% just missing the classification for a partial response, but with additional therapies, you can clearly see it almost disappears completely, clearly now showing that about 40% overall response rates are clearly a very nice partial response, and this patient is still ongoing. Next slide. This is a patient at the University of cargo, who is sixty nine year old male, who had an ex squamous cell, this time with metastases to the neck.
You could see a baseline, this patient presents with a large mass in his neck that we should go on therapy. And you can actually see the patient progress on therapy and that the tumor actually gets larger. And so when you talk about immunotherapies, there's a commonly described, a pseudo progression or false progression where due the immunotherapy treatment itself, a lot of immune cells will rush into the tumor and in gorgia, resulting in already a lot call appearance of progression, even though this is clearly a beneficial response. And so 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 radologically regress despite initially progressing. And that's what happened here.
And you will basically see that after the first scan, although radiologically progressing the patient stays on therapy and clearly see with the second scan of the tumor is indeed resolving, both visually as well as radiologically, and how the patient stays on therapy. And this classic kind of pseudo progression followed by a response to the very classic immunotherapy effect. Next slide. Finally, our last 12 case book filed here today, has to do with a sixty eight year old male, also had an ex squamous cell carcinoma, you can see in these photographs with a very large metastases also to his neck. This patient, again, heavily pretreated also having received point inhibitors twice before and their treatment is still in progress both times on a checkpoint inhibitor, is subsequent we went on our trial and you could see when you started a trial from baseline to the first scan, the patient was clinically progressing to see that quite clearly by the fact that the tumors began to break through the skin, more than it did so before.
The investigator images the patients, the, as you can see by the imaging, the tumor itself is relatively radiologically stable, but because the investigators suspects clinical progression based on these visual presentation. Pembrolizumab is added back yet for a third time, even though, it had 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 discounted this protocol should take in 3 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 2 independent much smaller Massus. And that is exactly what you're seeing in that red line that begins to slope down.
So a very nice response in terms of showing synergy with our drug in a situation on pembrolizumab independently failed twice. Before. Next slide. All right. So putting things in some perspective, the initial phase 1 cohorts from our ongoing 201 monotherapy in the advanced HPV-sixteen positive cancer patients suggested very favorable tolerability profile.
We show promising evidence of efficacy in heavily retreated patient of HBV16 positive cancers. Again, 18% unconfirmed response rates 73% disease control rate in the evaluable head and neck squamous cell carcinoma patients and many of those patients are ongoing and will have their stance repeated in 4 to 6 weeks. We specifically showed you evidence of one patient will confirm complete response. We've shown you one patient with unconfirmed partial response a case of pseudo tumor progression and response and a case of synergy in combination with a checkpoint inhibitor. In addition, of course, 6 patients stable disease.
The median progression of free survival is currently 72 days and ongoing. And again, to the degree that benchmarks could be done in the 3rd line in which there are no independent studies, but our ability to benchmark to 2nd 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. And so we continue to enroll patients on this trial. We continue to not only dose stand by doing more tighter dose schedules, not only dosing every 3 weeks, but we are beginning to dosing every 2 weeks and even every 1 week, to see if we can actually get responses sooner rather than later. We have additionally spoken about how we have begun doing our 2 vector replicating therapy of 202.02 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-twenty 21. And as we have told you, the phase 2 is coming in 2021 as well. For the monotherapy as we identify the recommended phase 2 dose and schedules. And 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. And now you may get consumers back over to Jorgen for some additional thoughts.
Jorgen?
On Slide 21, Thank you, Igor. You can see how excited we are. We showed last weak, the results from the non replicating single vector, which is a potent, but least potent technology that we're using in prophylactic vaccinations. That data showed, the strong safety profile immunogenicity, both with regard antibodies and T cells and efficacy. Now today, we've 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 pretreated and difficult to treat population.
Now the replicating 2 vector system has started initial patients have been dosed. And we're even more excited to see the results from this, which, visually you can see could potentially be driving on car still significantly higher T cell responses and with that potency for the benefit of our patients. So we're looking forward to those results that will be coming from HB-two zero two, two zero one combinations and and we'll be looking at, confirming and strengthening the results that we have discussed today. Thank you very much. Let me open this session now for Q And A.
Thank Your first question comes from Brian Abrahams from SVP 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 But the PR, the confirmation is still pending. Is that correct?
Yes. Patient is still on study doing really well and we've that repeated scans, probably in the January.
Okay. Is that something that will be updated with when it happens?
Will there be a deal? Yes, please, John.
We'll update on further data in the first half of next year.
Okay. And then I understand correctly there were head and neck patients that could have gotten systemic therapy plus and 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 in 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. So our preclinical data did suggest that intratumor 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, and all our responses to date had been, had been in the intravenous group. We continue to explore both to see if higher doses will result in this, but the preliminary data presented to date, you are correct.
All of our responses have been in the intravenous group is going to out perhaps supporting our hypothesis with, you know, are we our systemic therapy.
Okay.
But you are still planning to keep testing
This is still a phase 1 early study. It's still in the research phase. We will continue to do this. However, 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 answer the intravenous only, sorry, the phase 2 only with intravenous, but time will tell on that. Okay.
And then, you gave us some benchmarks for the patients that responded. And appreciate it. But thank you. If we wanted to put the stable disease into perspective, What will be the typical progression of these patients clinically? Is it from bodily indolent or is it an aggressive disease?
I mean, no, these patients are advanced metastatic patients with advanced disease. And 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 are going to get HBV positive. And if you actually broke out their, quote unquote progression free survival data set and other kind of indicators, they were not significantly different than non HBV positive. So this is not indolent disease by far, seen clearly by some of the other examples of our patients that progressed through other Epidly.
Right. Okay. Well, thanks for that and congrats again on the data.
Sorry, that was Andrew Berens from SVB. We now have Brian Abrahams from RBC. Please go ahead.
Hey guys. Thanks so much for taking my questions and 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?
And Have you also looked at any changes in the tumor microenvironment in terms of cytokine signals, T cell penetration or inflammatory indicators?
We have we are collecting both PBMCs at various time points during this trial as well as this protocol has more the pole. That for cohorts and options to obtain paired biopsies. I will say that all those efforts are in progress. We are 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 the other assets we have samples and tissue to do that analysis and we're simply waiting for it to batch it.
Got it.
We'll be hopefully getting that data early next year and updating it in mid-twenty 21 at our next update.
Got it. Great. We'll look forward to that. And then 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? I mean, you've had on a couple, including out of the are we seeing CD8 T cells in the blood? Are we seeing CD8 T cells in the tumors, create those response 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 can clearly imagine that if it doesn't, for one reason, rather replicate as well in some patients versus others, so they'll 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. But now, as I've shown you in the case studies, we had patients who were actively progressing on therapy. They responded very nicely. So we I have no answer.
This point, I'll even say we are collecting that kind of data and hoping to better identify to predict these patients might predict. And of course, you're seeing by the dose response curve, I think as we continue to both dose escalate, as well as the tighter dose schedules, we will simply be getting many more funders.
Great. And then one last one for 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 201, 202 combination mid next year and when we might be looking when we could look for the next cut of this 201 data with the tighter dosing schedule and some of the higher doses? Thanks again.
No, no, it's again, I would agree with Bjorn's earlier guidance. We're looking probably at mid-two zero one as an update I would simply say, we are accruing aggressively. And basically this year, the despite the COVID situation, we have put on 24 patients on this trial. And so if you can 3+3 cohort design, the 202201 combination is using the exact same schedule. And I would assume the same kind of a cool pace as we had for the monotherapy.
So with that, I think it can probably come up with a reasonable number of patients to expect to come middle of next year.
Great. Thanks again.
Your next question comes from Alex Anahan 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. So my first question is in patients who received a PD-one previously, could you give us a sense of the median time between discontinuation of PD-one therapy and the first injection of 201 was this greater than 4 weeks? And I guess, from the data so far, Do you see any particular tumor types being more amenable to 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? And then I have a follow-up.
Sorry, I didn't quite catch that second question. Let me answer your first one. First and the way you can repeat your second one for me. If you look at the slides on Slide 16, 17, '18 and 'nineteen, at least for the four cases, the number of the date, the time from the previous checkpoint inhibitor is listed. And you can see it there for the immunohist- sorry, cell guidance.
On Slide 16, you can actually see it's 84 days since last dose. And under the prior treatment category for patients 17, it's 21 days, for patients on Slide 18, it's 42 days. And for patient number 19. For patient on Slide 19, it's 30, 38 days. So I've shown you all of the 11 patients, I would say they've seen quite a spread from, the minimal washout of of over 21 days to anywhere over a year.
And I think these 4 patients are fairly good indicators. If perhaps to your question, the underlying points to your question is, do we know whether or not there's a lingual and checkpoint inhibitor effect? If it's a better way to ask that question, do we know whether these patients ever responded to a checkpoint inhibitor in the first place. And we definitely know, especially for patients who have gone, I hope tried this twice before that we have several patients who are literally primary progressors on checkpoint inhibitors that have now responded to our therapy.
Perfect. And then just to repeat the second question, just to try to get a sense of what you're thinking about in terms of specific tumor types for maybe, for the phase 2, or obviously it's early days?
Yes, yes, I mean, I think at this point, we are encouraged by that the majority of our responders have been in head and neck swamous 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 loop 1 focus on head and neck. And we are, I do encourage by the fact that all of our responders have been there for the moment. I think Hetanet remains a high priority and a high target area for us.
We are of course exploring other indications. We haven't had many patients as many patients with the others. We only had like a couple of 1 anal patients. We've had only 2 cervical and 1 vaginal, although we have not seen responses there as of yet. I think the days there are early.
So I think part of the phase 1 program is indeed to perhaps 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. Of a way of cooling patients, we're open to enroll WalH3D16 positive cancer patients and we're looking for additional signs of efficacy and other indications.
Okay, great. That makes sense. And then my last question is 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 And I'm wondering if you'd expect, this to differ between the inter tumoral and IV routes of administration.
So I'm sorry, I didn't catch the first part of the question, Tim, once again, is it different 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, whether this is expected to be different between the routes of administration?
Right. So, I mean, for the intravenous routes, we've seen effects on the target lesions so those are, of course, not intertumorally injected. For intertumor patients, we have not observed any decrease on either the tumor being injected or non injected lesions. So we have to observe no responses to either the into a tumor injection through the tumor injected or otherwise. We are specifically going to be open, I mean, opening some biopsy driven translational programs next year, where we'll be kind of injecting small group of patients with tumors in doing kind of biopsies, they both injects at a non injected lesions to find out if they're indeed evidence for scope of like effect but we have not seen our responses to date in either injected or uninjected regions following 2 more administration.
Okay, thanks. Congrats again on the data.
Your next question comes from Astra Guine 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 unique update. I was wondering with patient 1214, the ones that, Igor that you mentioned, maybe had pseudo progression. Did you I'm sorry if I missed this, did you obtain biopsies to verify T cell infiltration?
We have not obtained biases from this patient. We have done paired biopsies in multiple other patients. We have not, however, form the histological analysis, we're still batching those patients, but hopefully we'll have that data in multiple patients next year.
Got it. Okay. And then I'm going to ask the prior checkpoint question in a different way. So of those 3 to 4 profiles that had price checkpoints in, I think a day, 21 days ago, 42 days ago, 38 days ago. Igor, what's your thoughts about the residual receptor occupancy view on having a synergistic effect with HB-two zero one?
And also related, did you have any other patients that had checkpoints in the last 6 months that didn't have an SD?
Yes. So we've had patients both who were progressing on a checkpoint inhibitor, within 21 days and our therapy and bonded. So we've had those patients. That's an example of the patients showing on Slide 17. This patient came 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 funded. And we've also had patients who were on the checkpoint inhibitor, they recently started our therapy and progressed. So in short, I mean, 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? The what I can tell you is that the one, not 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 say kind of underlies the mechanism of disease, if you could imagine, our therapy being kind of bringing a massive antigen specific CD18 sauce. And then at checkpoint inhibitors suddenly coming off and taking quarter on quarter a few years away from the foot off the brakes. Letting OVOS CDAT sales kind of do their job. This is kind of what you would expect. So the real access would be is not where the shift was in here, but it was on first, but perhaps whether our therapy comes first followed by checkpoint inhibitor.
But that's just me putting everything together from the small amount of clinical data I have and some of our early preclinical
question comes from Roy Buchanan from JMP Securities. Please go ahead.
Just a couple of quick ones. Back to the inter tumoral injections, it looked from a non expert view, patients 3 and 4 looked like they might have been suitable for inter tumoral. Injection, is there some reason they didn't get that approach or was that a decision made kind of after you saw the initial clinical data? And then I have a follow-up.
No, for head and neck cancer patients, it is up to the investigators if they 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 the decision they are amenable to it. It's up to the investigator. And the other thing is, just keep in mind, to do an intro tumoral injection usually requires interventional radiology guidance. And for that, some sites are, let's just say, better equipped than others.
To do it. So it's not only investigators' decision as for our head and neck, but also what other side is can be set up to do it.
Okay. That's helpful. Thanks. And then for the phase 2 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 EBS, but they don't need to be that there's no concern about whether they're at the same status, but there are different lines of treatment, right? To enroll with concurrently with a checkpoint inhibitor between now these days first line patients. Patients who progressed a checkpoint NIM, but it would be 2nd line patients for the monotherapy. So the 2 groups can enroll at the same time because they don't actually compete with each other.
Got it. Okay. Thank you.
Thank you. And there are no further questions at the moment, but once again, And we still receive no further questions. I'd like to hand the call back to you.
Yes, hi. This is Jan again. Thanks a lot for participating in this call. We are hugely excited and are looking forward to what's coming, next 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.