Q3 2019 Earnings Call
Conference call.
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Juli P. Miller: I would now like to hand the call over to Juli Miller. Please go ahead. Good morning, and welcome to Adapt Immune's conference call to discuss our third quarter 2019 financial results and other business updates. We issued a press release earlier this morning, and I would ask you to please review the full text of our forward-looking statements there. As a brief reminder, we anticipate making projections during this call, and actual results could differ materially due to a number of factors, including those outlined in our latest filings with the SEC. Adrian Rawcliffe, our Chief Executive Officer, and Elliot Norry, our Acting Chief Medical Officer, are with me for the prepared portion of this call. Bill Bertrand, our Chief Operating Officer, Helen Tayton-Martin, our Chief Business Officer and Co-Founder, Mike Garone, our Interim Chief Financial Officer, and John Lunger, our Chief Patient Supply Officer, will all be available for Q&A after the prepared portion. With that, I'll turn the call over to Adrian Rawcliffe.
I'd like to hand, the call over the Julie Miller. Please go ahead.
Good morning, and welcome to adapt Immunes conference call to discuss our third quarter 2019 financial results and other business update we issued a press release earlier. This morning, and I would ask you to please review the full text of our forward looking statements. There as a brief reminder, we anticipate making projections during this call and actual results could differ material.
Early due to a number of factors, including those outlined in our latest filings with the FCC.
Adrian Rawcliffe, our Chief Executive Officer, and Eleonore are acting Chief Medical officer or with me for the prepared portion of this call.
We'll Bertrand our Chief operating Officer, Helen Peyton, Martin, our Chief business Officer, and co founder might Garone, our interim Chief financial Officer, and John longer Archie patient supply officer will all be available for acuity. After the prepared portion with that I'll turn the call over to Adrian Rawcliffe App.
Adrian G. Rawcliffe: Thank you, Julie. Good morning, everyone, and thank you for joining us. This is the first quarterly call since I took over as CEO at the beginning of September.
Thank you Julie.
Good morning, everyone and thank you for joining us.
This is the book quarterly calls since I took over as CEO at the beginning in September .
Adrian G. Rawcliffe: One of the commitments that I made when I took the role was to focus on execution to bring benefits to people with cancer and value to our shareholders in the short term. Our priority remains to bring our ADPA2M4 therapy to market in 2022 for people with sarcoma, which is a truly devastating cancer. Recently, we presented data at ESMO demonstrating a clear benefit for people with synovial sarcoma, and Dr. Van Tine, who presented these results, referred to them as phenomenal. I witnessed firsthand the excitement amongst the sarcoma community, and the interest from healthcare professionals has been reflected. Elliot, our acting CMO, will speak more about this later.
One of the commitments, but all I made when I took the ROE was to focus on execution to bring benefit people with council and value to all shareholders in the short term.
Oh priority remains to bring all HBP I too am for therapy to market in 22 Institute for people with sarcoma, which is a truly devastating council.
Recently, we presented data at ESMO, demonstrating a clear benefit for people with synovial sarcoma adoptive on time. He presented these results referred to them is phenomenal.
Well I witnessed firsthand the excitement amongst sarcoma community on the interest from health care professionals is being reflective of this.
That's all acting CFO , who will speak more about this later.
With these compelling results enrollments enough. They had one trial has started well and we believe will accelerate rapidly.
Adrian G. Rawcliffe: With these compelling results, enrolment in our Spearhead 1 trial has started well, and we believe will accelerate rapidly. We have opened multiple clinical sites with others lined up to screen and treat patients. Given the significant unmet medical need for these patients, we are pleased that the FDA granted orphan drug designation to ADPA2M4 for the treatment of soft tissue sarcomas, as we are eager to make this therapy available as quickly as possible. These achievements, in conjunction with our commercial readiness initiatives, are encouraging progress towards having our first marketed SPIR T-cell therapy in 2022. Next, I want to set out the basis upon which we believe that the SPHERE T-cell platform has broader applicability than sarcoma and how we are moving forward in these other solid, Firstly, the data in sarcoma demonstrate that the affinity-engineered T-cell receptor at the heart of our spear T-cells, in this case, the T-cell receptor targeting MAYJ4, can successfully engage with its target, trigger the T-cell to attack the tumour cells, and deliver compelling anti-tumour responses, clearing large tumour bulk over a period of six months.
We have opened multiple clinical sites with all this lined up the screen and treat patients.
Given the significant unmet medical need for these patients. We are pleased that the FDA granted orphan drug designation ATP I too am pool for the treatment of soft tissue sarcoma as we are eager to make this therapy available as quickly as possible.
These achievements in conjunction with all commercial readiness initiatives are encouraging progress towards helping off the list marketed spear T cell therapy in 2022.
Next I want to set up the basis upon which we believe the spear T cell platform has broader applicability than sarcoma and how we are moving forward in these other solid treatments.
Firstly, the data insight coma demonstrate that the affinity engineered T cell receptor at the heart of all spear T cells. In this case the T cell receptor targeting may Jay for Kinda successfully engage with its target trigger the T cell to attack the tumor cells and deliver compelling anti tumor responses clearing law.
Oh, it's cima bulk over a period of six months.
Through our translational research, we have demonstrated spear T cells infiltration into tumors as well as recruitment other T cells to the tumor side. We've also seen cytokine induction in respond as best as non responders.
Adrian G. Rawcliffe: Through our translational research, we have demonstrated spear T-cell infiltration into tumors, as well as recruitment of other T-cells to the tumor site. We have also seen cytokine induction in responders versus non-responders, and that spear T-cells isolated from patients post-infusion can kill target cells in vitro. The wealth of translational data underscores that SPIR T-cells targeting MAJ-A4 are functioning properly in people with synovial sarcoma.
And the spear T cells isolated from patients post infusion can kill target cells Mb Troy.
Well look the translational data on the schools spear T cells targeting major a pool of functioning properly in people with synovial sarcoma.
We will present, an update on the translational data. It sits see with a case study of two sarcoma patients from a ATP I too am for phase one trial.
Adrian G. Rawcliffe: We will present an update on the translational data at CITSE with a case study of two sarcoma patients from our ADP A2M4 Phase 1 trial. Secondly, we have seen activity in other solid tumors beyond sarcoma with our first generation products targeting NY-ESO, MAI-J4, MAI-J10, and AFP. In these other solid tumors, whilst no patients have had resistance responses to date, we have seen measurable reductions in the size of the target lesions in multiple patients across five different solid tumor types. Thirdly, building on these data and insights, we have three approaches to convert this activity we have seen outside sarcoma into meaningful benefit for patients. The first approach is our next generation program targeting MAJ-A4 designed to confer CD8 or killer T-cell functionality on all of the transduced T-cells, effectively increasing the potency of the cells administered.
Secondly, we have seen activity you know the solid you must be on sarcoma without first generation products targeting and why you saw major before May Jay 10, and I have paid.
In these other solid tumors was no patients have had resist responses to date, we've seen measurable reductions in the size of the target lesions in multiple patients across five different solid tumor types.
Thirdly building on these data and insights we have three approaches to convert this activity we have seen outside sarcoma, it's a meaningful benefit for patients.
First approach is all next generation program targeting major before designed to create a CD eight well killer T cell functionality on all of the Transduce T cells.
Actively increasing the potency of the cells administered.
Adrian G. Rawcliffe: As you know, this product is currently in a dose escalation trial, the SIPAS trial, with initial data expected in the first half of 2020. The second approach is our low-dose radiation sub-study at the MD Anderson Cancer Centre, designed to demonstrate the benefit of increased trafficking of T-cells to the tumor. Again, the study continues to enroll patients, and we anticipate results from this trial in 2020. And finally, the third approach, as announced today and based on emerging translational data to be presented at CITSE, is that we will initiate a clinical trial combining ADP A2M4 with a PD-1 pathway inhibitor in 2020. With these three approaches, we are progressing rapidly to convert the activity we've seen in a broad range of solid tumors into meaningful responses by increasing the potency of the cells, their trafficking to the tumor, and their activity in combination with checkpoint. We were the first company to demonstrate robust responses with an engineered T-cell therapy in solid tumors. We believe we are leading the efforts to show responses in a range of solid tumors, with initial data expected And with that, I'll turn the call over to Elliot to provide a clinical update before I conclude and open the Q&A. Elliot?
She knows this product is currently in a dose escalation trial to support strong with initial data expected in the first half 2020 .
The second approaches on low dose radiation sub study the MD Anderson cancer Center.
Demonstrates the benefits increased trafficking of T cells to the Cima.
Again, the study continues to him ROE and we anticipate results from this trial in 2020 .
And finally, the third approach as announced today and based on emerging translational data to be presented at city is that we will initiate a clinical trial combining ATP eight to him for the PD, one pathway inhibitor and 2020 .
With these three approaches we're progressing rapidly to convert the activity we've seen in a broad range of solid Gee whiz into meaningful responses by increasing the potency of the cells that traffic into the Cima and their activity in combination with checkpoint inhibitors.
We were the first company to demonstrate robust responses within engineered T cell therapy in solid Cima.
We believe we're leading the efforts to show responses in a range of solid tumors with initial data expected in the first half of 2020 .
With that I'll turn the call over to Elliott to provide a clinical update before I conclude and open the Q and I Elliott.
Thank you add and thanks, everyone for joining us my colleagues and I and our clinical group had been focused on delivering data from our clinical trials and most importantly, and developing meaningful therapies for patients who need them.
Elliot Norry: Thank you, Ed, and thanks, everyone, for joining us. My colleagues and I in our clinical group have been focused on delivering data from our clinical trials and, most importantly, on developing meaningful therapies for patients who need them. As Ed said, there is a high unmet medical need for patients with sarcoma. Sarcomas are cancers that typically occur in a younger patient population, striking people in their prime.
As Ed said, there's a high unmet medical need in patients with sarcoma.
Sarcoma as our cancer is it typically occur and a younger patient population striking people in their prime.
There are very few treatment options available for these patients.
And there are even fewer options available to patients like those in our trials with advanced disease, who have failed other lines of therapy.
To date, we have seen that 80 P. Eight two m. for works in synovial sarcoma with impressive data presented at ESMO from our phase one trial, we demonstrated a disease control rate of 92% and a response rate of 58% in 12 Evaluable patients.
Elliot Norry: There are very few treatment options available for these patients, and there are even fewer options available to patients like those in our trials with advanced disease who have failed other lines of therapy. To date, we have seen that ADP A2M4 works in synovial sarcoma, with impressive data presented at ESMO from our phase one trial. We demonstrated a disease control rate of 92% and a response rate of 58% in 12 valuable patients. These results are even more impressive given that most patients in our trial were heavily pre-treated and the median age was 53, which is older than the typical synovial sarcoma patient. We have also seen large, bulky tumors being reduced, and this has the potential to be a truly revolutionary therapy in this rare disease. Reducing large tumors, the size of which often negatively impacts patient quality of life and can preclude resection, to a smaller size that can be surgically addressed is a treatment goal for sarcoma. The durability of these responses continues to mature, and we will provide updates as data become available.
These results are even more impressive given that most patients in our trial were heavily pre treated and the median age was 53, which is older than the typical synovial sarcoma patients.
We have also seen large bulky tumors being reduced and this has the potential to be a truly revolutionary therapy. In this rare disease, reducing large tumors the size of which often negatively impacts patient quality of life and can preclude resection to a smaller size that can be serve.
Strictly addressed is a treatment goal for sarcoma.
The durability of these responses continues to mature.
And we will provide updates as data become available.
These data had been impressive enough to support starting our phase two spear had one trial in synovial sarcoma and another type of sarcoma mix Lloyd round, so like both sarcoma.
Following our presentation at ESMO, we have had physicians and clinical trial centers, reaching out to us eager to enroll patients.
We have also made progress in our 80 P. H M. P program in liver cancer with the recent endorsement from our safety Review committee to move to the third dose cohort in this trial.
Elliot Norry: These data have been impressive enough to support starting our Phase 2 Spearhead 1 trial in synovial sarcoma and another type of sarcoma, myxoid round cell liposarcoma. Following our presentation at ESMO, we have had physicians and clinical trial centers reaching out to us, eager to enroll patients. We have also made progress in our ADP A2-AFP program in liver cancer with the recent endorsement from our Safety Review Committee to move to the third dose cohort in this trial. I have had the privilege of serving as the clinical lead for this program, and given that the target, AFP, can also be expressed in non-cancerous liver tissue, it was incredibly important to ensure that this therapy would be safe for patients. To date, we have seen no evidence of liver toxicity or T cell-mediated toxicity in the first two dose cohorts.
I've had the privilege to serve as the clinical lead for this program and given that the target ASP can also be expressed in noncancerous liver tissue. It was incredibly important to ensure that this therapy would be safe for patients to date, we've seen no evidence of liver toxicity or T cell mediated taxes.
City in the first two dose cohorts in the third cohort patients will receive a target dose of 5 billion spear T cells with a range of 1.2 to 6 billion South.
And our standard Preconditioning regimen.
We have seen early indications of anti tumor activity at lower doses and with less intense preconditioning with evidence of tumor necrosis a degree a decrease in the size of lymph node metastasis and transient decreases in CRM ASP levels.
Beyond sarcoma and liver cancer, we have seen reductions in the size of lesions and for other solid tumor indications to date, including previously reported results. There are with 80 P. Eight to M. One patient with ovarian cancer, who had a 27% reduction in target lesion.
Elliot Norry: In the third cohort, patients will receive a target dose of 5 billion SPIR T cells with a range of 1.2 to 6 billion cells and our standard preconditioning. We have seen early indications of anti-tumor activity at lower doses and with less intense preconditioning, with evidence of tumor necrosis, a decrease in the size of lymph node metastases, and transient decreases in serum AFP levels. Beyond sarcoma and liver cancer, we have seen reductions in the size of lesions in four other solid tumor indications. To date, including previously reported results, there is, with ADP A2M4, one patient with ovarian cancer who had a 27% reduction in target lesions, and one patient with melanoma who had a 40% reduction, and one patient with head and neck cancer who had a 21% reduction.
And one patient with melanoma, who had a 40% reduction and one patient with head and neck cancer, who had a 21% reduction.
With 80 P. Eight to 10, we have seen at 28% reduction in one patient with lung cancer.
While none of these met the criteria for RECIST response, these data indicate that our speed and that our spear T cells are active we're working to convert these early indicators of activity into durable responses.
We have an ongoing next generation trial with our ATP eight two m. for C.D.A. here T cells targeting no Jay for the surpass trial as well as the radiation sub study of our ATP 82, M. for phase one trial.
And as Ed mentioned earlier, we plan to start a combination trial with a checkpoint inhibitor in 2020.
Elliot Norry: With ADP A2M10, we have seen a 28% reduction in one patient with lung cancer. While none of these met the criteria for a resistance response, these data indicate that our SPIR T-cells are active. We are working to convert these early indicators of activity into durable responses. We have an ongoing next-generation trial with our ADP A2M4 CD8 T-cells targeting MAGE-A4, the SURPASS trial, as well as the radiation sub-study of our ADP A2M4 Phase 1 trial. And, as Ed mentioned earlier, we plan to start a combination trial with a checkpoint inhibitor in 2020. I have been with Adaptimmune since 2015 and have been able to see our progress from the early days of NYESO up to where we are now, driving to launch ADP A2M4 in sarcoma in 2022. Making a Difference for Patients with Cancer is a passion for me and each and every one of my colleagues at Adaptimmune, and we are eager to deliver. And now, I will turn the call back to Ed.
I have been with Adaptimmune since 2015, and it's been able to see our progress from the early days of Nyet. So up to where we are now driving to launch ATP a two M in sarcoma in 2022.
Making a difference for patients with cancer is a passion for me and each and every one of my colleagues at Adaptimmune and we are eager to deliver.
And now I will turn the call back to add.
Thanks, Sandy yet.
Our first priority is patients by delivering patients. We believe we will deliver value for investors and we have compelling data, indicating that our spear T cells work and we'll continue to execute effectively.
I am aware the frustration around our current share price were implementing cost management initiatives and we're evaluating priorities across our preclinical and clinical portfolio.
And I continue to believe that we're in a strong position to deliver value for investors through the timely execution of the spearhead one trial to enable launch of ATP I too am foreign sarcoma in 2020 too.
By demonstrating the efficacy of our spear T cells and other solid tumors throughout the past ATP eye to eye SP and combination trials and by leveraging our world class capabilities beyond our current autologous spear T cell platform.
Now I'd like to open the call up questions operator.
Adrian G. Rawcliffe: Thanks, Elliot. Our first priority is our patients. By delivering for patients, we believe we will deliver value for investors, and we have compelling data indicating that our SPIR T-cells work and will continue to perform effectively. I am aware of the frustration around our current share price. We're implementing cost management initiatives, and we're evaluating priorities across our preclinical and clinical portfolio. And I continue to believe that we're in a strong position to deliver value for investors through the timely execution of the SPEARhead1 trial to enable the launch of ADPA2M4 in sarcoma in 2022, by demonstrating the efficacy of our SPEAR T-cells in other solid tumors through SURPASS, ADPA2, AFP, and combination trials, and by leveraging our world-class capabilities beyond our current autologous Operator?
As a reminder to ask a question you would need to press star one on your telephone.
Draw your question press the pound key.
Please standby, we compile the Q and a roster.
Our first question comes from Mohit Bansal of Citi. Your line is open.
Great. Thanks for taking my questions are just a couple of questions.
So if I may.
What's the fall.
You mentioned that the.
Your therapies.
Equally important I've seen some responses, but did not.
You seem to resist criteria at this point can you remind goes like this you have seen pieces sponsor and.
Would it require or.
So I was pair or how do you see how do you see.
The next generation that piece has actually moving these responses at this point.
Suddenly.
So so I would want to be clear we have seen we've seen what we're referring to as activity across a broad range of solid tumors.
We have been clear those do not rise level of recess criteria responses, but they are measurable reductions in a right in a range of different tumors across five different solid Jim is that patients across five difference on the chips.
Operator: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Mohit Bansal of Citi; your line is open. Can you just remind us at what process you are seeing these responses, and would it require more cell care, or how do you see the next generation, 30 cells, actually improving these responses?
The objective of the we also see with those patients we see expansion of the T cells and so the antigen driven expansion of the T cells and therefore, we do not believe necessarily that it is the question of dogs with dosing those patients in the 110 billion seller right.
Adrian G. Rawcliffe: Certainly. But I want to be clear, we have seen what we are referring to as activity across a broad range of solid tumors. We have been clear that these do not rise to the level of resistance criteria responses, but they are measurable reductions in a range of different tumors across five different solid tumors, so patients across five different solid tumors. The objective of the, we also see with those patients, we see expansion of the T cells and so the antigen-driven expansion of the T cells, and therefore we do not believe necessarily that it is a question of cell dose and we're We also see infiltration of those T cells into the tumors where we have biopsies.
We also see improved traction over those T cells into the tumors, where we have biopsies and so we believe the approaches that we're taking with the second generation approaches the I outlined Oh, the correct approaches to take to come but those levels of activity in two.
You're a bull responses for patients and just to reiterate the more potent T cells from ATP 82, M. for CB eight so Paul study the.
Driving further importation into the tumor using low dose radiation with the were low dose radiation sub study with MD Anderson and the just announced PD. One combination study, but we intend to initiate next year. Those a three approach is all of which address the potential mechanisms of risk.
Adrian G. Rawcliffe: And so we believe that the approaches that we're taking with the second generation approaches that I outlined are the correct ones to take to convert those levels of activity into durable responses for patients. And just to reiterate, the more potent T cells from our ADP, A2, M4, CD8 surpass study, driving further infiltration into the tumor using low-dose radiation with the low-dose radiation sub-study with MD Anderson, and the just-announced PD-1 combination study that we intend to initiate next year, those are three approaches, all of which address the potential mechanisms of resistance or lack of robust, durable responses in those patients.
Distance or lack of robust durable responses in those patients.
Our next question comes from Marc Frahm of Cowen and company. Your line is open.
Hey, Thanks for taking my question.
Just thinking forward to the surpass it you're guiding that we'll see some data in the first half of next year.
Maybe give a little bit of clarity as to.
How large of a data set or how it you know how robust in terms of follow up you you might expect to be able to present and.
And then yeah is there any competition that you're seeing kind of between spearhead unsurpassed for enrollment or are there are plenty of patients out there at the because there is some overlap the centers.
Yep Yep.
Operator: Our next question comes from Marc Frahm of Cohen & Co. Your line is open.
So.
Maybe I'll comment on the I'll comment on the.
First point on the the data and what we're planning to put out in the first off for next year, then our loss Kelly to comment on the.
Adrian G. Rawcliffe: Thanks for taking my question. Just thinking forward to the surpassed data you're guiding that we'll see some data in the first half of next year, can you maybe give a little bit of clarity as to how large of a data set or how robust in terms of follow-up you might expect to be able to present then?
Recruitment.
Between those two studies.
So with respect to the data next year, we are a dose escalation trials I would just point out we announced the study in May we announced the first site initiation visits in July we all recruiting patients in a in so Pos across multiple multiple sites at this point in time and we had.
Adrian G. Rawcliffe: And then, you know, is there any competition that you're seeing kind of between Spearhead and Surpass for enrollment, or, you know, are there plenty of patients out there because there is some overlap of centers?
I think just to remind everybody that dose escalation is I target dose of 1 billion sells a target dose of 3 billion sales on a target those of 6 billion cells in each of the cohorts.
And yes, I don't want to pre jobs, because we don't know what level of cells. We will see we will see efficacy and responses.
Adrian G. Rawcliffe: Yeah. Yeah.
Adrian G. Rawcliffe: So, uh... Maybe I'll comment on the first point about the data and what we're planning to put out in the first half of next year, and then I'll ask Elliot to comment on the recruitment between those two studies. So with respect to the data for next year, we are in dose escalation trials. I will just point out that we announced this study in May. We announced the first site initiation visit in July.
There is obviously stock is within those patients as well and so we anticipate being able to give a data from those dose dose escalation cohorts and potentially from patients from a small number of patients dosed in the expansion phase off once we've completed thought, but obviously that will depend on the.
Speed with which we're able to ramp up in the dose escalation cohorts. So the short answer there is no can be very many patients.
Adrian G. Rawcliffe: We are recruiting patients for Surpass across multiple sites at this point in time. And with dose escalation, just to remind everybody, the dose escalation is a target dose of one billion cells, a target dose of three billion cells, and a target dose of six billion cells in each of the cohorts. And I don't want to prejudge because we don't know at what level of cells we will see efficacy and responses. There are obviously staggers within those patients as well.
But I think it will be a useful data.
For the purposes of determining whether we are seeing a effect in the second generation that is in excess of the effects that we saw in the first generation product.
Elliott.
You want to comment on the on the recruitment between spearhead and support costs and whether we are saying.
Robust recruitment in those probably in those studies.
Sure. So specifically with respect to competition between surpassing spearhead for patients it's important to point out that surpasses a multi tumor study.
Adrian G. Rawcliffe: And so we anticipate being able to give data from those dose escalation cohorts and potentially from patients, from a small number of patients dosed in the expansion phase once we've completed that. But obviously, that will depend on the speed with which we're able to ramp up in the dose escalation cohorts. So the short answer is, it's not going to be very many patients. But I think it will be useful data for the purposes of determining whether we are seeing an effect in the second generation that is in excess of the effect that we saw in the first generation product. Elliot, do you want to comment on the recruitment between spearhead and surpass and whether we're seeing robust recruitment in those studies?
Recruiting patients in a in several different tumor types in spearhead is focused solely on synovial sarcoma and mix right around sell LIFO sarcoma.
So there may be.
A small amount of as you say competition for that for the sarcoma patients, but I think that they will tend to be traffic towards the spearhead study.
And the surpassed study will enroll patients predominantly from other tumor types.
There is some overlap of centers, but there are also sensors that are independent for each study. So I don't see competition between those two studies for patients to be a a major concern.
Elliot Norry: Sure. So specifically with respect to competition between SURPASS and Spearhead for patients, it's important to point out that SURPASS is a multi-tumor study, recruiting patients with several different tumor types, whereas Spearhead is focused solely on synovial sarcoma and myxoid round cell liposarcoma. So there may be a small amount of, as you say, competition for the sarcoma patients, but I think that they will tend to traffic toward the Spearhead Study, and the Surpass Study will enroll patients predominantly from other tumor types. There is some overlap of centers, but there are also centers that are independent for each study. So I don't see competition between those two studies for patients as being a major concern.
Okay, great. Thank you.
Our next question comes from Tony Butler of Roth Capital Partners. Your line is open thanks very much.
Adrian.
Okay and spearhead.
Yeah. Great response is obviously disease control rate is very strong 50% or.
Good news.
Registration trial.
Do you think you had a probable solution is in or or that would be part a and part b if not what.
What would it be X number of Prs and Crs or what would be.
Total rate that you feel comfortable DFT might feel comfortable with thanks very much.
Operator: All right, great. Thank you.
Operator: Our next question comes from Tony Butler of Roth Capital Partners. Your line is open.
Well go ask Elliot too so to the design of spare had what we think we can show.
Elliot Norry: Thanks very much, Adrian. In Spearhead, great responses, obviously. Disease control rate is very strong, 58% ORR. The question is, as a registration trial, do you think that a fileable solution is in ORR? That would be Part A and Part B. If not, what would it be?
Yeah. Thanks for the question so with respect to.
The spearhead design and hurdles that we may see we do think that that.
Our our is is potentially sufficient for ER for a registered double indication and then and.
Elliot Norry: X number of PRs and CRs? What would be a hurdle rate that you feel comfortable with, and the FDA might feel comfortable with? Thanks very much.
Thats occurred in in several indications with other programs in the past.
That being said it we do feel that we need to demonstrate clear benefit as compared to therapies that are currently available.
Elliot Norry: I'm going to ask Elliot to talk to the designer of Spearhead about what we think we can show.
Elliot Norry: Thanks for the question. So, with respect to the spearhead design and hurdles that we may see, we do think that ORR is, uh, potentially sufficient for a registrable indication, and that has occurred in several indications with other programs in the past. That being said, we do feel that we need to demonstrate clear benefit as compared to therapies that are currently available, and we've set this study up to be able to show statistically relevant differences at a 40% or approximately 40% overall response rate compared to the best responses being seen with other second-line treatments behind chemotherapy. Essentially, to answer your question directly, we do believe that this is a registrable approach, and we also believe that based on the 58% overall response rate seen in the phase one study, we're optimistic about the capability to achieve an overall response rate that is clinically meaningfully different from currently available treatments to be able to deliver this to patients as we progress through the trial.
And we've set this study up to be able to show a statistically relevant differences at a 40% for approximately 40% overall response rate compared to the best response is being seen with other other second line treatment beyond behind.
<unk> behind chemotherapy so.
Essentially we to answer your question directly we do believe that this is a registered double approach and we also believe that that based on the 58% overall response rate seen in.
In the phase one study that.
We're we're optimistic about the capability to achieve an overall response rate that is clinically meaningfully different from currently available treatments to be able to deliver this to patients as we as we progressed through the trial.
Adrian G. Rawcliffe: Thanks, Elliot.
Thanks, Charlie.
[noise] Thank study.
Operator: Thanks, Danny.
Operator: Thanks, Tony. Our next question comes from Jem Durkanoff of Wells Fargo Securities. Your line is open.
Our next question comes from Jim Dark enough of Wells Fargo Securities. Your line is open.
Good morning asphalt Nick on Cogen This morning.
Adrian G. Rawcliffe: Good morning, it's Nick on for Jim this morning. The first question just goes back to the data from ESMED. I think you had two unconfirmed responses in that data set, and also, I believe two of the partial responses, patients who achieved a partial response, had relapsed. So are you able to provide an update on those data? And what do you know about the mechanisms of resistance that limit the duration of a PR and perhaps the ability to induce a response with retreatment? I have a follow-up question. Thank you.
Question, just goes back to the data from ESMO I think you had to unconfirmed responses.
In that dataset and also I believe two of the partial response patients achieved a partial response header alone. So.
Able to provide an update on those data and once you know about the mechanisms of resistance limited duration, NXP and perhaps the ability to induce a response rate retreatment.
And I have a follow up thank you.
So I'm just going to say that we all going to be updating those data.
Elliot Norry: So I'm just going to say that we are going to be updating those data at CITOS shortly, so I don't think we want to give any further information on the progress of those patients. Elliot, would you like to comment on the potential mechanisms of resistance and the opportunity to have to treat with a second dose of cells?
Sito's shortly so I don't think we want to give any further information on on the progress of those patients.
Elliott do you would you like to comment on the potential mechanisms of resistance and the opportunity to.
Have.
To treat first with the second dose itself.
So I.
First of all with respect to mechanisms of resistance.
Elliot Norry: So I...
Elliot Norry: First of all, with respect to mechanisms of resistance, I don't think that we've seen the durability of response mature fully in the phase one study as yet. So ultimately, I do believe that there will be patients that progress. And mechanisms of progression are important. And our translation group is working diligently to try and understand that. As Ad mentioned earlier, we do see that the T cells traffic to the tumor, and we're employing in our other studies mechanisms by which to take that translational information around mechanisms of resistance that might relate to trafficking, that might relate to the potency of cells, and with our plan to combine with a PD-1 inhibitor, to explore whether there are ways around potential mechanisms of resistance going forward. With respect to second doses of ADP A2M4 in the Spearhead trial, we are not pursuing that as part of the study design. So I think that it remains a possibility for the treatment of patients with cell therapy to give second infusions, but I think we'll be looking to other mechanisms by which to extend durability beyond just second infusions.
I don't think that we've seen the durability of response mature fully in in the phase one study as of yet so ultimately I do believe that there will be patients that progress.
And and mechanisms of progression are important in our translational group is working diligently on to try and understand that as add had mentioned earlier, we do see that the T cells traffic to the tumor.
And we're employing in our other studies mechanisms by which to take that translational information.
Around mechanisms of resistance that might relate to trafficking that might relate to the potency of cells.
And with our plan to combine with a PD one inhibitor.
To explore whether there are ways around potential mechanisms of resistance going forward.
With respect to second doses of ATP, a two and four in in the spearhead trial, we're not pursuing that as part of the study design.
With respect.
So I think that.
It remains a possibility for the treatment of patients with cell therapy to give to SEC to give second infusions, but I think we'll be looking to other mechanisms by which to extend durability and beyond just second infusion.
Adrian G. Rawcliffe: Okay, thank you. And then, going back to the abstract CITI for Spearhead 1, the abstract states, you know, by IHC, 82% of synovial and 68% of myxoid round cell samples express MAGE A4. Is this in accordance with your definition of A4 positivity? And as you process the data coming from these biomarker studies, is that percentage positivity, is that something that is likely to be modified as you develop these products further?
Okay. Thank you and then on going back to the abstract city spearhead one.
Yes start states.
The 82% of snowmobile Inscape Sandoz makes toyed ran sale.
Samples Express May April has been in accordance with your definition of April positivity and and as you.
Process the data coming from the biomarker studies.
Is that it's Adam.
That percentage positivity is something that is likely to be modified issue.
Develop these products further.
So the.
Adrian G. Rawcliffe: So the rates that you quoted for MAYJ4 are the ones that conform to the hurdle rates for inclusion in the study. The majority, almost all of the patients that we see in sarcomas that express MAYJ4 do so at a reasonably high rate. We don't have that many very low MAYJ4 expressors in sarcoma, and so we don't anticipate, obviously, that those numbers would change given they're based on the latest information that we have. And we have got a decent sample set now of patients that have MAYJ4 in sarcoma with MAE-J4 expression based on the screening that we've done to date. So, don't anticipate, and I think it's fair to say the vast majority of patients, 80 patients who have synovial sarcoma and express MAE-J4 robustly would be eligible on that criteria for the trial.
Tim the rates that you quoted for major pool are the ones that conform to the hurdle rates for inclusion in the study.
The majority almost all of the patients that we see in South Korea was that express may Jay for do so at a reasonably high right. We don't have that many very low my Jay for expressed as in sarcoma.
And so we we don't anticipate obviously those numbers would change.
And that based on the the latest information that we haven't we have got a decent sample set now.
Of patients that.
Yep.
Im talking about with major before expression based on the screening that we've done to date. So I don't anticipate and the I think it's fair to say the majority of the vast majority of patients.
Well I hate to patients who.
Who have synovial sarcoma.
Express my Jay for robustly would be eligible on that criteria for the draw.
Okay. Thanks, and then my last one is obviously does the venn diagrams full anyway. So one expression in may Jay for expression overlap fairly substantially you could you think about bringing this to the marketplace. How do you think physicians will choose between anyway, so warm and it may take four problem.
Adrian G. Rawcliffe: Okay, thanks, and then my last one is, obviously, the Venn diagrams for NY-ESA-1 expression and MAJ-A4 expression overlap fairly substantially. As you think about bringing this to the marketplace, how do you think physicians will choose between an NY-ESA-1 or a MAJ-A4 product?
So we anticipate though do so on the basis of the data that's available at the time.
Adrian G. Rawcliffe: So we anticipate they'll do so on the basis of the data that's available at the time. And we also anticipate that, probably, in due course, they'll test for MAJ2, MAJ4, NYISO, and any other antigens that have relevant products associated with them. And so that will become part of the battery of tests, but then the products will compete on the efficacy that they're able to show. And that's why we think it's important that we're able to continue with the spearhead study, demonstrate the efficacy of the A4 targeting spear T cell in sarcoma, and get to market as quickly as possible with that product.
And.
We also anticipate that probably in due course, they will test for May Jay to my J. Paul.
And why you so and any other up.
Antigens that all have relevant products associated with them and so that will become part of the battery of tests that then the products will compete on the efficacy that they're able to show.
And that's why we think it's important that were able to continue with the.
The spearhead study demonstrates the efficacy of the April .
Targeting spear T cell in sarcoma and get to market as well as quickly as possible.
Operator: Great. Thank you very much. Thanks, Nick.
That product.
Great. Thank you very much like that just.
Operator: Thanks, Nick. Cheers.
Operator: Again, if you'd like to ask a question, that's star then 1. Our next question comes from Tony Butler of Roth Capital Partners. Your line is open.
Again, if you'd like to ask a question that Star then one our next question comes from Tony Butler from Roth Capital Partners. Your line is open.
Tony Butler: Sorry, one last one. With respect to enrollment sites, none exist, at least according to ClinTrials, outside the U.S. That may be, you know, a prohibitive cost to do so, but I'm just curious.
Sorry, one last one.
With respect to enrollment sorry, its non exists at least according to control outside the U.S.
That maybe you know what prohibitive costs to do so but I'm just curious.
Elliot Norry: Adrian and or Elliot your thoughts around not including that in spearhead? I appreciate it.
Peter in indoor Elliot your thoughts around not including that in spearhead appreciate it.
[laughter].
Elliot Norry: Elliot, do you want to take this?
Earlier do you want to take them.
Sure. So we do intend to conduct spearhead in North American and European sites and.
Elliot Norry: Sure, so we do intend to conduct spearhead at North American and European sites. Without getting into greater detail, it will not just be a U.S.-only trial.
[laughter].
And without getting into greater detail it will not just be a U.S. only trial.
Tony Butler: Agreed. Thanks a lot.
Great.
Thanks, a lot.
Operator: [inaudible]
Thanks.
Our next question comes from Michael Schmidt of Guggenheim. Your line is open.
Operator: Our next question...
Elliot Norry: Hey guys, thanks for taking my questions. I've heard one on the AFP program, maybe just wondering how safety has been looking there to date given the target. I think there's some expression potentially in healthy cells as well of AFP.
Hey, guys. Thanks for taking my questions.
On the ASP program, maybe I'm just wondering how.
He has been looking that today, given a target I think theres some some expression potentially unhealthy so thats what I'll say.
Thanks, Thanks Elliot.
Elliot Norry: Thanks for that. Elliot, as CMO and as lead of that program, do you want to take this?
As Sam I'm does lead about programs you want to Teva sure. So you know we've we've dose escalated through a cohort one and cohort two for those studies and we have seen no evidence of liver toxicity.
Elliot Norry: Sure. So, you know, we've dose escalated through cohort 1 and cohort 2 for those studies, and we have seen no evidence of liver toxicity in any of the patients treated today. So we'll obviously continue to monitor closely for that in cohort three where the cell dose is escalated to our target dose range of five billion, five billion SPIR T cells, dose range of 1.2 to six billion. But we are very encouraged by the fact that in the earlier dose cohorts, we really have seen no evidence.
In any of the patients treated today. So we'll obviously continue to monitor closely for that in cohort three where a the cell dose is escalated to our target dose range of EUR 5 billion 5 billion spear T cell dose range of 1.2 to 6 billion.
So we're continuing to monitor for that but we're very encouraged by by that.
By the fact that in the early or dose cohorts, we really have seen no evidence.
Operator: Okay, great. Thanks. And then, just maybe, a bigger picture question, I think.
T cell related liver toxicity.
Okay, great. Thanks, and then just maybe a bigger picture question I think youre guiding to having about one year worth of cash in terms of funding. The company just curious how you think about maybe.
Operator: Having about one year's worth of cash in terms of funding the company, just curious how you think about maybe bigger picture strategic initiatives to either, I guess, curb and reduce spend and or maybe leverage some of your infrastructure, maybe with partners, I don't know. Think about your manufacturing facility, for example. Is there something that can be done to better leverage the platform as it is with respect to cash burn, for example?
Big impact just strategic initiatives to either I guess carbon.
Yeah reduce.
Span and or maybe leverage some of your infrastructure, maybe but partners I'm enough thinking about your manufacturing facility. For example, if that's something that can be done to better leverage.
Format today.
With respect to cash burn for example.
Mike Garone: Okay, I'm going to ask Mike Garone, CFO, to answer that.
Okay, I'm going to ask Mike My garage and see if I talked about Mike Hi.
Mike Garone: Hi, As per our previous guidance, as has been clear for a while now, we remain funded through the third quarter of 2020. That's beyond the first half of 2020, during which we plan to have key clinical data points coming out. Additionally, we are implementing cost management initiatives and evaluating priorities across our preclinical and clinical portfolio. For example, ceasing enrollment in ADP A2M10 by the end of this year. As you can imagine, some of the strategies that we have in place or are currently exploring are not public information at this point, and we will update them in due course.
As per our previous guidance.
Been clear for while now we remain funded through the third quarter 2020.
Thats beyond the first half 2020 during which we plan to have key clinical data points coming out.
Additionally, we are implementing cost management initiatives and evaluating priorities across or whatever.
Portfolio.
For example, ceasing enrollment of baby aid to him and by the end. This year as you can imagine some of the strategies that we haven't place or currently exploring are not public information yet.
At this point and we will update in due course.
Mike Garone: Thanks for highlighting that.
Thanks for a for a highlighting that.
Mike Garone: Thanks, Michael.
Thanks, Michael.
Our next question comes from Daniel Leather of Polygon. Your line is open.
Operator: Our next question comes from Daniel Leather of Polygon. Your line is open.
Hi, Thanks for the cool two questions on the manufacturing sort of things have you heard me disruption when I'm sure. There is one of them with the Stevenage Castle Center.
Operator: Hi, thanks for the call. Two questions. On the manufacturing side of things, have you had any disruption, like one or two others might have done, with the Stevenage cast fault center? And secondly, just on the PD-1, will you be paying for that, or are you hoping to have somebody else contribute that towards the trial costs? Thank you.
And secondly, just from a PD one will you be paying so where are you happy to somebody else comes speed up to towards the pro cause. Thank you.
Adrian G. Rawcliffe: So I'll deal with the second one, and then I'll hand over to John Lunger, our Chief Patient Supply Officer, to talk about the manufacturing and catapult. So with respect to the second one, we've not given any further details as to the structure of that PD-1 combination study, so it would be inappropriate for me to say, but we will update in due course once we've got something to tell everybody about. And John, with respect to the catapult.
So there was the second one.
Then I'll hand over to John longer Archie patient supply officer to talk about the manufacturing cost about.
So with respect to second one we've not given any further details as to the structure of PD. One combination study so be inappropriate for me to say, but we will update in due course.
Once we got somebody to tell everybody about John we construct Campo.
John Lunger: Yes, so on Catapult, as you might know, we do our viral vector there. As a matter of fact, we just completed our first manufacturing of a GMP batch for our viral vector. So the short answer is no, we have not seen the same disruptions that other companies have seen out of that facility.
Yes on catapult as as you might know we do our viral vector there as a matter of fact, we just completed our first manufacturing ever GMP batch.
For our viral vector so the short answer is no we have not seen the same disruptions and other companies have seen out of that facility.
No.
Okay. Good thank you.
John Lunger: Okay, good. Thank you.
Thanks.
Operator: Thanks.
Our next question comes from Jonathan Chang of SB STB Leerink. Your line is open.
Operator: Our next question comes from Jonathan Chang of SBB Lyric. Your line is open. Good morning, and thank you for taking my questions. I just have... This is John Barrett on behalf of Jonathan. Just a couple of questions. Can you provide a status update for the low radiation sub-study and when we might expect to see data from that study?
Good morning, and I'm thinking for taking my questions.
Just have.
This is John bad on for Jonathan just a couple of questions can you provide a status update for the low radiation. So sub study and when we might expect to see data from that study.
Adrian G. Rawcliffe: Yep. So that study is enrolling, and as you know, I just want to point out, it's a 10 patient, up to 10 patient cohort at Single Centre University, MD Anson Cancer Centre, and so we are enrolling patients to dose, but we will have data from that in 2020. And the only other thing I will point out, just for level-setting purposes on this particular study. If you look at the...
Yes.
So it does not study is enrolling and as you know I just want to point out. It's a it's a 10 patients up to 10 patient cohort.
Single Senza University, MD Anderson cancer Center and so.
We are easy it in rolling and dosing patients, but we will have data from that in 2020 .
At the only other thing I will point out just.
The level setting purposes on this this particular study if you look at the.
Adrian G. Rawcliffe: If you look at the data that has given us confidence that low-dose radiation can drive T-cell infiltration into tumors, those data indicate that the responses often come many months after the radiation administration. And so I just want to give a warning that the timeline might not be the classical timeline that we're seeing in our sarcoma studies where within 6 weeks, 12 weeks, you're seeing responses.
If you look at the.
Data that has given us.
Confidence the low dose radiation can drive T cell and protection to chambers.
Those data indicate that the responses.
Often come many months off.
The radiation administration, and so I just want to give a warning that the timeline might not be the classical timeline that we're seeing in our sarcoma studies, where within six weeks 12 weeks youre seeing responses.
Adrian G. Rawcliffe: Interesting. Thank you for that color. And one additional one. Can you expand on your reasons for confidence in the PD-1 combo? And what types of tumor types would you imagine focusing in on for that trial in the future?
Interesting. Thank you for that color and one additional one can you expand on your reasons for competence in the PD, one combo and what type of tumor types would you envision focusing in on for that trial in the future.
Adrian G. Rawcliffe: So, we will be talking about some of the reasons for the confidence in the poster that we are presenting at CITSI shortly, and so it would be...
So we will be talking about some of the reasons for the confidence that the post the but we are presenting got fit C.
Shortly and so it would be inappropriate for me too.
Adrian G. Rawcliffe: in a
Adrian G. Rawcliffe: inappropriate for me to... comment on this. I think that the SITC poster is on Friday, the presentation is Friday, and so I'm not going to comment on that for obvious reasons, and we've not stated the tumor types yet or the nature of that study.
Comment on this topic that city poster is on Friday.
Inundations Pride I and so.
I'm not going to comment on that for obvious reasons and we've not been we've not stated of the tumor types yet.
All the nature of that study.
Thank you.
But.
There are no further questions like to turn the call back over to Adrian Rawcliffe for any closing remarks.
Adrian G. Rawcliffe: There are no further questions. I'd like to turn the call back over to Adrian Rawcliffe for any closing remarks.
Adrian G. Rawcliffe: Thank you all for your time today, and thank you also for your ongoing interest in our journey to bring effective T cell therapies to people with cancer and thereby deliver value for our investors. I look forward to updating everybody on the emerging data from the ADPA2AFP study and the sparse trials in the first half of 2020. Thank you again, and enjoy the rest of your day.
Thank you everyone for your time today I then thank you also for your ongoing interest in our journey to bring effective T cell therapies to people with cancer and thereby to deliver value for our investors I look forward to updating everybody.
On the emerging data on the IBP eye to eye a piece study on the small straws in the first half of 2020 . Thank you again and enjoy the rest of your day.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.