Q4 2020 Evelo Biosciences Inc Earnings Call
Okay.
Welcome to <unk> Biosciences conference call to discuss the fourth quarter and full year 2020 financial results and business highlights.
Operator: Welcome to Avelo Biosciences' conference call to discuss the fourth quarter and full year 2020 financial results and business highlights. At this time, all participants are in listen-only mode. Following the formal remarks, we will open the call up for your questions. Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn the call over to Jessica Catrone of Avelo. Please proceed.
At this time, all participants are in listen only mode.
Following the formal remarks, we will open the call up for your questions.
Please be advised this call is being recorded at the company's request.
At this time I'd like to turn the call over to Jessica Cotrone of Hello. Please proceed.
Jessica Catrone: Thank you. This morning, we issued a press release that outlines the topics we plan to discuss today. This release is available at www. EveloBio.com under the Investors tab. Today on our call, Cynda Gill, Chief Executive Officer, Mark Bodmer, President of R&D and Chief Scientific Officer, and Jonathan Zung, Chief Development Officer, will review our fourth quarter and full year 2020 financial results and recent business highlights. Before we begin, I would like to remind everyone that statements made during this conference call that do not relate to matters of historical fact, including statements about our objective and anticipated clinical milestones, the impact of any of our product candidates, and the timing and results of any clinical studies, should be considered forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
Thank you. This morning, we issued a press release that outlines the topics we plan to discuss today.
Relief is available at Www Dot <unk> dot.
Dot com under the investors tab today, and our call Simba Gill Chief Executive Officer, Mark Bodmer, President of R&D, and Chief Scientific Officer, and Jonathan Zhang Chief Development Officer will review, our fourth quarter and full year, 2020 financial results and recent business highlights before we begin I would like to remind everyone that state.
<unk> made during this conference call that do not relate to matters of historical facts, including statements about our objectives and anticipated clinical milestones and the impact of any of our product candidate and the timing and results of any clinical studies should be considered forward looking statements within the meaning of the private Securities Litigation Reform Act of 1009.
Five such forward looking statements are intended to be subject to the safe Harbor protection provided by the Reform Act actual results could differ materially from those indicated by the forward looking statements due to the impact of many factors.
Jessica Catrone: Such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. However, actual results could differ materially from those indicated by the forward-looking statements due to the impact of many factors. Participants are directed to the risk factors set forth in Evelo's annual report on Form 10-K for the fiscal year ended December 31, 2020, and the company's other filings with the Securities and Exchange Commission. Any forward-looking statements made today speak only to Evelo's operations as of today. Evelo disclaims any duty to provide updates to its forward-looking statements even if subsequent events cause the company's views to change. It is now my pleasure to pass the call over to Simba. Thank you, Jessica.
Participants are directed to the risk factors set forth and <unk> annual report on form 10-K for the fiscal year ended December 31, 2020, and the company's other filings with the Securities and Exchange Commission any forward looking statements made today speak only to <unk> operations as of today and <unk> disclaims any duty to provide updates to it.
We're looking statements even if subsequent events cause the company's views to change. It is now my pleasure to pass the call over to Simba.
Thank you Jessica good morning, everyone and thanks for joining.
Simba: Thank you, Jessica. Good morning everyone, and thanks for joining us. Over the last four years, we've generated clear preclinical and clinical data that show the effects of a small intestinal axis or syntax medicines, investigational medicines designed to work within the small intestine to change inflammation and immunity throughout the body. Syntax medicines have the potential to be not only effective, but easy to take, safe, and well-tolerated, and with the ability to be manufactured at large scale and low cost.
Over the last four years, we've generated clear preclinical and clinical data with.
And that showed the effects of a small intestinal axis or syntax medicines investigational medicines designed to work within the small intestine to change inflammation and immunity throughout the body.
Syntax medicines have the potential to be not only effective but easy to take safe and well tolerated and with the ability to be manufactured and.
<unk> scale and low cost.
And over the last 18 months, we have reported a series of clinical successes with the Edp $18 15, our lead anti inflammatory medicine candidate.
Simba: And over the last 18 months, we have reported a series of clinical successes with EDP-1815, our lead anti-inflammatory medicine candidate. In 1815, there have been clinical effects on Th1, Th2, and Th17-driven biology, the three major drivers of inflammatory disease, supporting the potential of EDP1815 as a broadly acting, well-tolerated oral medicine that may resolve inflammation without immunosuppression. Most recently, in December and January, we presented positive results from a cohort of patients with atopic dermatitis in our Phase 1B clinical trial, and today we are reporting a fifth set of positive clinical data with EDP1815.
And the 18, 15, escrow and clinical effects on ph, one ph two and th 17, driven biology, the three major drivers of inflammatory disease.
Supporting the potential of ETP 18, and 15.
And we'll be asking well tolerated oral medicine that may.
And resolve inflammation without immunosuppression.
Most recently in December and January we presented positive results from a cohort of patients with atopic dermatitis and all.
Phase <unk> clinical trial.
And today, we are reporting a fifth set of positive clinical data with Edp 18 and 15.
Today's announcement relates to human clinical experimental model of inflammation that evaluated a new more concentrated formulation of Edp 18 and 15.
Simba: Today's announcement relates to a human clinical experimental model of inflammation that evaluated a new, more concentrated formulation of EDP 1815. These new data suggest an ability to enhance the efficacy of EDP 1815. Mark will tell you more about this in a moment.
These new data, suggesting and ability to enhance the efficacy of Edp 18 15.
Mark will tell you the details of this and above.
And.
This is a time of great growth and progress for value as we execute on a series of clinical studies over the next year and.
Simba: This is a time of great growth and progress for Avelo as we execute on a series of clinical studies over the next year in preparation for Phase III trials. Jonathan will tell you more about our clinical studies and plans later in the call. Importantly, EDP1815 and our other inflammation programs, EDP 1867 and EDP 2939, go far beyond dermatology in their potential, and we intend to expand into broader areas of inflammation, including diarthritis, asthma, and inflammatory bowel disease. Additionally, beyond inflammation, we continue to develop our oncology program. Data from a preclinical study of EDP-1908, a bacterial extracellular vesicle, were published at CITSI in November.
Declaration two phase III trials.
Jonathan will tell you more about from clinical studies and plans later in the call.
Importantly, Edp 18, 15, and our other inflammation programs E D.
$18 67, and Edp 2000 1939.
Go far beyond dermatology and that potential and we intend to expand into broader areas of inflammation, including Dr. Richard These asthma and inflammatory bowel diseases.
Beyond inflammation, we continue to develop our oncology program.
Data from a preclinical study of Edp and 19, Oh wait a bacterial extracellular vehicle was published at Citi and November.
Simba: EDP-1908 has the potential to be a foundational immuno-oncology treatment for cancer. In building the company, we have expanded our leadership, hiring Jonathan Zung as Chief Development Officer to lead the execution of our clinical development program, and the recent appointment of John Honaker to our Board of Directors. Both Jonathan and John have deep and highly successful track records in drug development, regulatory approval, and commercial launches across inflammation and oncology. We have also strengthened our balance sheet and have the capital to fund the company past the next wave of clinical milestones and into the third quarter of 2022.
Edp and 19 awake and has the potential to be a foundational and me.
Oncology treatment and cancer.
And building the company, we have expanded our leadership hiring Jonathan zone, as Chief Development officer to lead execution of our clinical development programs.
And the recent appointment of John <unk> to our board of directors.
Both Jonathan and John had deep and highly successful track record and drug development regulatory approval and commercial launches across inflammation and oncology.
We've also strengthened our balance sheet and have the capital to fund the company pass the next wave of clinical milestones and into the third quarter of 2022.
Our main objectives first.
Simba: Our main objectives are, first, to complete a Phase II trial of EDP1815 in psoriasis, to also initiate a Phase II trial of EDP1815 in atopic dermatitis, and to begin preparations for Phase III trials of EDP1815. The second objective is to continue to progress a current clinical pipeline beyond ADP 1815, including EDP1867, where we're looking to generate clinical results. The third objective is to complete preclinical and manufacturing development of our inflammation and oncology extracellular vesicle drug candidates so that they are ready for clinical trials in 2022.
First to complete our phase II trial of Edp, 18, 15 and psoriasis.
To also initiate a phase two trial of Edp 18, and 15 in atopic dermatitis.
And to begin preparations for phase III trials, all the Edp 18 and 15.
Second objective.
We continue to progress.
Clinical pipeline beyond DDP $18 15.
Including Edp, 18, 67, where we're looking to generate clinical results.
With a separate anti inflammatory medicine.
And third objective is to complete preclinical and manufacturing development of our inflammation and oncology extra cellular vehicle drug candidates to be ready for clinical trials and 2022.
Simba: I'd like to turn the call over to Mark, who will talk to you about data on EDP 1815 in a Human Experimental Model of Inflammation, and to Jonathan, who will then summarize our clinical plan. Mark, over to you. Thank you.
I'd like to turn the call over to Mark who will talk to you about data on Edp 18 and 15.
And the human experimental and model of inflammation and to Jonathan who will then summarize our clinical plans.
Mark over to you.
Thank you.
I'd say the fed we've tested <unk> in humans and a higher concentration.
Mark: As Siva said, we've tested EDP-18-cysteine in humans at a higher concentration, not a higher dose, a higher concentration of the drug in each capsule. The data show that a higher concentration formulation had a greater effect at the same dose in a less concentrated formulation.
Does the higher concentration of the drug and each capsule.
The data show that a higher concentration formulation and a greater effect and the same dose and a less concentrated formulation.
Mark: This is a key advance in our understanding of how to get more effect from Syntax medicines.
This was a key advance and our understanding of how to get more effect from syntax medicines.
Over the last year and a half we reported a consistently positive series of full clinical results with Edp 18, 15. These trials abuse Edp 18, 15, there's a freeze dried powder and it's hurt.
Mark: Over the last year and a half, we've reported a consistently positive series of four clinical results with EDP1815. These trials used EDP1815 as a freeze-dried powder in enteric-coated capsules, which protect the drug from the acidity of the stomach and release the drug when the capsules get into the small intestine. We now have a fifth positive clinical reading in a human clinical experimental model of inflammation that showed this increase in the concentration of drug in the capsule resulted in an enhanced effect for the same overall dose and also allowed pure capsules to deliver that same overall dose. The increased concentration of drug results from improvements made in the commercial-scale manufacturing process. It's the same active drug at four times the concentration. We call this A2.
Coated capsule, which protect the drug from the acidity of the stomach and release the drug when the capsules get into the small intestine we.
We now have our fifth positive clinical reading and the human clinical experimental model of inflammation, but showed this increase and the concentration of drug and the capsule resulted in enhanced effects with the same overall boat and also allow pure capsules to live at that same day.
The increased concentration of drug results from improvements made and the commercial scale manufacturing process and it's the same active drug at four times that concentration we call. This a to.
Mark: The EDP-1815, which has repeatedly demonstrated positive effects on clinical scores in psoriasis and atopic dermatitis, is A'. It is currently being tested in the Phase II psoriasis trial. Now, in preclinical experiments, if we increase the concentration of the drug, we observe superior effects, a classic dose response. So far, though, the only option we've had in the clinic to increase the dose is to ask people to ingest more capsules. This increases the total dose that the patient swallows but does not necessarily alter the drug concentration for activity in the small intestine. This is because of gradual emptying from the stomach, which has been suspected for some time that there is more to dose response in humans than simply giving more capsules.
The Edp $18 15, which has repeatedly demonstrated positive effects on clinical scores and psoriasis and atopic dermatitis is a prime a prime is currently being tested and the phase III psoriasis trial.
And our preclinical experiments if we increase the concentration of drug we observe superior effects a classic dose response.
So far though the only option we've had in the clinic to increase the dose is to ask people to address more capsules. This.
This increases the total dose the patient flows but does not necessarily also the drug concentration.
And for activity and the small intestine and this was because of gradual and seeing from the stomach.
We suspect it for some time that there was more to dose response in humans from simply giving more capsules.
If you recall the results and the low and high dose cohorts of patients with psoriasis and all phase one B trial, both doses result, and similar clinical responses, even though one group from two capsules a day and the other took 10.
Mark: If you recall the results in the low- and high-dose cohorts of patients with psoriasis in our Phase 1b trial, both doses resulted in similar clinical responses, even though one group took two capsules a day and the other took ten. So, learning from preclinical results, we compared two strengths of EDP1815 capsules head-to-head in a human clinical inflammation model, where volunteers were imm After 28 days of oral treatment with EDP1815 or placebo, subjects were given a skin challenge with the same antigen, which caused measurable skin inflammation a day later.
So learning from preclinical results, we compared to strength of Edp 18, 15 capsules head to head and the human clinical inflammation modal book.
Volunteers were immunized with the same average and we use and preclinical inflammation experiments.
After 28 days of oral treatment with <unk> or placebo subjects will give her and her skin challenge with the same antigen, which causes measurable skin inflammation a day later.
Mark: 12 subjects were given 10 capsules of A'EDP1815. Another 12 subjects were given the same total dose of drug using the higher concentration A2-EDP1815 in fewer capsules, and there were eight subjects who received placebo divided between the two treatment groups. Both A' and A2 were effective. However, new today is that the higher A2 concentration given in fewer capsules resulted in numerically superior reductions across the full range of skin inflammation scores
12 subjects were given 10 capsules.
Prime Edp 18 15.
Another 12 subjects were given the same total dose of drug using the higher concentration to Edp, 18, 15, and fewer capsules and or <unk>.
Subjects, who received placebo divided between the two treatment groups.
Both a prime and a two were effective.
New today is that the higher a two concentration given and fewer capsules resulted and numerically superior reductions across the full range of skin inflammation scores five measures of inflammation, including basal blood flow by laser Speckle contrast imaging and for other readings of swelling flat redness and skin color.
Mark: 5 measures of inflammation, including basal blood flow by laser speckle contrast imaging and four other readings
Mark: and other readings of swelling, flare, redness, and skin color all show an improved effect of A2 over A' EDP 1815. In the press release accompanying this conference call, we include a figure showing the data that compare A' and A2. You will clearly see the differences, which we expect to translate into even better clinical scores in patients.
All show and approved effect of <unk> over a prime GBP 18 2014.
And the press release accompanying this conference call. We include a figure showing the data the compare a prime and a too you will clearly see the differences, which we expect to translate into even better clinical scores and patients.
For people and I said earlier this was a key evolves and our understanding of how to get ever more from syntax medicines capsule of tablet formulations with this quadruple concentrated drug will be used and future clinical trials of <unk> hundred 15.
Mark: To repeat what I said earlier, this is a key advance in our understanding of how to get ever more from syntax medicine.
Jonathan: Capsule and tablet formulations of this quadruple concentrated drug will be used in future clinical trials of EVP18-15. And what we are learning with EVP18-15, we expect to be able to apply to other product candidates in our pipeline. I'd now like to turn the call over to Jonathan to tell you about clinical plans for the next 18 months. Thank you, Mark, and good morning, everyone. I'm Jonathan Zung, Chief Development Officer at Avelo.
And what we're learning with Edp 18, 2014, we expect to be able to apply to other product candidates and our pipeline.
I would now like to turn the call over to Jonathan to tell you about clinical plans over the next 18 months telecom.
Thank you Mark and good morning, everyone.
Jonathan Zhang Chief Development Officer at Belo Im excited to join the Belo as we move to later stage drug development and closer to bringing a new and potentially transformative modality of medicine to patients around the world.
Jonathan: I'm excited to join Avelo as we move to later stage drug development and closer to bringing a new and potentially transformative modality of medicine to patients around the world. Over the last decade, I've had the privilege of leading the clinical operations organizations at Bristol-Myers Squibb, UCB, and COVAD. Through these roles, I have worked across various disease areas and all stages of development. As Mark and Simba mentioned, we have a catalyst-rich 18 months ahead of us.
Over the last decade, I've had the privilege to lead the clinical operations organizations at Bristol Myers Squibb, UCB and Covance through these roles I've worked across various disease areas and all stages of development.
And as Mark and Simba mentioned, we have a catalyst rich 18 months ahead of us for Edp Atms 15, our focus is on setting the stage for the phase III programs and psoriasis and atopic dermatitis.
Jonathan: For EDP1815, our focus is on setting the stage for the Phase III programs in psoriasis and atopic dermatitis. This means ensuring that we have identified the appropriate formulation and doses that will be used in the registrational study. Let me first discuss EVP 1815 in psoriasis. Our Phase 2 dose-ranging trial in psoriasis has completed enrollment ahead of schedule. This is quite remarkable given the COVID challenges.
And this means ensuring we have identified the appropriate formulation and doses that will be used and the Registrational studies.
Let me first discuss Edp 18, 15 and psoriasis.
Our phase two dose ranging trial in psoriasis has completed enrollment ahead of schedule. This is quite remarkable given the COVID-19 challenges.
Jonathan: Given the speed of recruitment, we will forego the interim readout and report top-line data for the full cohort of patients in the third quarter of this year. As a reminder, this is a 16-week trial evaluating three doses of A-prime EDP1815 in capsules versus placebo in approximately 225 patients with mild to moderate psoriasis. The primary endpoint is the mean percentage change in PASI score at 16 weeks.
Given the speed of recruitment, we will forgo the interim readout and report top line data for the full cohort of patients and the third quarter of this year.
As a reminder, this is a 16 week trial evaluating three doses of the a prime EVP and <unk> 15, and capsules versus placebo and approximately 225 patients with mild to moderate psoriasis the.
The primary endpoint is the mean percentage change and Patsy score at 16 weeks secondary endpoints include a range of scores of clinical efficacy and psoriasis, both physician and patient reported outcomes.
Jonathan: Secondary endpoints include a range of scores for clinical efficacy in psoriasis, both physician and patient-reported outcomes. We'll also be evaluating tablet and capsule formulations using the higher concentration A2-EDP1815 in three cohorts of patients with mild to moderate psoriasis as an extension of our Phase 1b trial. The purpose of these three cohorts is to select the most appropriate formulation, either tablets or capsules, for the Phase III program. The data will also allow us to further characterize the effect of the more concentrated A2 and to determine any potential benefits of using a tablet versus a capsule formulation. Each cohort will have 24 participants, 16 on EDP1815 and 8 on placebo. Dosing will be once daily for 56 days, followed by a 14-day follow-up.
We will also be evaluating tablet and capsule formulations using the higher concentration to Edp 18, and 15 and three cohorts of patients with mild to moderate psoriasis and and an extension of our phase one b trial.
The purpose of these three cohorts is to select the most appropriate formulation either tablets or capsules for the phase III program. The data will also allow us to further characterize the effect of the more concentrated <unk> and to determine any potential benefits of using tablet versus the capsule formulation.
Each cohort will have 24 participants 16 on Edp, 18th 2015, and eight on placebo dose wouldn't be once daily for five six days followed by a 14 day follow up.
The first cohort is evaluating the efficacy of Edp 18, and 15, eight two and a tablet formulation with four tablets the so-called eight X dose dosing has begun and we anticipate data and the third quarter of this year the.
Jonathan: The first cohort is evaluating the efficacy of EDP-1815A2 in a tablet formulation with four tablets, the so-called 8X dose. Dosing has begun, and we anticipate data in the third quarter of this year. The second cohort will evaluate the efficacy of EDP-1815A2 in a capsule formulation. This will be a single daily capsule comprising a 2X dose.
The second cohort will evaluate the efficacy of Edp 18, and 15, eight two and a capsule formulation.
This will be a single daily capsule, comprising a <unk> dose.
Jonathan: The final cohort will evaluate the efficacy of EDP1815A2 in a tablet formulation, but the EDP1815 subjects will be dosed with one tablet rather than the four tablets in the first cohort, another 2x dose. We anticipate initiating the 2nd and 3rd cohorts in the 2nd quarter of this year. Initial results from these three cohorts will be available in Q3, along with data from the Phase II psoriasis study. Together, this information will position us to go forward into Phase III trials with an optimized dose and formulation of EDP1815.
The final cohort will evaluate the efficacy of Edp 18, and 15, eight two and a tablet formulation, but the ETP $18 15 subjects will be dosed with one tablet rather than the four tablets and the first cohort another two X dose.
We anticipate initiation of the second and third cohorts in the second quarter of this year.
Initial results from these three cohorts will be available in Q3, along with data from the phase two psoriasis study.
Together this information will position us to go forward into phase III trials with the optimized dose and formulation of Edp 18 and 15.
Jonathan: Moving on to EDP1815, an atopic dermatitis treatment. We announced positive confirmatory Phase 1b data in January. All physician-reported measures of disease activity, EZ, IgA times BSA, and SCORAD showed a greater than 50% improvement in treatment with EDP1815 versus placebo. We also saw improvements in patient-reported outcomes, including the important areas of sleep and itch.
Moving onto EVP, and <unk> 15, and atopic dermatitis, we announced positive confirmatory phase <unk> data and January all physician reported measures of disease activity easy Iga times, BSA and score adds showed a greater than 50% improvement and treatment with <unk>.
<unk> versus placebo.
We also saw improvements and patient reported outcomes, including the important areas of sleep and edge.
Jonathan: EDP 1815 was well tolerated in this cohort with no treatment-related adverse events of moderate or severe intensity and no serious adverse events. We are on track to initiate the Phase 2 atopic dermatitis trial in the third quarter of this year. This will be a double-blind, placebo-controlled, multiple-cohort, adaptive design trial in participants with mild, moderate, and severe atopic dermatitis. It will use EDP 1815 A2. We will provide more details on this Phase 2 trial next quarter.
<unk> was well tolerated and this cohort with no treatment related adverse events of moderate or severe intensity and no serious adverse events.
We are on track to initiate the phase III atopic dermatitis trial and the third quarter of this year. This will be a double blind placebo controlled multiple cohort adaptive design trial and participants with mild moderate and severe atopic dermatitis. It will use ETP 18 15 eight two.
We will provide more details on this phase II trial next quarter during.
Jonathan: During the first quarter of this year, we also initiated a Phase 1B trial of EDP-1867 that will evaluate safety and efficacy in healthy volunteers and patients with mild atopic dermatitis. The study design includes the option to include cohorts of patients with mild psoriasis and or mild asthma. The five cohorts will be studied in this Phase 1 trial.
During the first quarter of this year. We also initiated a phase one b trial of Edp 18, 67 that will evaluate safety and efficacy and healthy volunteers and patients with mild atopic dermatitis study design includes the option to include cohorts of patients with mild psoriasis <unk> Meyer.
Asthma up to five cohorts will be studied in this phase one trial.
Cohorts, one and two of the Edp 18, 67 trial will be healthy volunteers cohort three will be patients with moderate atopic dermatitis. It will include a 56 day treatment period, followed by a 14 day follow up at the end of the treatment period.
Jonathan: Cohorts 1 and 2 of the EDP 1867 trial will be healthy volunteers, and cohort 3 will be patients with moderate atopic dermatitis. It will include a 56-day treatment period followed by a 14-day follow-up at the end of the treatment period.
Jonathan: Just a reminder that EDP1867 is from a different genus to EDP1815 and has been rendered non-live by gamma irradiation. EDP1867 has demonstrated robust anti-inflammatory effects in preclinical models of Th2 biology. By testing it in patients with atopic dermatitis, we will learn about its potential in treating Th2-mediated diseases.
Just a reminder, that Edp 18, 67% is from a different genus to ETP 18, 15 and has been rendered non live by gamma irradiation.
And 67 has demonstrated robust anti inflammatory effects in preclinical models of th two biology by testing it and in patients with atopic dermatitis, we will learn about its potential and treating th two mediated diseases.
Jonathan: All our other clinical programs are on track, as you can read in the press release we distributed today. I look forward to updating you on our programs during future calls. Now, I'll hand it back to Simba for closing remarks. Thanks, Jonathan.
All of our other clinical programs are on track as you can read and the press release, we distributed today.
Look forward to updating you on our programs during future calls now I'll hand, it back to Simba for closing remarks.
Thanks, Jonathan.
I wanted to conclude by reminding everyone that syntax is not just another biotech platform.
Simba: I wanted to conclude by reminding everyone that Syntax is not just another biotech platform, and EDP1815 is not just another biotech product candidate. We believe that syntax-based medicines have the potential to completely transform medicine globally, and that EDP1815 has the potential to be one of the world's most important medicines. We've already shown that EDP 1815 has the efficacy and profile to become a major medicine for unmet needs in patients with atopic dermatitis and psoriasis.
And Edp <unk> is not just another biotech product candidate.
We believe that syntax based medicines have the potential to completely transform medicine globally and that Edp <unk> has the potential to be one of the world's most important medicines.
We've already shown the Edp 18, 15 has the efficacy and profile to become a major mentioned from unmet needs of patients with atopic dermatitis and psoriasis.
Our expectations for psoriasis phase two study based on the phase <unk> data unchanged.
Simba: Our expectations for the psoriasis phase 2 study based on the phase 1b data are unchanged, and we remain on course to start the Phase III program in 2022, with an optimized dose and formulation of EDP1815. Today's results elevate its potential efficacy even further. This will apply both to skin diseases and much more broadly to inflammation.
And we remain on course to start the phase III program and 2022.
With an optimized dose and formulation of Edp $18 15.
Today's results and.
<unk> its potential efficacy even further.
And this will apply both to the skin diseases are much more broadly and inflammation.
Operator: To reinforce what Mark told you, the strides we are making with EDP1815 will apply to the whole Ebelo platform across our wide portfolio and range of clinical applications, and we continue to expand our portfolio with the new anti-inflammatory EDP-1867 and with our bacterial extracellular vesicle programs, EDP-1908 for oncology and EDP-2939 for inflammation. What we've highlighted today is possible because of the exceptional work of the team at Avelo and our external partners.
To reinforce what Marc told you. The strides we are making with Edp $18 15 will apply to the whole of <unk> plus platform across a wide portfolio and range of clinical applications.
And we continue to expand our portfolio with the new anti inflammatory Edp, 18, 67, and without bacterial extra cellular vehicle programs.
19, and wait for oncology and Edp 2939 for inflammation.
What we've highlighted today is possible because of the exceptional work the team and develop and our external partners.
Operator: Thanks to all of you. We have a data-rich 18 months ahead of us, and we look forward to updating you as our programs progress during the year. We'll now open the call to take questions. Thank you. Ladies and gentlemen, as a reminder to ask a question, you will need to press the star and then one on your telephone. To withdraw your question, press the pound key. Again, that's Star 1 to ask the question. Please stand by while we compile the Q&A.
Thanks to all of you.
We have a data rich 18 months ahead of us and look forward to updating you as our programs progress during the year.
We'll now open the call to take questions.
Thank you, ladies and gentlemen, and as a reminder to ask a question you will need to press Star then one on your telephone.
To withdraw your question press the pound key.
Again, Thats star one to ask a question. Please standby, while we compile the Q&A roster.
Operator: Please stand by while we compile the Q&A roster. Our first question comes from the line of Chris Howerton with Jeffries. Your line is open.
Our first question comes from the line of Chris Howerton with Jefferies. Your line is open.
Excellent and good morning, and thanks, so much for taking the questions and.
Chris Howerton: Excellent. Good morning, and thanks so much for taking the questions. And congratulations on the very broad progress.
And congratulations on the very broad progress.
Thanks, Chris I appreciate it.
Simba: Thanks, Chris. I appreciate it. Of course.
Of course, yeah, So I guess.
Chris Howerton: Of course, yes. So I guess, you know, the first one, perhaps, is a question for Mark. With respect to the skin inflammation experimentation that you've done, I think, if I recall correctly, this was a model that your team had developed. Has this ever been published?
The first one.
<unk> is a question for Mark.
With respect to the skin inflammation and experimentation that you've done I think as I recall correctly, and if I recall correctly excuse me and this was a model that your team and had developed has this ever been published and I guess, I'm, particularly interested and any kind of human exposure to this experimental design is.
Mark: And I guess I'm particularly interested in any kind of human exposure to this experimental design, if that's been published at all. And a second question that I would have is with respect to the drug product and formulation work that you're doing recently, in terms of the higher concentrations at the different levels of efficacy that you're observing. How is it that you're thinking about these learnings more broadly in terms of, you know, what is that target product profile with respect to formulation?
That's been published at all.
And.
Second question that I would have is that with respect to that.
And the drug product and formulation work that Youre doing recently in terms of the higher concentration and.
And the different levels of efficacy that youre observing.
How is it that youre thinking about these learnings more broadly in terms of.
What is that target product profile with respect to formulation is it a bacterial cell is and extra cellular vehicle is it.
Mark: Is it a bacterial cell? Is it an extracellular vesicle? Is it, you know, a gamma-irradiated organism? You know, what is the kind of ideal form factor that you're aiming for? And I think that's probably good. I'll stop there.
And gamma irradiated org.
Oregon Ism.
What is kind of the ideal form factor that youre aiming for.
And I think that's probably get us out there.
Okay.
Simba: Mark, if you want to take the first question, I'll take the second.
Okay do you want to take the last question and I'll take the second.
Mark: Okay, yeah, very good. So the human DTH skin model was developed at the Center for Human Drug Research in Leiden, in the Netherlands, where our collaborators are doing these experiments, and they have used a number of other agents in the skin model, and it's the odd thing if you dig around on websites, but there hasn't been a formal publication of this, and we will be publishing with them on this, and they may well be publishing with some of the other partners But late-type hypersensitivity in humans, of course, is not new. This particular protocol with keyhole-linked adenosine is one that they developed precisely to do this kind of experimental medicine.
Okay very good.
Human Dth skin model was developed with the set of human drug research and lightning and the Netherlands, where our collaborators.
Doing these experiments and they have used.
A number of other agents that have been.
Publications, and posters and the old, saying you could dig around on websites, but there hasn't been.
A formal publication of this and we will be publishing with them on this and they may well be publishing with some of the other partners.
And that they work on it but it's.
Delayed type hypersensitivity and humans and of course, it's not there's not new this particular protocol with keyhole limpet hemocyanin as one of the base develop precisely to do this kind of experimental medicine testing.
Simba: Okay, let me take the first question, Chris. So the most important thing is that we have, with EDP1815 and the current formulation, something that we're very confident in as a product we'll take forward. So, as we said, we're going full speed ahead with the intention to move into the Phase 3 side of things next year. We'll get the Phase II data in psoriasis very soon now on the full study, and we're feeling very confident in that lead product.
Okay, Let me take the first question Chris.
So the most important thing is that.
We have with <unk> 15, with the current formulation.
Something that we're very confident and as a product and we'll take forward.
So and we said we're going full speed ahead with it and to move into the phase three side of things next year.
Once we get the phase II data in psoriasis.
Soon now and the on the full study and we're feeling very confident and that and that leads per month.
Simba: Today's announcement obviously gives us an ability to very easily further improve the activity and efficacy beyond the great results we've seen already without meaningfully impacting the Phase III results. So the core point there, Chris, is we see 1815 in its current form as a very exciting product, and we intend to move that forward. From a longer-term perspective, what we've always said is that this is very similar to the experience Mark and I have had since the beginning of antibodies. As you know, Mark and I were both involved.
Today's announcements, obviously gives them the ability to very easily and further improve the activity and efficacy beyond the great results we've seen already.
Without meaningfully impacting phase III results. So the co point that Chris says.
We see $18 15, and its current form is a very exciting product and we intend to move that forward from.
Longer term perspective, what we've always said.
This is very similar to the experience Mark and I have had since the beginning of antibodies as you know Mark and I were both involved.
35, plus years ago.
Simba: 35 plus years ago, we were scratching our heads about that at the beginning of the monoclonal antibody world. And, you know, we're both so old that when we started working together, we were working on mouse antibodies, which was kind of cutting edge at the time. Mark's team at Celltech was one of the first groups in the world to come up with chimeric antibodies, and then we moved to CDR grafted antibodies, and then we moved to fat fragments.
And our heads about that.
And the beginning of the monoclonal antibody world and.
And what both sold that when we started working together, we will walk Youll mouse antibodies, which was kind of cutting edge Mark's team and cell type.
It was one of the first groups and the world to come up with Chimeric antibodies and then we moved the CVR graph does antibodies and then we'd move to correct. Once again, Mark you did a lot of work.
Simba: Again, Mark's team did a lot of that work. And to continue, as you know, Chris, we have uncovered, with the small intestinal axis, a fundamental area of biology as a whole new target for medicines. It has never existed before.
And if you continue as you know Chris so.
We have uncovered with the small intestinal axis, a fundamental area of biology as a whole new target for medicines, it's never existed before so there's going to be continual Inc.
Simba: So there's going to be continual evolution and innovation and improvement. What we said when we started the company was that we wanted to go far beyond Genentech. So getting to a $100 billion valuation, if you want to use those crude terms, is good. But actually, as the first company in the world to open up the small and the Tesla access, we want to make sure we're always the leaders, and we capture the breadth of the opportunity.
Felicia and and innovation and improvement.
And what we said when we started the company.
Was that we wanted to go far beyond Genentech, so getting to $100 billion valuation. If you want to use that as crude terms is good but actually is the first company in the world and open up the small intestinal axis, we want to make sure. We're always the leaders and we capture the breadth of the opportunity. So in that context, we're going to continue to invest Chris.
Simba: So in that context, we're going to continue to invest, Chris. We expect that there is a possibility, whether it's from EVs or other things, that we can get antibody-like efficacy in the end. And that would obviously be a pretty remarkable result that goes far above and beyond what we need to do to have a very important product in 1815. And we'll certainly work towards that as an ultimate goal, which would be an oral, very safe, well-tolerated, highly effective drug that was affordable. And that's always been our goal to get to that point, Chris. That'll take a bit of time, but in the interim, we've got a great product in 1815.
We expect that there is a possibility whether it's from evs or other things that we can get antibody like efficacy ultimately and that would obviously be a pretty remarkable.
Result that goes far above and beyond what we need to do to have a very important product and $18 15, and we'll certainly what was that.
And ultimate goal, which would be an oral and very safe well tolerated highly effective drug that was affordable and.
And that's always been our goal to get to that point, Chris that'll take a bit of time, but and the interim we've got great products and <unk>.
Okay.
Chris Howerton: Okay. All right. Well, that's very fair, and I'll hop back in the queue. Thanks so much.
Well, that's that's very fair and all.
APAC and the queue. Thanks, so much.
Operator: Our next question comes from the line of Matt.
Thanks, so much growth.
Our next question comes from the line of Matthew Luchini from BMO Capital. Your line is open.
Operator: This is a call from the line of Matthew Lucchini with BMO Capital. Your line is open.
Matthew Lucchini: Hi, good morning. Thanks for the question. So, I guess also on the formulation, you know... The model data that you presented today certainly looks compelling, and I guess I'd just like to understand how we should think about the relative benefits that you'd expect to see in man, such that you would advance A2 over A prime. In other words, what would cause you to not advance A2 over A prime?
Hi, good morning, Thanks for the questions. So I guess also on the formulation.
And the model data that you presented and it certainly looks compelling and I guess I'd just like to understand.
How we should think about the relative what's your expectation from a relative benefit that you'd expect to see and man.
And what you would advance a two over a prime and other words, what would cause you to non advanced <unk> Walgreens Prime.
And then secondarily.
Matthew Lucchini: I'm just curious, on atopic dermatitis, like I've mistaken, the inclusion of severe patients is something new for Velo. The focus has previously been on more mild to moderate patients in both inflammatory groups. So I just wanted to get a little sense as to what the thinking is there, why, you know, sort of move into this new patient population where there's certainly a good amount of entrenched patients.
And just curious on the atopic dermatitis and lack.
And last couple of stake and the inclusion of severe patients with something new from a value focus has traditionally been a more mild to moderate patients and both inflammatory diseases.
And probably get a little sample from what the thinking is there why.
Sort of move into the fall and.
And new patient population, where there's certainly a good amount of entrenched competition.
Okay.
Thanks, Martin do you want to take the first question and then throw off cash.
Simba: Thanks Matt. Mark, if you want to take the first question and then Jonathan... but you can take the second. Yeah, I will. So, Matt, yeah, that's a very important question. It's the same drug.
But you can take the second.
Yes, so Matt.
Yes, that's quite important question, it's the same drug active drug.
Mark: active drug material in the concentrated form. We're moving forward with the A2 material; it's very clear that's the right thing to do. And as I said in the comments during the full part of the call, this concentration resulted from improvements in process as we scaled up to phase three at commercial scale as a result of reducing the ratio of active drug to it.
Material and the concentrated full we're moving forward with the <unk> material, it's very clear that's the right thing to do and as I said in my comments and the <unk>.
Total part of the call. This concentration resulted from improvements in processes, we've scaled up to phase III and commercial scale as a result of reducing the ratio of active drug to excipient, sorry, excipient to active drug and.
Mark: Excipient to active drug in the capsule. So it's a
And the capsules. So it's absolutely clear that we are going to move forward with this and actually the studies with Jonathan was telling you about what we're doing and the future.
Mark: So, it's absolutely clear that we're going to move forward with this, and actually, the studies that Jonathan was telling you about that we're doing in the future to look at capsules and tablets and then going into the Phase 2 atopic dermatitis study will all be done with the A2 material.
Capsules and tablets and that going into the phase II.
Topic dermatitis study will be done within Youtube channel.
Jonathan: Thanks, Mark. And Jonathan, do you want to talk about Matt's question on moving into the more severe atopic dermatitis patient? Sure.
Thanks, Mark and Jonathan do you want to talk about Matt's question on moving into the more severe atopic dermatitis patient segment.
Sure sure so Matt for the logic behind exploring that and the phase II study and the phase one study we looked at mild to moderate.
Jonathan: So, Matt, the logic behind exploring that in the Phase II study is that in the Phase I study, we looked at mild to moderate participants, and obviously, we saw good efficacy in that population. In the Phase II trial, we're really going to be exploring primarily moderate patients, but we want to have exposure to those more severe patients so we can understand the true potential of 18-15. So we'll likely look at, you know, 15-20% of the patients in the Phase II study will be severe. We'll look at some on the mild side, but most of those participants will be moderate patients. And it's really to better understand the profile of 18-15.
Participants, obviously, we saw a good efficacy and that population and the phase II trial were really going to be exploring primarily moderate patients, but we want to have also.
Exposure to those more severe patients. So we can understand the true potential of 18, <unk>. So we'll likely look at 15 and 20% of the patients in the phase II study will be severe we'll look at some on the wild side, but most of those participants will be moderate patients and it's really to better understand the profile of <unk>.
Matthew Lucchini: Okay, fair enough. Thank you. And congratulations on the product.
<unk>.
Okay Fair enough. Thank you and congrats on the progress.
Thanks, a lot and that.
Operator: Our next question comes from the line of Matthew Harris.
Thank you.
Our next question comes from the line of Matthew Harrison with Morgan Stanley. Your line is open.
Operator: This call is on the line of Matthew Harrison with Morgan Stanley. Your line is open.
Matthew Harrison: Great, good morning. Thanks for taking the questions. I guess there are two parts to this for me.
Great. Good morning, Thanks for taking the questions I guess I guess two parts from me one.
And but could you just clarify a comment that you made earlier, it sounds like which which of these.
Matthew Harrison: for me. One, Simba, could you just clarify a comment that you made earlier? It sounds like which one
Different.
I guess formulations are you going to move ahead with psoriasis and it sounded like Youre going to just continue to move ahead with a prime and and not a too. So maybe you could just clarify that for me I I was unclear on the comment you made it and then I guess the second question, which is.
Matthew Harrison: Different, I guess, formulations.
Matthew Harrison: Are you going to move ahead with psoriasis treatment?
Matthew Harrison: [inaudible] Similar to the last question, it's just about...
Similar to the last question was just about <unk>.
Simba: Now that you have a higher potency formulation, are there other diseases that you might think about now that you maybe previously didn't in terms of indications? Thanks. Thanks, Matt. Let me take them in reverse order, Matthew.
Now that you have a higher potency formulation are there other diseases that you might think about now that you may be previously didn't in terms of the indications.
Yeah.
Thanks, Bob let me take them and with the soda Matthew so.
Simba: What we started the company on in terms of looking at the inflammatory space was the idea that we might, through the small intestinal axis, open up a completely new class of medicine in which we had something that was pleiotropic, active with polypharmacology, so something that acted on multiple different cytokine pathways to drive inflammation resolution without shutting down immunity. And from that, given that we had something that was oral, something that we believe would be very safe and well-tolerated, and something that could be developed and manufactured on a very affordable basis.
What we started.
The company on in terms of looking at the inflammatory.
Space was the <unk> and that we might be through the small intestinal axis.
Open up a completely new profile of medicine and.
And which we had something that was planned.
<unk>.
And with.
Poly Pharma College, and you said something like digital multiple different cytokine pathways to drive inflammation resolution without shutting down immunity.
And from that given that we had something that was oral and something that we believe would be very safe and well tolerated.
And something that could be developed and manufactured on a very affordable basis. Our goal was always to see if we could capture the breadth and inflammatory disease and a.
Simba: Our goal was always to see if we could capture the breadth of inflammatory disease in a stage manner. We started in dermatology because of the rapid readouts, the rapid path to approval, and the fact, as you know, there's an enormous unmet need, particularly in the moderate and milder forms of those diseases.
Page nine and we started and dermatology because of the rapid readouts.
The rapid path to approval and the fact as you know Matthew this is an enormous unmet need.
And the moderate amount of forms of those diseases, but our goal is always being to go broad across all of inflammation.
Simba: But our goal has always been to go broad across all of inflammation. The new data, obviously, gives us even more confidence that we have something with the desired profile, even better than what we've seen already. And so it actually doesn't change our plans, Matthew.
The new data obviously, it gives us even more confidence that we have something with the desired profile looks even better from what we've seen already.
And so it's actually it doesn't change our plans Matthew I think it gives us even more confidence and we have something that should be a very attractive broad inflammation resolving agents. So we would anticipate that in due course, we'll look to expand into the off switch. These obviously and the biology and stepwise, we'd anticipate for example, sorry sorry.
Simba: I think it gives us even more confidence that we have something that should be a very attractive, broad inflammation-resolving agent. So we'd anticipate that in due course, we'll look to expand into arthritis, obviously, in the biology and stepwise. We'd anticipate, for example, psoriatic arthritis, then rheumatoid arthritis, ATSPAR, on that part of the axis, we're already planning And then we'll continue to expand to that full breadth of inflammation.
Hi, Tech ops writers and rheumatoid arthritis, and small on that part of the access we're already planning to look at the asthma and terms of the atopic disease and then we'll continue to expand.
That full breadth of interest.
Simba: But definitely today's result gives us that next level of confidence that we've got something consistent with the original profile we'd hoped to see, Matthew. I think on the first question, so we expect we will move forward with the A2 manufacturing process. That's what Mark said, just given today's result.
Definitely today's result gives us that next level of confidence that we've got something consistent with the average.
While we come from seeing Matthew.
I think on the first question so.
We expect we will move forward with the <unk> manufacturing process and that's what.
Mark said, just given today's result, and we'll.
Simba: And we'll see what results we get in Q3 with the tablet versus the capsule. So in Q3, we'll get the next wave of data, which Jonathan's driving forward, in addition to the phase 2 study in psoriasis, which we'll get data on in that full study in Q3. We'll also get additional data on tablets versus capsules in psoriasis patients, and then we'll make the decision, state-driven, as to which exact formulation we take forward into the phase 3 study, and we'll get all of that relevant data in Q3.
We'll see what results we get in Q3 with tablet book.
Justice comp sales. So in Q3, we'll get our next wave of day style.
Which Jonathan driving forward. In addition to the phase two study and psoriasis, which we'll get data on to that full study and Q3 will also get additional data on tablets versus capsules and psoriasis patients and then we'll make the decision day grid.
And as to which exact formulation, we take forward into phase III studies, and we'll get all of that relevant data and Q3.
Simba: We certainly see a possibility to get even further improvement with the tablet formulation. But we don't have that data yet, Matthew. So we'll see what the data reveals, and we're in a position to take whichever formulation looks best into the phase 3 studies as we go forward.
We certainly see a possibility to get even further improvements.
And with the tablet formulation and we don't have that data yet and so we'll see what the data revealed and win a position to take whichever formulation looks best into the phase III studies as we go forward.
Okay.
Thanks, and unhelpful Matthew.
Simba: Thank you. Thanks. That's perfect. Thanks, Simba. Great, thanks a lot. Thank you. Our next question comes from the line of Peyton Bonsack with Cohen.
Thanks, that's perfect. Thanks Simba.
Great. Thanks, a lot.
Thank you.
Our next question comes from the line of paint and body.
Got you.
Operator: The line is open.
Your line is open.
Peyton Bonsack: Hi guys, this is Peyton on for Joe. Thanks for taking my question and congratulations on a really successful quarter. So, I was wondering if you could elaborate a little more on the decision not to show interim data and also what change in PASI score you're targeting in the Phase 2 EDP 1815 study. And then the second question is kind of more about the atopic dermatitis program. Since you're enrolling more severe patients, do you really plan to see any change in endpoint or, like, what is your what endpoint you're evaluating, like what percent change you'd like to see? Thank you. Hi Peyton.
Hey, guys. This is patent on for Joe. Thanks for taking my question and congratulations on a really successful quarter.
So I was wondering if you could elaborate a little more on the decision not to show interim data and also what change and pad before you're targeting and the phase two Edp Atms and 15 study and then the second question is kind of more on the atopic dermatitis program.
Since you're enrolling more severe patients do you really try and see any change and endpoint or like what you are.
And what endpoint you are evaluating.
Like what percent change you'd like to see thank you.
Hi, Peyton.
Simba: Hi Peyton. Thanks for the question. So, on the first question on PASI, what we've set historically, it's still consistent with the way we look at the current situation. So, the first target for us is that moderate and milder population in sterile assets, where, as you know, the only available oral therapy is a tesla. [inaudible] in terms of difference in PASI scores versus placebo. That's the critical thing to look at.
Thanks for the question.
On the first question on passing and what we've set.
Is that historically and it is still consistent with the way we look at the current situations. So.
First target for us is that correct and milder population and several assets where as you know.
And the only available oral therapy is at Tesla.
Which is doing quite well from a commercial perspective.
And what we will target is to be similar from a patent perspective.
Simba: And the other factor is obviously safety and tolerability, where, to date, we have a remarkably attractive profile on the safety and tolerability side of things. We're not seeing any differences from placebo at all so far, which is not the case for Atesa, which I'm sure you know has significant tolerability issues and a significant percentage of patients. So if we're within the broad range of Tesla efficacy with the safety profile we have, then we have something that we'd be very happy with.
<unk> a tesla.
In terms of difference and passive scores versus placebo and that's the critical thing to look at.
And the other two.
There is obviously safety and Tolerability.
To date, we have a remarkably.
Try and get profile and safety and Tolerability side of things, we're not seeing any differences from placebo at all so far.
Which is not the case for a cash out which I'm sure you know maybe.
Significant tolerability issues and a significant percentage of patients so with with within the broad range of potential of efficacy with the safety profile we have.
And then we have something that would be very happy with.
Simba: So that broadly translates to something around a 20 to 30% improvement in PASI versus placebo after 16 weeks of treatment. Something in that range, and we'd be very happy. And obviously, anything better than that, whatever is better than happy or very happy, this is the state we'd be in basically. And then on your question about the interim, it's really straightforward.
So that broadly translates to something around 20% to 30% improvement and patchy versus placebo.
After 16 weeks of treatment something in that range and we.
We'd be very happy.
And obviously anything better than that.
Whatever is better than happy very happy and pleased with the state, we'd be and Peyton and basically.
And then on your question on the insurance.
It's really straightforward so.
Simba: So, just a reminder that, you know, we kicked off these studies in the midst of the pandemic, in terms of the Phase 2 study. At the beginning of the pandemic, we, like everybody, were very concerned about the impact on recruitment. We were eager for both internal reasons as well as in terms of giving Wall Street guidance to make sure we could get data as early as possible. And so, as a hedge, if you want, we basically put in place a potential interim readout, which would have been 12 weeks for 50% of the patients, because it wasn't clear to us that we would be able to recruit on plan in the midst of COVID.
Just a reminder, that we kicked off the studies and.
In the midst of the pandemic and.
And the phase II study at the beginning of the pandemic, we like everybody. We're very concerned about impact from recruitment we were eager for both internal reasons as well as and so I'm just getting wall Street guidance to make sure.
We could get data as early as possible and so as a as a hedge if you want we basically put in place and potential interim readout, which would've been 12 weeks, 50% of the patients.
Because it wasn't clear to us that we would be able to recruit from plan in the midst of Covid and it turns out as Jonathan said quite remarkably and credit to Jonathan Dunkin' and our clinical teams we've recruited a head of plan.
Simba: It turns out, as Jonathan said, quite remarkably, and credit to Jonathan, Duncan, and the clinical teams; we've recruited ahead of plan. And so, given that, we can have the full study data in Q3, which is obviously a fantastic place to be. So given that, it was an easy decision. Let's get the full study data. It's coming up, you know, soon in Q3, and there's no need for the intro. That was the logic question.
And so given that we can have the full stop and.
In Q3, which is obviously a fantastic place to be so given that it was an easy decision, let's get the full study data that's coming out.
And in Q3 and no need for the interest that was the logic question.
Peyton Bonsack: Okay, cool. And in the Atopic Dermatitis Program, do we see any differences in the baseline?
And cool and on the atopic dermatitis program.
And we see any differences.
Peyton Bonsack: Do we see any differences in the baseline? Yeah, my apologies, Peyton.
So yeah.
Yeah policy paid and so and so actually no changes as Jonathan said, we want to how to look at what we're doing and and severe population, but the core initial targets.
Simba: So actually, no changes. As Jonathan said, we want to have a look at what we're doing in the severe population, but the core initial target remains in atopic dermatitis, also in the moderate and mild space, and that is even more wide open in atopic dermatitis than in the psoriasis situation. So, as you know, Peyton, it's an enormous market in terms of the number of patients. The majority of them have to take topicals because there are no effective oral agents in that space. It's one of the things that we talk about a lot, but patients don't want topicals. They take them because they have to take them. They often...
It remains and atopic dermatitis also the moderate and mild.
Space and and that is.
Even more wide open and atopic dermatitis, and then well have to survive such situations.
So as you know paid and it's an enormous market and to the number of patients. The majority of them have to take topical because there are no effective oral agents in that space. It's one of the things that we talked about a lot, but patients don't want tropicals, they take them because they have to pay them.
They often.
And we're quite a lot of time to apply to the body and they often have unpleasant and sticky and side effects some of them can be springing and.
And so.
What everybody has been looking for and the atopic dermatitis is and the 10-K is safe well tolerated.
Simba: Nothing else with that type of profile in that huge atopic dermatitis moderate and mild spec. So, you know, the nearest comparator to the things that have recently been approved would be something like Crisabarol. We had efficacy that was similar to something like Crisabarol or better, which is what we would expect. Again, given the fact that we have something that's oral, very well tolerated, and safe, we have, again, something that we see as kind of great, so we are confident we're going to get that type of effect.
And mezzanine and and that's what we have and net.
And nothing else with that type of profile and nothing that huge atopic dermatitis smelter and mass spec.
So the newest comparator and simple things that have recently been approved would be something like like Chris Eberle.
Efficacy that was and that's something like CRISPR I'll hold backdrop, which is what we would expect.
Again, given the fact, we have something and it's all very well tolerated safety, we have again, something we see as things go.
Great and so it's.
And we.
We are confident we're going to get that type of effect and if you look at our atopic dermatitis data that we released in January and December.
Simba: And if you look at our atopic dermatitis data that we released in January and December, it's looking extremely encouraging, as you know, from that perspective. So I think it is likely, based on the data right now, that we're above that target profile. And again, there is no competition in terms of... Active 4L. And take a well, Corrie, inflammation-resolving drugs for moderate and mild space, so wide open space, which we're very happy about. Cool, thank you very much, and I'll jump back into the queue. Our next question comes from the line of Gobind Singh with JMP. Your line is open.
And it's looking extremely encouraging and as you know.
And from that perspective.
And I think it is likely based on the data right now that went above that target personnel and again there is no competition in terms of.
Active oil and.
And taken a well tolerated.
Inflammation resolved and drugs for a couple of different types of smelter and mall space.
It's a wide open space.
We're very happy about.
Cool. Thank you very much and I will jump back in the queue.
Thanks, Mike.
Thank you.
Our next question comes from the line of Goldman <unk> with JMP.
Your line is open.
Operator: Hi, thanks for taking the questions and good morning to everyone. I guess I wanted to dig in a little bit more on the new results, and am I correct that this is one times ten to the eleven cells in terms of the concentration being used here, and if you could talk a little bit more about where any of these results are significant? How should we be understanding basal flow here as opposed to the previous results that you guys showed?
Hi, Thanks for taking the questions and good morning to everyone.
I guess wanted to dig in a little bit more on the new results and.
And I correct that this is a one times 10 to 11 and sells in terms of.
And the concentration being used here and if you.
You could talk a little bit more about where any of these results are significant.
How should we be understanding faisal flow here as opposed to the previous results that you guys showed there any similarities did you learn anything new and and Theres. Some new factors here that are shown like flare and redness, how how should we understand these kind of results.
Operator: Are there any similarities? Did you guys learn anything new? And there are some new factors here that are shown, like flare and redness. How should we understand these kind of results? in the context of atopic dermatitis and psoriasis. Thank you.
And the context of atopic dermatitis and right.
Gobind Singh: Thanks, Gobind. Hi Gobind. We guessed that you would want some detail and appreciate the fact that that is the level of understanding that you try and push towards gaining, so thanks for that, Gobind. Mark, do you want to take those questions?
Okay.
Yeah.
Thanks, Kevin and high government, we guess that you would want to see.
And when and appreciating the value but.
But.
That is the level of understanding that you try and push towards gaining share thanks to that growth and Mark do you want to take those questions.
Simba: Sure, yeah, so the cell number was the equivalent to the high-dose cell number we used before. It's roughly 8 by 10 to the 11th split amongst the capsules, and it was in a smaller number of capsules with the A2 material because it was more concentrated. And so I think that's a fairly straightforward answer to that question.
Sure, Yes, so they sell number was the equivalents of the hydro cell number we used before it's roughly eight by tend to be 11.
Split amongst the.
Capsules.
And it was and a flawed.
For a number of capsules would.
And would be a material because it was more concentrated.
And so.
So I think that's.
I think that's a fairly straightforward and I'll talk to that.
Mark: It was 8 by 10 to the 11th percentile per day in all subjects who took EDP-1815, just a different number of capsules due to the different concentration. So we have reported here a much fuller set of data. This is an ongoing study, Gobind, and so we've been taking data out of the ongoing study. It's probably, we were considering doing it for the cohorts, but we probably won't, so we'll probably finish it here because we've got what we needed from it, which was, first of all, evidence of efficacy of EDP-1815, which we reported previously, and that was with the A-prime version.
And it was eight by tends to be 11 per day and.
All subjects, who took EVP and <unk>, just a different number of capsules and the different concentration. So we have reported here a much fuller set of data. This is an ongoing study.
And so.
So we've been taking data out from from the ongoing studies, probably we were considering growth for the cohorts, we probably want and so we'll probably benefit here because we've got what we needed from it.
First of all evidence of efficacy of the EPA from 15, which we've reported previously and that was really a prime version.
Mark: And now this comparative study, which we did originally just to confirm that the A2 material in the... Revised Process was still active, but with the interest in knowing whether the higher concentration would give more activity, which actually was what we suspected might happen based on preclinical data and some of the things we'd seen clinically as well. So we've reported a broader range of endpoints, all of the endpoints that were measured in the study.
And now this comparative.
Ah study, which we did originally just to confirm that the <unk> material and the.
Revised process, we're still active but with the interest and knowing whether the higher concentration would give more activity, which actually was what we suspect it might happen based on preclinical data and some of the things we've seen clinically as well so we've reported a broader range of <unk>.
And points as it will be endpoints that were measured and the study.
And the actual.
And as will flow score.
Mark: The actual basal flow score looks slightly different here because it's a median score rather than a mean score, but it's the same data for the A' material that you saw previously. As I said on the call, what's new is the...
Looks slightly different here, because it's a medium school level and a means for but it's the same data that for the a prime material that you saw previously as I said on the call. What we view is the comparison with a more concentrated.
Mark: For more information, please visit www.fema.gov.
Materials.
Does that help.
Yeah, very much thank you and and the Fuller.
Gobind Singh: Thank you. And the fuller data with the skin color and average redness, that seems to be more different between the A-prime and the A-2, and I know you guys are talking about the ratio. There are any other comments you can add to, I don't know if there's a, if this ratio difference is resulting in a texture cellular vesicle? It just seems like there's a meaningful difference on these other factors, but without that... We should probably have a separate call on this, David, if you want to go into it in detail. There are various interesting things here.
Got it with the skin color and average redness and these are that seems to be more gift from was a prime and a two and I know.
You're talking about the ratio.
Is there any other comments he can add too I don't know is it.
With this ratio differences, resulting in a.
And that's driven extracellular vesicles.
Functional difference, but it just seems like the.
There's a meaningful difference from these other factors, but without that.
Therefore, we should probably have a separate colonoscope. It if you want to go into it and.
Detailed or various interesting things here.
Mark: So the notion that a higher concentration of drug drives a higher force on the system at the level of target engagement is not new, but there are some particular characteristics of delivering multiple capsules through the pyloric sphincter from the stomach into the small intestine that have provoked new thinking in terms of how PK-PD relationships work in this kind of system. And the higher concentration, which normally, if you've got an injected drug, you inject twice as much; you get twice the concentration. Here it doesn't quite work that way because there's a gradual emptying, as I said earlier, from the stomach into the small intestine.
And that a higher concentration of drug and drives a higher force on the system at the level of target engagement is not new but there is a particular characteristics of delivering multiple capsules through the pillow expected from the stomach into the small intestine, which are met.
And thinking in terms of how PK PD relationships work and this kind of system and.
The higher concentration, which normally and I forgot and injected drug and with jet price as much you get twice the concentration here it doesn't quite work that way because let's say.
Juul and seeing as I said earlier from the stomach and from small intestine and so.
And I like the mix too.
Mark: You can do as much work as you like trying to lift an object, but if you don't apply enough force at a particular time, you'll never move it. And so there's a sort of relationship with Newton's second law of mechanics here, which does it. It fits with the basic principles of PKPD, but our thinking has been adapted to work with these particular types of problems.
And do as much work as you like.
Lift and objects that you don't apply enough force and a particular time, you'll have to move it.
So there's a sort of relationship with me and the second book.
Mechanics here.
And with which doesn't fit.
<unk> fits with basic principles of PK PD.
And thinking has been adapted to how to work with.
And.
Mark: How to work with these particular types of delivery kinetics.
These particular types of delivery kinetics.
Fair enough. Thank you.
Thank you.
I'm not showing any further questions I would now like to turn the call back over to simple for closing remarks.
Operator: I'm not showing any further questions. I would now like to turn the call back over to Symbol for closing remarks.
Simba: Thanks very much. So I want to thank everyone for their continued interest in Novello. We're in an incredibly exciting period. We obviously began the year with positive data in atopic dermatitis, and we've now added to that and have something that increasingly looks to some of the questions you've asked on the call as if it's going to be a foundational treatment for broad inflammation with a unique profile, something that's not just efficacious but also safe, well-tolerated, and already delivered, and So lots of clinical data coming up between now and the end of this year. But we didn't talk about our COVID data in any detail.
Thanks very much.
And so I wanted to thank everyone for a continued interest and Nevada with an incredibly exciting period.
We obviously began the year with positive data in atopic dermatitis, and we've now added to that.
And perhaps something but increasingly looks to some of the questions are off from a cold.
And if it's going to be a day.
And on treatment for broad inflammation with a unique profile with something thats not just application applications, but also safe well tolerated.
Ward and deliberate and.
Split probably we'd hope to have.
And so lots of clinical data coming up between now and the and this year, we didn't think about COVID-19 data and any detail that's coming up over the next quarter and then we have a lot of data and Q3 and that just continues.
Operator: That's coming up over the next quarter, and then we have a lot of data in Q3, and that just continues. So I look forward to keeping everybody very much updated as we move towards potential Phase 3 trials. Thanks very much. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation.
So look forward to keeping everybody very much updated as we move towards a potential phase III trials in 2022, thanks very much everyone.
Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.
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All right.
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And.
Non-GAAP.
And.