Q4 2021 Evelo Biosciences Inc Earnings Call
Operator: Ladies and gentlemen, your call is scheduled to start momentarily. Please continue to stand by, and thank you for your patience.
Ladies and gentlemen, you'll call is scheduled to start momentarily. Please continue to standby and thank you for your patience.
[music].
Operator: Music, Evelo Biosciences Inc Evelo Biosciences Inc Evelo Biosciences Inc Evelo Biosciences Inc Thank you for watching! Good morning and welcome to a Velo Biosciences conference call to discuss this fourth quarter and full year 2021 business highlights, at the, All participants are in a listen-only mode. Following the formal remarks, we will open the call up for you. Please be advised that this call is being recorded at the, At this time, I'd like to turn the call over to Kendra Sweeney of Abello.
Good morning, and welcome Joe Valent Biosciences conference call to discuss its fourth quarter and full year 2021 business highlights at this time all participants are in a 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 Kendra Sweeney about Belo. Please proceed.
Kendra Sweeney: 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.
This morning, we issued a press release that outlines the topics we plan to discuss today.
This release is available at Www Dot velo bio dot com under the investors tab.
Kendra Sweeney: Today on our call, Simba Gill, Chief Executive Officer, Mark Bodmer, President of R&D and Chief Scientific Officer, and Jonathan Zung, Chief Development Officer, will review our 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 objectives 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. 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 statement due to the impact of many factors.
Today on 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 recent business highlights before.
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.
<unk> statements about our objectives and anticipated clinical milestones the impact if 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.
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.
Kendra Sweeney: Participants are directed to the risk factors set forth in Avella's annual report on Form 10-K for the fiscal year ended December 31, 2021, and the company's other filings with the Securities and Exchange Commission. Any forward-looking statements made today speak only to Avelo's operations as of today. Avelo disclaims any duty to provide updates to its forward-looking statements, even if subsequent events cause the company's use to change.
Participants are directed to the risk factors set forth Annabel its annual report on Form 10-K for the fiscal year ended December 31st 2021, and the company's other filings with the Securities and Exchange Commission.
Any forward looking statements made today speak only to with all those operations as of today.
<unk> disclaims any duty to provide updates to its forward looking statements even if subsequent events cause the company's views to change.
Simba Gill: It is now my pleasure to pass the call to Simba. Thank you Kendra. Good morning everyone and thank you for joining us to review our progress during the fourth quarter. We are fortunate to face the headwinds of the current financial market from a position of strength, clinically and scientifically. Our goal on this call is simple, to provide you with the evidence that Avelo has an exceptional opportunity to create value with a high probability of success.
It is now my pleasure to pass the call to Simba.
Thank you Kendra good morning, everyone and thank you for joining us to review our progress during the fourth quarter.
We are fortunate to face the headwinds of the current financial market from a position of strength.
Clinically and scientifically.
Our goal on this call is simple.
To provide you with the evidence that the velo has an exceptional opportunity to create.
<unk> value with a high probability of success.
Simba Gill: This bold statement from a mid-clinical stage company working in new biology on a new modality of medicine is objectively rooted in both clinical and preclinical data. However much we do not like our current share price, it represents an exceptional opportunity for investors in both the short and the long term.
This bold statement from a mid clinical stage company working in new biology on a new modality of medicine is objectively rooted in both clinical and preclinical data.
However, much we do not like our current share price. It represents an exceptional opportunity for investors in both the short and the long term.
Simba Gill: We started working on syntax medicines five years ago with a radically innovative proposal that there is a connection between the small intestine and the rest of the immune system that would enable orally delivered gut-restricted drugs to safely modulate immunity and inflammation throughout the body. Preclinical and clinical results have been remarkable. We have observed coordinated downregulation of multiple inflammatory pathways driving inflammation resolution in both lab animals and in humans.
We started working on syntax medicines five years ago.
With a radically innovative proposal, but there is a connection between the small intestine and the rest of the immune system, but would enable orally delivered gut restricted drugs to safely modulate immune ritchie and inflammation throughout the body.
Preclinical and clinical results have been remarkable.
We have observed coordinated downregulation of multiple inflammatory pathways driving inflammation resolution in both lab animals and in humans.
Simba Gill: And we now have a good understanding of the immunological mechanism that allows this to happen. The top-line EDP1815 Phase II psoriasis clinical data that we reported last September, demonstrated that a syntax medicine can have a therapeutic effect, with safety and probability comparable to placebo. And as we heard.., from both Dr. Stroeber as well as Dr. Daniel Rowling at a KOL event, Evelo's Phase II clinical data supports the potential use of EDP-1815 in almost all patients, including, importantly, the mild and moderate population, which represents over 85% of the 55 million patients with psoriasis worldwide who are generally not treated with biologics or oral small molecules. The primary unmet need in psoriasis is for this segment of patients.
We now have a good understanding of the immunological mechanism that allows this to happen.
The topline ETP 18, 15 phase two psoriasis clinical data that we reported last September .
Demonstrated that a syntax medicine can have a therapeutic effect.
With safety and Tolerability comparable to placebo.
And as we heard.
From both doctors stroke as well as the Doctor Daniel Rolling out of Kols event, if values phase II clinical data.
Support the potential use of Edp 18, 15 in almost all patients.
Including importantly, the mild to moderate population, which represents over 85% of the 55 million patients with psoriasis worldwide, who are generally not treated with biologics oral small molecules.
Primary unmet need and Suraj. This is but this segment of patients.
Simba Gill: We can't emphasize enough the importance of the clinical data. The trial addressed the central question, can targeting syntax be the basis for a completely new type and class of medicine? The answer is yes.
Yes.
We can't emphasize enough the importance of the clinical data.
The trial address the central question can targeting syntax be the basis for a completely new type of class of medicine.
The answer is yes.
Simba Gill: Since September, we have reported two further data sets from the Phase 2 trial. The first clinical data set was the reduced production of multiple inflammatory cytokines from blood immune cells of patients receiving EDP-1815. These reductions were statistically significant. Similar reductions were seen in skin biopsies for IL-12, IL-17, and IL-23, all validated cytokines in the skin pathology of psoriasis.
Since September we have reported to further data sets from the phase two trial.
The first clinical dataset was the reduced production of multiple inflammatory cytokines from blood immune cells.
Since receiving ETP 18 15.
These reductions were statistically significant.
Similar reductions was seen in skin biopsies for IL 12, IL 17, and IL 23, all validated cytokines in the skin pathology OPE psoriasis.
Simba Gill: This is human-mechanistic evidence for inflammation resolution, similar to what we have long observed in animal models. The second clinical data set was the 24-week follow-up data from psoriasis patients in Part B of the Phase II trial after they stopped taking EDP1815. Many patients had persistent and deepening responses with no flares or rebound of psoriasis consistent with what we now know about the cellular mechanism of action of EDP1815 from preclinical, We are delighted to announce data from this Phase 2 trial has been selected for a coveted late-breaking oral presentation this Saturday at 10.10 a.m. Eastern Time at the 2022 meeting of the American Association of Dermatology. Significant external recognition for the potential of syntax medicine.
This is human mechanistic evidence for inflammation resolution similar to what we have long observed in animal models.
The second clinical dataset was the 24 week follow up data from psoriasis patients in part B of the phase two trial after they stopped taking ETP 18 50.
Many patients had persistent and deepening responses with no flash a rebound of psoriasis consistent with what we now know about the cellular mechanism of action of Edp 18, 15 from preclinical studies.
We are delighted to announce data from this phase two trial has been selected for a complicated late breaking oral presentation. This Saturday at 10 10, a M. Eastern time at the 2022 meeting of the American Association of Dermatology significant external recognition.
The potential of syntax medicines.
Simba Gill: The broad set of data, of fundamental evidence for a new area of biology which we can harness to create effective, safe, oral, affordable medicines to treat all chronic inflammatory diseases. In a moment, I'm going to hand over to Mark Bodmer to talk about the scientific discoveries, that underpinned these clinical success. Before doing that, we wanted to announce today further exciting positive data from the clinical trial examining a faster-release capsule. As you know, we have been investigating the potential to consistently improve the release characteristics of our syntax methods.
Broad set of data a fundamental evidence for new area of biology, which we can harness to create effective safe oral affordable medicines to treat all chronic inflammatory diseases.
Yeah.
In a moment I'm going to hand over to Marc <unk> to talk about the scientific discoveries.
That underpin these clinical successes.
Before doing that we wanted to announce today further exciting positive data from our clinical trial examining our foster released capsule.
As you know we have been investigating the potential to consistently improve the release characteristics. All bus hidden tax mentioned the aim is to see consistent foster release higher up in the small intestine.
Simba Gill: The aim is to see consistent, faster release higher up in the small intestine. Imaging results from the next phase of the study demonstrated that the improved release capsules of EDP1815 are able to deliver drug faster and then higher up in the small intestine 88% of the time. Mark will explain these results in the context of preclinical evidence that clearly predicts the potential for increased efficacy with this release program. Putting all of this together, we will focus on this fast-release capsule as we advance our programs into later stage development.
Imaging results from the next phase of the study demonstrated that the improved released capsule of E. D. P 18 15 eight.
<unk> able to deliver drug foster and that's higher up in the small intestine, 88% of the time.
Mark will explain these results in the context of preclinical evidence, but clearly protects the potential for increased efficacy with this release profile.
Putting all of this together, we will focus on MS. Foster released capsule as we advance our programs into later stage development, but foster released capsule gives us confidence that we are likely to see even greater efficacy than we have seen to date.
Simba Gill: The fast-release capsule gives us confidence that we are likely to see even greater efficacy than we have seen to date, both in terms of proportion of responders and in depth of response. Mark and Jonathan will now talk about our science and the clinical development plans, and then we'll wrap up with a view of what to expect next. Mark, over to you.
Both in terms of proportion of responders and the depth of response.
Mark and Jonathan will now talk about our science and the clinical development plans and then we'll wrap up with a view of what to expect next mark over to you.
Mark Bodmer: Thanks, Simba. Two basic questions for any drug are, does it get to the right place, and how does it work when it gets there? Starting with the question of the right place, the goal of Simba said it's simple based on known immunology of the gut and pre-clinical evidence. It is to protect the drug from acid and suggestive enzymes in the stomach and release it as soon as possible in the small intestine.
Thanks Sandra.
Two basic questions with any drug or does it get to the right place and how does it work when it gets there.
Mark Bodmer: The new data that Simba mentioned have identified a solution. The headline result is that a faster capsule, faster release capsule of EDP-1815 opened in the jejunum, higher up in the small intestine, in 88% of human volunteers in the scintigraphy study, versus 18% with the original capsule. The release of EDP 1815 can be measured by giving human volunteers a capsule of EDP 1815 which contains a radioactive tracer, Technicium 99 M. Technicium emissions can be followed by centrifugal with an external gamma camera showing how long it takes the capsules to start releasing their contents and where in the gut this takes place.
Starting with the question of the right place the goal as Simba said, a simple based on known immunology, because some preclinical evidence it is to protect the drug from asset in digestive enzymes in the stomach and release it as soon as possible in the small intestine. The new data that Simba mentioned have identified a solution.
Yeah.
The headline result is it a.
Foster capsule Foxconn release capsule of Edp 18, 15 opened in mid two Jude them higher up in the small intestine and 88% of human volunteers and listen Secretary study. This is 18% with the original capsule.
The release of Edp 18, 15 can be measured by giving human volunteers a capsule of Edp 18, 15, which contains a radioactive tracer technetium 99.
Technician commissions can be followed by scintigraphy with an external gamma camera showing how long it takes a capsule to start releasing that content aware and look out this takes place.
Mark Bodmer: We first tested a capsule that was used in the Phase II psoriasis trial, and 18% of subjects, this capsule released EDP1815 in the jejunum, of the small intestine. The other 82% of subjects released in the ileum at the lower end... This profile was still sufficient to generate the Phase II efficacy. Now we know from preclinical experiments that a release profile higher in the small intestine can increase efficacy by as much as tenfold.
We first tested a capsule that was used in the phase II psoriasis trial.
And 18 percentage of subjects. This capsule released edp, 18th Athene and the jejunum.
At up a portion of the small intestine.
82% of subjects released in the helium at the lower end.
This profile was still sufficient to generate the phase II efficacy.
Now we know from preclinical experiments that will release profile higher in the small intestine can increase efficacy by as much as 10 fold.
Mark Bodmer: Based on this, we tested a version of EDP1815 capsules with faster release. 15 out of 17 of the human volunteers showed release higher up in the Dijunum at only two lower down in the Ilium. This is 88% higher up for the new profile versus 18% for the original one.
Based on this we tested a version of D. V. P 18, 15 capsules with foster release.
15 to 17 of the human volunteers showed release higher up in the June them.
We need to lower down in India. This is 88% higher up for the new profile versus 18% for the original one.
Mark Bodmer: This faster release gives much more consistent overall exposure to the active drug higher in the small intestine. We tested the efficacy of these different release profiles in mice using very small tablets formulated to replicate the profile of human capsules, which can be given orally. Fast to release in the jujube. Let's excellent preclinical efficacy. The version that released lower down works significantly less well.
MS Foster release, because much more consistent overall exposure to the active drug higher in the small intestine.
We tested the efficacy of these different release profiles and mice using very small tablets formulated to replicate the profile of human capsules, which can be given orally.
Foster a lease in the June let's excellent preclinical efficacy.
The version that released lowered down what significantly less well so comparing the humans in cigarettes, a release profile with the efficacy of equivalent profile in mice provides a clear path to building on the foundation of efficacy that we've already seen in the clinic. This is a significant result.
Mark Bodmer: So comparing the human integrity release profile with the efficacy of the equipment profile in mice provides a clear path for building on the foundation of efficacy that we've already seen in the clinic. This is a significant result. It's simple.
Mark Bodmer: The faster and higher in the small intestine the capsule opens, the more opportunity a drug has to exert its effect. Because the EVP-1815 drug substance is unchanged, the fast release profile can be evaluated within our current clinical development plans with minimal impact on timelines. We'll let you know the plans once the details are settled. Putting now to the second basic question posed at the beginning, how does it work?
It's simple will foster and higher in the small intestine. The capsule opens the more opportunity drug has to exert its effects.
Because the ETP 18, 15 drug substance is unchanged. The foster release profile can be evaluated within our current clinical development plans with minimal impact on timelines well, let you know the plans once the details are subtle.
Turning now to the second basic question posed at the beginning.
Mark Bodmer: What is the scientific basis for the clinical observations both about duration of efficacy after the drug is stopped and the range of inflammation-resolving effects? I've touched on this before, if we treat mice with EDP-1815, they induce a regulatory phenotype in circulating immune cells. We've now shown that this is due to reprogramming a circulating CD4 positive T cell. This was formally demonstrated by transfer of CD4 T-cells from drug-treated animals to drug-free animals, resulting in inflammation resolution in the recipients.
Does it work.
What is the scientific basis for the clinical observations both about duration of efficacy. After the drug is stopped and the range of inflammation resolving effects.
I've touched on this before if we treat mice with ADP 18, 15, they reduce our regulatory phenotype and circulating immune cells.
We've now shown that this is due to reprogramming of circulating C. D. Four positive T cells.
This was formerly demonstrated by transfer of CD four T cells from drug treated animals drug free animals, resulting in inflammation resolution in the recipients. This effect as from the transfer of <unk> four cells alone recipient animals received no drugs only.
Mark Bodmer: This effect is from the transferred CD4 cells alone. The recipient animals receive no drug, only T-cells from the treated mice. The induction of regulatory T-cells has been a major elusive goal of immunology drug discovery for 20 years.
T cells from the treated mice.
Production of regulatory T cells has been a major elusive goal of immunology drug discovery for 20 years, we've now achieved it with an oral agent, which has shown excellent safety and tolerability.
Mark Bodmer: We've now achieved it with an oral agent which has shown excellent safety and tolerability. This can explain the clinical observations in the Part B drug-free follow-up portion of the Phase II psoriasis trial. The clinical responses seen during the treatment period persisted and deepened after the drug was stopped, probably because cells that conferred efficacy remained even after the drug did not. We've also tested for this effect in mice with a number of systemic anti-inflammatory drugs, including JAK inhibitors and biologics. So far, we've not seen it. The only other drug that does it is dexamethasone, which is not suitable anyway for chronic use because of limiting side effects.
This can explain the clinical observations in the part B drug for a follow up portion of the phase two psoriasis trial. The clinical responses seen joined the treatment period persisted a deepened after the drug was stopped probably because cells that confer efficacy remained even after the drug did not.
We've also tested for this affected mice with a number of systemic anti inflammatory drugs, including JAK inhibitors and biologics so far we've not seen it the only other drugs that bezeq is dexamethasone, which is not suitable anyway for chronic use because of limiting side effects.
Mark Bodmer: His property of generating regulatory T-cells with a safe oral agent appears to be a unique characteristic of the small intestinal axis, has important implications for the breadth of potential benefit of Syntax Medicine. Most efforts to make more effective medicines, are based on breaking common diseases down into the diverse underlying molecular mechanisms, and then more precisely targeting those mechanisms in subsets of patients. The biology of the small intestinal axis seems to allow us to go in the other direction, towards a common mechanism for diverse diseases.
This property have generated regulatory T cells with a safe oral agent appears to be a unique characteristic of the small intestinal axis.
Has important implications for the breadth of potential benefit of syntax medicines.
Most efforts to make more effective medicines are.
But based on breaking common diseases down until the diverse underlying molecular mechanisms and then more precisely targeting those mechanisms in subsets of patients.
The biology of the small intestinal axis seems to allow us to go in the other direction towards a poem in mechanism diverse diseases.
Mark Bodmer: I'll just finish with a brief comment about extracellular vesicles. We've said before that the potential for EVs, based on preclinical data, is to approach biologic levels of efficacy with these oral gut-restricted products. The physical and pharmacological properties of EVs have provided evidence that they may enable this better diffusion and high-packing densities due to their much smaller size than, And with that, I'll hand over to Jonathan to update on our clinical programs, including EDP2939, our first EV product on track to enter the clinic later this year. Thank you, Mark.
Yeah.
I'll just finish with a brief comment about extracellular vehicles, we've said before that the potential for Evs based on preclinical data is to approach biologic levels of efficacy with these all got restricted products.
The physical and pharmacological properties of Evs have provided evidence that they may enable this diffusion and higher packing densities due to their much smaller size the microbes.
And with that I'll hand over to Jonathan to update on our clinical programs, including Edp twenty-nine thirty-nine I'll first EV product on track to enter the clinic later this year.
Jonathan Zung: This morning, I'd like to provide updates on several of our ongoing clinical trials, upcoming readouts, as well as planned trials. We announced last month the dosing in our Phase II trial of EDP1815 for the treatment of mild, moderate, and severe atopic dermatitis began. We continue to execute according to plan, and top-line results from this trial are expected in the first half of 2023. As a reminder, this is a 16-week multi-center double-blind, placebo-controlled trial being conducted in North America, Europe, and Australia.
Thank you Mark.
I would like to provide updates on several of our ongoing clinical trials upcoming readouts as well as planned trials.
We announced last month, the dosing in our phase II trial of <unk> for the treatment of mild moderate and severe atopic dermatitis began.
We continue to execute according to plan and topline results from this trial are expected in the first half of 2023.
As a reminder, this is a 16 week multicenter double blind placebo controlled trial being conducted in North America, Europe , and Australia approximately.
Jonathan Zung: Approximately 300 patients will be randomized into one of three cohorts. The cohort one will explore a dose of 1.6 times 10 to the 11th total spells of EDP 1815 who are matching placebo as two capsules administered once daily. Cohorts 2 and 3 are administered as a dose of 6.4 times 10 to the 11th total cells of EDP1815 or matching placebo, either as two capsules once daily or one capsule twice a day respectively.
Approximately 300 patients will be randomized into one of three cohorts.
Cohort one will explore a dose of one six times 10 to the 11 total cells of Edp, 18, 15 or matching placebo as two capsules administered once daily cohorts two and three are administered as a dose of six four times 10 to 11 total cells.
Of Edp, 18, 15 or matching placebo, either it's two capsules once daily or one capsule twice a day respectively.
Jonathan Zung: The primary endpoint is the percentage of patients achieving an EZ50, which is a reduction of 50% in the eczema area and severity index at week 16. Key physician-reported secondary endpoints are the investigator, global assessment, the IGA, and body surface area, or BSA.
The primary endpoint is the percentage of patients achieving an easy 50, which is a reduction of 50% in the eczema area and severity index at week 16.
Key physician recorded secondary endpoints are the investigator global assessment, the Iga and body surface area or BSA.
Jonathan Zung: Key patient reported secondary endpoints include The Dermatology Life Quality Index DLQI, Patient-oriented, excellent measure or poem, and the parietist numerical rating scale NRS. All patients in the Phase II trial will have the opportunity to join an open-label extension trial once they complete 16 weeks of dosing. All patients in the open label extension will receive EDP 1815 for up to 52 weeks. Results from our Phase I B trial of EDP 1867 in a cohort of patients with moderate atopic dermatitis are anticipated in the second quarter. As a reminder, EDP1867 is from a different genus to EDP1815 and has been rendered non-live by gamma irradiation.
Key patient reported secondary endpoints include the dermatology life quality index <unk>, the patient oriented eczema measure or poem and the pruritus numerical rating scale and Rs.
All patients in the phase II trial will have the opportunity to join an open label extension trial once they complete 16 weeks of dosing.
All patients in the open label extension will receive ETP 18, 15 for up to 52 weeks.
Results from our phase <unk> trial of Edp, 18, 67, and a cohort of patients with moderate atopic dermatitis are anticipated in the second quarter.
As a reminder, ETP 18, 67 is from a different genus to E. D. P. 18, 15 and has been rendered non live by gamma irradiation.
Jonathan Zung: We're excited to remain on track to bring our first extracellular vesicle, or EV candidate, EDP2939, for inflammatory diseases into the clinic in the third quarter. The Healthy Volunteer portion will be followed by a cohort of patients with psoriasis. We anticipate reporting Phase 2 results in psoriasis in the second half of 2023. In terms of next steps regarding the development of EDP1815 and psoriasis, we have had discussions with community and academic-based dermatologists around our clinical development plan. We anticipate meeting with different health authorities over the next several months to solicit their feedback.
We're excited and remain on track to bring our first extracellular vesicle or EV candidate Edp 29, 39 for inflammatory diseases into the clinic in the third quarter.
The healthy volunteer portion will be followed by a cohort of patients with psoriasis.
We anticipate reporting phase two results in psoriasis in the second half of 2023.
In terms of next steps regarding the development of Edp 18, 15 in psoriasis, we have had discussions with community and academic based dermatologists around our clinical development plans we.
We anticipate meeting with different health authorities over the next several months to solicit their feedback.
Jonathan Zung: This will in turn allow us to finalize our plans for advancing EDP1815 in psoriasis into the registrational trial. I'll now hand it back to Simba for closing remarks. Thank you, Jonathan.
This will in turn allow us to finalize our plans for advancing <unk> in psoriasis into the Registrational trials.
I'll hand, it back to Simba for closing remarks.
Thank you Jonathan.
Simba Gill: You've heard from Mark and Jonathan about the scientific and clinical progress we've made over the last quarter and last year. The data support a bold statement that we have proved that we can harness Syntax to open up a massive new field and type of medicine that goes beyond existing biotech and pharmaceutical products and opens up the treatment of all stages of inflammation with orally delivered, convenient, safe and well-tolerated, effective medicine. We have uncovered the science that underlies the fundamental connections that link our gut to the immune and inflammatory system throughout the body.
You've heard from Marc and Jonathan about the scientific and clinical progress we've made over the last quarter and last year.
The data support a bold statement that we have proved that we can harness syntax to open up a massive newfield and type of medicine that goes beyond existing biotech and pharmaceutical products and opens up the treatment of all stages in inflammation with orally delivered convenient safe and.
Well tolerated effective medicines.
We have uncovered the science that underlies the fundamental connections the link called duck to the immune and inflammatory system throughout the body.
Simba Gill: This is a medical and scientific breakthrough. To sum up, in the last quarter, we've hit all three of our major clinical milestones with very positive results. Firstly, the maintenance and deepening of clinical responses of psoriasis patients in the Phase 2 Part B follow-up.
This is a medical and scientific breakthrough.
To sum up in the last quarter, we've had all three of our major clinical milestones with very positive results.
Firstly, the maintenance and deepening of clinical responses of psoriasis patients in the phase two part B follow up.
Simba Gill: Secondly, the reduction in inflammatory cytokines produced by systemically circulating immune cells and inflammatory cytokine production at the site of disease, and then today, and thirdly, the improved faster release profile of the EDP1815 capsule. This puts the future of EDP1815 and of Syntax Medicines into an even stronger position as we move closer and closer to realizing our vision to improve health for the hundreds of millions of people living with inflammatory disease around the globe. I want to thank the Avelo team and our partners. These are very challenging times where remarkable commitment and resilience is needed. We are fortunate to have such an exceptionally committed and strong team.
Secondly, the reduction in inflammatory cytokines produced by systemically circulating immune cells and inflammatory cytokine production at the site of disease.
And then today and thirdly, the improved foster release profile of Edp 18, 15 capsules.
This puts the future of Edp, $18, 15, and up syntax medicines into an even stronger position as we move closer and closer to realizing our vision to improve health for the hundreds of millions of people living with inflammatory disease around the globe.
I want to thank the <unk> team and our partners. These are very challenging times.
Were remarkable commitment and resilience as needed we are fortunate to have such an exceptionally committed and strong team.
Operator: And with that, I'll now open the questions. Thank you. Ladies and gentlemen, if you would like to ask a question at this time, you will need to press the start and the 1 key on your touch-tone telephone.
With that I'll now open for questions. Thank you.
Ladies and gentlemen, if you'd like to ask a question at this time, you will need to press the star agenda, one key on your touched on telephones.
You May press the pound key to withdraw your question.
Operator: Please stand by while we compile the Q&A. And our first question coming from the line of Chris Howardson with Jefferies, your line, Hi, good morning. Thanks so much for taking the questions and appreciate the bold statement, Simba, from you and the team. So I guess for my questions would be, you know, with respect to 1815 and psoriasis, based upon the feedback that you're seeing so far from physicians, What do you think is going to be an acceptable endpoint for approval for that agent in mild to moderate psoriasis? So that would be one question. And then the second question I would have is, as you're progressing your programs into registrational studies, what is the strategic thinking with respect to business development opportunities?
Please stand by while we compile the Q&A roster.
And our first question coming from the line of Chris Howerton with Jefferies. Your line is now open.
Hi, good morning, Thanks, so much for taking the questions and appreciate the bold statements Simba from you and the team. So I guess for the my questions would be with respect to 18 15 in psoriasis based upon the feedback that youre seeing so far from physicians what do.
Do you think is going to be an acceptable endpoint for.
A approval for that agent in mild to moderate psoriasis.
So that would be one question and then the second question I would have is as youre progressing your programs into Registrational studies what is that.
Strategic thinking with respect to business development opportunities. Thank you.
Simba Gill: Thank you. Chris, thanks for the question, and of course, good, Chris. So on the first question with regards to endpoints, obviously, we do need to meet with regulators, the plan. Just to remind you and everybody, Chris, is to engage in complete regulatory interactions with FDA, MHRA, the European authorities around the middle of this year, and I'll be submitting all the relevant background information shortly. So we need to get through those meetings, obviously, to finalize what the endpoints would be. At the moment, we would anticipate that a TGA score of 0, 1, so clear or nearly clear skin is likely to be another clinical endpoint. So another.
Yes.
Great. Thanks for the question hopefully good Chris.
So.
On the first question with regards to endpoints, obviously, we do need to meet with regulators the plan.
Just remind you and everybody Chris is to engage and complete regulatory interactions with F. D. A I mentioned already that your piano authorities.
Around the middle of this year.
Submitting all irrelevant.
And information.
Shortly.
So.
We need to get through those meetings, obviously to finalize what the endpoint would be at the moment, we would anticipate that our PGA score of zero, one so clear or nearly clear skin is likely to be the.
The clinical endpoint so.
Simba Gill: The answer to the first question, with regard to moving towards registration studies and corporate partnering. My view has always been, Chris, that the opportunity with Syntax Medicines and with Avelo is so enormous that corporate partnering will be a key part of what we do. We cannot capture the massive breadth of the opportunity on our own.
That's.
The answer the first question with regards to moving towards registration studies and corporate partnering.
Our view.
As always been Chris that the opportunity with syntax mentioned him with the velo is so enormous that corporate partnering.
Will be a key part of what we do.
We cannot capture the massive breadth of the opportunity on our own.
Simba Gill: At the same time, we've always been unashamed and very clear that we have one of those rare opportunities in the history of science, medicine and biotech to create something that could completely transform healthcare and biotech. We've always said that syntax medicines have the potential to be.., even more transformative than monoclonal antibodies have become and in that context... Our view philosophically is the best way to develop that type of innovation to patients is to remain a strong independent company that forward integrates and becomes a key forever biotech company.
At the same time, we've always been unashamed, it very clear that we have one of those rare opportunities in the history of science medicine and biotech.
To create something that could completely transform healthcare and biotech.
We've always said that.
<unk> medicines have the potential to be.
Even more transformative monoclonal antibodies have become and in that context. Our view philosophically is the best way to develop that type of innovation to patients is to remain a strong independent company the forward integrate <unk>.
And becomes a key forever biotech company, but we will do that together with partners and what it translates to is an openness to forming partnerships, which allow us to do that Chris so capturing a lot of the forward value, where many of the products, including 18, 15 and lags to forward integrate.
Simba Gill: But we will do that together with partners and what it translates to is an openness to forming partnerships which allow us to do that risk. So capturing a lot of the forward value from any of the products including 1815 and allowing us to forward integrate and build towards that fully integrated company. Thank you so much, Simba, and I appreciate everything moving forward. Our next question coming from the line of Gary Nagler from BMO Capital Markets. Hi, good morning.
And build towards that fully integrated company.
Okay, all right awesome. Thank you so much and then I appreciate the everything moving forward.
Thanks, Chris.
Our next question coming from the line of Gary Nachman from BMO capital markets. Your line is open.
Operator: Data from this, Antigraphy study on the earlier release of 1815. Are there any additional GI side effects releasing drug earlier in the small intestine? patients were released earlier, 88% was clearly a good outcome, but is it ever possible to get to 100% with these formulations?" And is there a chance that you'll need a small clinical bridging study before moving into phase three for psoriasis and then I'll have just a couple of quick follow-up. Sorry, Gary. Hey, Gary. How are you doing?
Hi, good morning.
Data from the grocery study on the earlier release of <unk>.
Are there any additional Gi side effects, releasing drug earlier in the small intestine.
And so the two patients where it didn't release earlier.
88% was clearly a good outcome, but is it ever possible to get to 100% with these formulations.
And is there a chance that you'll need a small clinical bridging study before moving into phase three for psoriasis.
Just a couple of quick follow ups.
So sorry go Hey, Gary how are you doing just remind me on the first question Gary I couldn't write quickly enough.
Simba Gill: Just remind me on the first question, Gary. I couldn't write quickly enough. I've got it, actually. The GI, if there were any GI sites.
I've gone up actually signed up there.
Simba Gill: Oh, yeah. Got it. So, no on the first question. And very importantly, Gary, it's a core piece of the platform, as you know. We continue to see.., an extremely safe and well-tolerated profile in all of the clinical studies we've done. We've been in over 500 human subjects at this stage, and consistently seeing very, very clean safety and tolerability. So, nothing to.., to be concerned about there including with regards to the faster release capsule. In terms of 88% versus 100%, absolutely always possible to do better and better in life, Gary. It's one of my core life principles.
Gee I, if there were any Gi side, yeah got it and regarding drug no but on the on the first question.
And very importantly, Gary it's a core piece of the platform as you know we continue to see.
An extremely safe and well tolerated profile in all of the clinical studies, we've done we've been in over 500 Hume.
Human subjects at this stage.
Consistently saying very very clean safety and Tolerability, so nothing too.
To be concerned about there, including with regards to the foster release capsule in terms of the 88 versus 100%.
Absolutely always always possible to do.
Simba Gill: And that also includes with regards to the science around a release capsule, uh... efforts etc. Having said that 88% is a great result. We are ecstatic, Gary.
Better and better at life, Gary It's one of my cool.
Life principles and that also includes with regards to the science around our release.
FX etcetera, having said that 88% is a great result, we are ecstatic guy.
Simba Gill: Um, and just to remind you.., in the preclinical models exposure, early and over the full anatomy of the small intestine led to antibody-like efficacy consistently in animal models. So this type of result where we're seeing 88% releasing quickly in the genome is remarkable and is very, very encouraging for what we're likely to see in the clinic. And that then links to your next question in terms of any bridging studies. We don't anticipate there'll be a requirement to do that.
And just to remind you.
In the preclinical models.
Exposure.
Early and over the the full.
And that could be of the small intestine led to antibody like efficacy are consistently in animal models. So this type of results, we're seeing 88% are.
Releasing quickly in the genome is remarkable and is very very encouraging for what we're likely to see in the clinic.
In that vein links to your next question in terms of any bridging studies.
Don't anticipate there'll be a requirement to do that obviously, we do have to have the conversations with regulators, we will be moving as quickly as possible into.
Simba Gill: Obviously, we do have to have the conversations with regulators. We will be moving as quickly as possible into a phase two atopic dermatitis study and more details to follow on that, but we expect we'll be able to do that in short order, without impacting any of our existing clinical studies. Okay, that's great. And then congrats on getting the late breaker at 8B.
Our phase two atopic dermatitis study.
And more details to follow on that but we expect we'll be able to do that in in short order.
Without impacting any of our existing clinical studies.
Okay. That's great and then congrats on getting the late breaker at <unk>. So any additional phase two data on $18 15 that you'll present, there or will it be what we've seen already.
Simba Gill: So any additional Phase 2 data on 1815 that you'll present there or will it be what we've seen already. And then the 1867 in a topic, what should we be expecting to see from the interim 1D data and just remind us a little bit more what the differences between 1815 and 1867 and could you ultimately pursue both for a topic germ or will you just pick one? Yeah, so let me take the 1867 second question. I'll let Mark take the first in terms of the difference between 1867 and 1815. I've done it again actually.
And then the 18 67 in atopic derm.
What should we be expecting to see from the interim <unk> data and just remind us a little bit more what.
What the differences between <unk> 15, and 18 67 and could you ultimately pursue both for atopic derm or will you just pick one and yet yes.
Yeah. So let me take the 18 67 second question I'll, let mark take first in terms of the difference between.
867, and $18 15.
Simba Gill: I forgot your first question, but we'll come back to that in a moment. So in terms of, uh how it would develop at 1867 and what the is it's not an interim, the Phase 1B will be top line and we're looking at essentially top line efficacy data, which is what we'll report out in a similar way to what we've done historically and we should have that very soon actually. To the degree we get positive data there, the... One of the many beauties of both 1867 and 1815 is what we've seen preclinately as breadth of advocacy across, many different areas of inflammation including, for example, neuroinflammation.
Again, I should garner forgotten. Your first question will come back to that above it so in terms of.
How we would develop 18 67 and what's the.
Expectation is it's not an interim phase one b will be top line and we're looking at essentially top line efficacy data.
Which is what we'll report out in a similar way to what we've done.
Historically, we should have that very soon actually.
To the degree we got positive day to that.
The.
One of the many beauties of of both 18, six seven and 18 15 as what we've seen pre clinically is bret.
<unk> efficacy across.
Many different areas of inflammation, including for example, neuro inflammation. So if we were to see a positive result from 18 67, there's many different directions in which we could develop it we could potentially have two products in the atopic dermatitis, they could address potentially different segments of atopic dermatitis, we could also.
Simba Gill: So if we were to see a positive result from 1867, there's many different directions in which we could develop it. We could potentially have two products in atopic dermatitis. They could address potentially different segments of atopic dermatitis.
Simba Gill: We could also segment, obviously, inflammation and focus on 1867 in different indications to 1815. To be clear, atopic dermatitis is a clinical proof of principle for us and is not necessarily the indication in which we'll move forward with 1867. It's a way to get a fast positive result in the clinic with some fairly clear endpoints and the ability to, for example, look at patient biopsies, etc. So lots of different ways we could take it forward. Mark, do you want to answer the question on 1867 versus 1815 in terms of how they're different?
Segment, obviously inflammation and focus on the 18 67.
In different indications to 18 15 to be clear atopic dermatitis is a clinical proof of principle for us and is not necessarily the indication in which we'll move forward with 18 67, it's a way to get a false positive result in the clinic.
<unk>.
Some fairly clear endpoints and the ability to for example look at patient biopsies et cetera.
So lots of different ways, we could take it forward.
Mark do you want to answer the question on 18 67 versus $18 15 in terms of.
Mark Bodmer: Yeah, sure. Thanks, Gary. There are three or four points.
Yeah sure. Thanks, Gary are there are three or four points.
Mark Bodmer: The EDP1867 is isolated from a small intestinal sample. Just to reinforce that point, these are mucosally resident microbes, not microbes that come from stool samples. And it's in these mucosally resident microbes that we find the good activity. EDP1867 was from an ileal sample in a patient with Crohn's disease in remission. It's taxonomically quite distinct from EDP1815. And one of the things that we had as a strategy from the outset was to look at the range of taxonomy, which is effectively the range of biochemistry in these to find out what the potential of different types of bacterial isolates and their extracellular vesicles, in fact, would be for pharmacological properties. This one has a molecular mechanism of action, which is slightly overlapping but actually different from EDP1815.
The 18 67 is isolated from a small intestinal sample just to reinforce that point these will be closely resident microbes.
Microbes that come from stool samples and let some of these new codes and the resident microbes that we find the good activity maybe paintings seven was probably.
Emil Sopel AR in a patient.
Whose disease remission, it's Texan, obviously quite distinct from ETP 18, 15 Eduardo.
One of the things that we have is a strategy from the outset was to look at a range of taxonomy, which is effectively the range of biochemistry.
And these to find out what they are.
Potential all different types of bacterial isolates other extracellular vesicles impacted the pharmacological properties. This one has a molecular mechanism of action, which is slightly overlapping but actually different from ETP 18, 15, it's different patterns.
Mark Bodmer: It's different patterns of pattern recognition receptors, including toll-like receptors with very potent activity. The other thing which was key with this is that part of the manufacturing process involves gamma radiation. And we talked a lot about the fact that our products work through direct action and not through colonization and being live biotherapeutic products. EDP1867 is dead by design at the point when a patient takes it. So all of the activity that we've seen preclinically and what we're looking for clinically is due to direct interactions of microbial preparation with host cells in the gut. So, Gary, I remembered your other question with regards to the AIDS presentation. Yeah. It's an exciting one.
Recognition receptors, including toll like receptors with very potent activity. The other thing which was a key with this is that part of the manufacturing process and bowls gamma radiation.
You talked a lot about the fact that our products work through direct action and not through colonization.
Being live Biotherapeutic products ETP 18, 67 is that by design at the point when a patient a patient takes it so all of the activity that we've seen pre clinically and what we're looking for clinically is due to direct interactions with microbial preparation with host cells in the gut.
Okay.
Okay.
So Gary I remembered your other question with regards to the 18th presentation. So anyway.
Simba Gill: Yeah, so we're obviously thrilled, first of all, that we've been selected as the late-breaker. As you know, it is very unusual for that to happen for a mid-stage clinical biotech company. I think it's great validation for Hal.
Yeah. So so you know what it was he thrilled festival that we've been selected late breaker.
As you know very unusual for that to happen.
For a mid stage clinical biotech company I think it's great validation file.
Simba Gill: The Durham community has seen the potential for what we're doing. We will provide more colour obviously than we've been able to do so far. That said... Obviously, the three key pieces of data beyond the top line efficacy we reported out on obviously both today as well as recently, but I would encourage you to link it. Great. Okay. Thank you. All right. Thanks, Gary. Saturday morning, 10.10am.
Community is seeing the potential for what we're doing we will provide more color. Obviously then than we've been able to do so far.
Ed.
Obviously, the three key pieces of data beyond the top line of efficacy we've reported that one obviously.
Poked today as well as recently so.
So, but I would encourage you to listen to.
Great. Okay. Thank you.
Simba Gill: Good time to listen. [inaudible] I'll quiz you on it later, Gary. I'm from the land of Joseph Tomwood County, London.
Thanks, Gary.
Saturday morning, 10, 10 a M.
The time to listen.
Okay.
Of course, you're on it and I used to go to.
Our next question coming from the line of Joseph Thome with Cowen Your line is open.
Simba Gill: Good morning and thank you for taking our questions. Maybe the first one on the EV candidate. Are you going to be using the same formulation as this updated formulation that releases higher in the region and maybe is there anything differentiated about the release kinetics or kind of where the easy candidate should release. We are going to be using the same formulation that releases higher in the region and maybe is there anything differentiated about the release kinetics or kind of where the easy candidate should release.
Good morning, and thank you for taking my questions maybe the first one.
The E V candidate are you going to be using the same formulation.
This updated formulation that releases higher in the genome.
And maybe is there anything differentiated about the release kinetics or in a worthy candidates should release.
Simba Gill: In the intestine that might be different than... Inertion Candidate at all, or do you expect kind of better at it? [inaudible] The beauty of the faster release capsule formulation is that it's platform related as opposed to product related. So whether we're talking about microbes or EVs, it's a dramatically improved release profile that should be applicable for all our products going forward. So we anticipate we're going to use it for the EVs straight away as well. And again, I've said it already, but we are thrilled with that result. It's really the best possible result we could have expected.
In the intestine that might be different than the first generation candidates at all or.
Do you expect to kind of our advocacy.
Okay.
Yes, so hydro.
Well just skiing with you liked it today hopefully.
So.
But the beauty of the foster released capsule formulation is that its platform.
Related as opposed to product related so whether we're talking about microbes or evs.
It's a dramatically improved.
Release profile it should be applicable.
Going forward.
So are.
We will we anticipate we're going to use it for the EV straight away as well and again I've said it already but we are thrilled with that result.
It's really the best possible result, we could have expected and we see it as having potential to drive.
Simba Gill: And we see it as having potential to drive very significant increases, in efficacy across everything we're doing microbes or EVs. Perfect, and I know on the KOL call the other week, they mentioned potentially using 1815 and psoriasis in more severe patients, potentially as a combination approach. I guess, how straightforward is that clinically? Are you able to get reimbursement for combination therapies and have physicians prescribe this? Or would you need to have additional data showing combinatorial benefit in more severe patients? before uptick in that. Yeah, so in the real world, very straightforward. It was actually touched on very briefly at the KOL event we had recently.
A very significant increase.
And efficacy.
Everything we're doing microbes of where he piece.
Perfect and then I know in the K well call them. The other week, they mentioned potentially using 18 15 in psoriasis in more severe patients potentially as a combination approach I guess, how straightforward is that clinically.
Are you able to get reimbursement for combination therapies and have physicians prescribe this or would you need to have additional data showing combinatorial benefit in more severe patients.
Before uptake in that segment.
Yes, so in the real world very straightforward it was actually touched on very briefly.
K O L event, we had recently.
Simba Gill: So we may, for example, have to go through step through at least initially in the milder moderate, certain segments of milder moderate, where topicals are, you know, gold standard, Joe, but that will be very, very straightforward. The conditions are used to doing it, and it should be a very straightforward. Most of us, and what we've been through that, then in the real world, use and combination will be very, very straightforward. We expect, you know, patients will, for example, in practice, at least initially, go on acute topicals to treat acute flares, for example, and then essentially the equivalent of maintenance on 1815 with limited use of topicals as we expect where this will start off and then moving potentially to monotherapy with 1815. So we think it's going to be very, very straightforward. Perfect. Thank you very much and see you later.
So we May for example have to go through step through at least initially in the mild to moderate a sudden sequence of mild to moderate wet.
Wet pulp it goes all the gold standard.
Joe but.
That will be very very straightforward clinicians that used to doing it.
And it should be a very straightforward process and once we've been through that then in the real world use in combination.
We'll be very very straightforward we expect.
Patients will for example in that case.
At least initially.
Go on acute top goals are to treat acute flash for example, and then essentially the equivalent of maintenance of making 15 with intermittent use of topical says we expect where this will.
We'll start off and then moving.
Potentially to monotherapy with 18 15, so we think it's going to be very very straightforward.
Perfect. Thank you very much and see you later today.
Thanks, Joe look forward to that.
Simba Gill: Thanks, Joe. Look forward to that. A question coming from Delana of Christian Kuska with... Hey, good morning, everybody. Thanks so much for taking the questions. With the new data that you reported today, I wanted to ask how specific and, More interesting, always for to hear a voice. I'll let Mark answer that. Yeah, actually, Chris, that's a really interesting question, a more detailed view of the preclinical support for this hypothesis of higher release includes looking at the distribution of immune cells longitudinally throughout the gut.
Our next question coming from the line of Kristen <unk> with Cantor Your line is open.
Hey, good morning, everybody. Thanks, so much for taking the question with the new data that you reported today I wanted to ask.
<unk> and chemicals targeting.
Yes.
Related to the targeting of the.
I'm Jared itself.
And also how it correlates to be in touch.
So.
More interesting Oh, it's good to hear your voice.
Let mark answer that.
Yes, Chris that's a really interesting question a more detailed view of the preclinical support for this hypothesis of higher release includes looking at the distribution of immune cells logo shrewdly throughout the gut that should have been some very nice publications about this which we referred to interestingly the.
Simba Gill: There have been some very nice publications about this, which we refer to. Interestingly, the dendritic cells, in particular, are at higher densities in the gut wall, in the upper parts of the gut with the duodenum, which is relatively short and into the jejunum.
<unk> sells in particular.
Or at higher densities in the gut wall in the upper parts of the cut in the duodenum, which is relatively short and into the June them. So we had the hypothesis from the outset, but that would be a place to target. The other thing is if you think about the primary.
Mark Bodmer: So we have the hypothesis from the outset that that would be a place to target. The other thing is if you think about the primary role, job of the gut immune system, it's actually to stop the immune system responding to things because the gut via the mouth and the stomach is where massive amounts of foreign stuff are coming into the body constantly. And it would be a disaster if we had immune responses against all those things.
Whoa job of the immune system touching to stop the immune system responding to things because they've got Bob the mountain the stomach as well.
Those amounts of foreign stopped coming into the Baltic constantly and it would be a disaster. If we had immune responses against all those things. So actually what we're doing is we're harnessing the natural ability of that got to actually prevent inflammatory responses against Dolby.
Mark Bodmer: So actually, what we're doing is harnessing the natural ability of the gut to actually prevent inflammatory responses against all the foreign stuff that's coming in. And at a sort of principled level, I think that's what our drugs are doing. We're providing a pharmacological level stimulus at the right dose to engage those systems whose natural function is to maintain homeostasis in the face of continual foreign bodies of food and all the microbes and everything else that's in the food that we ingest and the dirt that we take in from our environment and things. That is focused in the higher parts of the small intestine.
Fallen stuff that's coming in.
Uh huh.
So principled level I think that's what I've done severely we're providing a pharmacological levels stimulus at the right dose to engage those systems with natural function is to maintain homeostasis in the face of a.
Continual foreign barrels of food and all of the microbes and everything else. It's in the food that we ingest them.
Mark Bodmer: So we don't talk about this very much because it gets a bit complicated in the immunology. We've actually built into the understanding of small intestinal immunology and actually taking a step back and thinking about what its real role is. Most people think the immune system's role is to protect against infection and cancer. And at one level, that's true.
<unk> taken for low volumes of things that is focused in the higher parts of the small.
Small intestine. So it was we have talked about this by much because it gets a bit complicated didn't even can be apology because he built into the understanding of small intestinal immunology attitude, just taking a step back and thinking about it when it's real well with most people think the immune system's role is to protect against infection.
Mark Bodmer: But if you've got a system like that, you need an even more potent system to prevent it continuously being an uproar. And that's essentially what harnessing syntax with these types of medicines appears to be doing. And doing it, as Sundar always emphasizes, for immune resolution on multiple pathways of inflammation. So this is not a molecularly targeted single pathway intervention. As occurs naturally, all systems are taken down in parallel to reestablish normal homeostasis, just as the body normally does.
Cancer at one level, that's true, but if you've got a system like that you need an even more potent system's preventive.
And instead of being in a pool and that's essentially what policy since.
<unk> with these types of medicines appears to be doing and doing it as simba always emphasizes for immune resolution or multiple pathways of inflammation. So this is north molecular targeted single pathway intervention as occurs naturally all systems are taken bounded parallel to.
The the normal homeostasis and just what the body normally does.
Mark Bodmer: And of course, one final point, it's able to do that because of the way the gut immune system works without generating immunosuppressive responses. We do not immunosuppress ourselves by failing to have adverse reactions to most of the foreign antigens we're exposed to. So this whole clinical profile that we're describing makes complete sense in terms of the distribution of immune cells in the gut and in terms of the predominant requirement functionally for the gut immune system. I hope that was clear enough. Yes, it was.
One final point, it's able to do that because of the way the immune system works without generally I think immunosuppressive responses, we do not immunosuppressed ourselves by failing to have adverse reactions to most of the part of passengers were exposed to so this whole.
Clinical profile that we're describing makes complete sense in terms of the distribution of immune cells in the Gulf and in terms of the.
Predominant requirement functionally mcgough immune system.
I hope that was clear enough.
Simba Gill: Thank you for that. And then wanted to ask you about the pediatric market for psoriasis how you view this and in light of everything that you've communicated the KOL has said about route of administration, safety, et cetera. Is there anything that you would emphasize or perhaps say is different about the opportunity for an oral therapy for pediatric thank you. So I'd go above psoriasis in terms of responding to the question.
Yes. It was thank you for that and then wanted to ask about the PD.
Pediatric market for psoriasis, how are you.
And.
In light of everything that you have.
Okay.
Sad about.
Stringent safety et cetera is there anything that you would emphasize or perhaps.
Different about the opportunity for an oral therapy for pediatric thank you.
Yeah. So I could go above psoriasis list and then in terms of responding to the question. So if you look at inflammatory diseases, particularly H p's.
Simba Gill: So if you look at inflammatory diseases, particularly ATPs, a massive issue in children and pediatric populations. And, obviously, when we're dealing with children, the safety and tolerability side of things becomes even more paramount than it is normally. And it is a major limitation of almost all current inflammatory products. Very, very hard to prescribe them to the pediatric population. I don't even know if you've got children, Kristin, but anybody who has a child, just to put it in context, has about a one in four chance of an atopic inflammatory disease and condition.
A massive issue.
In children and pediatric populations.
And obviously when we're dealing with children.
The safety and Tolerability side of things becomes even more powerful than it is normally.
And it is a major limitation of almost all current inflammatory products.
Very very hot to prescribe them to the pediatric population.
I don't even know if you've got children Christina.
But anybody who has a child just to put it in context. It was about a one in four chance of an atopic inflammatory disease and condition and obviously as a parent.
Simba Gill: And, obviously, as a parent of those children, you want safe, very well-tolerated products. So we have the safety and tolerability profile, which I'll keep emphasizing. It is essentially completely unique in the world of inflammation and is ideally suited to use in the massive pediatric population who suffer from inflammatory diseases. HPs in particular, but more broadly. The next piece is, obviously, what you're touching on, which is how do you give children, particularly little ones, medicines from a formulation perspective? Obviously, if we're talking about teenagers and so on, relatively straightforward.
All of those.
Children, you want safe very well tolerated.
So we have the safety and Tolerability profile, which will keep emphasizing it is essentially.
Completely unique in the world of information and is ideally suited to use and the massive pediatric population suffering from inflammatory diseases hps in particular, but more broadly. The next piece is obviously, what you're touching on which is how do you give children.
Particularly the little ones.
Our medicines from a formulation perspective, obviously, if we're talking about teenagers and so on are relatively straightforward.
Simba Gill: Even unruly teenagers are able to swallow tablets and capsules. So no issue there in terms of formulation. The issue is, obviously, as you go younger, administration, can not be done through an oral capsule delivery, for example, in very young patients.
Even unruly teenagers are able to swallow tablets and capsules.
So no issue that in terms of formulation issue is obviously as you go younger.
<unk> administration.
It cannot be done through our a and.
Oral capsule delivery for example in very young patients. So we're working already on alternative formulations, which would allow ingestion format that pediatric population and that's what comparative programs basically Christian.
Simba Gill: So we're working already on alternative formulations which will allow ingestion for that pediatric population, and that's a work in progress, basically a Christian. Confident will be able to get there, so no issues around all of that. And I think the most important thing is we're really excited about the potential here for the pediatric population, very, very happy to have clear paths forward in the first instance. And we see huge potential for what we're doing in pediatric. Great, thank you.
We'll be able to get that so no issues around all of that and I think the most important thing is we're really excited about the potential here for the pediatric population very very happy to have no clear path forward.
And in the first instance, and we see huge potential for what we're doing in pediatrics.
Great. Thank you.
Operator: Our next question coming from the line of ReconProHIT from Morgan Stanley, Elanis, Alberta. Good morning, everyone. This is gospel unfold victim.
Okay.
Our next question coming from the line of Brian <unk> from Morgan Stanley . Your line is open.
Operator: We have one question. And the question is, what would the planned clinical study of the first release, ADP 1850 capsule look like in terms of design and size? and has there been any regulatory input to guide the study design that you have in mind here?
Good morning, everyone. This is gospel on falling victim Oh, we have one question and the question is what would be planned clinical study of the first release ADP 50 capsule look like in terms of design and size.
And how has that been any regulatory input to guide just started design that you have in mind here.
Simba Gill: Good morning. I appreciate the single focus one question, and I think you focused on the right topic. So again, most importantly, we are thrilled with the faster release, capsule and it dramatically improves the likelihood that we're going to be able to get great responses in a very significant proportion of patients. We have just got the data gospel so we have not yet interacted with regulators. We're working through clinical study designs more to follow on that but we expect we will move forward with a powered phase to study the show clear, benefit in atopic dermatitis and that will get going very quickly and we expect we'll likely have results from that. Certainly there's not yet formal guidance but I would expect somewhere around first half of next year as an informal directional sense of what we're expecting and we'll interact with regulators in due course.
Good morning.
Appreciate the single focus one question and I think you focused on the right.
The REIT topic. So again, most importantly, we are thrilled with the foster release.
Capsule.
And it dramatically improves the likelihood that we're going to be able to get.
Great responses in a very significant proportion of patients.
We just got the data gospel so we.
We have not yet interacted with regulators, we're working through clinical study designs more to follow on that but we expect we will move forward with a pilot phase two study to show a clear.
Benefit in atopic dermatitis, and that will get going very quickly and we expect we'll likely have results from that suddenly.
There's not yet formal guidance, but I would expect somewhere around the first half of next year.
Informal directional.
Sense of what we're expecting and will interact with regulators in due course costs.
Simba Gill: Thank you very much. Thank you. And I'm showing no further questions at this time. I would now like to turn the call back over to Simba Guild for any closing, Thank you very much.
Alright, Thank you very much.
Okay.
And I'm showing no further questions at this time I would now like to turn the call back over to Joseph Zhou for any closing remarks.
Simba Gill: So, thanks very much, everyone. Obviously, a remarkably exciting time for us. Things continue to progress from strength to strength, so we are extremely excited about where we are and very confident that we're going to be able to realize the broad vision that we have for Avelo. It is very clear at this stage that the small intestinal axis exists.
Thank you very much. So thanks very much everyone. Obviously at a remarkably exciting time for as things continue to progress from strength to strength.
So we are extremely excited about where we are and are very confident that we're going to be able to realize the broad vision that we have for value. It is very clear at this stage that the small intestinal axis.
Simba Gill: I'm at an investor conference, right now and I've had some very interesting discussions on ski slopes and over nice glasses of wine, but what's very clear from those conversations is what we've always said. This is one of the rare.., situations in biotech in medicine and science where we've uncovered a fundamental platform linked to a completely new era of human biology that we didn't know existed before that plays a fundamental role in regulating systemic immunity and inflammation throughout the body.
I'm at our Investor Conference.
Right now and they've had some very interesting discussions on the ski slopes and have a nice glasses of wine.
But.
What's very clear from those conversations is what we've always said this is one of the rat.
Situations in biotech in medicine, and science, where we've uncovered a fundamental platform linked to a completely.
New Arab human biology that we didn't know existed.
People that plays a fundamental role in regulating systemic immunity in inflammation throughout the body as you've heard from us repeatedly including today from Mark.
Simba Gill: As you've heard from us repeatedly including today from Mark, we have uncovered the key connection between the gut and systemic immunity and inflammation that probably links to the evolutionary background of microbes needing to make sure, as Mark said, they don't trigger a systemic inflammatory response.
We have uncovered the key connection between the cup and systemic immunity in inflammation that probably linked to the evolutionary background of microbes needing to make sure as Mark said, they don't trigger a systemic inflammatory response.
Simba Gill: And very quickly, we've now generated very clear positive phase 2 clinical data showing that we can harness that with something that's very safe and well-tolerated. And today's faster release capsule formulation really takes it to the next level. So we're in a fantastic place and look forward to keeping everybody updated. We've got a lot of continuous news flow, in the near future. Thanks very much, everyone. Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. [music]
And very quickly we've now generated very clear.
Positive phase two clinical data showing that we can harness that with something that's very safe and well tolerated in today's foster release capsule formulation really takes it to the next level. So we're in a fantastic place and look forward to keeping everybody updated we've got a lot of continuous news flow.
In the near future, Thanks, very much everyone.
Yeah.
Ladies and gentlemen that does conclude our conference for today. Thank you for your participation you may now disconnect.
[music].
Yes.
[music].