Q3 2021 Evelo Biosciences Inc Earnings Call

Yes.

Operator: Good morning, and welcome to the BioSciences conference call to discuss its third quarter 2021 business highlights. At this time, all participants are in a listen-only mode.

Okay.

Good morning, and welcome Jeff L.

Biosciences Conference call.

Scott its third quarter 2021 business highlights.

At this time all participants are in a listen only mode.

Operator: 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 would like to turn the call over to Kendra Sweeney of Ibella. Please proceed. Thank you.

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 question.

At this time I would like to turn the call over to conduct me I'll take that.

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.efelobios.com under the Investors tab. 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 and third quarter 2021 financial results. Before I 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 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 their impact on many factors.

Thank you. This morning, we issued a press release that outlines the topics we plan to discuss today.

The release is available at Www Dot if velo bio dot com under the investors tab.

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 and third quarter 2021 financial results.

Before I 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 in the.

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 $19 95.

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 Avelo's quarterly report on Form 10-Q for the quarter ended September 30, 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 views to change. It is now my pleasure to pass the call over to Simba. Thank you, Kendra.

Participants are directed to the risk factors set forth in <unk> quarterly report on Form 10-Q for the quarter ended September 32021, 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.

<unk> disclaims any duty to provide update 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.

Simba Gill: Good morning, everyone, and thank you for joining us to review our progress during the third quarter. The major news for the last quarter was, of course, the positive top-line results of a Phase II trial of EDP1815 in patients with mild and moderate psoriasis. The Phase II clinical data prove, beyond reasonable doubt, that we can indeed harness syntax to create medicine. I can't emphasize enough the importance and value of these data. The trial addressed the central question we have been asking since we first started DEVELO.

Thank you Kendra.

Good morning, everyone and thank you for joining us to review our progress during the quarter.

A major news good last quarter was of course, the positive topline results of our phase II trial of Edp $18 15 in patients with mild and moderate psoriasis.

The phase II clinical data prove beyond a reasonable doubt that we can indeed harnessed syntax to create medicines.

Emphasize it enough.

And value of these data.

The trial address central question, we've been asking since we first started debello.

Simba Gill: Can targeting syntax be the foundation for a new profile of medicine? The answer is yes. With EDP1815, we have now shown in a well-controlled phase 2 clinical trial that we can harness syntax to make a clinical impact on patients with an oral product candidate, with safety and tolerability data comparable to placebo. Together with Affordable Manufacturing.

Try and talk think syntax.

The foundation for new profile of Medicine.

The answer is yes.

With the <unk> 15, we have now shown in a well controlled phase III clinical trial, but we can harvest impacts to make clinical impact on patients with an oral product candidate.

With safety and Tolerability data comparable to placebo.

Together with affordable manufacturing.

Simba Gill: These data support the potential of Syntax medicines to address an enormous unmet need in the global treatment of patients with mild and moderate inflammatory disease. The data from the Phase 2 trial underscore two drivers of value. First, there is the potential of EDP1815 as an important new medicine in the treatment of psoriasis.

These data support the potential of syntax medicines.

An enormous unmet need in the global treatment of patients with mild and moderate inflammatory disease.

The data from the Phase II trial under school two drivers of value.

First is the potential of Edp <unk> 15 is an important new medicine in the treatment of Suraj.

Simba Gill: Based on this data, we are advancing EDP1815 towards registration trials in mild and moderate psoriasis, because the primary unmet need in psoriasis is in this segment of patients. There are over 55 million patients with psoriasis worldwide, and patients with mild and moderate disease represent over 90% of this patient population. The second driver of value is that this is proof of concept for the Syntax Platform in a Phase II clinical trial. The potential implications of this are immense.

Based on the data we are advancing <unk> towards registration trials in mild to moderate psoriasis.

The primary unmet need in psoriasis is for this segment of patients there are over 55 million patients with psoriasis worldwide and patients with mild and moderate disease represent over 90% of this patient population.

The second driver of value is that this is proof of concept for the syntax platform in a phase two clinical trial.

The potential implications of that are met.

Simba Gill: This research reveals a previously unknown branch of biology that touches on a broad mechanism for the resolution of inflammation, which impacts a considerable number of diseases and for which we have shown a new type of medicine that works in humans. In dermatology alone, there are globally over 200 million people who suffer from mild and moderate diseases for which there are limited treatment options. In broader inflammatory diseases, including arthritis, asthma, and chronic obstructive pulmonary disease, there are about a billion people worldwide in need of better treatment. I'd like to touch on one specific aspect of syntax-based products as a new type of medium.

It reveals a previously unknown branch of biology.

Which touches on a broad mechanism for the resolution of inflammation.

Which impacts a considerable number of diseases and for which we have shown a new type of medicine that works in humans.

In dermatology alone there globally over 200 million people, who suffer from mild to moderate diseases for which there are limited treatment options.

And broader inflammatory diseases, including arthritis, asthma, and chronic obstructive pulmonary disease. There are about 1 billion people worldwide in need of better treatment.

I'd like to touch on one specific aspect of syntax based products as a new type of medicine.

Simba Gill: We are developing orally-delivered microbial products that are non-live biotherapeutics. This is a completely different concept from live biotherapeutics and the microbiome. There is no colonization or modification of the microbiome.

We are developing orally delivered microbial products that are non life biotherapeutics.

This is a completely different concept the life biotherapeutics and the microbiome.

There is no colonization or modification of the microbiome.

Simba Gill: They have a direct pharmacological effect through interactions with host cells in the gut, which in turn modulates systemic inflammatory responses throughout the body via the small intestinal axis. The clinical responses to EDP-1815 opened the door both to EDP-1815 as a potentially important medicine in dermatology and to the broader potential of the platform. Our aim has always been to develop an entirely new profile of medicine that will transform healthcare rather than another incremental improvement on what already exists.

They have a direct pharmacological effect through interactions with host cells in mcgough, which in turn modulate systemic inflammatory responses throughout the body.

The small intestinal axis.

The clinical responses to Edp 18, 15 opened the door both to Edp <unk> as a potentially important medicine in dermatology and to the broader potential of the platform.

Our aim has always been to develop an entirely new profile. It mentioned that will transform health care rather than another incremental improvement to what already exists we did not invent the small intestinal axis, we discovered it by inventing syntax medicines, which harness this extraordinary.

Simba Gill: We discovered it by inventing Syntax medicines which harness this extraordinary natural system that controls inflammation throughout the body. What we have discovered is how to harness nature to create something that has never existed before. We have discovered and pioneered new principles and new approaches for developing and manufacturing syntax medicine. Our Phase II data, together with other clinical and preclinical data we have generated, gives us high confidence that we will realize our vision to transform global healthcare. Let me repeat the core point.

Full system, which controls inflammation throughout the body.

What we have discovered just have harnessed nature to create something that has never existed before we have discovered and pioneered new principles of new approaches for developing and manufacturing syntax medicines.

Our phase II data together with other clinical and preclinical data we have generated gives us high confidence that we will realize our vision to transform global health care.

Simba Gill: We have demonstrated that we can harness syntax to drive clinical effects throughout the body with an orally delivered gut-restricted age. Syntax medicines are a substantial new platform in our industry with the potential to help hundreds of millions of patients globally at all stages of disease. Most of these patients have so far not received the benefits of biotech innovation. Think of this in terms of combining the discovery of cytokine biology with the discovery of therapeutic antibodies. Newly discovered biology underpinning many diseases together with the means to do something about it, and then delivering it to patients as a convenient oral pill. With that, I will hand it over to Mark.

Let me repeat the coal point, we have demonstrated that we can harness syntax to drive clinical effects throughout the body with an orally delivered gut restricted agent.

Syntax medicines are substantial new platform in our industry with the potential to help hundreds of millions of patients globally at all stages of disease.

Most of these patients have so far not received the benefits of biotech innovation.

Think of this in terms of combining the discovery of cytokine biology with the discovery of therapeutic antibodies newly discovered biology underpinning many diseases.

Together with the means to do something about it.

And then delivering it to patients as a convenient oral pill.

With that I will hand over to Mark.

Thanks, Joe Bob.

Mark Bodmer: We're often asked the reasonable question, "What are the risks of success for Avelo's medicine?" Of course, there's one overarching risk. Is syntax biology important, and can syntax medicines work? Yes, it is important, and yes, EDP1815 was observed to have a clinical impact on patients with psoriasis. There are also the risks around manufacturing and the regulatory path to the clinic, both potentially significant hurdles for new modality. These, too, have been overcome.

We're also though the reasonable question what are the risks of success of medicines closer as one overarching risk is synthetic biology important constant.

Syntax medicines work, yes. It is important and yes, Edp 18, Christine was observed to have a critical impact on patients with psoriasis.

We're also the risks around manufacturing and regulatory path to the clinic, both potentially significant hurdles for new modality.

These two have been overcome.

Mark Bodmer: The Phase II results take us past these fundamental risks and on to the practical challenges of making SYNPACS medicines work for the largest numbers of people as effectively as possible. The breadth of opportunity that Simba talks about comes directly from the breadth of the mechanism of action, that is, the coordinated resolution of multiple pathways involved in the inflammatory response. Now that we have shown syntax functions in humans to modulate systemic immunity, it's reasonable to expect that syntax medicines may be beneficial in almost any condition in which inflammation plays an adverse role, which is most diseases.

The phase two results take of course these fundamental risks also.

The practical challenges of making syntax medicines work with <unk>.

Largest numbers of people as effectively as possible.

The breadth of opportunities of similar talks about comes directly from the breadth of the mechanism of action that is the coordinated resolution of multiple pathways in gold and the inflammatory response.

Now that we have shown syntax functions in humans modulate systemic immunity, it's reasonable to expect that some such medicines may be beneficial in almost any condition in which inflammation plays an adverse role which is most diseases. As an example, two weeks ago. The effect of Edp $8 67 in a mouse model of Europe.

Mark Bodmer: As an example, two weeks ago, the effects of EDP1867 in a mouse model of neuroinflammation were presented at a European multiple sclerosis conference. These were extraordinary data showing the gut immune system reaching into the central nervous system under the influence of one of our drug candidates. It is the same principle that allows the gut to reach into the skin.

Inflammation were presented at the European multiple sclerosis confirms these were extraordinary data showing the immune system, reaching into the central nervous system under the influence of one of our drug candidates.

The same principle that allows that got to reach into the skin.

Apparently disparate effects of <unk>.

As a result of the pre appropriate mechanism, which is the glue that holds together this whole concept with the small intestinal axis could impact inflammation throughout the body.

Mark Bodmer: The apparently disparate effects in skin and CNS are the result of the pleiotropic mechanism, which is the glue that holds together this whole concept that the small intestinal axis can impact inflammation throughout the body. I'm now going to turn to two related topics that are part of making EDP1815 and future Syntax Medicines work as effectively as possible. The first topic has to do with the responder rate to EDPH in 15 that we observed in the phase 2 psoriasis trial.

I'm now going to turn to two related topics that are part of making Edp 18, 15, and future syntax medicines work as effectively as possible.

The first topic is to do with the responder rate to <unk> 15 that we observed in the face and psoriasis trial.

As you recall approximately 30% of patients who received <unk> in the trial achieved deposit 50 response by the 16 week endpoint.

However, this does not mean that <unk> 16 does not have any effect in the other 70% of people.

There was a continuous distribution of housing responses with 30% who were reported as has a 50 responders to simply.

Mark Bodmer: As you recall, approximately 30% of patients who received EDP-1815 in the trial achieved a PASI-50 response by the 16-week endpoint. But this does not mean that EVP 1815 does not have any effect in the other 70% of people.

Overall distribution after 16 weeks of treatment.

The phase II study showed the efficacy of crude as patients continue to take <unk> 16, which suggests with treating for longer could result in higher response rates.

Rising tide lifts all boats anything that increases overall response rates has the potential to benefit more patients.

Mark Bodmer: There was a continuous distribution of PASI responses, but 30% who were reported as PASI-50 responders were simply a cut of that overall distribution after 16 weeks of treatment. The Phase II study showed that efficacy accrued as patients continued to take EDP18-15. This suggests that treating for longer could result in higher response rates.

We have also done further sensitivity analyses since the phase II data were released last month and I'd like to highlight one of them.

The proportion of patients who achieved Iga zero or one of the certifying that baseline body surface area psoriasis was evaluated.

Zero and one are expected to be clear and nearly clear skin. These are the targets with treatment in patients with mild to moderate psoriasis mild disease is defined as body surface area of less than or equal to 5% moderate disease was greater than 5%.

Mark Bodmer: Anything that increases overall response rates has the potential to benefit more patients. We've also done further sensitivity analyses since the Phase II data were released last month, and I'd like to highlight one of them. The proportion of patients who achieved IgA0 or 1 after stratifying their baseline body surface area, psoriasis, was evaluated. IGA 0 and 1 are, respectively, clear and nearly clear skin. These are the targets of treatment in patients with mild and moderate psoriasis. Mild disease is defined as a body surface area less than or equal to 5%.

The proportion of patients with moderate disease that is greater than 5%.

Who reached Iga zero or one compared to placebo with a P value of less than <unk>.

0.05.

Patients with mild disease also trended to efficacy with a P value that was not significant.

Cross the entire study population stratified by BSA group of baseline <unk> was also found to be significantly better than placebo in the number of PTA zero, one responders with a P value less than 0.5.

This was an important result.

It does not mean that Edp 18, 15 doesn't work in milder patients. It does mean that the effect is more readily detected in patients with more expense extensive disease not surprising since there is a larger window, leading the effect of the treatment.

The observed response rate in the phase II study was already within a clinically and commercially attractive range from mild to moderate disease reinforced by placebo like safety and Tolerability.

Mark Bodmer: Moderate disease is greater than 5%. The proportion of patients with moderate disease, that is, greater than 5%, who reached IgA 0 or 1 compared to placebo had a p-value of less than p0.05. Patients with mild disease also trended to efficacy with a p-value that was not significant. Across the entire study population, stratifying by BSA group at baseline, EDP1815 was also found to be significantly better than placebo in the number of PGA0 or 1 responders with a p-value less than 0.05. This is an important result, but it does not mean that EDP-1815 won't work in milder patients. It does mean that the effect is more readily detected in patients with more expensive diseases.

These further analyses are evidence for <unk>.

Additional improvement of efficacy in future studies based on clinical data, but we already have.

The second point about making syntax medicines work as effectively as possible as based on the observation in the phase II psoriasis trial, but we saw continued improvements in some patients after the end of the treatment periods.

Generally drug levels to be maintained to suppress the pathway.

Dosing has stopped.

And a rebound in disease symptoms.

The mechanism of action that allows us continued effect with Edp 18, 15 ties into broad inflammation resolution that I was talking about a moment ago. GBP 18, 15 in several of our other product candidates and jus, a regulatory phenotype and circulating immune cells.

We can show this experimentally with preclinical studies by isolating peripheral immune cells from animals that have been treated with drug.

If we then transfer these isolated cells of animals that was not previously withdrawn.

Mark Bodmer: Not surprising, since there is a larger window for reading the effect of the treatment. The observed response rate in the Phase II study was already within a clinically and commercially attractive range for mild and moderate disease, reinforced by placebo-like safety and tolerability. These further analyses are evidence for additional improvement of efficacy in future studies based on clinical data that we already have. The second broad point about making syntax medicines work as effectively as possible is based on the observation in the Phase II psoriasis trial that we saw continued improvement in some patients after the end of the treatment period. Generally, drug levels need to be maintained to suppress the target pathway. When dosing is stopped, there is often a rebound in disease symptoms.

These non drug treated animals at the same anti inflammatory.

Inflammation resolution of this space have been treated with.

The transferred cells.

<unk> inflammation resolved and the effect of the drug.

Hmm.

This is called adoptive cell transfer.

Core proof of mechanism for the therapeutic cellular phenotype induced by a syntax consider what this means the efficacy of a gut restricted drug is carried out by modified immune cells in the periphery.

Evidence of this in mice.

Cell transfer are evidence of this in humans as well.

Hindering effect after the drug is stopped.

<unk> regulatory cells continue to overcome the effects of inflammatory cells resident in the scam, leading to skin healing after the administration of the drug.

<unk>.

The modified immune cells can last for weeks in circulation perhaps longer.

<unk> response, yet so consider again, what this means we've created a regulatory T cell phenotype, which is induced institute by product candidate Dth in 15, but it has been observed to have placebo like tolerability and safety that can be manufactured at scale.

Mark Bodmer: The mechanism of action that allows this continued effect with EDP1815 ties into the broad inflammation resolution that I was talking about a moment ago. EDP1815 and several of our other product candidates induce a regulatory phenotype in circulating immune cells. We can show this experimentally in preclinical studies by isolating peripheral immune cells from animals that have been treated with drugs. If we then transfer these isolated cells into animals that are not treated with drugs, then these non-drug-treated animals have the same anti-inflammatory inflammation resolution as if they had been treated. Transcript cells mediate the inflammation-resolving effect of the drug. This is called adoptive cell transfer, and it is a core proof of mechanism for the therapeutic cellular phenotype induced by syntax. Consider what this means.

Compare this to the current interest in cellular therapies with ex vivo conditions regulatory T cells with skip that entire process step and concentrate with such a generation with an old product candidate.

Uses the body's natural programming.

This is one of those scientific results to profoundly opens one frame of reference but.

Got restricted Asia create active regulation of systemic inflammation, north immuno suppression with restoration of normal volume claims stake.

I'd like to finish with some more forward looking comments about our aspirations for the future of the syntax platform.

<unk> is now nicely set up as a treatment for mild to moderate psoriasis and I should also be true for other inflammatory diseases.

We have reported repeatedly that in preclinical studies, our drug candidates are as effective as the best standard of care Biologics and oral <unk>. This suggests potential so in severe inflammatory disease, our Gulf with future versions of syntax medicines is to reach biologic levels of efficacy in humans.

Syntax medicines beyond mild moderate or severe disease.

Preclinical data suggests this is biologically feasible.

Mark Bodmer: The efficacy of a gut-restricted drug is carried out by modified immune cells in the periphery. Our evidence for this in mice is the adoptive cell transfer. Our evidence for this in humans is the continuing effect after the drug is stopped. Induced regulatory cells continue to overcome the effects of the inflammatory cells resident in the skin, leading to skin healing after administration of the drug is ended. The modified immune cells can last for weeks in circulation, perhaps longer. However, we don't know the duration of the response yet. So consider again what this means.

Effective target engagement in humans is harder than in mice. The physics of the delivery of some facts medicines with a target with the larger human cost.

So in particular challenges.

We think that extracellular visa calls without volume 1000, south of a micro but help to address these challenges.

The small size advantage of Evs allows them to diffuse more readily in the gut.

And allows us to pack a higher concentration into each pill. Besides advantages will be combined with formulations, but ensure that the drug is based as much of the small intestine as possible.

A reasonable prediction, but these factors size packing and formulation.

We'll combine to increase efficacy.

It's how we got the high levels of efficacy pre clinically.

Mark Bodmer: We've created a regulatory cell phenotype, which is induced in situ by a product candidate, EEP1815, that has been observed to have placebo-like tolerability and safety, and that can be manufactured at scale. We can compare this to the current interest in cellular therapies with ex vivo conditioned regulatory T cells, which skip that entire process step and go straight to in situ generation with an all-product candidate that uses the body' This is one of those scientific results that profoundly alters one's frame of reference. The Gut Restrictive Agent can create active regulation of systemic inflammation.

And we are now learning how to do it in humans, our vision for the <unk>.

<unk> medicines is efficacy which is competitive.

<unk> added a cap all stages of disease with oral delivery of the safety and Tolerability seen with Edp <unk> theme.

Scientific platform, which was constructed methodically over the last five years supports this possibility.

With that I'll hand, it over to Jonathan to update you on our clinical programs.

Thank you Mark and good morning, everyone.

I will provide an update on our ongoing clinical trials upcoming readouts as well as planned studies.

Part B of our phase II trial in mild to moderate psoriasis is ongoing and assessing the durability of treatment response.

And completion of 16 weeks of dosing and 102004 patients. These participants are being evaluated monthly and we look forward to learning more about the lasting effects of Edp $18 15, we expect to report topline results in the first quarter of 2022.

Mark Bodmer: This is not immunosuppression; it is restoration of the normal, non-inflamed state. I'd like to finish with some more forward-looking comments about our aspirations for the future of the Syntax Platform. EDP1815 is now nicely set up as a treatment for mild and moderate psoriasis, and that should also be true for other inflammatory diseases. We have reported repeatedly that in preclinical studies, our drug candidates are as effective as the best standard of care biologics and oral.

The results from part a and part B of the Phase III trial will allow us to refine our next phase clinical plans for Edp $18 15 in psoriasis as well as seek feedback from health authorities.

Our phase <unk> trial, with Edp, $18, 67, and a cohort of patients with moderate atopic dermatitis is ongoing.

While participants are being dosed.

Days with a 14 day follow up period we.

We anticipate results from this trial in the first half of 2022 based on slower than projected recruitment.

Group.

Mark Bodmer: This suggests potential also in severe inflammatory disease. Our goal for future versions of syntax medicines is to reach biological levels of efficacy in humans to take syntax medicines beyond mild and moderate disease into severe disease. The preclinical data suggests this is biologically feasible, although getting effective target engagement in humans is harder than in mice. The physics of the delivery of syntax medicines to the target in the larger human's gut provides some particular challenges.

We previously reported that the U S. FDA had requested additional information in a clinical hold letter in the Edp 18, 15 phase two atopic dermatitis trial in patients with mild moderate and severe disease we.

We have satisfactorily responded to the FDA request and the hold has been lifted the IND is now open and we anticipate dosing late in the fourth quarter.

This trial will be 16 weeks in duration with the primary endpoint of percent of patients who achieve in eczema area and severity index easy 50 score at week 16.

Mark Bodmer: We think that extracellular vesicles, with their volume 1,000th that of a microbe, have helped to address these challenges. The small size advantage of EVs allows them to diffuse more readily in the gut milieu and allows us to pack a higher concentration into each pill. These size advantages will be combined with formulations that ensure that the drugs bathe as much of the small intestine as possible.

In addition, we will be collecting various physician and patient reported outcomes. We anticipate reporting results from this trial in the fourth quarter of 2022.

Patients on active and placebo from this trial will have the opportunity to join an open label extension once they complete 16 weeks of dosing all patients in the open label extension will receive edp $18 15 for up to 52 weeks.

Mark Bodmer: It's a reasonable prediction that these factors, size, packing, and formulation, will combine to increase efficacy. It's how we get high levels of efficacy pre-clinically, and we are now learning how to do it in humans. Our vision for the future of Syntax Medicines is efficacy that is competitive for the best standard of care for all stages of disease with oral delivery and the safety and tolerability seen with EDPH and cathine. The scientific platform which we have constructed methodically over the last five years supports this possibility. With that, I'll hand over to Jonathan to update you on our clinical program. Thank you, Mark, and good morning everyone.

We remain on track to bring our first extracellular vesicle or EV candidate Edp 29, 39 for inflammatory diseases into the clinic in 2022.

We continue to recruit patients in the phase III three tactic <unk> trial for the prevention and treatment of life threatening complications associated with COVID-19, and hospitalized patients in the U K, Brazil, Mexico and India.

Tactically is progressing well and is very close to the initial recruitment goal of 125 patients in each of the initial three arms of the trial, including Edp $18 15.

Getting this recruitment target will trigger an interim safety and futility analysis by the independent data monitoring Committee.

Jonathan Zung: I will provide an update on our ongoing clinical trials, upcoming readouts, as well as planned studies. Part B of our Phase II trial in mild and moderate psoriasis is ongoing and assessing the durability of treatment response following completion of 16 weeks of dosing in 124 patients. These participants are being evaluated monthly, and we look forward to learning more about the lasting effects of EDP1815. We expect to report top-line results in the first quarter of 2022.

Based on the progress in scale of tactically, we have decided to focus our efforts on this trial and to close our smaller U S phase III trial evaluating the safety and efficacy of Edp $18 15 in the treatment of patients hospitalized with COVID-19 infection.

It is now clear the smaller trial will not make a meaningful contribution to our understanding of edp $18 15, and hospitalized COVID-19 patients.

I'll hand, it back to Simba for closing remarks.

Thanks, Jonathan.

This is a pivotal moment for battery, we now have proof of concept from a phase two study for syntax.

Jonathan Zung: The results from Part A and Part B of the Phase II trial will allow us to refine our next phase clinical plans for EDP1815 and psoriasis, as well as seek feedback from health authorities. Meanwhile, our Phase 1b trial of EDP1867 in a cohort of patients with moderate atopic dermatitis is ongoing. Trial participants are being dosed with a 14-day follow-up period. We anticipate results from this trial in the first half of 2022, based on slower than projected recruitment.

We are advancing Edp ATM <unk> in psoriasis towards later stage development and potential commercialization.

In parallel we are advancing edp $18 15 in the phase II study in atopic dermatitis.

And a second anti inflammatory microbial product.

867 is in the clinic.

Our EV development platform is making strong technical progress towards the clinic and.

And we have shown pre clinically the potential of syntax medicines in neuro inflammation.

Jonathan Zung: We previously reported that the U.S. FDA requested additional information in a clinical hold letter for the EDP1815 Phase II atopic dermatitis trial in patients with mild, moderate, and severe disease. We have satisfactorily responded to the FDA request, and the hold has been lifted. The IND is now open, and we anticipate dosing late in the fourth quarter.

All of this is only the beginning we have a better and better understanding of how to capture the full breadth of our syntax platform and you can expect much more from a platform as we continue to grow <unk> towards our vision.

Thank you for your attention and we will now open for questions.

Ladies and gentlemen to ask a question you will need to press. The Star then the one key on your Touchtone telephone.

We try your question press the pound key please standby, while we compile the Q&A roster.

Jonathan Zung: This trial will be 16 weeks in duration with the primary endpoint of percent of patients who achieve an eczema area and severity index EZ-50 score at week 16. In addition, we'll be collecting various physician and patient-reported outcomes. We anticipate reporting results from this trial in the fourth quarter of 2022. Patients on active and placebo in this trial will have the opportunity to join an open-label extension once they complete 16 weeks of dosing. All patients in the open-label extension will receive EDP 1815 for up to 52 weeks.

And our first question coming from the lineup.

Chris Howerton with Jefferies. Your line is open.

Hi, good morning, everybody and thank you very much for taking the questions.

For me I think the first would be with.

With respect to atopic dermatitis.

I'd be curious to hear the companys start on both kind of the regulatory path of using easy 50, as a primary endpoint if that would be possible.

Then secondarily.

What would be a clinically meaningful effect size on such an endpoint within I guess, the mild to moderate patient population.

So that would be question one.

Jonathan Zung: We remain on track to bring our first extracellular vesicle or EV candidate, EDP2939, for inflammatory diseases into the clinic in 2022. Additionally, we continue to recruit patients in the Phase 2-3 Tactic E trial for the prevention and treatment of life-threatening complications associated with COVID-19 in hospitalized patients in the UK, Brazil, Mexico, and India. Tactic E is progressing well and is very close to the initial recruitment goal of 125 patients in each of the initial three arms of the trial, including EDP1815.

And then question two is with respect to cohort b of the psoriasis study.

Maybe if you could just compare and contrast that to cohort a and how that's going to inform.

The phase III design moving forward. Thank you.

Chris had simba. Thanks for your question sorry could you just repeat the last question.

Yes, Im sorry. The last question was comparing contrast cohort a and cohort b for the psoriasis study and what exactly in the cohort B results is going to help you kind of figure out the phase III design moving forward.

Okay, alright, thanks, So let me.

Take the middle one first which was what would be a clinically meaningful effect on the easy 50 side.

Jonathan Zung: Hitting this recruitment target will trigger an interim safety and futility analysis by the Independent Data Monitoring Committee. Based on the progress and scale of Tactic E, we have decided to focus our efforts on this trial and to close our smaller U.S. Phase II trial evaluating the safety and efficacy of EDP1815 in the treatment of patients hospitalized with COVID-19 infection.

As you know Chris atopic dermatitis.

For mild to moderate patient does not have any approved oral.

Treatments.

And.

Dermatitis patients essentially with mild to moderate disease are limited to taking a range of top goals, including topical steroids.

A number of limitations.

The reason leading to that Chris is the bar is actually very low for safe well tolerated oral drug and as long as we continue to confirm safety and Tolerability.

Jonathan Zung: It is now clear that the smaller trial will not make a meaningful contribution to our understanding of EDP1815 in hospitalized COVID-19 patients. I'll hand it back to Simba for closing remarks. Thanks, Jonathan.

If we see easy 50 responses or equivalent and I'll hand over to Duncan in the moment you can answer the first question.

Simba Gill: This is a pivotal moment for Avelo, and we now have proof of concept from a Phase 2 study for Syntax. We are advancing EDP1815 in psoriasis towards later stage development and potential commercialization. In parallel, we are advancing EDP1815 in a Phase II study in atopic dermatitis, and our second anti-inflammatory microbial product, EDP1867, is in the clinic. Our EV development platform is making strong technical progress towards the clinic, and we have shown in preclinical studies the potential of Syntax medicines in neuroinflammation. But all of this is only the beginning.

And.

A reasonable percentage of patients we have a very attractive drug I would say somewhat similar to <unk> that we have.

<unk>, 50, or greater and 25% to 30% of patients or more.

Then we have an attractive drug as a general guidance for you Chris.

We expect we have a good probability of doing better than that if you look at all phase one b data in atopic dermatitis, we already had.

Seven out of 16 patients.

Plus or minus that easy 50 level after only eight weeks of treatment.

So.

Operator: We have a better and better understanding of how to capture the full breadth of our Syntax platform, and you can expect much more from our platform as we continue to grow Avelo towards our vision. Thank you for your attention, and we will now open the floor to questions. Ladies and gentlemen, to ask a question, you will need to press the star, then the 1 key on your touch-tone telephone.

Operator: To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Now, the first question coming from the line-up: Chris Howerton with Jeffries and Jelena Seltzen.

We have no concerns about that as the scale from regulate perspective.

Remember will also this is the fate study. We also will have score at will have ijn's BSA PSA so teeth get points. So what we will do.

Chris Howerton: Hi, good morning everybody, and thank you very much for taking the questions. For me, I think the first would be, with respect to atopic dermatitis, I'd be curious to hear the company's thoughts on both the regulatory path of using EZ-50 as a primary endpoint, if that would be possible, and then secondarily, what would be a clinically meaningful effect size on such an endpoint within, I guess, the So, that would be question number one.

We will look at all of that data, we will understand which of those endpoints actually best standpoint to capture the benefit of <unk> 15 in mass murderer atopic dermatitis and then we'll go to have those discussions with with the health authorities, but all of that is a pretty well established.

<unk> is a very well validated and pointless.

Don't expect to have any concerns from the regulated with easy.

And then Johnson do you want to do the pump. The this is Shaun sure. So Christopher for the Phase two psoriasis study from the corner.

Chris Howerton: And then question two is, with respect to cohort B of the psoriasis study, maybe if you could just compare and contrast that to cohort A and how that's going to inform the Phase III design moving forward. Thank you. Chris. This is Simba.

Clearly learned the dosing longer.

Is going to be important to capture the full breadth of activity of 18 15.

When we think about the part B data.

B data will inform us around relapse, how long has benefit maintained obviously that'll that'll be incorporated in our thinking but certainly as we think about the next study in the registration pathway it'll be longer dose and quite will be looking at an endpoint.

Simba Gill: Thanks for your question. Sorry, could you just repeat the last question? Yeah, I'm so sorry.

Chris Howerton: The last question was, you know, comparing cohort A and cohort B for the psoriasis study and, you know, what exactly in the cohort B results is going to help you kind of figure out the phase 3 design moving forward? Okay, all right, thanks. So let me take the middle one first, which was what would be a clinically meaningful effect on the EZ50 side. As you know, Chris, atopic dermatitis for mild and moderate patients does not have any approved oral treatment, and atopic dermatitis patients essentially with mild and moderate disease are limited to taking a range of topicals, including topical steroids, which have a number of limitations.

As we've mentioned before most likely at six months and then extending out for another six months or you get a full year of data so.

Real I think data that will support the thinking behind that is part of it.

Okay did you want to add just.

Just one point for Christmas one point for clarity that.

Cohort pay is not a separate cohort it's the same patients.

<unk> of the study carried over.

B I just wanted to make sure you didn't.

It took me a question that we have a separate cohort of patients that we were looking at for longer.

Yeah now that that is helpful. I appreciate the clarification and.

I, maybe I'll hop back in the queue and give other people the chance, but I I appreciate you taking my questions.

Simba Gill: The reason I'm leading with that, Chris, is the bar is actually very low for a safe, well-tolerated oral drug, and as long as we continue to confirm safety and tolerability. If we see easy 50 responses or equivalent, and I'll hand over to Duncan in a moment who can answer your first question, a reasonable percentage of patients, we have a very attractive drug. I would say, somewhat similar to psoriasis, if we have effects at ET50 or greater in 25 to 30% of patients or more, then we have an attractive drug as a general guidance for you. We expect we have a good probability of doing better than that.

Thanks, Chris.

And can I next question I'm coming from the liner Martin Mcshane with B M.

B M O Captain all your line or something.

Hi, Good morning, guys. Thank you very much for taking the question Congrats on I continued progress.

So maybe first on the part B.

Yes.

Everything that you've just talked about and the importance of looking beyond 16 weeks are you able to provide some preliminary perspective on the level of additional follow up you expect to have beyond that 15, 16 week data point, when you really say that will everyone be it checks months or what the medium be somewhere.

Below that and if so around aware.

And then secondarily.

Want to know if you're able to provide any incremental color on the formulation work since the last update.

And when you may be able to.

Simba Gill: If you look at our Phase 1B data in atopic dermatitis, we already had 7 out of 16 patients who were plus or minus at that easy 50 level after only 8 weeks of treatment. So, we're feeling confident right now that we'll get to that level or better, Chris, that I talked about. I'd also emphasize that in psoriasis, we did already see some patients that... different diseases, different biology, but it's certainly encouraging in terms of where we think we may end up.

Have something more concrete to say about your efforts here.

And then maybe lastly, if I could on 18 67.

Just understand a little bit more of the recruitment challenges that you've seen and maybe more broadly.

How the a D data.

Will inform your development strategy not only for this drug but for Edp 18, 15 as well. Thank you so much.

[noise], So let me take.

Take a couple of others I'll, let Jonathan takes a detailed questions on policy.

<unk>.

On formulation.

Simba Gill: So that's the first. And then I'll let Duncan ask your question on EC50 as usual. Easy is a well-established scale; it's a scale that the authorities will clearly notice and benefit from. So we have no concerns about that at the scale from a regulatory perspective. Remember, this is the Phase 2 study. We also will have SCORAD.

We expect will have.

Next level of data and understanding of of the next wave of activity in Q1 next year. So I think we should be on trial for.

For that on that front.

Matt on recruitment of 18 67.

Trying to understand exactly why recruitment slower than we had expected it may be because of the COVID-19.

Studies being recruited in the U K.

Duncan: We will have IGATEMPS, and BSA. BSA is sort of a key secondary. So what we will do is we will look at all of that data, we will understand which of those endpoints actually is the best endpoint to capture the benefit of EDP-1815 in mild to moderate atopic dermatitis, and then we'll go and have those discussions with the health authorities. All of those are pretty well established, are very well-balanced, and then Jonathan, do you want to do Part B versus Part A? Sure. So, Chris, for the Phase II psoriasis study... Part A, we clearly learned that dosing longer... It's important to capture the full breadth of it.

And probably no there's been a rise of Covid patients, we don't know that Matt it's.

It's it's definitely.

Puzzling for us, but we're trying to understand that right now we don't really have any additional information.

At this stage when that recruitment situation and then Jonathan do you want to talk about the details on puppy, yeah, So as part knee.

Have 124 subjects, who.

We are open to that portion of the study.

It goes up for an additional 20 weeks.

To have a fair number of those subjects, who will be completing the 20 weeks. We've got about 70 plus percent subjects, who are now complete and that and.

Worth the data.

The first quarter of next year.

And we'll have a large proportion of those subject to go out to the full 20 meters, great and then actually Duncan do you want to constantly 18 67 atopic dermatitis.

Okay, So just to be.

Jonathan Zung: Think about the Part B data. Part B data will inform us about relapse, how long... That'll be incorporated into our thinking. Certainly, as we think about the next study in the registration path, it'll be longer dosing, right? We'll be looking at an endpoint, you know, as we've mentioned before, most likely at six months and then extending out.

Using atopic dermatitis here because I actually.

It's a very useful and valuable kind of like early indication that we've got a good attitude pharmacy in fact, we will.

If you have the 850 takes as well, but we intend to it not faded 18 67 is I know the drug drug that we're following exactly the same footsteps is 18 50.

Debate will be studying demonstrates an anti inflammatory effect and then there's a whole range of indications.

Jonathan Zung: The real, I think, data that will support the thinking behind that is, There's one point for clarity that Cohort B is not a separate cohort; it's the same patient, and part A of the study carried over. Part B. I just wanted to make sure you weren't under the impression that we had a separate cohort of patients that we were looking at. Yeah, that is helpful. I appreciate the clarification. Maybe I'll hop back in the queue and give other people a chance, but I appreciate you taking the time to answer my questions.

We talked about before that could range from Catholic immunome inflammatory diseases like inflammatory bowel disease from the authenticity to diseases, such as new information is the key here is to just demonstrate the safety tolerability on the anti inflammatory effect.

And then the future development plan will that.

Will involve other indications.

Great. Thank you for taking my questions.

Thank you Matt.

Our next question coming from the lineup Christina <unk>, Kansas. This child, Yeah line itself.

Hi, good morning, everyone. Thanks for taking the question. The first one I have is I noticed that your most recent corporate deck expands and further emphasizes some other comorbidities that are typically associated with psoriasis any topic dermatitis [laughter]. So as your recent data that was important for your broad understanding of.

Chris Howerton: Thank you, and our next question comes from the line of Matthew Lukshiny with BMO Capital, Yolana Selfin. Hi, good morning guys. Thank you very much for taking the questions and congrats on the continued progress. So maybe first on the Part B section. Given everything that you've just talked about and the importance of looking beyond 16 weeks, are you able to provide some preliminary perspective on the level of additional follow-up you expect to have beyond that 16-week data point when you release the data? Will everyone be at six months, or will the median be somewhere else? below that, and if so, around where?

The potential Madison curious as you are near starting the phase two study and a topic dermatitis. If you have up to enroll some patience where perhaps some of these comorbidities are more apparent to even better understand some of the some stomach impact.

Yeah.

Chris and types of picking up on that point.

Won't be specifically looking to recruit patients with Comorbidities, obviously to the degree we pick it up anyway.

And the.

Detailed analysis.

Will obviously be looking for those things in that context book beyond the face to I think the more fundamental point you pick your phone Christian is this acute breath of opportunity.

With 18, 15, and with the syntax platform to treat many different types of information, a and b, both psoriasis and atopic dermatitis.

Systemic diseases as to your question suggests impact.

Matthew Lukshiny: and secondarily want to know if you're able to provide any incremental color on the formulation work since the last update and when you may be able to have something more concrete to say about your efforts here. And then maybe lastly, if I could, on 1867, just understand a little bit more of the recruitment challenges that you're seeing, and maybe more broadly, how the AD data will inform your development strategy, not only for this drug but for EDP1815 as well. Thank you so much.

Not just skin, but.

But have comorbid conditions in multiple different dimension. So we won't be looking specifically for that no croutons in face to the good point is an important one in terms of the potential treatment.

As we go forward.

[noise], Okay, Thanks, and looking at the profile differences between E. D. P 18, 15 N E. D. P. 18, 67 based off some of these trends you've observed post dosage and longer term with E. D. P. 18, 15 wondering if based on the differences with the her move whether you might expect.

Look to see something similar with E. D. P. 18, 67, and then you know you'd think longer term here. How do you think about expansion opportunities for E. D. P. 18, 16, 18 67 excuse me in light of these reason preclinical findings you had as well as the greater focused on E V.

Simba Gill: So let me take a couple of those. I'll let Jonathan take the detailed questions on Part B. On formulation, we expect we'll have, Next slide, please. Matt on recruitment in 1867.

Candidates given the recent pine could address both.

Yeah. So I think three level of course, it's a festival wood.

Simba Gill: We're trying to understand exactly why recruitment's slower than we had expected. It may be because of COVID. That study's been recruited in the UK, and you probably know there's been a rise in COVID patients. But we don't know that, Matt.

<unk>, we need the human clinical data to see if we see similar or different.

Responses with 18, 67 versus 18 15 that different and.

And.

So the frequency that difference so we'll be able to answer that question with daycare then I'll do this a few chili peppers.

In terms of how we think about 18 15, 18 67 expansion N E V side of things, Let me tell you that together, what we talked about historically is that we see where we all know.

Simba Gill: It's definitely puzzling for us, but we're trying to understand it right now, and we don't really have any idea at this stage about that recruitment. And then Jonathan, do you want to talk about the details? Yeah, so in part B, we have 124 subjects who have rolled into that portion of the study. We expect to have a fair number of those subjects who will be completing the 20 weeks. We've got about... the first quarter of next year.

I talked about to tell you today, even as the equivalent of uncovering cytokine biology.

And.

Discovery of antibodies happened to work without except peroni decades ago, Kristen two Pasadena cause the first lifetime biology company in the world fairly remarkable uncovering of a central Eric Human Biology, Mark and I wasn't I would cause you know in the earliest days of antibodies and mop headed up when it was.

First 1940 engineering groups.

And with very much in the early days all.

Jonathan Zung: And then actually, Duncan, do you want to comment on the 1867 atopic dermatitis? Yeah, that is a good question. So just to be clear, we're using atopic dermatitis here because actually it's a very useful and valuable, like early indication that we've got good answers. © The Bulletproof Executive 2013, [inaudible] and this is the Phase 1B study we want to demonstrate an anti-inflammatory effect and then actually there's obviously a whole range of indications that we talked about before that could range, The key here is to just.

Uncovering the potential of syntax platform and pushing fix for the last month say a little bit more about this right now, but as we start to understand more and more how the biology works potentially visas as Mark said, we C E D and the ultimate future of syntax platform is being.

An opportunity you have already delivered agents and people do like advocacy, whilst being say well tolerated and affordable and all of the science right now points us in the direction of that be a very real possibility and it's not too far away.

We will have our first E b data.

Some time.

And the not too distant future as we said on the cool we're on track to go into the clinic with Eev's next year.

Jonathan Zung: Safety, Tolerability, and the Anti-Inflammatory Effect, and then the future development plan. Great, thank you for taking the questions. Thank you. Our next question coming from the line is from Kristen and Kristen with Cancer First Cheryl. Your line is open.

And inflammation and we haven't given formal guidance when that date will read out but.

It won't be too far away.

So that's where we see the sky pretty quickly actually right.

Right now we have is you know 18 15, that's looking like a an attractive drug and psoriasis and quite probably in a totally done the prices.

Duncan: Hi, good morning everyone. Thanks for taking the questions. The first one I have is I noticed that your most recent corporate deck expands and further emphasizes some of the comorbidities that are specifically associated with psoriasis and atopic dermatitis. As your recent data set was important for your broad understanding of the potential syntax medicine, I'd be curious, as you are near starting the phase two study in atopic dermatitis, if you would look to enroll some patients where Yeah, so Kristen, thanks for picking up on that point.

But that's really the first weight and we look at E D as rapid fall ones.

The kenaf dramatically better potency in terms then of 18, 67, 18, 15 or indeed any of our other.

Microbes and microbial extracellular vehicles.

Versus 18 15.

As you know and again, it's mark talked about today.

You are inflammatory side of 18 67 is already looking very interesting as Duncan said, we don't see 18 67 is nee totally dermatitis drug necessarily atopic dermatitis as a quick way of getting clinical information in human patients and they will figure out how we move it forward depending on that day typically see potential breaking.

Kristen: We won't be specifically looking to recruit patients with comorbidities, obviously, to the degree we pick it up anyway in that context. But beyond phase two, I think the more fundamental point that you're picking up on, Christian, is there's a huge breadth of opportunity with 1815 and with the Syntax Platform to treat many different types of inflammation. A, and B, both psoriasis and atopic dermatitis are systemic diseases that, as your question suggests..., not just skin, but have comorbid conditions in multiple different dimensions. So we won't be looking specifically for that in your treatment plan. Okay, thanks.

67 45.

Put in your information as well as in the number of other areas and then milk always like to remind everybody. How lucky would we be to have 18, 15, and 18 67 is great products.

So we look forward to that possibility, obviously, kristen and it's it's a great luxury if we do end up that so hopefully that was helpful. I'll have mark say, a little bit more about <unk> side of things.

Because as I said, all the science right now is pointing us to that being incredibly exciting possibility effects of our Christian let me play into that.

First part of your question about 18, 15, and 18 67 and the duration of effect. This episode returned are politically but preclinically we do.

<unk> 67, and juices this regulatory phenotype in treated animals that could be transferred to untreated animals.

Simba Gill: And looking at the profile differences between EDP1815 and EDP1867, based on some of these trends you've observed post-dosage and longer term with EDP1815, wondering if, based on the differences with v. parvula, whether you might expect or look to see something similar with EDP1867. And then, you know, as you think longer term here, how do you think about expansion opportunities for EDP1867, excuse me, in light of these recent preclinical findings you had, as well as the greater focus on EV candidates, given the recent patent could address both? Yeah, so I think there are three levels of questions. So, first of all, we need both human clinical data to see if we see similar or different responses with 1867 versus 1815. They're very different.

Exactly the same way as ADP 18, 15, Burger, but it does it with a different molecular background, which is fascinating Archie is driving a lot of research and discovery because there is alright, but some common parts of the pharmacological pathway here, which are induced by different molecular pathways in the primary.

This is not to say that we've identified specific targets Mccann look at.

Differences in Wyoming toy Preceptors, we can look at differences in doctrine of various transcripts of I've got quite a different pages, we'd like to take that to the easy part we've been doing a lot of work of a extra side of a vehicle of the microbe of the lives Pvp 18 67.

Also does these things.

It doesn't look.

<unk> exactly like the current microbe, but pharmacologically it does a much lower level. So if you think about this from a dose point of view, which I thought was driving some of my comments about.

Efficiency of movement of these things with the medium that it got to the targets got it also talking so we get typically it takes them about 10 to the nine microbial cells per day in an animal model.

Simba Gill: So we'll be able to answer that question with data and then not do this. In terms of how we think about 1815-1867 expansion and the EV side of things, let me take that all together. What we've talked about historically is that we see where we are now, the discovery of antibodies. I happened to have worked with Alex Zaffaroni decades ago, who started D-NACS, the first cytokine biology company in the world. Fairly remarkable uncovery of a central area of human biology.

B E V from Edp 18, 67, we can take that down several orders of magnitude tend to the sixth sense of the seven.

And the smaller at the same time, so the differential is about a million fold up it was quite quite an extraordinary effect. That's why we're so excited about the future of the platform because we were both base of efficacy with about Kobe preparation. So then we have this additional weight.

Way to go forward, which is why I talked about the potential to get through to get into severe disease. I suspect. This is all about the cemetery, where we all have a dose response curve in relation to formulation in relation to the concentration.

Simba Gill: Mark Bodmer and I worked, as you know, in the earlier stages of antibodies when Mark headed up one of the world's first antibody engineering groups. We're very much in the early days of, [inaudible] as being an opportunity to have orally-delivered agents that have antibody-like efficacy whilst being safe, well-tolerated, and affordable, and all of the science right now points us in the direction of that It's not too far away.

Let's give it to the target than just very briefly be old Matt. Most about discovery work is now focused on looking at a extra side of their vehicles from quite a wide taxonomic range of microbes comparing the pharmacology that underlying molecular mechanisms to get paid spectrum, which is going to support the future.

Of a pipeline by the way it critically importantly, it supports the breath of patent claim that we get around medicine, just to reemphasize, but.

Simba Gill: We'll have our first EV day in the not-too-distant future. As we said on the call, we are on track to go into clinical trials with EVs next year. Inflammation, and we haven't given formal guidance on when that data will read out, but, Right now, we have, as you know, 1815 that's looking like an attractive drug in psoriasis and quite probably atopic dermatitis. But that's really the first wave, and we look at EVs as a rapid follow-on that could have a dramatically better chance in terms of 1867 and 1815, or indeed any of our other microbes and microbial extracellular versus 1815.

I'm thinking around the use of extra solar vehicles from new kozol anaerobic microbes as oil treatments is Virgin territory and so we're firing very Toby on math nothing issued yet of course, but.

Discovery work, which gives us the product candidates also gives us the book of support for those putting forward. So I hope that helps to give a bit of context of the whole thing.

Yes, Thank you Sinbad Mark.

Thanks Christian.

The next question coming from the lineup Calvin seemed like Chante, you're on a cell phone.

Okay. Thank you for taking the question Sir just appear for me I think Mark you had I wanted to bring the conversation back to the the results have been Kid mentioned was that'd be S, a greater than 5% and below 5% and.

I'm just trying to figure out what the comparator is if there is any and it just seems like the way M. As in as President Roosevelt's from the advance trial booked.

Simba Gill: As you know, and again, as Mark talked about today, the neuroinflammatory side of 1867 is already looking very interesting. But, as Duncan said, we don't necessarily see 1867 as an atopic dermatitis drug. Atopic dermatitis is a quick way of getting clinical information in human patients, and then we'll figure out how we move it forward depending on that data, but we see potential, for example, in urinary inflammation, as well as in a number of other areas. And then Mark always likes to remind everybody how lucky we would be to have 1815 and 1867 as great products.

It looks really different compared to how they have kind of a dumb thing to worry about the trials I don't even think there's a pause it says to Europe has your 75 or any kind of traditional pansy ever presented someday advanced Charles So.

Can you maybe give us some context to have that kind of view.

Those results and then one follows that's right.

Some concern yes.

Thanks for the question so.

Can't really comment on why Amgen particular nine.

Then they chose obviously they they.

Sex and violence, and then went to advance in terms of the body surf terrier threshold of 5%.

That the sort of that's one of the ways in which people can.

Simba Gill: So we look forward to that possibility, obviously, Kristen, and it's a great luxury if we do end up there. So hopefully, that was helpful. I'll have Mark say a little bit more about the EV side of things, because, as I said, all the science right now is pointing us to that being an incredibly Let me play into that with the first bit of your question about 1815 and 1867 and the duration of effect.

Sort of classify psoriasis is two miles and Margaret disease.

It's not necessarily true from a patient perspective does anything from the physician perspective, we tend to sort of take the body said Tara five centric model, it's greater than 5%.

But it's Margaret and I I am.

Assuming that is the reason that they cut that takes.

Fights.

Samson and as you saw we done something similar and I looked at that.

P J zero, one to the ability to get clear on nearly clear skin broken.

Both in the mild and moderate disease, we've also actually going easy PGA too and T. J, three which is another way of categorizing mild.

Mark Bodmer: As Simba said, we don't know clinically, but preclinically, we do. So EDP-1867 induces this regulatory phenotype in treated animals that could be transferred to untreated animals in exactly the same way as EDP-1815 does it, but it does it with a different molecular background, which is fascinating. It's actually driving a lot of our research and discovery because there are some common parts of the pharmacological pathway here. It's not to say that we've identified specific targets, but we can look at differences in finding toll-like receptors. We can look at differences in induction of various transcripts in the gut by the different agents. And we then take that to the EV part.

Moderate disease, and and both of those settings, we have a statistically significant results in terms of immediate.

<unk>.

I agree to play a role in any case skin to from our perspective it just Ah.

Another way of looking at the clinical benefit that we're getting the DDP preseason and seeing a sort of a clinic and meaningful.

Benefit to patients that does that use the the targets the patient they want to get to the client skin or.

Their tk's can cause it's quite hot get truly tastes good.

But.

We fight Sandy.

Does reflect some of what I'm 10 data but.

But I can't tell you why they didn't.

Avatar in that case.

We did because we use it early and it to what established.

Well validated endpoint.

We will look we will look it over the all the end points and two are one and we will decide which one we view is the best in terms of capturing ebay 15 activity and that's what will prepare it to the health authorities in terms of thinking about database development.

Mark Bodmer: We've been doing a lot of work on the exocellular vesicle of the microbe that underlies EDP-1867 and that also does these things. It doesn't look molecularly exactly like the current microbe, but pharmacologically, it does on a much lower level. So if you think about this from a dose point of view, which I think is driving some of my comments about the efficiency of movement of these things in the media to get to the target in the gut and also packaging.

Studies.

Just add one comment cogan is.

I'm sure you understand very well what.

It was important in this was federal focal analysis to deposit 50.

Sure the robustness of the underlying data.

So unlike a comparison.

Cause he would deposit 50. This is this is a different.

Data circuit was collected looking at PSA and looking at RGA at it reinforced the fact that there is an effective ADP 18 15. This is separate from the question of the proportion of responders, but they will talk of analysis picked it up as well so if it.

Mark Bodmer: So we typically give a dose of about 10 to the 9 microbial cells per day in an animal model. With the EV from EDP 1867, we can take that down several orders of magnitude, 10 to the 6, 10 to the 7, and they're smaller at the same time. So the differential is about a million times smaller.

Really for us at our evaluation of the study.

Deal of robustness in our estimation hopefully.

Effectively DPA 215.

Mark Bodmer: I mean, this is quite an extraordinary effect. That's why we're so excited about the future of the EV platform because we have a base of efficacy with the microbial preparation. So then we have this additional way to go forward. Why I talked about the potential to get into severe disease is because I suspect this is all about dosimetry and where we are on the dose-response curve in relation to formulation and in relation to the concentration of the drug that's given to the target.

That's that's helpful and I know there was a mention about the lower the I guess less than 5% Psa population.

Being statistically significant but the dark, but there was a third and all that.

If I'm is that I mean, just eyeballing it that's about what 10% 20% of your population. So I'm I'm I'm, assuming the numbers are probably pretty small there anyway can I can I confirm that with you guys and then maybe the follow up would be I'm I'm looking at those pictures that you guys presented earlier with like <unk> and P. G. A N D O Q I N P. S I N.

Mark Bodmer: Then, just very briefly, beyond that, most of our discovery work is now focused on looking at extracellular vesicles from quite a wide taxonomic range of microbes, comparing their pharmacology, and their underlying molecular mechanisms to get a spectrum which is going to support the future of the pipeline. And by the way, critically important, www.pearson.com.au at www.thevenusproject.com is Virgin Territory, and so we're filing very broadly on that.

Is it like the clinical effect, you know quite clearly, we're having I'd like to buy them drug it's not shutting off the pathway or more normalizing the underlying disease process. So one might imagine the the time to kind of see the peak effect you might be different than the small molecule like a tesla or Jack.

You know is there.

Is there any rationale or a precedent for how long this could take like for example, with 20 a week for.

For example would be enough time for us to be able to see this in and then maybe it is P. G. A the right way of looking at this not Patty or maybe D. O T Y or I don't know if you can comment because the D. O T Y responses that you guys presented.

Mark Bodmer: Issued yet, of course, but the DiscoveryWay product candidates also give us breadth of support. So I hope that helps to give a bit of context. Yes, thank you, Simba and Mark. And our next question comes from the line of Govind Singh with JMP. Your line is open. Hey, thanks for taking the question. So, just a few from me.

Pretty good and I think they are focusing more on P. B, a and then the other the other metric not pleasant.

But.

Let me say a few things and then Duncan can expand Covid. So festival you raise a really important point on small molecules verses mechanism of action.

And.

Govind Singh: I think, Mark, you had a, I wanted to bring the conversation back to the results that I think you had mentioned with the BSA greater than 5% and below 5%. And, you know, I'm just trying to figure out what the comparator is, if there is one. And it just seems like the way Amgen has presented results from the advanced trial. It looks really different compared to how they've kind of done things with other trials.

Mark's comments today, we talked about the fact that we've done very elegant adoptive sell trumps of studies Preclinically that show that our effects.

Driven from.

Immune cell.

Impact versus classic impact of antibodies or small molecules. So we're pushing the immune system back to a homey started regulatory status through cellular effects on the immune system.

That is completely the same as you are saying is open to anything else, it's cool very.

Govind Singh: I don't even think there's a PASI-50 or a PASI-75 or any kind of traditional PASI ever presented from the advanced trials. Can you maybe give us some context on how to kind of view those results and then one follow-up after that? Thanks for the question. I can't really comment on why Amgen chose the particular end point that they chose, www.ilo.org.uk [inaudible]. It's not necessarily true from a patient perspective, but certainly from the physician's perspective, we tend to sort of say if the body surface area is less than 5%, it's mild; if it's greater than 5%, it's mild, that it's moderate, and I

Very close to potential implications.

Because obviously, having a healthy homeostatic immune system is a lot better than shutting down part of the immune system, which is essentially what antibodies are small molecules.

As you suggest also likely means it will take a little bit longer for effects to kick in but then effects and that's part of what we're looking for a puppy may well be sustained the longest of all of those things are very positive for us.

We can't quantitatively answer your question now is to.

Is 20 weeks the right time.

We certainly already seen at 20 weeks and we've reported alpha.

With the initial data released from the phase two psoriasis study that we see.

Continue depth of response post dosing so that is already indicative of a likely cellular affect the Pacific.

Govind Singh: Assuming that is the reason that they cut that data at five percent, and as you saw and looked at that PGA01, so the ability to get clear or nearly clear skin, both in the mild and the moderate. [inaudible] from our perspective. That's sort of the clinic, www.ilo.org.uk, and does reflect some of what Amgen did, but I can't tell you why they used PASI or didn't use PASI in that case. We will look at, obviously, all the endpoints in 2019, and we will decide which one we view as the best in terms of capturing EDF 1815 activity.

And continues for presuming weeks after we stopped dosing.

But we don't have it quantified yet.

So just a few initial comments that and then function you can answer the other processes yet.

Yeah, just a couple of points ever done that since it just to be clear when we.

Talked about that day to being a statistically significant what we were looking at that is.

When we looked at the P J zero one across.

The groups I just.

By BSA or actually split by that starting PGA at baseline of being two or three.

In the face you study reasonable side, but if you start to.

Look at the various upset they come out of it too. So it's not that we looked at each of those individual subject. What we've done is we looked at.

Mark Bodmer: And that's what we'll propose to the health authorities in terms of thinking about later phase development studies. I just have one comment, Govind, as I'm sure you understand very well, what was important in this was that an orthogonal, showed the robustness of the underlying data. So unlike a comparison of the primary mean-PASI with the PASI 50, this is a different dataset that was collected looking at BSA and looking at IGA, and it reinforced the fact that there is an effect of EDPH, separate from the question of the proportion of responders, but the orthogonal analysis picked it up as well.

The total population, but divided into why the BNP J, two or three a baseline for less than 5% greater than 5% of baseline and the two analyses and when you analyze all of the data with that to the stratification variable.

In either of those two cases, we see a statistically.

Excellent results.

In terms of what will be the best.

And points as we go forward will keep continuing to look at the data. The one thing I would say that.

If we look at the faces when we get very nice clear kind of Connecticut in response to Edp 18 15.

The derived class on <unk>.

Can see them actually clearing earlier on and they tend to care thankfully between the BSA is one of the lengthening rapidly shift.

Mark Bodmer: So it really, for us in our evaluation of the study, added a lot of robustness to our estimation of that. That's helpful. And I know there was a mention about the lower, I guess, less than 5% BSA population not being statistically significant with the orthogonal assay analysis. If I'm, is that, I mean, I'm just eyeballing it.

And we will take that into account as we think about what the later.

So what the endpoints are for the beta trial.

Let us talk this way are actually directed clearing and actually Benny.

Chief investigator.

But it is one of our in house dermatologist and that it's a fascinating way in which actually to pay 250 drive to Tibet.

Govind Singh: It's about 10%, 20% of your population? So I'm assuming the numbers are probably pretty small there anyway. Can I confirm that with you guys? And then maybe the follow-up would be, I'm looking at those pictures that you guys presented earlier, like PASI and PGA and DLQI and PSI. And is the, like, clinical effect, you know? Clearly, we're having a microbiome drug. It's not shutting off the pathway. We're more normalizing the underlying disease process. So one might imagine the time to kind of see the, you know, peak effect here might be different than for a small molecule like a Tesla or, you know, Jack.

Thankfully clearing and the last thing declared the agent at the back.

Could I just add one comment COVID-19 related to what service set up a mechanism of action because you're actually asking a question about the.

<unk>.

Duration of the time scale of the cellular effects versus factor inhibitions. So if one imagines for instance.

Armature response was driven by 17.

C N F. One puts a directive habituated takes that.

If you drive around to those Lawrence inhibitors publicly drivers taken away.

But it does not generating a re mapping of the immune system and its.

And its function so while the effect may be a bit quicker.

The ability to the correct will be less so I don't think so imagine here from an analytical point of view was inflamed.

Inflamed skin, whether it so I'm, so sorry, atopic dermatitis or joint or spinal cord whatever it is you've got a bunch of residents are inflammatory cells.

Govind Singh: You know, is there any rationale or precedent for how long this could take? Like, for example, would 20 weeks, for example, be enough time for us to be able to see this? And then maybe PGA is the right way of looking at this, not PASI or maybe DLQI or I don't know if you can comment because those DLQI responses that you guys presented look pretty good. And I think in advance they are focusing more on, you know, PGA and these other metrics, not PASI. Let me say a few things, and then Duncan can expand.

Which need to be suppressed a displaced now if you've got a directed habits are about the climate is perfect. Shortly.

Leftovers of climate for itself, what we're looking at here is a different process where.

There is a semi replacement over the time of the inflammatory cells. So the residents in the inflamed tissue.

Let me ask you inflammatory or regulatory cells.

It used by the drug that's why similar talks about the reprogramming for very long term effects. This has been the Holy Grail anti inflammatory therapy for years, we haven't known how to how to get out of it. So.

When we saw the adoptive sell transfer effective mites and then we saw the continuing accrual of effects.

Simba Gill: So first of all, you raise a really important point on small molecules versus our mechanism of action. In Mark's comments today, he talked about the fact that we've done very elegant adoptive cell transfer studies preclinically that show that our..., are driven from impact versus the classic impact of antibodies or small molecules. So we're pushing the immune system back to a homeostatic balance. All Rights Reserved.

Humans. This was a real eye opener for us It was why I made the comment to move scripted remarks about profoundly.

Profile by changing the way when it takes about an area.

Suddenly we could do something in the system, which we don't we wanted to do for decades, but haven't figured out how to do it that is not just to suppress the inflammatory response, but to reprogram immune system. So that it controls its owner's fault. So that is what the data are telling us or happening very clearly preclinically, because we could show it by direct experimental methods.

And it retorts, what we're seeing clinically which is consistent with what we're saying preclinically.

Simba Gill: 2012 University of Georgia College of Agricultural and Environmental Sciences UGA Extension Office of Communications and Creative Services. That is completely distinct, as you're saying, compared to anything else. It's got very positive potential implications, because obviously, having a healthy homostatic immune system is a lot better than shutting down part of the immune system. It, as you suggest, also likely means it will take a little bit longer for effects to kick in, but then effects, and that's part of what we're looking for in Part B, may well be sustained for longer.

Thank you.

Perfect. Thanks.

The question.

And our next question coming from the lineup Kenai K.

Mm Chardan your line is Nelson.

Yes. Thank you maybe just a little.

Further drill down on the effort to improve the release kinetics, obviously I think.

[noise] coating Campbell shoes are well understood. So.

What's what's really the gating item of that initiative.

Yeah.

So.

We're just generating supply.

Key for for the next wave formulations to test and the Scintigraphy model that we touched on briefly on the last Sunday School. So we just generated supply and as I said, we should be ready to test different formulations in Q1 at the next day.

Simba Gill: So all those things are very positive for us. We can't quantitatively answer your question now; it's 20 minutes, the right time. We've certainly already seen, and we've reported out, with the initial data released from the Phase 2 psoriasis study that we see continued depth of response post-dosing, so that is already indicative of a likely cellular effect and continues for presumably weeks after we've stopped dosing, but we don't have it quantified yet.

Okay, Yeah, all my other questions or answers will take you.

Thank you very much.

[noise] now next question coming from the lineup just that song at colony on line or something.

They're good morning, and thank you for taking our questions maybe the first one just a clarification on the phase two eight of its repititis.

Data readout that we're gonna be able to see I know, it's a phase two we saw the Bayesian analysis for superiority, but then also maybe more of like a traditional P value comparison on the the that reached a certain patsy cut out what should we expect in terms of the the data readout for the atopic dermatitis will this be sort of a traditional.

Simba Gill: So just a few initial comments there and then Duncan, you can answer the other one. Yes, just a couple of points. So just to be clear, when we talked about that data... end, when we looked at the PGA-01, 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29, https://www.pearsons.com look at the various subsets that come down a bit.

Disproportionate patient copy easy 50 on drawn versus placebo or is there a vision.

Comparison that would be appropriate here as well.

And then second in terms of the novel formulation work you can move that into clinic in the queue won the phase two for a tech to rotate us a starting in Q4 is there any way to expand the phase too.

If what you're seeing what the novel formulations is interesting to add that cohort or will these novel formulations be used kind of ready for the pivotal studies.

<unk>, it's a cordless thanks, yeah, I'm going to let Duncan answer about those questions.

Duncan: So it's not that we looked at each of those individual subsets. What we've done is we looked at the total population but divided into either being PGA2 or 3 at baseline or less than 5% or greater than 5% at baseline, and when you analyze all of the data with that as a stratification variable, In either of those two cases, we see a statistically significant result, in terms of what would be the best, at www.ilo.org.uk, If we look at the photos where we get very nice, clear kinetics of response to EDP-1815, the psoriasis plaque.., you can see them actually clearing sort of earlier on and they tend to clear centrally which means that BSA is one of the later things, and we'll take that into account as we think about what the later... [inaudible] and it's a fascinating way in which, actually, the PHQ-15 drives us forward.

The first question that can be straightforward because it is a proportionate analysis.

The number of subject team reached easy 50.

Baking approaches are less well established and validated for that.

The more traditional frequentist approach.

From that side of things in terms of the the potential to add a new formulation partway through the phase two study.

I think that would be.

Very difficult to sort of do that and be able to sort of have a robust adaptable.

Asking for that so we will run.

Any potential new formulations in a separate study rather than try and.

Complicate the current state.

Yeah.

Great. Thank you.

So I hope that hasn't stopped you from becoming an expert on basis statistical amount.

Which.

I will it is not any of the futures to pop.

Probably we tried to educate.

Educate people some of it is 300 years old which is basically statistics, but anyway. That's just the.

Humorous comment for the danger.

[laughter].

Thank you very much.

[noise] I'm showing no further questions at this time I would now like to tend to call back of the car speakers for any goes into my ex.

Duncan: I just have one comment, Govind, related to what Simba said about the mechanism of action because you're actually asking a question about the... You can find out more information at www.ncbi.nlm.nih.gov, Climatary Responses Driven by Aisle 17, but it is not generating a remapping of the immune system. So while the effect may be a bit quicker, the So one of the things to imagine here from an immunological point of view is that if you've got inflamed skin, whether it's psoriasis or atopic dermatitis or an inflamed joint.

Thank you everybody for your attention thanks to a wonderful analysts for their attention on their excellent questions. As we said in the scripted months'. This is a pivotal moment for us.

We are.

Thrilled with the phase two day turned psoriasis, but that.

Is absolutely just the beginning.

Of what we see as an incredibly exciting future to the syntax platform I will remind everybody that we are true pioneers ultimate talked about the extracellular vehicle.

Duncan: Spinal cord, whatever it is, you've got a bunch of resident pro-inflammatory cells in there which need to be suppressed. Now, if you've got a direct inhibitor of that inflammatory effect, sure, it'll act on those inflammatory cells.

Intellectual property, but we were the first company to uncover the small intestinal axis. We're the first company to think of using non live microbes as 40 delivered therapeutics. We all the first company to think about using already delivered my quirky legs were sending the vehicles.

Mark Bodmer: What we're looking at here is a different process where there is a steady replacement over time of the anti-inflammatory regulatory cells that are being induced by the drug. And that's why Simba talks about the reprogramming or the long-term effects. This has been the holy grail of anti-inflammatory therapy for years, and we haven't known how to get at it. So, you can imagine when we saw the adopted cell transfer effect in mice, www.biosciencesinc.com, Science. Suddenly, we can do something which we've known we've wanted to do for decades but haven't figured out how to do it. That is, not just a suppressant so that it controls its own response.

So a goal has always been to be the pioneer and the leader ever and thinking about how to capture the values. The small intestinal axis, which we know absolutely no plays a central role in human biology.

Still not widely appreciated by the scientific or political community and we now know that we can harness. This morning test lapses with clinical effects with something that is very safe and well tolerated. Some extremely exciting moment of course, thank you very much everyone.

Ladies and gentlemen that that can dot com. That's all today. Thank you for your participation you may not disconnect.

[music].

Mark Bodmer: And that is what the data are telling us is happening very clearly preclinically because we can show it by direct experiment, and it reads off what we're seeing clinically, which is consistent with what we're seeing pre-clinically. Thank you.

Operator: I appreciate the question. And our next question comes from the line of Tina K. from Chardon. Your line is open. Yes, thank you.

Tina K.: Maybe just a further drill down on the effort to improve the release kinetics. Obviously, I think the entire coating chemistry is well understood. So, what's really the gating item of that initiative? So, we're just generating the supply key for the next wave formulation. The Cintigraphy Model that we touched on briefly in the last learning score. So we're just generating supply, and as I said, we should be ready with different formulations in Q1. All my other questions were answered, so thank you. Now the next question coming from the line of Joseph Tong at Cowan. Your line is open.

Joseph Tong: Good morning, and thank you for taking our questions. Maybe the first one, just a clarification on the Phase 2 atopic dermatitis data readout that we're going to be able to see. I know with Phase 2, we saw the Bayesian analysis for superiority, but then also maybe more of a traditional p-value comparison on those that reached a certain PASI cutoff. What should we expect in terms of the data readout for atopic dermatitis?

Joseph Tong: Will this be sort of a traditional disproportion of patients got the EV50 on drug versus placebo, or is there a Bayesian comparison that would be appropriate here as well? And then second, in terms of the novel formulation work, you can move that into clinical trials in Q1. The Phase 2 for atopic dermatitis is starting in Q4. Is there any way to expand the Phase 2 if what you're seeing with the novel formulations is interesting to add that cohort, or will these novel formulations be used kind of ready for the pivotal studies if that path is supported? Thanks. Yeah, I'm going to let Duncan answer both those questions.

Duncan: The number of, very difficult to sort of do that and be able to sort of have a robust interpretation. Great, thank you. So, Joe, I hope that hasn't stopped you from becoming an expert on Bayesian Statistical Analysis, which I will. It is not only the future; it's the past. So part of what we try to do at Velo is educate people on something that is 300 years old, which is Bayesian Statistics. But anyway, that's just my humorous comment for the day, Joe.

[music].

Operator: Thank you very much. I'm showing no further questions at this time. I would now like to turn the call back over to our speakers for any closing remarks. Thank you, everybody, for your attention. Thanks to our wonderful analysts for their attention and their excellent questions. As we said in the scripted marks, this is a pivotal moment for us. We are, I'm thrilled with the Phase II data and seritis, but that... I will remind everybody that we are true pioneers. Mark Bodmer talked about the extracellular vesicle. It's a great question. I think the answer is yes. It's a good question.

Operator: We're not an intellectual property, but we were the first company to uncover the small intestinal axis. We were the first company to do that, and we were the first to think of using non-living microbes as orally-delivered therapeutics. We are the first company to think about using orally-delivered microbial extracellular vision. A goal has always been to be the pioneer and the leader forever in thinking about how to capture the value of the small intestine, which we now absolutely know plays a central role in human biology, and we now know that we can harness the small... Clinical effects with something that is very. Thank you very much.

Operator: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

Operator: Tolstoy Directed by J.R.R. Tolstoy, Cinematography by J.R.R. Tolstoy, Editing by J.R.R. Tolstoy, Music by J.R.R. Tolstoy

Operator: Tolstoy Cinematography by J.R.R. Tolstoy Editing by J.R.R. Tolstoy Sound by J.R.R. Tolstoy Music by J.R.R.

Operator: Tolstoy Cinematography by J.R.R. Tolstoy © BF-WATCH TV 2021 ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? This is a video on the Biosciences Inc. website, for more information. This is a video on the Biosciences Inc. website, for more information. This is a video on the Biosciences Inc. website, for more information. This is a video on the Biosciences Inc. website, for more information. This is a video on the Biosciences Inc. website, for more information.

Operator: This is a video on the Biosciences Inc. website. For more information, This is a video on the Biosciences Inc. website. For more information, This is a video on the Biosciences Inc. website. For more information, This is a video on the Biosciences Inc. website. For more information, This is a video on the Biosciences Inc. website. For more information, This video was made in cooperation with the U.S. Department of Agriculture and the U.S. Department of Land and Forestry.

Operator: The video was made in cooperation with the U.S. Department of Agriculture and the U.S. Department of Land and Forestry. This video was made in cooperation with the U.S. Department of Agriculture and the U.S. Department of Land and Forestry.

Operator: [inaudible] Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music Meditation Music [inaudible] [inaudible] Good morning, and welcome to the BioSciences conference call to discuss its third quarter 2021 business highlight. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised that this call is being recorded at the company's question. At this time, I would like to turn the call over to Kendra Sweeney of Ivelo. Please proceed. Thank you.

Operator: This morning, we issued a press release that outlines the topics we plan to discuss today. This release is available at www.ivelobio.com under the Investors tab. 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 and third quarter 2021 financial results. Before I 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.

[music].

Operator: 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 their impact on many factors. Participants are directed to the risk factors set forth in Avelo's quarterly report on Form 10-Q for the quarter ended September 30, 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 views to change. It is now my pleasure to pass the call over to Simba. Thank you, Kendra.

Operator: Good morning, everyone, and thank you for joining us to review our progress during the third quarter. The major news for the last quarter was, of course, the positive top-line results of a Phase II trial of EDP1815 in patients with mild and moderate psoriasis. The Phase II clinical data proves beyond reasonable doubt that we can indeed harness syntax to create medicine. I can't emphasize enough the importance and value of these data. The trial addressed a central question we have been asking since we first started Develo.

Operator: Can targeting syntax be the foundation for a new profile of medicine? The answer is yes. With EDP1815, we have now shown in a well-controlled Phase II clinical trial that we can harness syntax to make a clinical impact on patients with an oral product candidate, with safety and tolerability data comparable to placebo. Together with Affordable Manufacturing.

Operator: These data support the potential of syntax medicines to address an enormous unmet need in the global treatment of patients with mild and moderate inflammatory disease. The data from the Phase 2 trial underscore two drivers of value. First, there is the potential of EDP1815 as an important new medicine in the treatment of psoriasis.

Operator: Based on this data, we are advancing EDP1815 towards registration trials in mild and moderate psoriasis, because the primary unmet need in psoriasis is in this segment of patients. There are over 55 million patients with psoriasis worldwide, and patients with mild and moderate disease represent over 90% of this patient population. The second driver of value is that this is proof of concept for the Syntax Platform in a Phase II clinical trial. The potential implications of this are immense.

Operator: This research reveals a previously unknown branch of biology that touches on a broad mechanism for the resolution of inflammation, which impacts a considerable number of diseases and for which we have shown a new type of medicine that works in humans. In dermatology alone, there are globally over 200 million people who suffer from mild and moderate diseases for which there are limited treatment options. In broader inflammatory diseases, including arthritis, asthma, and chronic obstructive pulmonary disease, there are about a billion people worldwide in need of better treatment.

[music].

Operator: I'd like to touch on one specific aspect of syntax-based products as a new type of medicine. We are developing orally delivered microbial products that are non-live biotherapeutics. This is a completely different concept from live biotherapeutics and the microbiome. There is no colonization or modification of the microbiome.

Good morning, and welcome to <unk> Biosciences Conference call.

Scott its third quarter 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 question.

At this time I would like to turn the call over to conduct me Oh by the way.

Operator: They have a direct pharmacological effect through interactions with host cells in the gut, which in turn modulates systemic inflammatory responses throughout the body via the small intestinal axis. The clinical responses to EDP-1815 opened the door both to EDP-1815 as a potentially important medicine in dermatology and to the broader potential of the platform. Our aim has always been to develop an entirely new profile of medicine that will transform healthcare rather than another incremental improvement on what already exists.

Percy. Thank you. This morning, we issued a press release that outlines the topics we plan to discuss today.

This release is available at Www Dot if velo bio dot com under the investors tab.

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 and third quarter 2021 financial results.

Before I 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.

Operator: We discovered it by inventing syntax methods that harness this extraordinary natural system which controls inflammation throughout the body. What we have discovered is how to harness nature to create something that has never existed before. We have discovered and pioneered new principles and new approaches for developing and manufacturing syntax medicine. Our Phase II data, together with other clinical and preclinical data we have generated, gives us high confidence that we will realize our vision to transform global healthcare. Let me repeat the core point.

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.

Participants are directed to the risk factors set forth in <unk> quarterly report on Form 10-Q for the quarter ended September 30th 2021 and the company's other filings with the Securities and Exchange Commission.

Operator: We have demonstrated that we can harness syntax to drive clinical effects throughout the body with an orally delivered gut-restricted age. Syntax medicines are a substantial new platform in our industry with the potential to help hundreds of millions of patients globally at all stages of disease. Most of these patients have so far not received the benefits of biotech innovation. Think of this in terms of combining the discovery of life-kind biology with the discovery of therapeutic antibodies. Newly discovered biology underpinning many diseases together with the means to do something about it, and then delivering it to patients as a convenient oral pill. With that, I will hand it over to Mark.

Any forward looking statements made today speak only to <unk> 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.

It is now my pleasure to pass the call over to Simba.

Thank you Kendra.

Good morning, everyone and thank you for joining us to review our progress during third quarter.

A major news called last quarter was of course, the positive top line results of our phase II trial of Edp 18, 15 in patients with mild and moderate psoriasis.

Operator: We're often asked the reasonable question, "What are the risks of success for Avelo's medicine?" Of course, there's one overarching risk. Is syntax biology important, and can syntax medicines work? Yes, it is important, and yes, EDP1815 was observed to have a clinical impact on patients with psoriasis. There are also the risks around manufacturing and the regulatory path to the clinic, both potentially significant hurdles for new modality. These, too, have been overcome.

The phase II clinical data prove beyond a reasonable doubt that we can indeed harnessed syntax to create medicines.

I can't emphasize it enough.

And value of these data.

The trial address the central question, we've been asking since we first started debello.

Try and talk think syntax visa foundation for new profile of medicine.

The answer is yes.

With a U D. P. A T 15, we have now shown in a well controlled phase II clinical trial, but we can harvest syntax to make clinical impact on patients with an oral product candidate.

Operator: The Phase II results take us past these fundamental risks and on to the practical challenges of making syntax medicines work for the largest numbers of people as effectively as possible. The breadth of opportunity that Simba talks about comes directly from the breadth of the mechanism of action, that is, the coordinated resolution of multiple pathways involved in the inflammatory response. Now that we have shown syntax functions in humans to modulate systemic immunity, it's reasonable to expect that syntax medicines may be beneficial in almost any condition in which inflammation plays an adverse role, which is most diseases.

With safety and Tolerability data comparable to placebo.

Together with affordable manufacturing.

These data support the potential of syntax medicines to address an enormous unmet need and the global treatment of patients with mild and moderate inflammatory disease.

The data from the phase two trial on the school to drivers of value.

Operator: As an example, two weeks ago, the effects of EDP1867 in a mouse model of neuroinflammation were presented at a European multiple sclerosis conference. These were extraordinary data showing the gut immune system reaching into the central nervous system under the influence of one of our drug candidates. It is the same principle that allows the gut to reach into the skin.

Just on the data we are advancing ETP 18, 15 towards registration trials in mild or moderate psoriasis.

The primary unmet need in psoriasis is for this segment of patients there are over 55 million patients with psoriasis worldwide and patients with mild and moderate disease represent over 90% of this patient population.

Operator: The apparently disparate effects in skin and CNS are the result of the pleiotropic mechanism, which is the glue that holds together this whole concept that the small intestinal axis can impact inflammation throughout the body. I'm now going to turn to two related topics that are part of making EDP1815 and future Syntax Medicines work as effectively as possible. The first topic has to do with the responder rate to EDPH of 15% that we observed in the phase 2 psoriasis trial.

The second driver of value is that this is proof of concept for the syntax platform in a phase two clinical trial.

The potential implications of that alright.

It reveals a previously unknown branch of biology, which touches on a broad mechanism for the resolution of inflammation.

Which impacts a considerable number of diseases and for which we have shown a new type of medicine that works in humans.

In dermatology alone there are globally over 200 million people, who suffer from mild or moderate diseases for which there are limited treatment options.

Operator: As you recall, approximately 30% of patients who received EDP1815 in the trial achieved a PASI-50 response by the 16-week endpoint. However, this does not mean that EDP1815 does not have any effect in the other 70% of people. There was a continuous distribution of PASI responses, but 30% who were reported as PASI-50 responders were simply a cut of that overall distribution after 16 weeks of treatment. The Phase II study showed that efficacy accrued as patients continued to take EDP18-15. This suggests that treating for longer could result in higher response rates. A rising tide lifts all boats.

And broader inflammatory diseases, including arthritis, asthma, and chronic obstructive pulmonary disease. There are about a billion people worldwide and need better treatments.

I'd like to touch on one specific aspect of syntax space products as a new type of medicine.

We are developing orally delivered microbial products that are non life biotherapeutics.

This is a completely different concept the life biotherapeutics and the microbiome.

No colonization or modification of the microbiome.

Have a direct pharmacological effect through interactions with host cells in the gut.

Operator: Anything that increases overall response rates has the potential to benefit more patients. We've also done further sensitivity analyses since the Phase II data were released last month, and I'd like to highlight one of them. The proportion of patients who achieved IgA0 or 1 after stratifying their baseline body surface area, psoriasis, was evaluated. IGA 0 and 1 are, respectively, clear and nearly clear skin. These are the targets of treatment in patients with mild and moderate psoriasis. Mild disease is defined as a body surface area less than or equal to 5%.

Which in turn modulate systemic inflammatory responses throughout the body via the small intestinal axis.

The clinical responses to Edp 18, 15 opened the door both to ETP 18, 15, as a potentially important medicine in dermatology and to the broader potential of the platform.

Our aim has always been to develop an entirely new profile of medicine that will transform health care rather than another incremental improvement to what already exists we did not invent the small intestinal axis, we discovered it by inventing simplex medicines, which harness this extraordinary.

Operator: Moderate disease is greater than 5%. The proportion of patients with moderate disease, that is, greater than 5%, who reached IgA 0 or 1 compared to placebo had a p-value of less than p0.05. Patients with mild disease also trended to efficacy with a p-value that was not significant.

Natural system, which controls inflammation throughout the body.

Yes.

What we have discovered this has harnessed nature to create something that has never existed before we have discovered and pioneered new principles of new approaches for developing and manufacturing syntax medicines.

Our phase II data together with other clinical and preclinical data we have generated.

Operator: Across the entire study population, stratifying by BSA group at baseline, EDP1815 was also found to be significantly better than placebo in the number of PGA0 or 1 responders with a p-value less than 0.05. This is an important result. This does not mean that EDP1815 doesn't work in milder patients, but it does mean that the effect is more readily detected in patients with more expensive diseases. Not surprising since there is a larger window for reading the effect of the treatment.

US high confidence that we will realize our vision to transform global health care.

Let me repeat the Cove point, we have demonstrated that we can harvest and tax to drive clinical effects throughout the body with an orally delivered.

Restricted agents.

Syntax medicines are substantial new platform in our industry with the potential to help hundreds of millions of patients globally at all stages of disease.

Most of these patients have so far not received the benefits of biotech innovation.

Operator: The observed response rate in the Phase II study was already within a clinically and commercially attractive range for mild and moderate disease, reinforced by placebo-like safety and tolerability. These further analyses are evidence for additional improvement of efficacy in future studies based on clinical data that we already have. The second broad point about making syntax medicines work as effectively as possible is based on the observation in the Phase II psoriasis trial that we saw continued improvements in some patients after the end of the treatment period.

Think of this in terms of combining the discovery of cytokine biology with the discovery of therapeutic antibodies newly discovered biology underpinning many diseases together with the means to do something about it.

And then delivering it to patients as a convenient oral pill.

With that I will hand over to Mark.

Thanks Deborah.

We're off the reasonable question what are the risks of success.

Addison.

Of course with one overarching risk is since that's filed its important and sometimes impacts medicine work, yes, which is important and yes, GDP 18, Christine was observed to have a clinical impact on patients with psoriasis.

Operator: Generally, drug levels need to be maintained to suppress the target pathway. When dosing is stopped, there is often a rebound in disease symptoms. The mechanism of action that allows this continued effect with EDP1815 ties into broad inflammation resolution that I was talking about a moment ago. EDP1815 and several of our other product candidates induce a regulatory phenotype in circulating immune cells.

They're also the risks around manufacturing and regulatory path to the clinic, both potentially significant hurdles for new modality.

These two have been overcome.

The phase II results take us past these fundamental risks almost the practical challenges of making syntax medicines work the largest numbers of people as effectively as possible.

The breadth of opportunity that similar talks about comes directly from the breadth of the mechanism of action that is the coordinated resolution, but multiple pathways involved in the inflammatory response.

Operator: We can show this experimentally in preclinical studies by isolating peripheral immune cells from animals that have been treated with drugs. If we then transfer these isolated cells into animals that are not treated with drugs, then these non-drug-treated animals have the same anti-inflammatory inflammation resolution as if they had been treated, mediated by the information-resolving effect of the drug. This is called adoptive cell transfer, and it is a core proof of mechanism for the therapeutic cellular phenotype induced by syntax. Consider what this means. The efficacy of a gut-restricted drug is carried out by modified immune cells in the periphery.

Now that we have shown syntax functions in humans modulate systemic immunity, it's reasonable to expect that syntax medicines may be beneficial in almost any condition in which inflammation plays a role.

As most diseases as an example, two weeks ago the effect of Edp $8 67 in a mouse model of neuro inflammation were presented at the European multiple sclerosis Conference. These were extraordinary data showing the immune system, reaching into the central nervous system under the influence of one of our drug candidates.

Same principle, but allows the got to reach into the skin.

Apparently desperate effects and scan and CNS are the result of the pay appropriate mechanism, which is the glue that holds together this whole concept with the small intestinal axis can impact inflammation throughout the body.

Operator: Our evidence for this in mice is the adoptive cell transfer. Our evidence for this in humans is the continuing effect after the drug is stopped. Induced regulatory cells continue to overcome the effects of the inplanetary cells resident in the skin, leading to skin healing after administration of the drug is ended. The modified immune cells can last for weeks in circulation, perhaps longer. We don't know the duration of the response yet, so consider again what this means.

I'm now going to turn to two related topics, but a part of making Edp 18, 15, and future syntax medicines work as effectively as possible.

The first topic is.

With the responder rate to <unk> 15 that we observed in the phase two in psoriasis trial.

You recall approximately 30% of patients who received GBP 18 15 in the trial achieved how's. It 50 response by the 16 week endpoint.

Operator: We've created a regulatory cell phenotype, which is induced in situ by a product candidate, the EP1815, that has been observed to have placebo-like tolerability and safety, and that can be manufactured at scale. This is one of those scientific results that profoundly alters one's frame of reference. The gut-restricted agent can create active regulation of systemic inflammation.

This does not mean that <unk> 16 does not have any effect in the other 70% of people.

Continuous distribution of <expletive> responses, the 30% who were reported as past 50 responders.

Overall distribution after 16 weeks of treatment.

The phase II study showed the efficacy of crude as patients continue to take GBP 18, 15 to suggest the treatment for longer could result in higher response rates, a rising tide lifts all boats anything that increases overall response rates.

So to benefit more patients.

Operator: This is not immunosuppression; it is restoration of the normal, non-inflamed state. I'd like to finish with some more forward-looking comments about our aspirations for the future of the FinTax platform. EDP1815 is now nicely set up as a treatment for mild and moderate psoriasis, and that should also be true for other inflammatory diseases. We have reported repeatedly that in preclinical studies, our drug candidates are as effective as the best standard of care biologics and oral.

We've also got further sensitivity analyses since the phase II data were released last month and I'd like to highlight one of them.

The proportion of patients who achieved Iga zero or one off to stratify that baseline body surface area psoriasis was evaluated Iga zero and one I would expect to be clear and nearly clear skin lesions.

These are the targets of treatment in patients with mild to moderate psoriasis.

<unk> disease is defined as body surface area of less than or equal to 5% moderate disease was greater than 5%.

The proportion of patients with moderate disease that is greater than 5%.

Operator: This suggests potential also in severe inflammatory disease. Our goal for future versions of syntax medicines is to reach biological levels of efficacy in humans to take syntax medicines beyond mild and moderate disease into severe disease. The preclinical data suggests this is biologically feasible, although getting effective target engagement in humans is harder than in mice. The physics of the delivery of syntax medicines to the target in the larger human gut provides some particular challenges.

Who reached Iga zero or one compared to placebo with a P value of less than <unk>.

Zero point zero fun.

Patients with mild disease also trended to efficacy with a P value that was not significant.

Across the entire study population stratified by BSA group at baseline <unk> was also found to be significantly better than placebo in the number of PTA zero, one responders with a P value less than 0.5.

Operator: We think that extracellular vesicles, with their volume 1,000th that of a microbe, have helped to address these challenges. The small size advantage of EVs allows them to diffuse more readily in the gut milieu and allows us to pack a higher concentration into each pill. These size advantages will be combined with formulations that ensure that the drugs bathe as much of the small intestine as possible.

This was an important result.

It does not mean that Edp 18, 15 doesn't work in milder patients. It does mean that the effect is more readily detected in patients with more expense extensive disease not surprising since there is a larger window for reading the effects of the treatment.

The observed response rate in the phase II study was already within a clinically and commercially attractive range from mild to moderate disease reinforced by placebo like safety and Tolerability.

Operator: It's a reasonable prediction that these factors, size, packing, and formulation, will combine to increase efficacy. It's how we get high levels of efficacy pre-clinically, and we are now learning how to do it in humans. Our vision for the future of synthax medicines is efficacy that is competitive for the best standard of care for all stages of disease with oral delivery and the safety and tolerability seen with EDPH and caffeine. The scientific platform which we have constructed methodically over the last five years supports this possibility. With that, I'll hand over to Jonathan to update you on our clinical program. Thank you, Mark, and good morning everyone.

Further analysis or evidence.

<unk> improvement of efficacy in future studies based on clinical data that we already have.

The second broad point about making medicines work as effectively as possible as based on the observation in our phase III psoriasis trial.

We saw continued improvements in some patients after the end of the treatment period.

Generally drug levels need to be maintained surplus deposit pathway with <unk>.

<unk> stocks there was often a.

A rebound in disease symptoms.

The mechanism of action that allows us continued effect with Edp 18, 15 ties into broad inflammation resolution that I was talking about a moment ago.

D. C 18, 15 in several of our other product candidates abuse of regulatory phenotype and circulating immune cells.

Operator: I will provide an update on our ongoing clinical trials, upcoming readouts, as well as planned studies. Part B of our Phase II trial in mild and moderate psoriasis is ongoing and assessing the durability of treatment response following completion of 16 weeks of dosing in 124 patients. These participants are being evaluated monthly, and we look forward to learning more about the lasting effects of EDP1815. We expect to report top-line results in the first quarter of 2022.

We can show this experimentally.

Preclinical studies by isolating peripheral immune cells from animals that have been treated with drug.

We then transfer these isolated cells of animals that have not previously withdrawn.

There is no drug treated animals at the same anti inflammatory.

Inflammation resolution has this space have been treated with <unk>.

<unk> sells.

Mediated inflammation resolved in effect of the drug.

Hmm.

This is called adoptive cell transfer and it was a core proof of mechanism for the therapeutic cellular phenotype induced by a syntax consider what this means the efficacy of a gut restricted drug is carried out by modified immune cells in the periphery.

Operator: The results from Part A and Part B of the Phase 2 trial will allow us to refine our next phase clinical plans for EDP1815 and psoriasis, as well as seek feedback from health authorities. Meanwhile, our Phase 1b trial of EDP1867 in a cohort of patients with moderate atopic dermatitis is ongoing. Trial participants are being dosed with a 14-day follow-up period. We anticipate results from this trial in the first half of 2022, based on slower than projected recruitment.

Evidence of this in mice.

Dr cell transfer.

Evidence of this in humans as the continuing effect of the drug is stopped.

Jus regulatory cells continue to overcome the effects of inflammatory cells residents in the skin to.

Skin healing after administration of the drug is ended.

The modified immune cells can last for weeks in circulation perhaps longer.

If your ratio response, yet so consider again, what this means we've created a regulatory T cell phenotype, which isn't just in situ by product candidate Dth in 15, but it's been present observed to have placebo like tolerability and safety that can be manufactured at scale compare this to the current interest in cellular therapies.

Operator: We previously reported that the U.S. FDA requested additional information in a clinical hold letter for the EDP1815 Phase II atopic dermatitis trial in patients with mild, moderate, and severe disease. We have satisfactorily responded to the FDA request, and the hold has been lifted. The IND is now open, and we anticipate dosing late in the fourth quarter.

With ex vivo conditions regulatory T cells, we skip that entire process step and concentrate with such a generation with an old product candidate, which uses the body's natural programming.

This is one of those scientific results are profoundly opens once frame of reference.

Operator: This trial will be 16 weeks in duration with the primary endpoint of percent of patients who achieve an eczema area and severity index EZ-50 score at week 16. In addition, we'll be collecting various physician and patient-reported outcomes. We anticipate reporting results from this trial in the fourth quarter of 2022. Patients on active and placebo in this trial will have the opportunity to join an open-label extension once they complete 16 weeks of dosing.

Sticking with Asia can create active regulation of systemic inflammation.

North immuno suppression with restoration of normal volume claims stake.

Yeah.

I'd like to finish with some more forward looking comments about our aspirations for the future of the syntax platform Edp.

<unk> is now nicely set up as a treatment for mild to moderate psoriasis and I should also be true for other inflammatory diseases.

We have reported repeatedly that in preclinical studies, our drug candidates are as effective as the best standard of care of biologics and oral <unk>. This suggests potential also in severe inflammatory disease, a golf with future versions of syntax medicines is to reach biologic levels of efficacy in humans.

Operator: All patients in the open-label extension will receive EDP 1815 for up to 52 weeks. We remain on track to bring our first extracellular vesicle or EV candidate, EDP2939, for inflammatory diseases into the clinic in 2022.

Syntax medicines beyond mild and moderate to severe disease.

Preclinical data suggests this is biologically feasible.

Getting effective target engagement in humans is harder than in mice. The physics of the delivery of some facts medicines with a target of a larger human.

Operator: We continue to recruit patients in the Phase 2-3 Tactic E trial for the prevention and treatment of life-threatening complications associated with COVID-19 in hospitalized patients in the UK, Brazil, Mexico, and India. Tactic E is progressing well and is very close to the initial recruitment goal of 125 patients in each of the initial three arms of the trial, including EDP1815. Hitting this recruitment target will trigger an interim safety and futility analysis by the Independent Data Monitoring Committee.

Provide some particular challenges.

We think that extracellular vehicles without volume 1000, south of a microbe helped to address these challenges.

Small size advantage of Evs allows them to diffuse more readily in the gut and allows us to pass a high concentration into each pill. Besides advantages will be combined with formulations, but ensure that the drug is based as much of the small intestine as possible. It's a reach.

Reasonable prediction, but these factors size packing and formulation will combine to increase efficacy.

Operator: Based on the progress and scale of Tactic E, we have decided to focus our efforts on this trial and to close our smaller U.S. Phase 2 trial, evaluating the safety and efficacy of EDP 1815 in the treatment of patients hospitalized with COVID-19 infection.

How we got the high levels of efficacy pre clinically.

And we are now learning how to do it in humans, our vision for the future of syntax medicines is efficacy, which is competitive with the best standard of care for all stages of disease with oral delivery and the safety and Tolerability <unk> seen with Edp agents Hussein.

The scientific platform, which we have constructive methodically over the last five years supports this possibility.

With that I'll hand over to Jonathan to update you on our clinical programs.

Operator: It is now clear that the smaller trial will not make a meaningful contribution to our understanding of EDP1815 in hospitalized COVID-19 patients. I'll hand it back to Simba for closing remarks. Thanks, Jonathan. This is a pivotal moment for Avelo.

Thank you Mark and good morning, everyone I will provide an update on our ongoing clinical trials upcoming readouts as well as planned studies.

Part B of our phase II trial in mild to moderate psoriasis is ongoing and assessing the durability of treatment response. Following completion of 16 weeks of dosing and 124 patients. These participants are being evaluated monthly and we look forward to learning more about the lasting effects of <unk>.

Operator: We now have proof of concept from a Phase 2 study for Syntax, and we are advancing EDP1815 in psoriasis towards later stage development and potential commercialization. In parallel, we are advancing EDP1815 in a Phase II study in atopic dermatitis, and our second anti-inflammatory microbial product, EDP-1867, is in the clinic. Our EV development platform is making strong technical progress towards the clinic, and we have shown pre-clinically the potential of Syntax medicines in neuroinflammation. All of this is only the beginning.

<unk>.

We expect to report topline results in the first quarter of 2022.

The results from part a and part B of the Phase III trial will allow us to refine our next phase clinical plans for <unk> in psoriasis as well as seek feedback from health authorities.

Our phase <unk> trial of <unk>, 67, and a cohort of patients with moderate atopic dermatitis is ongoing.

Trial participants are being dosed.

Stays with a 14 day follow up period we.

We anticipate results from this trial in the first half of 2022 based on slower than projected recruitment.

Group.

We previously reported that the U S. FDA had requested additional information in a clinical hold letter in the ETP 18, 15 phase two atopic dermatitis trial in patients with mild moderate and severe disease we.

Operator: We have a better and better understanding of how to capture the full breadth of our Syntax platform, and you can expect much more from our platform as we continue to grow Avelo towards our vision. Thank you for your attention, and we will now open the floor to questions. Ladies and gentlemen, to ask a question, you will need to press the star, then the 1 key on your touch-tone telephone.

We have satisfactorily responded to the FDA request and the hold has been lifted the IND is now open and we anticipate dosing late in the fourth quarter.

This trial will be 16 weeks in duration with the primary endpoint of percent of patients who achieve in eczema area and severity index easy 50 score at week 16 in.

Operator: To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Now, the first question coming from the line-up: Chris Howerton with Jefferies.

In addition, we will be collecting various physician and patient reported outcomes. We anticipate reporting results from this trial in the fourth quarter of 2022.

Operator: Your line is open. Hi, good morning everybody, and thank you very much for taking the questions. For me, I think the first would be, with respect to atopic dermatitis, I'd be curious to hear the company's thoughts on both the regulatory path of using EZ-50 as a primary endpoint if that would be possible, and then secondarily, what would be a clinically meaningful effect size on such an endpoint within, I guess, the mild-to-moderate patient population. So that would be question one.

Patients on active and placebo from this trial will have the opportunity to join an open label extension once they complete 16 weeks of dosing all patients in the open label extension will receive edp $18 15 for up to 52 weeks.

We remain on track to bring our first extracellular vesicle or EV candidate Edp 29, 39 for inflammatory diseases into the clinic in 2022.

We continue to recruit patients in the phase III three tactic <unk> trial for the prevention and treatment of life threatening complications associated with COVID-19, and hospitalized patients in the U K, Brazil, Mexico and India.

Operator: And then question two is, with respect to Cohort B of the psoriasis study, maybe if you could just compare and contrast that to Cohort A and how that's going to inform the Phase III design moving forward. Thank you. Chris.

The key is progressing well and is very close to the initial recruitment goal of 125 patients in each of the initial three arms of the trial, including Edp 18 15 hitting.

Operator: Thanks for your question. Sorry, could you just repeat the last question? Yeah, I'm so sorry.

Hitting this recruitment target will trigger an interim safety and futility analysis by the independent data monitoring Committee.

Operator: The last question was, you know, compare and contrast Cohort A and Cohort B for the psoriasis study, and, you know, what exactly in the Cohort B results is going to help you kind of figure out the Phase III design moving forward? Okay, alright. Thanks. So let me take the middle one first, which was what would be a clinically meaningful effect on the EZ50 site. As you know, Chris, atopic dermatitis, for mild and moderate patients, does not have any approved oral treatment. And atopic dermatitis patients with mild or moderate disease are limited to taking a range of topicals, including topical steroids, which have a number of limitations.

Based on the progress in scale of tactically, we have decided to focus our efforts on this trial and to close our smaller U S phase II trial evaluating the safety and efficacy of Edp 18, 15 in the treatment of patients hospitalized with COVID-19 infection. It.

It is now clear the smaller trial will not make a meaningful contribution to our understanding of ETP 18, 15, and hospitalized COVID-19 patients.

Ill hand, it back to Simba for closing remarks.

Thank you Jonathan.

This is a pivotal moment for appellate we now have proof of concept from our phase two study for syntax.

We are advancing edp $18 15 in psoriasis towards later stage development and potential commercialization.

Operator: The reason I'm leading with that, Chris, is the bar is actually very low for a safe, well-tolerated oral drug, and as long as we continue to confirm safety and tolerability. If we see easy 50 responses or equivalent, and I'll hand over to Duncan in a moment who can answer your first question, and a reasonable percentage of patients, we have a very attractive drug. I would say, somewhat similar to psoriasis, if we have effects at ET50 or greater in 25 to 30% of patients or more, then we have an attractive drug as a general guidance for you. We expect we have a good probability of doing better than that.

In parallel we are advancing ETP 18, 15 in a phase III study in atopic dermatitis.

Second anti inflammatory microbial product ETP 18, 67 is in the clinic.

On the EV development platform is making strong technical progress towards the clinic.

We have shown pre clinically the potential of syntax medicines in neuro inflammation.

All of this is only the beginning we have a better and better understanding of how to capture the full breadth of our syntax platform and you can expect much more from a platform as we continue to grow <unk> towards outpatient.

Thank you for your attention and we will now open for questions.

Operator: If you look at our Phase 1B data in atopic dermatitis, we already had 7 out of 16 patients who were plus or minus at that easy 50 level after only 8 weeks of treatment. So... We're feeling confident right now that we'll get to that level or better, Chris, that I talked about. I'd also emphasize that in psoriasis, we did already see some patients that... Different diseases, different biology, but it's certainly encouraging in terms of where we think we may end up.

Ladies and gentlemen to ask a question you will need to press. The Star then the one key on your Touchtone telephone to withdraw your question press the pound key please standby, while we compile the Q&A roster.

No first question coming from the line of.

Chris Howerton with Jefferies. Your line is open.

Yeah.

Hi, good morning, everybody and thank you very much for taking the questions for me I think the first would be.

With respect to atopic dermatitis.

Operator: So, that's the first part, and then I'll let Duncan ask your question on ET50 as a regular. Easier is a well-established scale; it's a scale that the authorities are very familiar with. In terms of the 50 benchmark itself, it is a clinically meaningful change that patients with mild to moderate and, in fact, severe will clearly notice and benefit from. So we have no concerns about that at the scale from a regulatory perspective. Remember, this is the Phase 2 study. We will also have SCORAD; we will have IJ times BSA. BSA is sort of a key secondary.

I'd be curious to hear the company's thoughts on both kind of the regulatory paths of using easy 50, as a primary endpoint if that would be possible.

Then secondarily.

What would be a clinically meaningful effect size on such an endpoint within I guess, the mild to moderate patient population.

So that would be question one.

And then question two is with respect to cohort b of the psoriasis study.

Maybe if you could just compare and contrast that to cohort a and how that's going to inform.

The phase III design moving forward. Thank you.

Chris said Simba. Thanks for your question I'm, sorry could you just repeat the last question.

Operator: So what we will do is we will look at all of that data, we will understand which of those endpoints actually is the best endpoint to capture the benefit of EDP1815 in mild to moderate atopic dermatitis, and then we'll go and have those discussions with the health authorities. All of those are pretty well established. Particularly easy, it's very well-balanced, and then Jonathan, do you want to do Part B versus Part A? Sure. So, Chris, for the Phase II psoriasis study... Part A, we clearly learned that dosing longer... It's important to capture the full breadth of that.

Yes, Im sorry.

Question was comparing contrast cohort a and cohort b for the psoriasis study and what exactly in the cohort B results is going to help you kind of figure out the phase III design moving forward.

Okay, alright, thanks, So let me.

Take the middle one first which was what would be a clinically meaningful effect on the easy 50 side as.

As you know Chris atopic dermatitis.

For mild to moderate patient does not have any approved oral.

Treatments.

And atopic dermatitis patients essentially with mild to moderate disease are limited to taking a range of top goals, including topical steroids, which have a number of limitations.

Operator: Think about the Part B data. Part B data will inform us about relapse, how long... that'll that'll be incorporated in our thinking. Certainly, as we think about the next study in the registration path, it'll be longer dosing, right? We'll be looking at an endpoint, you know, as we've mentioned before, most likely at six months and then extending out for another six months so you get a full

The reason I'm, leading with that Chris is the bar is actually very low for a safe well tolerated oral drug and as long as we continue to confirm safety and Tolerability.

If we see easy 50 responses or equivalent and I'll hand over to Duncan in a moment, who can answer your first question.

And.

A reasonable percentage of patients we have a very attractive drug I would say somewhat similar to psoriasis. If we have an effective easy 50 or greater.

In 25% to 30% of patients or more.

Operator: The real, I think, data that will support the thinking behind that is, There's one point for clarity that Cohort B is not a separate cohort; it's the same patient. Part A of the study carried over to Part B. I just wanted to make sure you weren't under the impression that we had a separate cohort of patients that we were looking at. Yeah. No, that is helpful.

Then we have an attractive drug as a general guidance for you Chris.

We expect we have a good probability of doing better than that if you look at our phase <unk> data in atopic dermatitis, we already had.

Seven out of 16 patients, who are plus or minus that easy 50 level. After only eight weeks of treatment.

So.

We're feeling.

Confident right now that will get to that level or better Chris that I talked about.

Operator: I appreciate the clarification, and maybe I'll hop back in the queue and give other people a chance, but I appreciate you taking my questions. Thank you, and our next question is coming from the line of Matthew Lukshiny with BMO Capital. Your line is open.

I would also.

Besides the in psoriasis, we did already see some patients yet.

Passing 75, or even greater cause of 19.

Different diseases different biology, but it's certainly encouraging in terms of where we think we may end up so that's.

The first point Chris.

Operator: Hi, good morning guys. Thank you very much for taking the questions and congratulations on the continued progress. So maybe first on the Part B seritis. Given everything that you've just talked about and the importance of looking beyond 16 weeks, are you able to provide some preliminary perspective on the level of additional follow-up you expect to have beyond that 16-week data point when you release the data? Will everyone be at six months, or will the median be somewhere below that, and if so, around where?

Then I'll, let Duncan asked your.

Question on easy 50, as a regulatory endpoint.

Yes.

So easy is a well established scale.

The authorities.

We're.

Very familiar with.

In terms of the 50 benchmark yourself it is a clinically meaningful.

Change that patients with them.

About the module.

Yes.

Clearly.

Benefit from so we have no concerns about that at the scale from a regulator perspective.

But remember we're also this is the phase II study. We also will have score at <unk> PSA, it's sort of key secondary endpoints. So what we will do is we will look at all of that data, we will understand which of those endpoints actually best endpoint to capture the benefit of 80 to $80.

Operator: and then secondarily... want to know if you're able to provide any incremental color on the formulation work since the last update and when you may be able to have something more concrete to say about your efforts here. And then maybe lastly, if I could, on 1867, just understand a little bit more of the recruitment challenges that you're seeing, and maybe more broadly, how the AD data will inform your development strategy, not only for this drug but for EDP1815 as well. Thank you so much.

Most of them have atopic dermatitis, and then we'll go and have those discussions with the health authorities, but all of them.

Pretty well established.

He's a very well validated endpoint that we don't expect to have any.

Some of the regulations and easy.

And then Jonathan do you want to do the part B. This is sure sure. So Christopher for the Phase two psoriasis study from the part a we clearly learned that dosing longer.

Important to capture the full breadth of activity of <unk> when.

When we think about the part B data.

Operator: So let me take a couple of those. I'll let Jonathan take the detailed questions on Part B. On formulation, we expect we'll have, Next slide, please. Matt, on recruitment in 1867.

P data will inform us around relapse.

How long this benefit maintained obviously that'll that'll be incorporated in our thinking but certainly as we think about the next study in the registration pathway.

It'll be longer dosing quite we'll be looking at an endpoint.

Operator: We're trying to understand exactly why recruitment's slower than we had expected. It may be because of COVID. That study's been recruited in the UK, and you probably know there's been a rise in COVID patients. But we don't know that, Matt.

As we've mentioned before most likely at six months and then extending out for another six months. So you get a full year of data so.

I think data that will support the thinking behind that is part of that.

Okay.

Okay do you want to add.

Just one point for Chris just one point of clarity.

Cohort B is not a separate cohort it's the same patients.

Operator: It's definitely puzzling for us, but we're trying to understand it right now, and we don't really have any idea at this stage about that recruitment. And then Jonathan, do you want to talk about the details? Yeah, so in part B, we have 124 subjects who have rolled into that portion of the study. We expect to have a fair number of those subjects who will be completing the 20 weeks. We've got about... the first quarter of next year.

Atlas study carried over into part B I just wanted to make sure you didnt.

What are the impression that we had a separate cohort of patients that we were looking out for longer.

Yeah, No that is helpful. I appreciate the clarification and.

Maybe I'll hop back in the queue and give other people a chance, but I appreciate you taking my questions.

Thanks, Chris.

Okay.

Thank you and our next question is coming from the line of Matthew Luchini with BMO.

BMO capital your line is open.

Hi, Good morning, guys. Thank you very much for taking the question congrats on the continued progress.

Operator: And then actually, Duncan, do you want to comment on the 1867 atopic dermatitis? Yeah, that is a good question. So just to be clear, we're using atopic dermatitis here because, actually, it's a very useful and valuable early indication that we've got a good antigen, and this is the Phase 1B study we want to demonstrate an anti-inflammatory effect, and then actually, there's obviously a whole range of indications that we talked about before that could range from. The key here is just to demonstrate.

So maybe first on the part B.

Yes.

Given everything that you've just talked about and the importance of looking beyond 16 weeks are you able to provide some preliminary perspective on the level of additional follow up do you expect to have beyond that 15, 16 week data point when you release data will ever want be it six months or what the median be somewhere.

So that and if so around where.

And then secondarily.

Want to know if youre able to provide any incremental color on the formulation work.

The last update.

And when you may be able to have something more concrete to say about your efforts here.

And then maybe lastly, if I could on <unk> 67.

Just understand a little bit more of the recruitment challenges that youre seeing and maybe more broadly.

How the data.

We'll inform your development strategy not only for this drug but for <unk> 15, as well. Thank you so much.

Operator: Safety, Tolerability, and the Anti-Inflammatory Effect, and then the future development plan. Great, thank you for taking the questions. Thank you. Our next question comes from the line of Kristen and Quiscom with Kansas' Cheryl. Your line is open.

So let me.

Take a couple of those I'll, let Jonathan take the detailed questions on part B.

On formulation.

We expect we will have.

Next level of data and understanding of the next wave of activity in Q1 next year. So I think we should be on track for.

Operator: Hi, good morning everyone. Thanks for taking the questions. The first one I have is, I noticed that your most recent corporate deck expands and further emphasizes some of the comorbidities that are specifically associated with psoriasis and atopic dermatitis. As your recent data set was important for your broad understanding of the potential syntax medicines, I'd be curious, as you are near starting the phase 2 study in atopic dermatitis, if you will look to enroll some patients Yeah, so Kristen, thanks for picking up on that point.

For that on that front.

Matt on recruitment of $18 67.

Trying to understand exactly why recruitment slower than we had expected it may be because of COVID-19.

But he has been recruited in the U K.

And you probably know there's been a rise of Covid patients, we don't know that Matt.

It's definitely a plus.

And for us, but we're trying to understand that right now and we don't really have any additional information.

At this stage on that recruitment situation and then Jonathan do you want to talk about the details on pumping yes. So as part D. We have 124 subjects who have.

Rolled into that portion of the study.

It goes out for an additional 20 weeks.

To have a fair number of them.

Subjects, who will be completing the 20 weeks, we've got about 70 plus percent of subjects, who are now completed on that end.

Operator: We won't be specifically looking to recruit patients with comorbidities, obviously, to the degree we pick it up anyway in that context. But beyond phase two, I think the more fundamental point that you're picking up on, Christian, is there's a huge breadth of opportunity with 1815 and with the Syntax Platform to treat many different types of inflammation. A, and B, both psoriasis and atopic dermatitis, are systemic diseases that, as your question suggests... Okay, thanks.

The data.

The first quarter of next year.

We'll have a large proportion of those subjects, who will go out to the full 20 meters, great and then actually Duncan do you want to call. It in the 18 67 to atopic dermatitis, yes.

Okay.

Just to be clear, we're using atopic dermatitis here because that actually.

It's a very useful and valuable kind of like early indication that we've got good anti inflammatory effect.

Obviously happy $80 50 days as well and we intend to it not paid at 18 67, if they know the drug drug that we're following exactly the same footsteps as 2015.

The phase <unk> study demonstrated anti inflammatory effect and then there's obviously a whole range of indications.

We talked about before that could range from classic immuno inflammatory diseases like inflammatory bowel disease, <unk> disease and effective new information. The key here is to just demonstrate the safety tolerability and anti inflammatory effect.

Operator: And looking at the profile differences between EDP1815 and EDP1867, based on some of these trends you've observed post-dosage and longer term with EDP1815, wondering if, based on the differences with v. parvula, whether you might expect or look to see something similar with EDP1867. And then, you know, as you think longer term here, how do you think about expansion opportunities for EDP1867, excuse me, in light of these recent preclinical findings you had, as well as the greater focus on EV candidates, given the recent patent could address both?

And then the future development plan.

But we'll involve other indications.

Great. Thank you for taking the questions.

Thank you Matt.

Our next question coming from the line of Christian <unk> with Cantor Fitzgerald. Your line is open.

Hi, good morning, everyone. Thanks for taking the questions. The first one I have is I noticed that your most recent corporate deck expands and further emphasizes some of their comorbidities that are specifically associated with psoriasis and atopic dermatitis. So as you recent data that was important for your broad understanding of it.

The potential tax Maddison I'm curious as you are near starting the phase two study in <unk>.

Topic dermatitis, if you will look to enroll some patients where perhaps some of these comorbidities are more apparent to even better understand some of the systemic impact.

Yeah, sure, Chris and types of picking up on that point.

<unk> be specifically looking to recruit patients with Comorbidities, obviously to the degree we pick it up anyway.

In the.

Operator: Yeah, so I think there are three levels of questions. First of all, we need both human clinical data to see if we see similar or different responses with 1867 versus 1815. They're different, at the end of the webinar.

Detailed analysis.

We'll obviously be looking for those things.

And in that context Buck beyond the phase two.

The more fundamental point that you're picking up on Christian is huge breath of opportunity with $18 15, and what this impact platform to treat many different types of inflammation.

B, both psoriasis and atopic dermatitis.

Systemic diseases as to your question suggests impact.

Not just skin.

Co morbid conditions in multiple different dimensions. So we won't be looking specifically for that new recruitment in phase II, but the point is an important one in terms of the potential treatment.

Operator: In terms of how we think about 1815-1867 expansion and the EV side of things, let me take that together. What we've talked about historically is that we see where we are now, discovery of antibodies. I happened to have worked with Alex Zaffaroni decades ago, who started D-NAX, which is the first cytokine biology company in the world. Fairly remarkable uncovery of a central area of human biology. Mark Bodmer and I worked, as you know, in the earliest days of antibodies, when Mark headed up one of the world's first antibody engineering groups, were very much in the early days of, Uncovering the Potential of Syntax Platforms and pushing things forward allows Mark to say a little bit more about this right now, but as we start to understand more and more how the biology works what the potential of EDs is as Mark said, we see EDs and the ultimate future of syntax platforms, as being an opportunity to have orally delivered agents that have antibody-like efficacy whilst being safe, well-tolerated, and affordable, and all of the science right now points us in the direction of that being a very real possibility. It's not too far away.

We go forward.

Okay, Thanks, and looking at the profile differences between Edp 18, 15 in Edp <unk> 67 based off some of these trends you've observed post dosage and longer term with Edp 18, 15 wondering if based on the differences with the harvest of the.

Whether you might expect or love to see something similar with Edp $18 67, and then as you think longer term here. How do you think about expansion opportunities for Edp, 18th 16, 18 67 excuse me in light of these recent preclinical findings you had as well as the <unk>.

Greater focus on EV candidates given the recent pattern could address both.

Yes, so I think three levels of questions. So first of all.

We need the human clinical data to see if we see similar or different.

Okay.

<unk> with 18 67 versus $8 15 that different.

And.

So the pre clinically that different so we'll be able to answer that question with data in the not too distant future pre Christmas.

In terms of how we think about $18 15 to 867 expansion and the EV side of things, let me take that together.

And what we've talked about historically is that we see where we are now.

I talked about earlier today, even as the equivalent of uncovering cytokine biology and.

Discovery of antibodies.

Two of work without except peroni decades ago Kristen.

I'll start with Dean acts as the first cytokine biology company in the world fairly remarkable uncovering central Aric human biology, Mark and I apartment I'd work because you know in the earliest days of antibodies when mop headed up one of the world's first antibody engineering groups.

Operator: We'll have our first EV day in the not-too-distant future. As we said on the call, we are on track to go into the clinic with EVs next year. Inflammation, and we haven't given formal guidance on when that data will read out, but right now, we have, as you know, 1815 that's looking like an attractive drug in psoriasis and quite probably atopic dermatitis. But that's really the first wave, and we look at EVs as rapid follow-on, that could work dramatically better. In terms then of 1867 and 1815, or indeed any of our other microbes and microbial extracellular versus 1815,

We're very much in the early days of <unk>.

On covering the potential of syntax platform.

And pushing things forward ill ask mark to say a little bit more about this right now but as.

As we start to understand more and more how the biology works what the potential of Evs is as Mark said we.

We see Evs and the ultimate future of syntax platform as being an opportunity to have already delivered agents and people do like efficacy, whilst being safe well tolerated and affordable and all of the science right now points us in the direction of that being a very real possibility and its not too.

Far away well have our first <unk> data.

On time.

In the not too distant future as we said on the call. We're on track to go into the clinic with Evs next year.

Operator: As you know, and again as Mark talked about today, the neuroinflammatory side of 1867 is already looking very interesting. But, as Duncan said, we don't necessarily see 1867 as an atopic dermatitis drug. Atopic dermatitis is a quick way of getting clinical information in human patients, and then we'll figure out how we move it forward depending on that data, but we see potential, for example, in urinary inflammation, as well as in a number of other areas. And then Mark always likes to remind everybody, "How lucky would we be to have 1815 and 1867 as great products?"

In inflammation.

And we haven't given formal guidance when that data will read out but.

It won't be too far away.

So that's where we see this growing pretty quickly actually.

Right now we have as you know $18 15, that's looking like an attractive drug in psoriasis and quite probably in atopic dermatitis, but.

But thats really the first wave and we look at.

Evs as rapid follow ons.

That could have dramatically better potency in terms, then of 18, 67% and $18 15, or indeed any of our other <unk>.

<unk> microbial extracellular vehicles.

Versus $18 15.

As you know and again as Mark talked about today.

Neuro inflammatory side of $18 67 is already looking very interesting.

As Duncan said, we don't see 18, 67 is an atopic dermatitis drug.

Necessarily atopic dermatitis is a quick way of getting clinical information in human patients and then we'll figure out how we move it forward depending on that data, but we see potential for $19 67 for example in your inflammation.

Operator: So we look forward to that possibility, obviously, Kristen, and it's a great luxury if we do end up there. So hopefully, that was helpful. I'll have Mark say a little bit more about the EV side of things. Because, as I said, all the science right now is pointing us to that being an incredibly... Let me play into that with the first bit of your question about 1815 and 1867 and the duration of effect.

Well as in a number of other areas and then Marc always like to remind everybody. How lucky would we be to have $80 15, and $18 67 has great products.

We look forward to that possibility, obviously, kristen and it's a great luxury if we do end up that so hopefully that was helpful. I'll have Marc say, a little bit more about your EV side of things.

Because as I said, all the science right now is pointing to that being an incredibly exciting possibility, yes effects of our Christian let me play into that with the first part of your question about <unk> 15 of $18 67, and the duration of effect of simplicity, we don't know clinically, but pre clinically we do.

Operator: As Simba said, we don't know clinically, but preclinically, we do. So EDP-1867 induces this regulatory phenotype in treated animals that can be transferred to untreated animals in exactly the same way as EDP-1815 does it, but it does it with a different molecular background, which is fascinating. It's actually driving a lot of our research and discovery because there are some common parts of the pharmacological pathway here. It's not to say that we've identified specific targets, but we can look at differences in finding toll-like receptors.

So <unk> 67 in juices this regulatory phenotype in treated animals that can be transferred to untreated animals.

The same way as ETP 18, 15 does it but it does it with a different molecular background, which is fascinating is driving a lot of our research and discovery because there is some cause.

Common parts of the pharmacological pathway here, which were introduced by different molecular pathways and the primary action of the drug which is not to say that we've identified specific targets. We can look at.

Operator: We can look at differences in induction of various transcripts in the gut by the different agents. And we then take that to the EV part. We've been doing a lot of work on the exoskeletal vesicle of the microbe that underlies EDP-1867 and that also does these things. It doesn't look molecularly exactly like the parent microbe, but pharmacologically, it does on a much lower level. So if you think about this from a dose point of view, which I think was driving some of my comments about efficiency of movement of these things in the milieu to get to the target in the gut and also packing. So we typically give a dose of about 10 to 9 microbial cells per day in an animal model.

Differences in binding toll like receptors, we can look at differences induction of various transcripts in Macau by the different patients. We then take that to the easy part we've been doing a lot of work on the extracellular vehicle all the microbe, otherwise Pvp $18 67.

Also does these things.

It doesn't look molecularly exactly like the microbe, but pharmacologically.

Does either.

A much lower level. So if you think about this from a dose point of view, we took what was driving some of my comments about.

Efficiency of movement of these things in the media as I get to the target. It also parking so we get typically a dose of about 10% of annoying microbial cells per day in an animal model.

Operator: With the EV from EDP 1867, we can take that down several orders of magnitude, 10 to the 6, 10 to the 7, and they're smaller at the same time. So the differential is about a million times smaller. I mean, this is quite an extraordinary effect.

The EV from Edp 18, 67, we can take that down several orders of magnitude 10 to the six tenths of the seven.

And the smaller at the same time, so the differential was about $1 million all of it is quite quite an extraordinary effect thats why were so excited about the future of the DB platform, because we've got a base of efficacy with the microbial preparations. So then we have this.

Operator: That's why we're so excited about the future of the EV platform because we have a solid base of efficacy with the microbial preparation. So then we have this additional way to go forward. Why I talked about the potential to get into severe disease is because I suspect this is all about dosimetry and where we are on the dose-response curve in relation to formulation and in relation to the concentration of the drug that's given to the target.

Additional wave.

Way to go forward, which is why I talked about the potential to get to to get into severe diseases. I suspect. This is all about our symmetry and where we are on the dose response curve in relation to formulation in relation of the concentration of drug.

Operator: Then, just very briefly, beyond that, most of our discovery work is now focused on looking at extracellular vesicles from quite a wide taxonomic range of microbes, comparing their pharmacology, and their underlying molecular mechanisms to get a spectrum which is going to support the future of the pipeline, and, by the way, critically important. The Patent Claims We get around this, and just to reemphasize the patenting around the use of extracellular vesicles from mucosal anaerobic microbes as oral treatments, Virgin Territory, and so we're filing a Bordeaux matter. DiscoveryWay, product candidates also give us breadth of support.

That's given to the target then just very briefly beyond that most of our discovery work is now focused on looking at extracellular vehicles from quite a wide taxonomic range of microbes comparing the pharmacology that underlying molecular mechanisms to get paid spectrum, which is going to support the future.

Of the pipeline by the way critically importantly, it supports the breadth of patent claim that we get around this and just to reemphasize that.

I'm thinking around the use of extracellular vehicles from kozol anaerobic microbes as oral treatments.

Judge in territory, and so we're finding very broadly on that.

Issued yet of course, but.

The discovery work, which gives us great product candidates also gives us the support for those coming forward. So I hope that helps to give a bit of context of the whole thing.

Operator: So I hope that helps to give a bit of context. Yes, thank you Simba and Mark. And our next question comes from the line of Govind Singh with JMT. Your line is open. Hi, thanks for taking the question. So, just a few from me.

Yes, Thank you Simba Mark.

Thanks Christian.

Yeah.

Yeah.

Okay.

And our next question coming from the line of Goldman Zhang with JMP. Your line is open.

Hey, Thanks for taking the questions just a few for me I think Mark you had Oh, what does it bring the conversation back to the results. I think you had mentioned was the BSA greater than 5% and below 5% and.

Operator: I think, Mark, you had a, I wanted to bring the conversation back to those results that I think you had mentioned with the BSA greater than 5% and below 5%. And, you know, I'm just trying to figure out what the comparator is, if there is one. And it just seems like the way Amgen has presented results from the advanced trial. It looks really different compared to how they've kind of done things with other trials.

I'm just trying to figure out what the comparator is if there is any and it just seems like the way. It's Amgen has presented the results from the advance trial booked.

It looks really different compared to how they've kind of have done things with other trials I don't even think there's a pathway to Europe has this 75 or any kind of traditional paas. He ever presented some of the advanced trial. So.

Operator: I don't even think there's a PASI-50 or a PASI-75 or any kind of traditional PASI ever presented from the advanced trials. Can you maybe give us some context as to how to kind of view those results and then one follow-up after that? Thanks for the question. I can't really comment on why Amgen chose the particular end point that they chose and then went to advanced. In terms of the body surface area threshold of 5% that they use,

Can you maybe give us some context as to how that kind of view.

Those results and then one follow up that's right.

Yes.

Thanks for the question.

So.

Can't really comment on why Amgen particular endpoint.

Obviously they.

At their own data centers in Maryland that went to advance in terms of the body surface area threshold of 5%.

Operator: That's one of the ways in which people can classify psoriasis into mild and moderate disease. It's not necessarily true from a patient perspective, but certainly from the physician perspective, we tend to sort of say if the body surface area is less than 5%, it's mild; if it's greater than 5%, it's moderate, and I am.

That the sort.

Sort of.

One of the ways in which people can.

Sort of classify psoriasis into mild and moderate disease.

It's not necessarily.

From a patient perspective.

Physician perspective, we tend to sort of say everybody stepped salary flattened.

<unk> centric model, it's greater than 5%.

Operator: Assuming that is the reason that they cut that data at 5%. And as you saw, and looked at that PGA01, so the ability to get clear or nearly clear skin, both in the mild and the moderate, at www.ncbi.nlm.nih.gov www.cdc.gov.uk. From our perspective, sort of a clinic, at www.ilo.org.uk, It's quite hard The 5% does reflect some of what Amgen did, but I can't tell you why they used Addy or didn't use Addy. We will look at, obviously, all the endpoints in 201, and we will decide which one we view as the best in terms of capturing EDF 1815's activity, and that's what we'll propose to the health authorities.

But its module.

Im.

Assuming that is the reason that they cut that phase five.

And as you saw we've done something similar and I looked at that.

P J zero or one or two the ability to get clear on nearly clear skin baked.

Baked into mild and moderate.

Disease, we've also actually got it using pega to and P. J, three which is another way of categorizing mild to.

Moderate disease and in both of those settings, we have a statistically significant results in terms of 80 to $80 50 versus placebo.

And we can play a role for nearly clear skin so from our perspective it just yet.

Another way of looking at the clinical benefit that we're getting with <unk> 16, and I'm seeing a sort of a clinically meaningful.

The benefit to patients.

Usually the targets the patient they want to get too clear skin or that Teekay scheme, because it's quite hard to get truly tastes. Good.

But.

5%.

It does reflect some of what Amgen data.

But I can't tell you why they.

In that case.

Because we use it early and it's a well established.

Well validated.

Point.

Look we will look at all the all the endpoints in 201, and we will decide which one we.

View is the best in terms of capturing 80 to $80 15 activity and that's what will.

Operator: I'm thinking about later phase development. I'd just add one comment, Govind, as I'm sure you understand very well. What was important in this was that an orthogonal analysis to the PASI-50 showed the robustness of the underlying data.

To the health authorities in terms of thinking about later phased development.

Yeah.

Can I just add one comment COVID-19.

As.

I'm sure you understand very well.

What's important in this was federal Falcon Hall analysis to the past 50.

Operator: So unlike the comparison of the primary mean PASI with the PASI-50, this is a different data set that was collected looking at BSA and looking at IGA, and it reinforced the fact that there is an effect of EDPH, separate from the question of the proportion of responders, but the orthogonal analysis picked it up as well. So it really, for us, in our evaluation of the study, added a great deal of robustness, in our estimation of, That's helpful.

The robustness of the underlying data.

So unlike a comparison of the prime remained positive with deposits 50. This is this is a different day.

Data set that was collected looking at PSA on looking at RGA.

First the fact that there is an effect of <unk> separate from the question of the proportion of responders, but they'll talk about analysis picked it up as well so.

<unk>.

It really for us in our evaluation of the study.

Deal of robustness.

Our estimation oxy.

Effective <unk> thousand 15.

Operator: And I know there was a mention about the lower, I guess, less than 5% BSA population not being statistically significant with the orthogonal assay analysis. If I'm, is that, I mean, I'm just eyeballing it. It's about what, 10%, 20% of your population?

That's helpful.

I know there was a mention about the lower I guess less than 5% DSA population.

Being statistically significant but the thoughts there.

The analysis.

Is that just broke.

Eyeballing it that's about what 10% 20% of your population.

Operator: So, I'm assuming the numbers are probably pretty small there anyways. Can I confirm that with you guys? And then maybe the follow-up would be, I'm looking at those pictures that you guys presented earlier with like PASI and PGA and DLQI and PSI, and the, like, clinical effect, you know, clearly we're having a microbiome drug. It's not shutting off the pathway. We're more normalizing the underlying disease process. So, one might imagine the time to kind of see the, you know, peak effect here might be different than for a small molecule like a Tesla or a Jack.

I'm, assuming the numbers are probably pretty small there anyway.

Can I confirm that with you guys and then maybe the follow up would be I'm looking at those pictures that you guys presented earlier with like Patheon, PGA and deal QA and Tsi and <unk>.

The clinical effect clearly, we're having a microbiome drug it's not shutting off the pathway more normalizing the underlying disease process. So one might imagine the time to kind of see the peak effect here might be different than a small molecule like a tesla or Jack.

Operator: You know, is there any rationale or precedent for how long this could take? Like, for example, would 20 weeks, for example, be enough time for us to be able to see this? And then maybe PGA is the right way of looking at this, not PASI, or maybe DLQI, or I don't know if you can comment, because the DLQI responses that you guys presented look pretty good. And I think, in advance, they are focusing more on, you know, PGA and these other metrics, not PASI.

Is there.

Is there any rationale or any precedent for how long this could take like for example, with.

With 20 week for example would be enough time for us to be able to see this in and then maybe as PGA. The right way of looking at this not patchy or maybe <unk> or I don't know if you can comment because the D. L. T Y responses that you guys presented looks pretty good and I think.

We are focusing more on <unk>.

And then these other methods not present.

Yes.

Operator: Let me say a few things and then Duncan can expand, go ahead. So first of all, you raise a really important point about small molecules versus our mechanism of action. [inaudible] are driven from impact versus the classic impact of antibodies or small molecules. So we're pushing the immune system back to a homeostatic balance, which is completely distinct, as you're saying, compared to anything else.

Let me say a few things and then Duncan can expand Covid So festival.

It's a really important point on small molecules versus our mechanism of action.

<unk>.

And Mark's comments today, we talked about the fact that we've done very elegant adoptive cell transfer studies pre clinically that showed that our FX driven.

Immune cell.

Impact versus classic impact of antibodies or small molecules.

Pushing the immune system back to our homepage that regulatory status through cellular effects.

On the immune system.

That is completely distinct because youre, saying anything else, it's got very positive potential implications.

Operator: It's got very positive potential implications because obviously, having a healthy homostatic immune system is a lot better than shutting down part of the immune system. It, as you suggest, also likely means it will take a little bit longer for effects to kick in, but then effects, and that's part of what we're looking for in part B, may well be sustained for longer. So all of those things are very positive for us. We can't quantitatively answer your question now as to whether it's 20..., the right time.

Obviously, having a healthy homeostatic immune system is a lot better than shutting down part of the immune system, which is essentially what antibodies and small molecules.

As you suggest also likely means it will take a little bit longer for effects to kick in but then effects and that's part of what we're looking for a puppy may well be sustained for longer. So all of those things are very positive for us.

Quantitatively answer your question now.

As 20 weeks the right time.

Operator: We've certainly already seen it, and we've reported out, with the initial data released from the Phase 2 psoriasis study that we see continued depth of response post-dosing, so that is already indicative of a likely cellular effect and continues for presumably weeks after we've stopped dosing. But we don't have it quantified yet.

We certainly already seen at 20 weeks and we were.

Sorted out from it with the initial data release from the Phase II psoriasis study that we see.

Continued depth of response post dosing so that is already indicative of a likely cellular effects of per se.

And continues for presumably weeks after we stopped dosing.

Operator: So just a few initial comments there. And then, Duncan, you can answer the rest. Yes, just a couple of points. So just to be clear, when we talked about that data, when we looked at the PGA-01 across the groups, either split by BSA or actually split by their starting PGA baseline. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29, if you look at the various subsets; they come down a bit.

But we don't have it quantified yet.

So just a few initial comments.

Then you can answer the other clusters.

Yes.

A couple of points.

Hey, everyone.

Just to be clear when we.

Talked about that being a statistically significant what we were looking at that.

When we looked at the PGA zero one across.

Great.

Hi, PSA will actually split by that starting PGA at baseline of being two or three.

We still face.

Phase III study.

It's a reasonable size, but as you start to sort of read.

Look at the various subset they come down a bit too. So it's not that we looked at each of these individual subset. What we've done is we looked at.

Operator: So it's not that we looked at each of those individual subsets. What we did was we looked at the total population but divided it into either being PGA2 or 3 at baseline or less than 5% or greater than 5% at baseline, and when you analyze all of the data with that as a stratification variable, in either of those two cases, we see a statistically significant result. In terms of what will be the best endpoint as we go forward, we'll keep continuing to look at the data.

Total population, but divided into either being pega to be a baseline for less than 5% of greater than 5% of baseline into two analyses and when you.

Like all of the data with after the stratification variable.

In either of those two cases, we see a statistically.

Significant result.

In terms of what will be the best.

Endpoint as we go forward, we'll keep continuing to look at the data the one thing I would say that.

Operator: The one thing I would say is that... If we look at the photos where we get very nice, clear kinetics of response to EDP1850, the psoriasis flap you can see them actually clearing sort of earlier on and they tend to clear centrally, which means that BSA is one of the later things, and we'll take that into account as we think about what the later... [inaudible] and it's a fascinating way in which, actually, the PHQ-15 drugs are being used, is a joint project with the National Institute of Health and Human Services.

No.

If we look at the factors, where we get very nice clear kind of kinetics of response to <unk> 15.

The thoracic flat you can see them actually clearing sort of earlier on and they tend to clear tactfully, which means the PSA is one of the latest thing lastly.

Shift.

And we will take that into account as we think about what the later.

So what the endpoints are for later trials to well established way of actually corrected back to clearing and actually if any.

Chief investigator.

But it is one of our in house dermatologist.

It's a fascinating way in which actually to pay $2 50.

Right.

The clearing and the last thing declared at the edge of the block.

Operator: We are working on a joint project with the National Institute of Health and Human Services, and we're called Climate Responses Driven by Aisle 17, Planetary Drive-Out, and as long as the inhibitors are there, the planetary drive-out..., but it's not generating a remapping of the immune system. So while the effect may be a bit quicker, the durability of the effect will be less. So one of the things to imagine here from an immunological point of view is that if you've got inflamed skin, whether it's psoriasis or atopic dermatitis or an inflamed joint, spinal cord, whatever it is.

I'll just add one comment COVID-19 related to what sort of a set about the mechanism of action because you're actually asking a question about the.

Duration of the timescale of these cellular effects versus factor inhibition. So if one imagines for instance.

Inflammatory response was driven by IL 17 TNF.

TNF, one puts a direct inhibitor and it takes that inflammatory drive aisles and as long as the inhibitors publicly drivers to take it away.

It does not generating a re mapping of the immune system.

Its function so while the effect may be a bit quicker.

The durability of effect will be less so one of the things we're matching here from an immunological point of view is that he's got inflamed skin, whether it's psoriasis or atopic dermatitis or their plant joint plant spinal cord whatever it is you've got a bunch of resident pro inflammatory cells.

Operator: You've got a bunch of resident pro-inflammatory cells in there, which need to be suppressed. Now, if you've got a direct inhibitor of that inflammatory effect, yes, it'll act on those inflammatory cells. What we're looking at here is a different process where there is a steady replacement over time of the anti-inflammatory regulatory cells that are being induced by the drug. And that's why Simba talks about the reprogramming or the long-term effects. This has been the holy grail of anti-inflammatory therapy for years, and we haven't known how to get at it.

Which need to be suppressed and displace now if you've got a direct inhibitor by the climate could affect shortly.

<unk> inflammatory cells, what we're looking at here is a different puts us where.

There is a steady replacement over time of inflammatory cells that are resident in the inflamed tissue.

The anti inflammatory or regulatory cells.

It's used by the drug and that's why Simba talks about the reprogramming or long term effects of this has been the Holy Grail anti inflammatory therapy for years, we haven't learned how to how to get out of it. So you can buy.

Operator: So, you can imagine when we saw the adoptive cell transfer effect in mice. We'll see you next time, which we've known we've wanted to do for decades but haven't figured out how to do it. That is, not just suppressed so that it controls its own response.

When we saw the adoptive cell transfer effective mice and then we saw the continuing accrual of effects.

Humans. This was a real eye opener for us and it was why I made the comment in the scripted remarks about.

Profoundly change the way one thinks about an area of science suddenly we could do something in this system, which we've known we've wanted to do for decades, but haven't figured out how to do it that is not just the suppress inflammatory response with a reprogramming immune system. So that it controls its own response. So that is what the data are telling us are happening very clearly.

Operator: And that is what the data are telling us is happening very clearly preclinically because we can show it by direct experiment, and it reads off what we're seeing clinically, which is consistent with what we're seeing pre-clinically. Thank you. Thanks, Joe.

The pre clinically because we can show it by direct experimental methods and it reads on what we're seeing clinically which is consistent with what we've seen pre clinically.

Operator: I appreciate the question. And our next question comes from the line of Tina K. from Chardon. Your line is open. Yes, thank you. Maybe just to further drill down on the effort to improve the release kinetics. You know, obviously, I think the entire coating chemistry is well understood.

Thank you.

Okay. Thanks, Kevin I appreciate the question.

Okay.

And our next question coming from the line of Keenan K Chardan.

Chardan Your line is now open.

Yes. Thank you.

Maybe just.

Further drill down on the effort to improve the release kinetics.

Obviously I think.

Coding chemistries are well understood. So.

Operator: So, you know, what's really the gating item of that initiative? So, we're just generating a supply key for the next wave formulation. The Cintigraphy Model that we touched on briefly in the last learning score.

What's what's really the gating item of that initial.

You too.

Okay.

So.

Generating supply.

Keefer.

For the next wave formulations to test and the Scintigraphy model that we touched on briefly on the last earnings call. So we're just generating supply and as I said, we should be ready to test different formulations in Q1 of next year.

Operator: So we're just generating supply, and as I said, we should be ready with different formulations in Q1. All my other questions were answered, so thank you. Now, next question coming from the line of Joseph Song at Cowan, your line is open.

Okay, Yes.

All my other questions were answered so thank you.

Thank you very much.

And our next question coming from the lineup Joseph Tung at Cowen. Your line is now open.

Operator: Good morning, and thank you for taking our questions. Maybe the first one, just a clarification on the Phase 2 atypical dermatitis data readout that we're going to be able to see. I know with Phase 2, we saw the Bayesian analysis for superiority, but then also maybe more of a traditional p-value comparison on those that reached a certain PASI cutoff. What should we expect in terms of the data readout for atypical dermatitis? Will this be sort of a traditional proportion of patients got the EV50 on the drug versus placebo, or is there a Bayesian comparison that would be appropriate here as well?

Good morning, and thank you for taking my questions. Maybe the first one just a clarification on the phase III atopic dermatitis.

Data readout that we're going to be able to see.

I know what the phase two we saw the Bayesian analysis for superiority, but then also.

Maybe more of a traditional P value comparison on that reached a certain pad the cutoff.

What should we expect in terms of the data readout for the atopic dermatitis will this be sort of a traditional disproportionate patient kind of the easy 50 on drug versus placebo or is there a beeson.

Parison that would be appropriate here as well.

Operator: And then second, in terms of the novel formulation work, you can move that into the clinic in Q1. The Phase 2 trial for atypical dermatitis is starting in Q4. Is there any way to expand Phase 2 if what you're seeing with the novel formulations is interesting to add that cohort, or will these novel formulations be used kind of ready for the pivotal studies if that path is supported? Thanks. Yeah, I'm going to let Duncan answer both those questions. So the first question is relatively straightforward because it is a proportion analysis.

Then.

Second in terms of the novel formulation work.

Can you move that into the clinic in the Q1, the phase III for atopic dermatitis in starting in Q4 is there any way to expand the phase two.

If what youre seeing with the novel formulations as interesting.

To add that cohort or are these novel formulations to use kind of ready for the pivotal studies.

Thanks, Yes, I am going to let Duncan answer both those questions.

For the first question relatively straightforward because it is a proportionate Alex.

Number of subjects.

<unk> easy 50.

Bayesian approach is a well established and validated that.

Operator: The number of, [inaudible] very difficult to sort of do that and be able to sort of have a robust interpretation, and I'll finish with that. So we will run the next session on the next session on the next session. Thank you. We're going to start now. We're going to start now. We're going to start any potential new formulations in a separate study rather than try and, Great, thank you. So, Joe, I hope that hasn't stopped you from becoming an expert on Bayesian statistical analysis, which I will. It is not only the future; it's the past, so part of what we try to do at Velo is educate people on something that is 300 years old, which is Bayesian statistics.

The more traditional frequentist approach.

Yes.

From that side of things in terms of the potential to add a new formulation partway through the phase III study.

I think that would be.

Very difficult to sort of do that and be able to sort of have a robust capital.

On office for that so we will run.

Any potential new formulations in a separate study rather than trying.

Complicate the current study apparel.

Sure.

Great. Thank you.

So I hope that hasn't stopped you from becoming an extra one basis statistical amount.

Which.

Well it is not any of the future is the path.

Pavel we tried to.

Educate people is 300 years old, which is basically statistics, but anyway.

But anyway, that's just my humorous comment for the day, Joe. Thank you very much. I'm showing no further questions at this time. I would now like to turn the call back over to our speakers for any closing remarks. Thank you everybody for your attention. Thanks to our wonderful analysts for their attention and their excellent questions. As we said in the scripted marks, this is a pivotal moment for us. I'm thrilled with the Phase II data in psoriasis.

My humorous comment for the data.

Yes.

Thank you very much.

Right.

And I'm showing no further questions at this time I would now like to turn the call back over to our speakers for any closing remarks.

Thank you everybody for your attention thanks to our wonderful hours for their attention and their excellent questions. As we said in his scripted remarks. This is a pivotal moment for us.

We are.

Thrilled with the phase III data in psoriasis.

Ah.

It's absolutely just the beginning.

Of what we see is an incredibly exciting future for the syntax platform I'll remind everybody that we are true pioneers augment talked about the extracellular visco.

I will remind everybody that we are true pioneers. Mark Bodmer talked about the extracellular vesicle, and it was action to think of using non-living microbes as orally-delivered therapeutics. We are the first company to think about using orally-delivered microbial extracellular b-cells. So a goal has always been to be the pioneer and the leader forever in thinking about how to capture the value of the small intestine, which we now absolutely know plays a central role in human biology, still not widely appreciated by the scientific or clinical communities, and we now know that we can harness the small brain. Clinical Effects was something that his very...

Intellectual property, but we were the first company to uncover the small intestinal axis. We were the first company to think of using non life microbes as 40 delivered therapeutics.

The first company to think about using already delivered microbial extracellular vehicles.

So our goal has always been to be the pioneer and leader ever in <unk>.

Thinking about how to capture the value of the small intestinal axis, which we know absolutely no plays a central role in human biology.

Still not widely appreciated by the scientific or clinical community. We now know that we can harness the small intestinal axis with clinical effects with something that is very safe and well tolerated certain extremely exciting moment for us thanks very much everyone.

Thank you very much. Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

Yeah.

Ladies and gentlemen that does conclude this call today. Thank you for your participation you may now disconnect.