Q4 2022 Evelo Biosciences Inc Earnings Call
Speaker 3: on a listen-only mode. Following the formal remarks, we will open the call for your questions.
Speaker 3: Please be advised this call is being recorded at the company's request. At this time, I'd like to turn the call over to Shamira Sherif-Oden of Avello. Please proceed.
Speaker 4: Thank you. This morning we issued our fourth order of Interpoint for 22 financial results and this is update.
Speaker 4: This release is available at AvellaBio.com under the investors tab.
Speaker 4: Today on the call we have Chief Executive Officer, Mirelle S.O.R.L., Chief Financial Officer, and Mark Wadler, Chief Scientific Officer.
Speaker 4: Before we begin, I would like to remind everyone that statements made during this conference call do not relate to matters of historical fact, including statements about our objectives and anticipated clinical milestones.
Speaker 4: The impact of the NMR product candidates and the timing and results of any clinical trials should be considered forward-looking statements.
Speaker 4: including within the meaning of the Kubernetes Litigation Reform Act of 1995.
Speaker 4: Such forward-looking statements are intended to protect the safe harbor protection provided by the Reform Act and all other applicable law.
Speaker 4: Actual results could defer materially from those indicated by the forward-looking statement due to the impact of many factors.
Speaker 4: Participants are directed to the risk factors set forth in Avello's annual report on Form 10K for the period ended December 31, 2022, and the company's other filings with the Securities and Exchange Commission.
Speaker 4: The statements made today speak only to Avella's operations as of today. Avella disclaimed any duty to provide updates to the company's statements, even if subsequent events caused the company's views to change.
Speaker 4: The statements made today speak only to Avelo's operations as of today. Avelo disclaims any duty to provide up to a 40-day period, even if subsequent events cause the company's views to change. I will now hand the call over to Sipha.
Speaker 5: Thanks for coming. Good morning everyone and thank you for joining us.
Speaker 5: We wanted to spend some time reviewing our progress over 2022, current status, and key milestones when the pandemic is free.
Speaker 5: I'll begin by highlighting an important advance which we announced in February .
Speaker 5: The progress of the EDP 2939, the first bacterial...
Speaker 5: EDP 2939 has begun dosing in patients with moderate psoriasis.
Speaker 5: P2939, clear safety and tolerability in healthy volunteers in the initial therapeutic dose above the three escalating dose stages of the phase one from the public to start.
Speaker 5: Psoriasis patients are now receiving EDP2939 in the phase 2 study at the initial therapeutic test.
Speaker 5: As far as we know, this is the first phase two for an orally delivered microbial extracellular B skull being investigated for the treatment of a systemic intraclamatory disease.
Speaker 5: We expect data from the Phase 2 study with EDP 2939 to be available in the next half of this year.
Speaker 5: A reminder that EDP 2939 is the EV product candidate that is derived as a pure active substance from EDP 1815.
Speaker 5: The science and preclinical data in E2939 strongly suggest the potential to drive greater efficacy than EDP1815 After Whitney.
Speaker 5: Safety and tolerability.
Speaker 5: Mark will review more on our extracellular vesicle program in a short time, but I have other potentials that EDP 2939 builds on clinical experience with EDP 1815.
Speaker 5: Beyond progress on our EV programme, I wanted to recap a few highlights from last year.
Speaker 5: In late 2021, we reported that our phase two mild to moderate psoriasis study
Speaker 5: on EDPC18-15 significantly improved the response versus placebo at the end of the 16 week treatment period.
Speaker 5: PASI 50 or greater responses were 25 to 32 percent versus 12 percent for placebo with statistical significance of p-value less than 0.05 to include superimposable active cohorts.
Speaker 5: Into early 2022, we continued to follow the same expectations for 24 additional weeks.
Speaker 5: after they ceased treatment with EDP-1815 in part B of the study.
Speaker 5: Clinical responses were maintained or even improved off treatment.
Speaker 5: Specifically, 66% of patients in Part B with a PASI 50 response or greater maintain this response with no preferred guarantee.
Speaker 5: of these 45% of patients who had an initial improvement from beta-based allergy between 50 to 75%.
Speaker 5: experienced a deepening of response to PASI 75 or greater in the follow-up period.
Speaker 5: This durability of clinical effect is differentiated from standards of care anti-inflammatory medicines.
Speaker 5: It is consistent with the mechanism of action that we have elucidated showing that syntax is made to act locally in the small intestine to activate a non-canonical system that can activate regulatory T cell population.
Speaker 5: This is a fundamental breakthrough in the treatment of inflammatory diseases which suggests great potential for syntax medicines.
Speaker 5: In November 2022, we published a scientific review in frontiers of immunology explaining the science behind the small intestinal acid based on this growing understanding of the mechanism of action of syntax and essence.
Speaker 5: A core EDP-1815 program goal for 2022 was to advance interactions with regulators regarding a potential phase of re-
Speaker 5: If a second strategy were completed with the FDA, EMA and MHRA over the past few months providing a path to phase 3.
Speaker 5: Advancing EDP 1815 interfaces will be dependent on evapability, test finance, and income or video prioritization.
Speaker 5: As you know, we are also investigating the potential of BDP-18-15 in the Phase II Atopic Demotitis Study.
Speaker 5: The first three cohorts of this study get a statement of primary endpoint.
Speaker 5: due to an unusually high placebo rate, which we cannot explain. The fourth cohort results using the faster release capsule are expected in the second quarter of 2023.
Speaker 5: Beyond clinical science, I wanted to also remind everyone of our accomplishments on the financial side in 2022.
Speaker 5: In May 2022, we raised $79.2 million through a registered direct offering with participation from key investors.
Speaker 5: In December 2022, we refinanced our existing $45 million debt with a loan agreement with Horizon Technology Finance.
Speaker 5: The term is by three years of interest only payments followed by a two-year amortization period.
Speaker 5: I'll now turn over to our Chief Scientific Officer and President of R&D, Mark Bodmer, to provide more detail on our EV platform and report recent updates from our EDP 2939 clinical program. You know, you're the needle in the wrong door.
Speaker 5: Thank you Simba. Bacterial exocytolibesicles or EVs are naturally occurring with the nanosol to get by bacteria. They're thought to be the main means of communication amongst bacteria and between bacteria and host cells.
Speaker 5: in some ways makes them well suited as potential drugs engaging the small intestinal axis when given orally to induce regular cell and achial logic information throughout the body. This leads to striking efficacy that has matched anti-cytokine biologics and JAK inhibitors because not each of them studies.
Speaker 5: The simple mention that ED product Canada EDP 2939 derives from EDP 1815. They're both prepared from fermentation of the same single-strain mental bacteria.
Speaker 5: EDB1815, a microbial product prepared from the cell pellet after fermentation. EDB2939 is the ED product prepared from the supermeth.
Speaker 5: Now, BDP-1815 provided proof of concept of the underlying syntax biology that drug action in the small intestine could lead to clinical benefit around the body in some applications unless it was all biologics and JAK inhibitors as the results of similar...
Speaker 5: described earlier.
Speaker 5: How the overall level of response that we've seen in clinical studies so far has actually not been as great as that actually been from what I've seen. We propose that this is most likely due to limitations in the dose response.
Speaker 5: that could be achieved with EDP1815. The critical factor in understanding why we expect EDP29 mycogenomics to improve on EDP1815 in psoriasis is experimental evidence that the main active substance in EDP1815 is the
Speaker 5: the EDs that purify in the drug substance. That is EDP1815 contains Samar studies.
Speaker 5: Preparations of EVs like 2939, with a tree of like the probe itself, have consistently shown higher preclinical potency of up to two orders of magnitude in preclinical experiments.
Speaker 5: So to give some comparison for what that could mean clinically, published dose response modeling of Cofacetanib, the broad JAK inhibitor, in surprise indications suggested about a five-fold range of dose from no response for the maximum response, for the maximum tolerated dose. A five-fold range is actually much smaller than the range that we think we're...
Speaker 5: basic principles of pharmacology, the increased potency of HOPE and BDCD2939 is predicted to be more than adequate for meaningful shift of that dose response curve.
Speaker 5: Speaking of which, I have a 39, it may cause the possibility to improve clinical activity while maintaining the potential for the placebo-like safety and tolerability in research expected.
Speaker 5: The two clinical developments reported last month from EDP 2939 in its phase 1.2 cell sounded scenes and
Speaker 5: The first, as Sima mentioned, was the outcome of Phase 1 safety cohort of EDP2939 in the human volunteers at the initial therapeutic dose level. The Trial Safety Review Committee determined that EDP2939 met the safety and tolerability criteria. For more information about EDP2939, please visit www.edp2939.com
Speaker 5: at this therapeutic post-proposed regression to phase 2 in patients with moderate psoriasis. Applying that the recruitment of psoriasis in patient can initiate with some phase 2 study is now progressing well based on the current recruitment ramp we anticipate reporting with psoriasis results in second half of 2023.
Speaker 5: as well as prior generation microbial product candidates by the high intrinsic potency of BBs and the number of concentration of BBs that can be packed into a single capsule.
Speaker 5: This first safety evaluation has a criminal evidence that at the proposed therapeutic dose, EDP 2939 with these properties maintains the placebo-polarity we previously observed with EDP 1815.
Speaker 5: evaluations could well have evidence that, at the proposed therapeutic dose, EDP2939 with these properties maintains the placebo-polarity we previously observed with EDP1815. We'll now hand back to Simba.
Speaker 6: EDP 2939 to the clinic is the culmination of years of discovery in the lab, building on a previous experience with the EDP 1815.
Speaker 6: Working out new modalities based on new biology!]
Speaker 6: and some offering the potential for great advances. All I think of just as a discovery of the pharmacology of bacterial EVs as an example of the latter, a step change in opportunity and potential value for the great advances.
Speaker 6: In closing, I'd like to thank patients involved in our studies, our partners, our shareholders, and our remarkable team for their commitment and efforts to enable the progress we have discussed today. I'll now open to questions.
Speaker 3: As a reminder, if you'd like to ask a question, please press star 1 1 on your telephone and wait for your name to be announced.
Speaker 3: star 11 again.
Speaker 3: one again. Please stand by while we compile the Q&A roster.
Speaker 3: Our first question comes from the line of Gary Nachman with BMO.
Speaker 7: Hi, guys. Good morning. First, for the fourth cohort in the ATOPIC germ trial, looking at the faster release capsule, was there anything you were able to do to modify that cohort to manage the high placebo response you saw with the first three cohorts, or was that locked already? So, is there anything you were able to do to modify?
Speaker 6: that the study is being run according to protocol, that patients are respecting a credible redesign. I raise that because one of the possible explanations for the high placebo rate.
Speaker 6: that the study is being run according to protocol, that patients are respecting the design. I raised that because one of the possible explanations for the high placebo rate couldn't be...
Speaker 6: off-protocol use of topical steroids for example in placebo patients. So we've done that. Beyond that the study was the fourth cohort was already underway and
Speaker 6: I don't know what we can do, what I just described.
Speaker 7: Okay, great. And then depending on the results of the force cohort, are there any other tweaks you could potentially do to the faster release capsule if necessary, if you don't have the exact data that you're hoping for, or is that profile fully optimized?
Speaker 7: And if the fast release capsule looks good in atopic germ, is there anything you would need to do before using it in the phase three psoriasis trial? Assuming that's still the plan.
Speaker 6: Let me keep those in reverse order.
Speaker 6: If what we get is with the fast release
Speaker 6: There's nothing further that we need to do to take it into the phase 3 trial in Siraju.
Speaker 6: In terms of whether or not it's optimized, the clinical data, as you know, remind everybody else, in humans on the release profile of the faster releases is very positive. Releasing the vast majority of the world's population,
Speaker 6: of product in the right place in the proximal small intestine with the current capsule release. So I think it is very well positioned. There's all the ways that you will need them.
Speaker 7: Okay, and you guys are bringing up a little bit, but I think you had said that you wouldn't be able to start the phase 3 in psoriasis until you have the appropriate financing. So maybe just comment, Simba, about partnership discussions, if those are ongoing for both.
Speaker 7: 18-15 or 29-39 and the timing of that potentially. And then just, you know, what's the expected cash burn for this year, given what you have in front of you. Thanks.
Speaker 6: Thanks Gary. I'll take the first question on partnering and then I'll hand over to Marella our Chief Financial Officer to discuss cash burn.
Speaker 6: So on partnering, we're in a significant number of discussions around different partnering possibilities that fall into the obvious buckets. So I explore the past on 1815.
Speaker 6: from a clinical development and commercialization perspective both in psoriasis as well as in a and then partnership discussions on EDP 29 39 and the broader EV platform So multiple discussions going on across the breadth
Speaker 8: Our fundamental goal is to get a partnership over the course of this year. So I think I'll hand over to Mirelle to talk about the cash flow. Good morning, Gary. Thanks for the question. So we have had a task in the partnership this year and following a number of the
Speaker 9: PASH preservation is that we earlier this year, we are prioritizing our investment in our two key clinical programs and milestones. This year, we are looking for a VAD program and advancing 2939 in a moderate derived study. We will be in the second half of this year.
Speaker 10: Okay, great. Appreciate that. Thank you.
Speaker 11: Thanks, Gary. Our next question comes from the line of Vikram Parohit with Morgan Stanley .
Speaker 12: Hi everyone, good morning. This is Gospel on for Vikram. We have two questions. So for the AD data expected in 2Q, I guess what is the efficacy hurdle that you are looking to cross?
Speaker 13: And then also to same for the 29.9 data in psoriasis expected in the second half. What do you see as the bar for success in terms of efficacy and safety?
Speaker 14: Yeah. Hi, Gosh, good morning. So on the AD data, we've given previous guidance that on the Seed
Speaker 15: PASI 50, oh sorry, ED50 or greater. 40% of patients on active with ED50 or greater.
Speaker 16: or placebo separation of 15%, so separation in terms of percentage of patients with EZ50 or greater of 15%. For more information, visit www.drsusan.org
Speaker 17: That's what we're looking for on the cohort 4 data. And that's been consistent guidance for some time possible. Onworthy data withdata with Donald Trump Att resort to allocations like this indulge the Russian citizens as thezi Mastro eh
Speaker 18: EP 2939 A few thoughts, first a reminder of the integrated profile.
Speaker 19: but underpins everything we're doing. Very uniquely, the potential for that is a drug that's not just an oral drug, but a drug that's not just an oral drug, but a drug that is not an oral drug.
Speaker 20: very safe and well tolerated and has meaningful efficacy and can be priced with flexibility. What is something that has...
Speaker 21: a Tesla-like efficacy or greater with safety and tolerability. And at that level or greater would be a big win. You're aware, Gospel, that I'm sure you guys have a forecast for a Tesla, but I think most people consider it on track to be a $3 billion a year drug with significant tolerability issues.
Speaker 22: So in the case of at least a Tesla-like efficacy, with safety and tolerability, we've got a major drop.
Speaker 23: We're very close to that level of effort to say what we see in the community. And I think we have...
Speaker 24: strong conviction that that is a likely result. Even more exciting is what Mark talked about, which is the fact that pre-clinically we're seeing JAK-like or biologic-like epidemiology that's a big range between a TESL-like efficacy at that level, but anyway in that range of the wind force.
Speaker 25: with E2P2915. Awesome, thank you very much.
Speaker 26: Awesome, thank you very much.
Speaker 27: Our next question comes from the line of Kristin Kluska with Cantor.
Speaker 28: Hi, good morning. Thanks so much for taking my questions. I just have one this morning. So I understand you haven't necessarily discovered what has caused the high response and placebo, but I'm curious if there's anything that you're able to rule out at this time. Thanks again.
Speaker 29: So we have essentially ruled out the obvious possibility that the mix up in supply of drugs, i.e. the patients took active instead of placebo and vice versa. So we looked at the blockchain and we worked through all of that.
Speaker 30: that does not seem to be the cause of our next delivery. So that's the one thing we're going to do.
Speaker 31: seem to be the cause of our next year. So that's the one thing we're working on. Thank you.
Speaker 32: As a reminder, if you'd like to ask a question at this time, please press star 1 1. Our next question. You're all aware of that you guys explain what support you guys have with your video? Yup. Cool. Thank you.
Our next question comes from the line of Peyton Bonsec with Cowen.
Peyton, your line is now open. Oh, hi. Thanks. Thanks for taking our questions. I guess just to start out, could you discuss what gave you the confidence to move forward with the lower dose and psoriasis patients, and did you see any evidence of target engagement or biomarker changes in healthy volunteers in that study?
in the 29-39. Hi, Pete. Now let Mark take those questions. We've used a very conservative scaling factor to get from preclinical studies to clinical studies to the dose of 4x10 to the 12.
particles of the extracellular vesicle all day, actually based on the scaling factor by volume, if you know your PKPD and pharmacology, and allometry, that's a hundred times higher than would be predicted. The ability to do that is actually based on the small size of the EVs and their potency.
And that's a big part of the comparison of EDP-1815. As you go back to Sima's answer a moment ago, the question about the expected outcome in the case of AB-20, AB-29, and AB-39, which is the whole point of what I was saying was to do with the estimate of the probability of getting a profile.
based on my environmental efficacy, based on very, very basic principles of pharmacology in terms of potency and first it goes forward. So the first one that we spent a lot of time debating, how do we pick?
A single dose for a skinny study for a phase 2A, and the answer is we went way above what we thought was likely to be the minimum effective dose.
Great, and did you guys see a target engagement or biomarker changes in the health of volunteers? We didn't do that. Sorry, you need to get me for an hour separately. So these drugs work in an inflamed state. It's better to pick it up and see what it's about to see unless there's information going on. It's the same with these. So in the health of volunteers, we're going to see a target engagement or biomarker change.
we don't even bother to look at that because there's nothing to note.
Great. And then, I guess, just could you kind of explain how you're thinking currently on whether you move forward with EDP-1815, assuming that funding or a partnership deal is reached, or would you kind of wait for a readout from EDP-2939 in the second half of this year?
Yeah, so we're working through all of that because there's a couple of key components you touched on. Both of them are a pain. So one is...
That is certainly a new and pur posely defeed on formiz, and we give rel toers.
Okay, thanks. Sorry, you broke up a little there. I'm repeating that for me.
Sorry Peyton, actually you broke up.
Thank you guys for taking the questions.
Yeah, sorry. So, never mind. I'll take it offline. Thank you, guys, for taking the questions. All right. Thanks, Pacey.
That concludes today's question and answer session. I'd like to turn the call back to Simba Gill for closing remarks.
Thank you very much everyone. I appreciate everybody continuing to follow us. This is a very exciting time for us. And we look forward to updating our program, on our clinical programs. And as we talked about on this call, updates on EDP 2939 in the EV program. I'm really excited about it.
to the next level of efficacy and beyond. Thanks very much everyone. This concludes today's conference call. Thank you for participating. You may now disconnect.
The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.
I I.
The.
Good morning and welcome to Avello Biosciences conference call to discuss its fourth quarter and full year 2022 financial results and business updates.
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, this call is being recorded at the company's request.
At this time, I'd like to turn the call over to Shamira Sherif, who will be up a bellow. Please proceed.
Thank you. This morning we issued our fourth quarter of the year 2020 financial results and business updates. This release is available at abellabio.com under the investors tab. Today all of the calls we have are from Chief Executive Officer Mirella Thorel, Chief Financial Officer and Mark Brodmer, Chief Scientific Officer.
Before we begin, I would like to remind everyone that statements made during this conference call do not relate to matters of historical fact, including statements about our objectives and anticipated clinical milestones.
The impact of our end-of-product candidates and the timing and results of any clinical trials should be considered forward-looking statements.
including within the meaning of the Securities Litigation Reform Act of 1995. Such forward-looking statements are intended to protect the safe harbor protection provided by the Reform Act and all other applicable law.
Actual results could defer materially from those indicated by the forward-looking statement due to the impact of many factors.
Participants are directed to the risk factors set forth in Avello's annual report on Form 10K for the period ended December 31, 2022, and the company's other filings with the Securities and Exchange Commission.
The four M-1 statements made today speak only to Avela's operations as of today.
Avello disclaims any duty to provide data up to the point of even if subsequent events cause the company's views to change. I will now hand the call over to
Thanks, Camille. Good morning everyone and thank you for joining us. We wanted to spend some time reviewing our progress over 2022, current escape tips.
and key milestones when it's a 10- century. I'll begin by highlighting an important advance which we announced in February .
The progress of the EDP 2939, the first bacterial to make sure that we hold the EDP product.
EDP 2939 has begun dosing in patients with moderate psoriasis.
EDP 2939, clear safety and tolerability in healthy volunteers in the initial therapeutic dose and above the three escalating dose stages of the phase one from the part of the study.
psoriasis patients are now receiving EDP 2939 in the phase 2 study at the initial therapeutic dose. As far as we know this is the first phase 2 for an orally delivered microbial extracellular vesicle being investigated.
for the treatment of a systemic inflammatory disease. We expect data from the Phase II study with EDP-2939 to be available in the summer of this year. A reminder that EDP-2939 is the EV product candidate that is derived as a pure active substance.
from EDP-1815. The science and preclinical data, PPE2939, strongly suggests the potential to drive greater efficacy than EDP-1815, after containing
EDP1815. The science and preclinical data in E2939 strongly suggest the potential to drive greater efficacy than EDP1815 while sustaining safety and tolerability.
Mark will review more on our extracellular bicycle program in a short way and explain the potential that EDP 2939 builds on clinical experience with EDP 1815. Beyond progress on our EV program, I wanted to recap a few highlights from last year. In late 2021, we reported that our phase 2...
mild to moderate psoriasis study on EDPD 18-15 significantly improved the response versus placebo at the end of the 16-week treatment period. PASIE 50 or greater responses were 25 to 32% versus 12% for placebo with statistical significance
of p-value less than 0.05 to include 3 active cohorts. Into early 2022, we continued to follow the same expectations for 24 additional weeks.
after they ceased treatment with EDP-1815 in part B of the study.
Clinical responses were maintained or even improved off treatment.
Specifically, 66% of patients in Part B with a PASI 50 response or greater maintain this response with no preferred therapy. Of these, 45% of patients who had an initial improvement have a PASI 50 response with no preferred therapy.
from Facebook's bad policy between 50 to 75% experienced a deepening of response to PASI 75 in the follow-up period.
This durability of clinical effect is differentiated from standard of care anti-inflammatory medicines.
It is consistent with the mechanism of action that we have elucidated showing that syntax is made to act locally in the small intestine to activate a non-canonical system that can activate regulatory T cell population. This is a fundamental breakthrough in the treatment of inflammatory diseases.
which suggests great potential for syntax methods. In November 2022, we published a scientific review in Frontiers of Immunology explaining the science behind the small intestinal acid based on this growing understanding of the body.
of the mechanism of action of syntax mechanisms. A core EDP-1815 program goal for 2022 was to advance interactions with regulators regarding a potential phase of re-production for EDP-1815 enseriocese. Interactions that were completed with the FDA for which we respect your
EMA and MHRA over the past few months, providing a path to phase 3.
Advancing EDP 1815 interfaces through funding dependent on evapability, finance, income, or vehicle prioritization.
As you know, we are also investigating the potential of UDP-1815 in the Phase II atopic dermatitis study.
The first three cohorts of this study get a stable to primary endpoint due to an unusually high placebo rate, which we cannot explain. The fourth cohort results using the faster release capsule are expected in the second quarter of 2023.
Beyond clinical health and cybernetics, I wanted to also remind everyone of our accomplishments on the financial side in 2022. In May 2022, we raised $79.2 million through a registered direct offering with participation from key investors and new investors. In December 2022,
we refinanced our existing $45 million debt with an agreement with Horizon Technology Finance. The term is defined as three years of interest only payments followed by a two-year amortization period.
I'll now turn over to our Chief Scientific Officer and President of R&D, Mark Bodmer, to provide more detail on our EV platform and report recent updates from our EDP 2939 clinical program. …
Thank you, Simba. Bacterial extracellular vesicles or EVs are naturally occurring with the nanotides of the bacteria. They're thought to be the main means of communication amongst bacteria and between bacteria and host cells.
that sometimes makes them well suited as potential drugs, engaging the small intestinal axis when given orally to induce regular detail and keep logical information throughout the body. This leads to striking efficacy that has matched anti-cytokine biologics and JAK inhibitors in people's studies.
The simple mention the ED product Canada EDP 2939 derives from EDP 1815. They're both prepared from fermentation of the same single-strength mental bacteria.
EDP-1815, a microbial product prepared from the cell pellet after fermentation. EDP-2939 is the ED product prepared from the supernet. Now EDP-1815 provided proof of concept of the underlying syntax biologically the drug action in the small intestine.
could lead to clinical benefit around the body and some of the patients of the electric result of biologics and JAK inhibitors as well as the results that Simba described earlier.
How the overall level of response that we've seen in clinical studies so far has actually not been as raised as that might have been in college. I would propose that this is most likely due to limitations in the dose response that can be achieved with ED 1815.
The critical factor in understanding why we expect EV29 by 30 times improved on EVP1815 in psoriasis is experimental evidence that the main active substance in EVP1815 is the EVs that are purified in the drug substance.
that is EDP1815 contains other species of chemicals as well as one microbial content. Preparations of EVs like 2939, with a period like the probal cell, have consistently shown higher preclinical potency of up to two orders of magnitude in preclinical experiments.
To give a more detailed comparison for what that could mean clinically, published dose response modeling of co-cocitinib, the broad JAK inhibitor, in-sensorized mutations suggested about a five-fold range of dose from no response to the maximum response of the maximum tolerated dose.
This five volt range is actually much smaller than the range that we think we can achieve with the potency improvements between EDP2939 and EDP1815.
The phase two efficacy that Simba described that we saw with the EDP-18-15 in the phase two psoriasis study was evidence of a lot of the dose response code for clinical response. So on the basis basic principles of pharmacology the increase in the EDP-29-39 is predicted to be more than adequate.
for a meaningful shift up that dose response curve. So, speaking of that, I've already made the possibility of approved clinical activity while maintaining the potential for the placebo-like safety and tolerability in science.
The two clinical developments reported last month from EDD2939 in its Phase 1, 2 cell, were milestones in the progress of the product candidate. The first, as Simba mentioned, was the outcome of Phase 1 safety cohort of EDD2939 systems in the human volunteers at the initial therapeutic dose level.
The Trial Safety Review Committee determined that E2939 met the safety and tolerability criteria at this therapeutic post-proposal regression to Phase II in patients with moderate psoriasis. The following improvement of psoriasis to patient E and in the Phase II study is now progressing well. Based on the current recruitment ground, we anticipate.
reporting with the psoriasis results in the second half of 2023.
The safety review was important. The organizing is differentiated from of our prior-generation microombial product candidates by the higher trinit prudtency of DV of re ANS and the number concentration of evvs that can be packed into a single capsule.
This first safety evaluation has a critical evidence that at the proposed therapeutic dose, EDP 2939 with these properties maintains the placebo vulnerability we previously observed with EDP 1815.
This first safety evaluation has been put on the evidence that at the proposed therapeutic dose, EDP2939 with these properties maintains the placebo-polarity we previously observed with EDP1815. We'll now hand back to Simba.
is that at the proposed therapeutic dose, EDP2939 with these properties maintains the placebo-concatheter tolerability we previously observed with EDP1815.
We are taking the winds of the current environment for small cat biotech at a time of increasing the quality of our platform and medicines. Bringing EDP2939 to the clinic is the culmination of years of discovery in the lab, building on our previous experience with EDP1815. Working out new modalities based on new biology, taking the time to present some challenging,
We are taking the winds of the current environment for small cat biotech at a time of increasing potential on our platform and medicines. Bringing EDP-2939 to the clinic is the culmination of years of discovery in the lab, building on our previous experience with EDP-1815. Working out new modalities based on new biology takes time and then presents some challenging and some offering the potential for great advances.
All I think of is the discovery of the pharmacology of bacterial EVs as an example of the latter, a step change in opportunity and potential value. In closing, I'd like to thank patients involved in our studies, our partners, our shareholders, and our remarkable team for their commitment and efforts to enable the progress we have discussed today. I'll now open to questions. As a reminder, if you'd like to ask a question, please raise your hand.
please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Gary Nachman with BMO. Hi guys, good morning.
First, for the fourth cohort in the atopic germ trial, looking at the faster release capsule, was there anything you were able to do to modify that cohort to manage the high placebo response you saw with the first three cohorts, or was that locked already? Is there anything you were able to do to modify it?
Hi, Gary. So.
Two things, one we obviously have engaged very deeply with the sites at which the study is being run to ensure as much as possible that the study is being run according to protocol that patients are expecting for a design. I raise that because one of the possible explanations for the high placebo rate is that the study
things. One, we obviously have engaged very deeply with the sites at which the study is being run to ensure as much as possible that the study is being run according to protocol that patients are respecting for design. I raise that because one of the possible explanations for the high placebo rate could be
off-protocol use of topical steroids for example in placebo patients. So we've done that. Beyond that the study was the fourth cohort was already underway and
or what we can do than what I just described. OK, great. And then depending on the results of the FORCE cohort, are there any other tweaks you could potentially do to the faster release capsule if necessary, if you don't have the exact data that you're hoping for, or is that profile fully optimized?
And if the fast release capsule looks good in a topic term, is there anything you would need to do before using it in the phase three psoriasis trial? Assuming that's still the plan.
Let me take those in reverse order. If what we get based is with the fast release, there's nothing further that we need to do to take it into the phase 3 trial in Serasi. In terms of whether or not it's optimized, the thing will take as you know better mind everybody else.
in humans on the release profile with the faster releases is very positive. So we're releasing the vast majority of product in the right place in the proximal small intestine with the current capsule release. So I think it is very well positioned. There's all the ways that they can make contact with everybody, but I don't think we'll need them.
Okay, and you guys are bringing up a little bit, but I think you had said that you wouldn't be able to start the phase 3 in Psoriasis until you have the appropriate financing. So maybe just comment, Simba, about partnership discussions if those are ongoing for both.
18-15 or 29-39 and the timing of that potentially. And then just, you know, what's the expected cash burn for this year, given what you have in front of you. Thanks. Thanks, Gary. I'll take the question on partnering and then I'll hand over to Morella, our Chief Financial Officer to discuss cash burn.
So on partnering, we're in a significant number of discussions around different partnering possibilities that fall into the obvious buckets. So I explored the past on 1815.
from a clinical development and commercialization perspective both in psoriasis as well as in a and then partnership discussions on EDP 2939 and the broader EB platform so multiple discussions going on across the breadth our fundamental goal is to get a partnership
Over the course of this year, so I think I'll hand over to Morales. Good morning, Gary. Thanks for the question. So we have Here and following a number of the past preservation is that we are prioritizing our
Okay, great. Appreciate that. Thank you.
Okay, great. Appreciate that. Thank you. Thanks, Gary.
Our next question comes from the line of Vikram Parohit with Morgan Stanley . Hi everyone, good morning. This is Gospel Anfel Vikram. We have two questions. So for the AD data expected in 2Q, I guess what is the efficacy hurdle that you are looking to cross? For the limited period Soviets are
And then also too, same for the 29.9 data in psoriasis expected in the second half, what do you see as the bar for success in terms of efficacy and safety? Yeah, hi Gosh, good morning. So on the AD data, we've given previous guidance that on the efficacy, we'd be looking for around 40%
EZ50 or greater, 40% of patients on active with EZ50 or greater, or placebo separation of 15%, or placebo separation in terms of percentage of patients with EZ50 or greater of 15%.
That's what we're looking for on the cohort 4 data. And that's been consistent guidance for some time possible. On the sensitive data with EP2939,
It takes a few folds. First a reminder of the integrated profile that underpins everything we're doing. Very uniquely, the potential alpha-lactamidacin is an oral drug that is...
very safe and well tolerated and has meaningful efficacy and can be priced with flexibility. What's important is something that has a Tesla-like efficacy or greater with safety and tolerability. And at that level or greater would be a big win. So if you're aware, go hold it.
I'm sure you guys have a forecast for a Tesla, but I think most people consider it on track to be a $3 billion a year drug with significant tolerability issues. So in the case of at least a Tesla-like efficacy with safety and tolerability, we've got a major drug.
We're very close to that level of efficacy. And I think we have strong conviction that that is a likely result. What's even more exciting is what Mark talked about, which is the fact that pre-clinically we're seeing jacked light or biological light at a big range between the petals.
Hi, good morning. Thanks so much for taking my questions. I just have one this morning. So I understand you haven't necessarily discovered what has caused the high response in placebo, but I'm curious if there's anything that you're able to rule out at this time. Thanks again.
So we have essentially ruled out the obvious possibility that the mix up in supply of drugs, i.e. the patients took active instead of placebo and vice versa. So if we look at my chain, we've worked through all of that, that does not seem to be.
the core of our advocacy program.
So that's the one thing we're looking for. Thank you. As a reminder, if you'd like to ask a question at this time, please press star 1 1.
So that's the one thing we're doing. Thank you. As a reminder, if you'd like to ask a question at this time, please press star 1 1. Our next question.
Our next question comes from the line of Peyton Bonsack with Cowen.
Our next question comes from the line of Peyton Bonsack with Cowen. Peyton, your line is now open.
Oh, hi. Thanks. Thanks for taking our questions. I guess just to start out, could you discuss what gave you the confidence to move forward with the lower dose and psoriasis patients? And did you see any evidence of target engagement or biomarker changes in healthy volunteers in that study in the 2939? Hi, Pete. Now let Mark take those questions.
So we've used a very conservative scaling factor to get from preclinical studies to the clinical studies that have been issued. The doses fall by 10 to the 12 particles of the extracellular vesicle a day, actually based on the scaling factor by volume, if you know.
PKPD and pharmacology, and allometry, that's a hundred times higher than would be predicted. The ability to do that is actually based on the small size of the EVs and their potency. And that's a big part of the comparison of EVPH in 15. And it actually goes back to...
Sima's answer a moment ago to the question about the expected outcome in the case of A-birth of 2029-39. Actually, the whole point of what I was saying was to do with the estimate of the probability of getting above that a test of a baseline of efficacy based on very, very basic principles of pharmacology in terms of potency and first that goes forward. So the first one that we spent a lot of time debating, how do we pick?
single dose for a skinny study for a phase 2a and the answer is we went way above what we thought was likely to be the minimum effective dose.
And did you guys see a target engagement or biomarker changes in the health of volunteers? We didn't do that. So you need to get me for an hour separately. So these drugs work in inflamed states. It's not to see unless there's information going on. It's the same with these. So in the health of volunteers...
we don't even bother to look at that because there's nothing to note. So we're just going to keep it. Great. And then I guess just could you kind of explain whether how you're thinking currently on whether you'd move forward to the EDP 18-15 assuming that funding or partnership deal is reached or would you kind of wait for a readout from EDP 29-39 in the second half of this year? Yeah. So we're working through all of that because there's a couple of key components you touched on.
Both of them are really paying attention.
Okay, thanks. Sorry, you broke up a little there. Do you mind repeating that for me? Sorry, Peyton. Actually, you broke up. Sorry, Trevor, just say it again. Yeah, sorry. Never mind, I'll take it offline.
Thank you guys for taking the questions. All right. Thanks, Jason. That concludes today's question and answer session. I'd like to turn the call back to Simba Gill for closing remarks.
Thank you very much everyone. I appreciate everybody continuing to follow us. This is a very exciting time for us. And we look forward to updating our program, on our clinical programs. And as we talked about on this call, updates on EDP 2939 in the EB program. That's really important. That's the next level of efficacy and beyond.
Thanks very much everyone. This concludes today's conference call. Thank you for participating. You may now disconnect.