Q3 2019 Earnings Call
Good morning, and welcome to Analyst Conference call to discuss the interim clinical data from its phase one be trial of MDP 18 15.
Operator: Good morning, and welcome to Avelo's conference call to discuss the interim clinical data from its Phase 1b trial of EDP1850. At this time, all participant lines are in listen-only mode.
At this time all participant lines are in listen only mode. Following the formal remarks, we will open up the call for your questions.
Operator: Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn the call over to Jessica Catrona-Vivello. Please proceed. Thank you, Operator.
Please be advised at this call is being recorded at the company's request.
At this time I'd like to turn the call over to Jessica Katrona Bigelow. Please proceed.
Thank you operator. This morning, we issued a press release the outlines the topics we plan to discuss today. This release is available at Www Dot Velo bio dotcom under the investors cat today in our call Cinda, Gail Chief Executive Officer, Dunkin, Mikael, Chief Medical Officer, and Mark Bodmer President.
Jessica Catrona-Vivello: This morning, we issued a press release that outlines the topics we plan to discuss today. This release is available at www. AveloBios.com under the Investors tab. Today on our call, Simba Gill, Chief Executive Officer, Duncan McHale, Chief Medical Officer, and Mark Bodmer, President of R&D and Chief Scientific Officer, will review the positive interim clinical data for EDP-1815 and discuss its significance for our strategy and future development plans. Before we begin, I would like to remind everyone that statements made during this conference call that do not relate to matters of historical fact, including statements about our objectives and anticipated clinical milestones for 2019 and 2020, the impact of any of our monoclonal microbials, 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.
R&D and Chief Scientific officer overview, the positive interim clinical data for ATP, 18, 15, and disgusted significance for our strategy in future development plans before we begin I would like to remind everyone that statements made during this conference call that do not relate to matters of historical facts, including statements about our.
Objectives in anticipated clinical milestones for 2019 and 2020 the impact if any of our monoclonal microbials and the timing and results in any clinical studies should be considered forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995, such forward looking statements are intended to be.
Jessica Catrona-Vivello: Such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act. However, actual results could differ materially from those indicated by the forward-looking statements due to the impact of many factors. Participants are directed to the risk factors set forth in Avelo's quarterly report on Form 10-Q for the quarter ended June 30, 2019, 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 view to change. It is now my pleasure to pass the call over to Simba.
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 as many factors.
She spends are directed to the risk factors set forth in a valid quarterly report on Form 10-Q for the quarter ended June Thirtyth 2019, and the company's other filings with the Securities and Exchange Commission.
Any forward looking statements made today speak only two of fellows operations as of today, a valid disclaims any duty to provide updates to its forward looking statements. Even a subsequent events cause the company's view to change. It is now my pleasure to pass the call over December .
Simba Gill: Thank you, Jessica. Good morning everyone, and thank you for joining us. Today is another exciting and important day for Revelo. For the second time, we are reporting positive interim clinical data. Our preclinical and clinical data support the validation of our platform. Clinical data provides evidence regarding our ability to harness the power of the small intestinal axis to treat systemic inflammatory disease. We believe we are the first company to have demonstrated this.
Thank you Jessica good morning, everyone and thank you for joining us.
Today, there's another exciting unimportant day for Valerie.
For the second time, we're reporting positive interim clinical data.
A preclinical and clinical data support the validation of our platform.
Clinical data provides evidence regarding our ability to harness the power of the small intestine access to treat systemic inflammatory disease.
We believe we all the first company to have demonstrated this.
The implications all enormous we're developing medicines with the potential to be effective safe convenient and affordable.
Simba Gill: The implications are enormous. We are developing medicines with the potential to be effective, safe, convenient, and affordable. We believe our platform opens up the potential for broad global treatment of patients, with all stages of disease helping millions of people. Slide 3 summarizes the key highlights from today's announcement of interim clinical data for EDP1815 in mild to moderate psoriasis, in the high-dose cohort. A few things to note.
We believe a platform opens up the potential for broad global treatment of patients with all stages of disease, helping millions of people.
Slide three summarizes the key highlights from today's announcement of entering clinical data in <unk>, 18, 15, and mild to moderate psoriasis.
In the high dose cohort.
A few things to note.
Firstly, ATP 18, 15 continues to be well tolerated.
Simba Gill: Firstly, EDP1815 continues to be well tolerated. We continue to see safety and tolerability as an important area of competitive advantage for the treatment of inflammatory disease. The mean reduction in lesion severity score after 28 days of dosing in the high-dose cohort is consistent with data we reported in August with the low-dose cohort. At day 42, two weeks post the completion of dosing, individuals treated with the high dose showed continued reductions from baseline in both LSS and in PASI, which may be indicative of a sustained clinical effect and dose response. These clinical efficacy results, taken together with EDP1815 We look forward to advancing EDP1815 into Phase 2 early next year. Before turning the call over to Duncan to review the data, I'd like to outline the opportunity ahead of us at Evelo.
We continue to see safety and Tolerability as an important area of competitive advantage for the treatment of inflammatory disease.
The mean reduction in lesions severity school up to 28 days of dosing in the high dose cohort is consistent with data we reported in August with a low dose cohort.
A day 42.
Two weeks post the completion of dosing.
Individuals treated with the high dose showed continued reductions from baseline in both Lss and in Patty.
Which may be indicative of a sustained clinical effect and dose response.
These clinical efficacy results taken together with GDP 18, 15 safety results potentially represent an unparalleled oral therapy for mild to moderate psoriasis patients.
We look forward to advancing EGP 18, 15 interface too early next year.
Before turning the call over to Duncan to refuse a data I'd like to outline the opportunity ahead of us actually fellow.
Slide four shows the chronic inflammation is the central driver of some of the most burdensome diseases.
Simba Gill: Slide four shows that chronic inflammation is the central driver of some of the most burdensome diseases. As you know, many important and common chronic diseases, including arthritides, neurodegenerative diseases, atopies, and metabolic syndrome conditions, are linked to chronic inflammation. Worldwide, one in seven people suffer from a chronic inflammatory disease, and it is estimated that one in three die due to chronic inflammatory disease-related conditions. Targeting the small intestinal axis with Avelo's platform.
As you know many important and Coleman chronic diseases, including the all three studies neuro degenerative diseases, Hps and metabolic syndrome conditions are linked to chronic inflammation.
Worldwide wanting to seven people suffer from a chronic inflammatory disease and it is estimated that one and three die future chronic inflammatory disease related conditions.
Targeting the small intestine access with the valleys platform. We believe we have the potential to treat millions of people.
Simba Gill: We believe we have the potential to treat millions of people. We chose psoriasis as one of our first inflammatory disease targets as it allows for rapid and informative clinical trial readouts which have broad relevance in inflammation, as well as allowing for potential rapid approval in psoriasis patients with mild to moderate disease for whom there is significant unmet need. Moving on to the unmet need in psoriasis, on slide 5. You can see that a significant number of mild to moderate patients are not treated today, do not initiate or maintain treatments, are concerned about long-term safety or tolerability, and also, to some degree, the efficacy of currently available therapies. Slide 6 shows the results of a study conducted over nearly 10 years by the National Psoriasis Foundation, surveying approximately 5,000 patients with psoriasis.
We chose psoriasis as one of a first inflammatory disease targets as it allows for rapid uninformative clinical trial, retirements, which have broad relevance and inflammation.
As well as allowing for potential rapid approval in psoriasis patients with mild to moderate disease for whom there is significant unmet need.
Moving onto the unmet need in psoriasis on slide five you can see that a significant number of mild to moderate patients on not treated today.
Primary reasons physicians do not initiate will maintain treatment or concerns about long term safety or tolerability.
And also to some degree the efficacy of currently available therapies.
Slide six shows the results of the study conducted over nearly 10 years by the National Psoriasis Foundation.
So thing approximately 5000 patients with psoriasis.
Simba Gill: Of these, about 40% of patients with mild disease and over 50% of patients with moderate disease reported being dissatisfied with their treatment options. There is clearly a need in several million patients for an effective, safe, and affordable oral therapy. Evelo's platform allows us to develop medicines with this unparalleled profile. I now turn the call over to Duncan, who will review the new data for EDP 1850.
All these about 40% of patients with mild disease and over 50% of patients with moderate disease reported being dissatisfied with that treatment options.
There is clearly a need in several million patients for an effective safe an affordable oral therapy.
[noise] if those platform allows us to develop medicines with this unparallel profile.
Let me now turn the call ever to Duncan, who will review the new data for ATP Eighteenfifty.
Thank you Sarah and good morning, everyone I'm pleased to be able to share with you today positive interim clinical data observed to the high dose of GDP 18 15.
Duncan McHale: Thank you, Simba, and good morning everyone. I'm pleased to be able to share with you today positive interim clinical data observed for the high dose of EDP1850. I'd like to begin by reminding everyone of the design of the trial, which is presented on slide 7. The high-dose cohort enrolled 18 individuals with mild to moderate psoriasis. They were randomized in a 2 to 1 ratio to receive 2.76 grams of EDP-18-15 orally or placebo once a day for 28 days. However, subjects were followed for 42 days in total due to the two-week follow-up post-completion of dosing. The primary endpoint of the trial is safety and tolerability, and, as Sima mentioned, EDP-1815 continues to be well tolerated in this cohort with no overall difference reported from. The study is also investigating a number of secondary and exploratory endpoints to evaluate potential pharmacodynamic responses.
I'd like to begin by reminding everyone on the design of the trial, which is presented on slide seven.
The high dose cohort and road 18 individuals with mild to moderate psoriasis.
They were randomized in a two to one ratio to receive 2.76 grams of GDP eighteenfifty orally or placebo.
Today, the 28 days.
Subjects were followed for fortune to date in total due to the two week follow up post completion of dosing.
The primary endpoint is to try the safety and Tolerability and December mentioned ATP Eighteenfifty continues to be well tolerated in this code with no overall difference reported from placebo.
The study is also investigating a number of secondary and exploratory endpoints to evaluate potential pharmaco dynamic responses.
Slide eight describes the endpoints we reporting today.
Duncan McHale: Slide 8 describes the endpoints that we're reporting today. We're focusing today on the clinical scores, including both the lesion severity score and the PADI scores from both the low and high dose cohorts. The data from these endpoints provide insights into the pharmacodynamic effects and potential clinical benefits of EDP18. Now moving to slide 9, I'd like to remind you about the lesion severity score and how it relates to PASI. We have initially focused on the lesion severity score, which is a sensitive clinical measure of disease change in psoriasis. The lesion severity score is generally considered a more sensitive measure for patients with mild to moderate disease, in which individual lesions may be quite severe but the overall affected body surface area is small.
We're focusing today on the clinical scores, including both the lesions severity score and the Paddy schools from both the low and high dose cohorts.
The data from these endpoints provide insights into the pharmacodynamic effects and potential clinical benefit of ATP 18 15.
So moving to slide nine I'd like to remind you about the leasing severity school and how it relates to Patty.
We have initially focused on leases Veggie school, which is a sensitive clinical measure of disease change in psoriasis.
The lesions Vitesse scores generally considered a more sense to measure for patients with mild to moderate disease.
Which individual lesions, maybe quite severe but the overall affected body surface area is small.
Duncan McHale: It is also more sensitive when the dosing period is short as it can detect smaller changes from baseline. The lesion severity score is a fundamental component of the PASI scoring system and measures the underlying changes in lesion severity from a single psoriatic lesion across the duration of treatment. The lesion severity score measures redness, thickness, and scaling on a 12-point scale for the same individual lesion. The PASI scoring system measures the same underlying changes in psoriasis skin lesions as the lesion severity score, which captures those changes across all skin lesions and weights the score by body surface area affected for each region of the body.
It is also more sensitive when the dosing period as short as it can detect smaller changes from baseline.
Collision severity score is a fundamental component the party, scoring system and measures the underlying changes in lesion severity from a single sorry ethic lesion across the dosing period.
The lesion severity school measures redness thickness and scaling on a 12 point scale for the same individual lesion.
The party, scoring system measures the same underlying changes and it's rice is skin lesions as lesion severity score.
Good catches those changes across all skin lesions awaits the school by body surface area affected for each region of the body.
Oh, the lesions of 80 school and patchy scores are strongly correlated and wouldn't be anticipated to move in tandem as is evidenced by the data we will present today.
Duncan McHale: The lesion severity score and PASI scores are strongly correlated and would be anticipated to move in tandem, as evidenced by the data we will present today. So moving to slide 10, we can see the lesion severity score data from the high-dose cohort. The graph plots the change in lesion severity score observed over the 28-day dosing period and the subsequent two-week follow-up at day 42. As I specified in the analysis plan, we've pulled the placebo arms from both the low- and high-dose cohorts. This allows a correction for the asymmetric 2-to-1 randomization and improves the robustness of the placebo data. We saw a mean lesion severity score reduction from baseline of 15% in the individuals taking the high dose of EDP1815 at day 28.
Moving to slide 10, we can see the lesions severity score data from the high dose cohorts.
The graph plus the change in leasing severity school observed over the 28 day dosing period and the subsequent to eat follow up a day 42.
Hi specified in the analysis plan.
We've pulled the placebo arms from both the low and high dose cohort.
This allows a correction for the asymmetric two to one randomization and improves the robustness of the placebo data.
We saw a mean lesions very high school reduction from baseline, a 15% and individuals taking the high dose of eating eighteenfifty.
Day 28.
Duncan McHale: We were further encouraged to see that two weeks post-completion of dosing, at day 42, the mean lesional score reduction continued to 24%, suggesting a sustained clinical effect. Slide 11 shows that the observed lesion severity score changes were consistent between the high and low dose cohorts over the 28-day dosing period. On day 42, however, you can see the low-dose cohort returns almost to baseline, while the reduction continues in the high-dose cohort, which suggests a possible dose response. Slide 12 shows the individual changes from baseline in the lesion severity score at day 42 for each of the individuals in the cohort. On the bottom, we have a numeric score, and this is the baseline lesion severity score for the lesion that was tracked. There are a few things to note about this score.
We were further encouraged to see that two weeks post completion of dosing at day 42.
To me leaves no school reduction continue down to 24%, suggesting a sustained clinical effect.
Slide 11 shows the observed lesions veggie score changes were consistent between the high low dose cohort over the 28 day dosing period.
They 42, however, you can see the low dose cohort returns almost a baseline.
While the reduction continues in the high dose cohort, which suggests the possible dose response.
Slide 12 shows the individual changes from baseline in lesions Verity School, a day 42 for each of the individuals in the cohort.
On the bottom we haven't numeric school and this is the baseline lesions severity score for the lesion that was trial.
There are few things to note about the school.
Duncan McHale: There was no baseline difference between the individuals who were dosed with placebo or those dosed with EDP-1850. And although the individuals were classified as having mild disease in terms of their body surface area, the actual lesions that were tracked had quite active disease. In most of these individuals, the scores are between 8 and 10 out of 12. Nine out of the 12 individuals receiving EDP1815 showed a reduction in their lesion severity score. And in seven of these nine, the reduction was 25% or greater.
There's no baseline difference between individuals who dates with placebo or those states with GDP eighteenfifty.
And although the individuals were classified as having milder disease in terms of their body surface area. The actual lesions that would track at quite active disease that most of these individuals. The scores are between eight and 10 as of 12.
And nine out of the 12 individuals receiving ATP eighteenfifty shouldn't reduction in their lesion severity score.
And in seven of these nine the reduction was 25% or greater.
Duncan McHale: The maximum observed reduction in the EDP1815 dose group was 80%. We believe the magnitude of this effect at 42 days is remarkable, given both the short duration period and the fact that these measurements were taken two weeks after individuals discontinued therapy. Slides 13 and 14 show the analysis of the PASI data over the same dosing period. Slide 13 shows the population patty result.
The maximum observed reduction in the ATP 18, 15 dose group with 80%.
We believe the magnitude this affected at 42 days is remarkable given both the short duration period and the fact that these measurements were taken two weeks after individuals discontinued therapy.
Slide 13, and 14 showed the analysis of the party data over the same dosing period.
Slide 13 shows the population Patti result.
The main reduction impact the score the high dose is 16% at 28 days.
Duncan McHale: The mean reduction in PASI score on the high dose was 16% at 28 days, and the reduction continued to improve over the next two weeks despite stopping dosing, and the reduction at day 42 was 21 percent. The observed effects on the PASI score were very consistent with the trends observed in lesion severity. Again, it is very encouraging that we get this level of response after four weeks. Slide 14 shows the individual changes from baseline in PASI at day 42 for each of the individuals in the high-dose category. On the bottom, we have the baseline PASI score, which ranges from as low as 1.2 to 18, reflecting the mild level of disease as measured by PASI that was present in these individuals.
And the reduction continues to improve over the next two weeks, despite stopping dosing and the reduction a day 42 was 21%.
The observed effects on the Patti school was very consistent with the trends observed in these in severity score.
Again, it is very encouraging that we get this level of response after four weeks of treatment.
Slide 14 Jersey individual changes from baseline in Patty day 42 for each of the individuals in the high dose cohort.
On the bottom we have to baseline Patsy school, which ranges from as low as 1.2 to 18.
Reflecting the model level of disease as measured by policy that was present in these individuals.
Duncan McHale: PASI reductions of up to 61% were observed in the EDP 1815 treated patients. So, on slide 15, I'd like to summarize the data that we've presented today. This interim data strongly supports the potential of EDP1815 as a new therapy for patients with mild to moderate psoriasis, and EDP 1815 continues to be very well tolerated.
Patrick reductions of up to 61% were observed in the ATP eighteenfifty treated individual.
So on slide 15, I'd like to summarize the data that we presented today.
This interim data strongly supports that potentially BDP 18, 15, as a new therapy for patients with mild to moderate psoriasis.
ATP 18, 15 continues to be very well tolerated.
Duncan McHale: At two weeks post dosing, the mean reduction in lesion severity score was 24%, and the mean reduction in PASI score was 21%, with maximal observed reductions of 80% and 61%, respectively. EDP 1815 is showing the results we had hoped for as we look to develop an effective, safe, convenient, and affordable medicine for psoriasis. The data from the high- and low-dose cohorts provide a clear rationale for us to advance interface. Slide 16 shows our current plan for Phase 2. This study will be a placebo-controlled trial in individuals with mild to moderate psoriasis and will evaluate clinical benefit, dose, and formulation. The primary endpoint will be a change in PASI score at week 16, which is a slight change from our previous guidance following Key Opinion Leader feedback.
A two weeks post dosing the mean reduction lesions back to school was 24% and the mean reduction in policy school was 21% with maximal observed reductions of 80% and 61% respectively.
ATP 18, 15 is showing the results we had hoped for as we look to develop an effective safe convenient and affordable medicine for psoriasis.
The data from the high and low dose cohorts provide a clear rationale for us to advance interface to.
Slide 16 shows our current plan for phase two.
This study will be a placebo controlled trials in individuals with mild to moderate psoriasis, and we'll evaluate clinical benefit dose and formulation.
Primary endpoint will be a change in pozzi score at week six feet, which is a slight change from our previous guidance following key opinion leader feedback.
In addition, psoriasis, we remain focused on evaluating ATP 18, 15 in clinical trials in other inflammatory diseases as part of our core portfolio strategy.
Duncan McHale: In addition to psoriasis, we remain focused on evaluating EDP1815 in clinical trials in other inflammatory diseases as part of our core portfolio strategy. We anticipate initiating these trials following the interim data from the Phase 2 study. Preclinical data supports the investigation of EDP1815 in diseases such as psoriatic arthritis, axial spondyloarthritis, rheumatoid arthritis, atopic dermatitis, and asthma. Taken together, there are millions of patients that could potentially benefit from monoclonal microbial therapy. Let me now turn the call over to Mark to discuss how we consider these data in the context of our broader platform.
We anticipate initiating these trials following the interim data from the phase two study.
Preclinical data supports investigation, BDP eighteenfifty and diseases, such as so radek arthritis actually has been lost riders rheumatoid arthritis, atopic dermatitis and best.
Taken together there are millions of patients potentially benefit from monoclonal microbial.
Let me now turn the call over to Mark to discuss how we consider these data in the context of our broader platform.
Mark Bodmer: Thanks Duncan. The small intestinal axis fundamentally changes our understanding of how our bodies are regulated. We evolved from our small intestine over hundreds of millions of years, and this evolutionary process has laid down physiological pathways from the intestines to the immune, nervous, and metabolic systems of the whole body.
Thanks Duncan.
The small intestinal axis fundamentally changes our understanding of how our bodies are regulated.
We are both from a small intestine over hundreds of millions of years and this evolutionary process has laid down physiological pathways from intestines, three immune nervous and metabolic systems over the whole body.
Mark Bodmer: Our physiology is controlled by what happens in our small intestine in ways that we have not previously imagined. It turns out that we can create monoclonal microbials whose action on cells within the small intestine has effects throughout the body without a drug needing to be distributed around the body. These two insights, the small intestinal axis and its drugability, are the foundation for Avelo's platform. We are harnessing central biology that has not been targeted by drugs. This is a rare conjunction of profound new biology and drug development with the potential to have even greater impact than antibodies and cytokines.
Our physiology is controlled by what happens on a small intestine and ways that we have not previously imagined.
Turns out, but we can create monoclonal microbials, whose action on cells within the small intestine as effects throughout the body with a drug not needing to distribute the rubber Bobby.
These two insights the small intestinal axis and its drug ability of a foundation for others platform. We are harnessing central biology that has not been targets what drugs before.
As a reference function, a profound new biology, and drug development with the potential to have even greater impact than antibodies insight occurrence.
We've shown over the last three years, a preclinical studies the remarkable pharmacology of oral therapies that act in the small intestine with systemic effects without systemic exposure for the drug.
Mark Bodmer: We've shown in the last three years of preclinical studies the remarkable pharmacology of oral therapies that act in the small intestine with systemic effects without systemic exposure to the drug. Today's interim clinical results demonstrate the effect of the small intestine axis on inflammation in humans and our ability to make medicines which harness this effect. Our continuing research shows that we may be able to extend this new principle beyond inflammation to neurology and metabolism. We have a candidate product for neuroinflammation, which clears inflammatory cells from the central nervous system in preclinical models through its action in the small intestine. We've also begun to screen microbials for metabolic diseases, and we've demonstrated effects on systemic metabolic parameters and weight in preclinical metabolism models. In all of these models, we see a consistent ability of agents acting only in the small intestine to have effects at least comparable to standard of care. We now have the first clinical evidence that this is true for inflammation, which also underpins the potential translation of our preclinical evidence for neuroinflammation and metabolism.
Today's interim clinical results demonstrate the effect of the small intestinal axis on inflammation in humans, and our ability to make medicines, which brought us this effect.
While continuing research shows that we maybe able to extend this new principal beyond inflammation to neurology metabolism.
We have a candidate products when youre inflammation, which clears inflammatory cells from the central nervous system in preclinical models protection in the small intestine.
We've also begun to screen microbials for multiple at diseases, we have demonstrated effects on systemic metabolic parameters of weight in preclinical metabolism models in all of these models, we see a consistent ability of agents acting only in the small intestine have effects at least comparable to standard of care.
We don't have the first clinical evidence. This is true for inflammation, which also underpins the potential translation of our preclinical evidence for newer information and metabolism.
As what does expanding the disease scope, we continue to discover improved ways to engage the small intestinal access with up at central drugs.
Mark Bodmer: As well as expanding the disease scope, we continue to discover improved ways to engage the small intestinal axis with our potential drugs. We are learning how to deliver the drugs to the right part of the small intestine for optimal therapeutic effect, and we have pre-clinical candidate drugs comprising sub-factions of microbes with potencies two to three orders of magnitude greater than whole microbes by weight of drug. There's one final point I'd like to emphasize.
We are learning how to deliver the drugs in the right part of the small intestine for optimal therapeutic effects.
I would have preclinical candidate drugs comprising sub functions of microbes with potency is two to three orders of magnitude writer that whole microbes by weight of drugs.
It was one final point I'd like to emphasize.
Mark Bodmer: Our drug candidates are modulators of cells in the small intestine. The key to their effects is the network connecting the small intestine to the rest of the body. Our medicines have no impact on the microbiome, either in animals or in humans. They are not intended to, and they cannot. They are effective when non-viable. Our approach is much more than a hypothesis; it's evolutionarily, anatomically, and pharmacologically demonstrable, and it has enormous therapeutic potential, which we've only just begun to discover.
Our drug candidates are modulators, upsells and the small intestine the key to their effects is the network connecting the small intestine. So the rest of the body.
Medicines had no impact on the microbiome either in animals or in humans, they're not intended to and they cannot be effective when non viable.
Our approach is much more than apotheosis, it's evolutionarily anatomically and pharmacologically demonstrable, but it has enormous therapeutic potential scope, which we've only just begun to discover.
Simba Gill: Thank you, Mark. Mark highlighted the exceptional work of our scientists here at Avelo to create a platform that has breadth of applicability across inflammatory, neuroinflammatory, metabolic diseases, cancers, and beyond. We are developing medicines with a potentially unparalleled integrated profile of efficacy, safety, convenience, and affordability. Slide 19 shows the unmet need among patients with mild to moderate inflammatory conditions, including psoriasis.
Back to you.
Thank you Mark.
Mark has highlighted the exceptional work of our scientists here at Ovelar to create a platform that has breadth of applicability across inflammatory neuro inflammatory metabolic diseases cancers and beyond.
We are developing medicines with a potentially unparalleled integrated profile of efficacy safety convenience and affordability.
Slide 19 shows the unmet need among patients with mild to moderate inflammatory conditions, including psoriasis.
Simba Gill: With EDP 1815, we aim to create a new market as a midline therapy and defer the use of injectable biologics and other specialty drugs, which can be burdensome to administer and or may not fit the risk-benefit profile for individuals living with more moderate forms of disease. Over time, we expect to expand into frontline treatment and early intervention and offer EDP 1815 as a foundational therapy for millions of people around the world. To that end, we are preparing for our Phase 2 trial and plan to initiate the study in early 2020, with 16-week interim data expected in late 2020. In parallel, we continue to advance our broader pipeline.
With ETP 18, 15, we aim to create a new market as a mid line therapy and to further use of injectable biologics and other specialty drugs, which can be burdensome to administer handle may not fit the risk benefit profile for individuals living with more moderate forms of disease.
Yeah.
Over time, we expect to expand into frontline treatment early intervention and offer ATP 18, 15, as a foundational therapy for millions of people around the world.
To that and we are preparing for a phase two trial and plan to initiate the study in early 2020 with 16 week interim data expected in late 2020 .
In parallel we continue to advance our broader pipeline.
Simba Gill: Again, I want to emphasize the breadth of applicability of our platform and the breadth of the pipeline we are developing, several potential product candidates, product forms, and formulations for the treatment of a broad range of inflammatory diseases and cancers. As we reported in our earnings release this morning, and as you can see on slide 20, we expect a catalyst-rich 2020 with expected data from each of our clinical stage programs, including data with our new formulations of EDP1815 and EDP1066 in atopic dermatitis in the second quarter and first quarter, respectively. We reported a progress update on EDP-1503 in microsatellite-stable colorectal carcinoma this morning and continue to expect to report further data from this study in the first half of 2020. I'd like to conclude with slide 21. We are excited by the interim clinical data for EDP1815 announced today, which, consistent with data from a low-dose cohort, represent striking effects on both the lesional severity score and PASI. We also observed a potential dose response and sustained effect at the high dose.
Again, I want to emphasize the breadth of applicability of our platform and the breadth of the pipeline, we're developing several potential product candidates product forms and formulations for the treatment of a broad range of inflammatory diseases and cancers.
As we reported earnings release this morning, and as you can see on slide 20.
We expect a catalyst rich 2020 with expected data from each of our clinical stage programs, including data with our new formulations of ATP 18, 15, and EGP Tensixty six in a topic dermatitis in the second quarter and first quarter respectively.
We've reported a progress update on ATP 50, no three and microsatellite stable colorectal carcinoma. This morning, and continue to expect to report further data from this study.
In the first half of 2020 .
I'd like to conclude with slide 21.
We are excited by the entering clinical data for ATP, 18, 15 announced today, which consistent with data from a low quote dose cohort represent striking effects on both lesions severity score and Patty.
We also observed a potential dose response and sustained effect at the high dose.
These interim results support the validation of our platform and the potential of approach to deliver an unparalleled profile of effective safe convenient and affordable medicines that can benefit millions of people.
Operator: These interim results support the validation of our platform and the potential of our approach to deliver an unparalleled profile of effective, safe, convenient, and affordable medicines that can benefit millions of people. In closing, I'd like to thank our remarkable team at Avelo for their passion and dedication to our science and our vision. I'd also like to thank the patients and physicians who are participating in our studies. Your trust and support in Avelo are critical for allowing us to advance our vision. We'd now like to open the call to take any questions you may have.
In closing I'd like to thank a remarkable team added fellow for that passion and dedication to our science and our vision.
I'd also like to thank the patients and physicians who are participating in a studies your trust and support into velo are critical for allowing us to advance our vision.
We'd now like to open the call to take any questions you may have.
Ladies and gentlemen to ask a question you will need to press star one on your telephone to.
Operator: Ladies and gentlemen, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.
To withdraw your question press the pound key.
Operator: Please stand by while we compile the Q&A roster. Our first question comes from Connor Meehan with Morgan Stanley. Your line is now open.
Please standby will be compiled acuity roster.
Our first question comes from Konami hand, with Morgan Stanley . Your line is now open.
Hi, This is a decrement on from matters team so.
Vikram: Hi, this is Vikram from Matthew's team. So, two quick questions from our side. First, how does the data that you reported today frame your expectations for the next generation formulation, data from which is expected starting next year? And then, secondly, would you ever consider an active comparator study? versus therapies that are currently on the market.
Two quick questions from our side.
First.
How does the data that you reported today.
Frame your expectations for the next generation formulation.
For which the expected starting next year and then secondly, you ever consider an active comparator study.
15 versus therapies that are probably on the market.
Simba Gill: Thanks, Vikram. Let me take the first question, and then I'll let Duncan take the second. So, in terms of new formulations, just to remind everybody, we reported a short while ago that in preclinical data, we have a novel formulation that shows up to 30-fold improvement in activity. And what we are now planning on doing is going forward in the Phase II studies with 1815, comparing the efficacy of 1815 with the novel formulation to the efficacy that Duncan summarized earlier with our existing formulation. So that will be the first part of our Phase 2 study. Obviously, given the positive data that we've seen with the existing formulation and the fact that, in preclinical data, again, we had a 30-fold improvement in activity, we're optimistic about what we will see in Phase 2 as we compare the different formulations. So, on the second question, Duncan, where would you like to answer?
Yeah.
Thanks for growth.
Let me take the first question and then I'll flip Duncan take the second so in terms of new formulations, just to remind everybody. We reported a short while ago that in preclinical data. We have a novel formulation that shows up to 30 fold improvement in activity.
And what we're now planning on doing is going forward in the phase two studies with 18 15 comparing.
Efficacy of 18 15 with the novel formulation with the efficacy the Duncan summarized earlier with our existing formulation.
So that.
We'll be the first part of our phase two study obviously given the positive data that we've seen with the existing formulation and the fact that in preclinical data again, we had a 30 fold improvement in activity well optimistic about what we will see interface to as we compare the different formulations.
So on the second question Duncan where would you like to answer yes. The question about the active comparator.
Duncan McHale: Yes, the question about the active comparator. As is usually the case in early development, we're focusing very much on demonstrating the clear clinical benefit of EDP1815. As we move through development, we will bring in active comparator at the appropriate time point.
Usually the case in early development, we're focusing very much on demonstrating the clear clinical benefit VTP 18, 15, as we move through development, we will bring in active compared to the appropriate time point.
Okay. Thank you.
Vikram: Okay, thank you.
Simba Gill: Thanks, Riku.
Thanks, Rick.
Operator: Our next question comes from Chris Shibutani with Cowen. Great, thank you very much. We appreciate this update.
Our next question comes from Chris Shibutani with Cowen. Your line is now open.
Great. Thank you very much we appreciate the update can you just remind us what.
Chris Shibutani: remind us what kind of expectation we should have. You describe the new formulation as having a 30-fold improvement in activity, and it seems certainly from the data that you've updated us with that we're seeing some evidence, as you describe, of dose response and sustained effect. So when we think about anticipating what the data may look like for the new formulation, can you maybe quantify to some extent, if in ranges at all possible, where you think that incremental benefit may be? What is your hypothesis? Should we see greater depth of responses? Or should we see quicker onset? And then as a follow-up to that question on the timing, if your time points at which you're measuring your endpoints for the various studies have been moving around, can you help us understand the rationale for the most recent update, in particular why you're choosing to measure PASI where you are now, which contrasts with your August analyst meeting? Thank you.
End of expectation, we should have you you described the new formulation is having a 30 fold improvement in activity and it seems certainly from the data that you've updated us when that we're seeing some evidence as you described of dose response and sustained effect. So when we think about.
Anticipating what the data may look like for the new formulation can you maybe quantify to some extent efrain ranges and all possible, where you think that incremental benefit may be what is your hypothesis should we see greater depth of responses should we see quicker onset.
And as a follow up to that question on the timing if your time point at which are measuring your endpoints for the various studies has been moving around can you help us understand the rationale for the most recent updates in particular, while you're choosing to measure policy, where you are now which contrasts from August analyst meeting. Thank you.
Simba Gill: Thanks Chris. I'll let Mark answer the first question and then Duncan answer the second.
Thanks, Chris I'll, let mark onto the first question then then Dunkin' the second.
Mark Bodmer: So Chris, hi, it's Mark. So there are two parts to the preclinical formulation story. One is that the reformulation gives us
Criticized mark so two parts to the preclinical formulation story, one is that the re formulation gives us.
Mark Bodmer: greater depth of efficacy at lower doses. So, as Simba said, with the underpinning of the effect that we're seeing in the current formulation, one thing this will do is to move us down the dose-response curve, and the other thing it has the potential to do is to improve the depth and duration of responses. Just to be specific about our understanding of the biology of this, what we find now very clearly in preclinical models is that the higher up the small intestine, particularly in the duodenum, we can release Ebolus with the drug, the more potent the effect is. This has been our hypothesis for some time about how this would work, and it's very clear that that's the case. So, the fact that the current formulation is effective with its release profile compared to the new formulation, which will give us the release high up in the duodenum, if we continue to get translation from animal models preclinically to the clinic as we've seen it before, sets an expectation or an aspiration that we will see these effects on dose-response and depth of efficacy as we take the new formulation into clinical trials.
Great to death of efficacy at lower doses, So Super said with the underpinnings of the effect that we're seeing in the current formulation. One thing. This will do is to reduce down the dose response curve.
The other thing it has potential to do is to improve the depth and duration of responses just to be specific about our understanding of the biology of this what we find now very clearly in preclinical models is the higher up the small intestine.
Typically in the duodenal, we can release a bolus of drugs.
The effect is this has been our hypothesis.
For some time about how this would work of its very clear, but thats. The case. So the fact of the current formulation is effective with its release profile compared to the new formulation, which will give us the release higher up the dudina. If we continue to get translation from.
Animal models Preclinically to the clinic as we've seen it before.
That's an expectation or what aspiration.
We will see these effects on those response adaptive efficacy as we take the new formulation into clinical trials.
Simba Gill: Thanks Mark. Yeah, just before handing over to you Duncan, just to be clear Chris on your question, just wanted to emphasize that the current formulation, as we've just described, is driving very positive clinical data. So we were very pleased with that formulation, and a new formulation basically represents something but is unexpectedly positive, but we're feeling very good about the current formulation.
Thanks, Mark just before any of you Duncan just to be clear Chris on your question, but just wanted to emphasize at the current formulation.
We've just described is driving very positive clinical data. So we where we're very pleased with that formulation and the new formulation basically represent something.
But.
His unexpectedly positive, but we're feeling very good about the comp formulations.
Duncan McHale: With regard to the endpoints, we haven't changed the primary endpoints at all for the Phase 2 study. This is always going to be PASI, the reason to do the lesional severity score in 1B.
Doug when we've got the endpoints because we havent changed the primary endpoint tool for the phase two study. It is always going to be highly the reason to delusional severity score and it won't be study as we said previously is just the sensitivity given the short dosing period.
Duncan McHale: Right. No, I realize that the endpoints have not changed. I meant the time point at which you measure them, I think, has been modified. And you described it as being based upon KOL feedback, but help us understand what's driving that decision.
No I realize what the endpoint have not changed I meant the time point at which you measure them. I think has has been modified and you describe it as being based on care, while feedback, but can help us understand what's driving that decision show. So yes. The original 12 week into an endpoint based on key opinion leader feedback and precedence with other anti inflammatory age.
Duncan McHale: So, yes, the original 12-week interim endpoint, based on key opinion-led feedback and precedent with other anti-inflammatory agents, the 16-week time point is probably a better time point to fully understand the clinical benefit of EDP1815. And by taking individuals out to 16 weeks before the interim, there's little additional benefit of going out to 24 weeks. So we'll use 16 weeks as our primary endpoint. The key opinion-leader opinions were in line with ours there, and, in addition, going out to 24 weeks with placebo was felt to be a challenge from a recruitment perspective. So primarily, it's because 16 weeks is a much clearer time point to understand the full clinical benefit of EDP1815 rather than 12 weeks.
And.
The 16 week time point is probably a better time point to fully understand the clinical benefit of GDP 18 15.
Taking a individuals out to 16 weeks before the end trim, there's little additional benefit going up to 24 weeks. So we'll use 16 weeks as our primary endpoint. This is keeping Anita opinions were in line with Al is there and in addition, going out to 24 weeks with placebo with.
Well to be challenged from a recruitment perspective, so primarily it's because 16 weeks is a much clear at time point to understand the full clinical benefit really dating 15, rather than 12 week.
Duncan McHale: And is that 16 weeks at all vetted against any discussions with regulators? Thank you.
And is that 16 weeks at all vetted against any discussions with regulators. Thank you.
Okay.
Duncan McHale: 16 weeks is a well-accepted end point. We're obviously in the process of discussing it with regulators right now, but that hasn't been an issue at all because it's well-accepted with precedented molecules.
16 weeks is a well accepted and point, we obviously in the prices of discussing with regulators right now, but thats not seen been Ed issue at all because it's well accepted with precedented molecule.
Chris Shibutani: Great. Congratulations on the updates. Thanks, Chris. Our next question comes from Nassan with BMO Capital. Your line is now open. Hey guys, congratulations on the data. I have two questions from me.
Great Congrats on the uptake.
Nice.
Our next question comes from Nelson with BMO Capital. Your line is now open.
Hey, guys.
Congratulations on the data HM.
Two questions from me.
Nassan: Learning from the psoriasis data updates, how does it inform you for atopic dermatitis? Are we also going to be, you know, getting, should we also anticipate..., reporting of a component of EZ or atopic dermatitis because, you know, there's also a lesion security score included within EZ. And then a second one is... We have seen a signal for a longer duration of benefits post-dosing at a higher dose. Does this open up the possibility of extending the final treatment protocol from daily oral to maybe once a week? Thanks.
Learning from the Horizon data update how how does that inform you for atopic dermatitis also going to be.
Getting should we also anticipate.
Reporting of a component of easy or atopic dermatitis Uh huh.
There's also a lesions security score included within easy.
And then second one.
Yes.
We have seen a.
Signal for a longer duration of benefits.
Dosing at a higher.
The possibility of extending the final treatment protocol from daily oral to maybe you know they like once weekly.
Simba Gill: Thanks. So, there are a number of questions. Let me frame your first question, and I'm going to let Mark expand on that, and then I'll let Duncan answer the two clinical questions. So, in terms of how this data with 1815 and psoriasis informs what we're doing in atopic dermatitis, the highest-level point, which I'd like Mark to expand on, is that what we've now shown in two independent clinical studies is positive data, not just for psoriasis, but actually for the central notion of the small intestinal axis and our ability to create a new So the first thing is that a few years ago when we started the company, it was just an idea.
Thanks, So number of questions let me.
Frame. Your first question I'm going to let mark expand on that and then I'll, let dunkin' us onto the budget clinical related question. So in terms of how does this stage with 18 Fifteenand psoriasis inform on what we're doing in a topic dermatitis, the highest level point, which are like mark to expand on is that what we've now shown into.
Independent clinical studies.
Is positive data.
Not just for psoriasis, but actually for the central notion.
All the small intestinal access and our ability to create a new Clos all medicines that acts on the small intestinal access. So the first thing is that a few years ago. When we started the company was an idea.
Mark Bodmer: Most people did not accept the hypothesis. There was lots of confusion with what I would call classical microbiome, eco-biotic approaches, which are not what we are. But what we've now done is very importantly shown that the principle works not just preclinically but clinically in two independent studies. So the most important part of the validation is around that central thrust of the small intestinal axis, which has application and relevance across all inflammatory diseases. So we've shown again, I'm emphasizing this because it is a core point that we can deliver single strains of microbes in relevant formulations to drive systemic therapeutic effects, the highest level and most important point in terms of the relevant biology linking psoriasis and atopic dermatitis and additional points. I'll hand over that set of questions to Mark, and then Duncan can answer your clinical questions.
Most people.
Did not except the hypothesis there was lots of confusion with what I would call classical Microbiomes eco biotic approaches, which is not what we all but what we've now done is very importantly shown that the principal works not just preclinically, but clinically in two independent studies. So the most important part of the validation is around that central for.
So the small intestinal access which has application and relevance across all inflammatory diseases.
So weve shown again I'm emphasizing this because it is a call point that we can deliver.
Single strains of microbes in relevant formulation to drive systemic therapeutic effects.
That.
Is the highest level and most important point in terms of the relevant biology, linking psoriasis, NATO dermatitis and additional points I'll hand over that.
Set of questions the Mark.
And then Duncan can answer your clinical point, so given the reach from a small intestine.
Duncan McHale: So given the reach from the small intestine to other parts of the body, such as the skin here, there are a couple of points in the biology that we understand preclinically about this that we expect to translate. The first is that we've simply looked at relevant models of both Th17 biology in support of psoriasis studies and Th2 biology in support of atopic dermatitis and actually a range of other atopic March diseases, and we get effects in both types of models, which indicates that we're getting broad inflammation resolution across multiple pathways. Another comment to make is that although psoriasis and atopic dermatitis are described as distinct, one being Th17 and the other being Th2, in reality, these dermatological conditions exist on a spectrum.
Two other parts of the body the scheme here there a couple of points on the biology that we understand preclinically about this we expect to translate the first is simply we've looked at relevant models or both th 17 biology in support of psoriasis studies, and CH to biology and support they topic dermatitis and that's the range of other right.
Topic March diseases, and we get effects on.
Both types of models, which is indicating that we're getting a broad inflammation resolution across multiple pathways. Another comment to make us, although psoriasis and they topic done as tight as I've described as distinct one being th 17, the other being th two in reality bitterness of logical conditions exist on a spectrum.
Duncan McHale: And actually, we think it's one of the strengths of this approach that we're not pathway limited, that we're getting coordinated resolution of multiple inflammatory pathways. So the two parts of the answer to your question, one is that we have direct preclinical evidence, but secondly, for the reasons that Simba said and also for the reasons of the spread biological boundaries between these diseases, the psoriasis data will have some predictive value for the atopic dermatitis clinical studies to be determined by the outcomes of the studies that we're doing at the moment.
Actually we think it's one of the.
Strengths of this approach that we're not pathway limited that we're getting coordinated resolution of multiple.
Inflammatory pathways. So the two partially answered your question one because we have direct preclinical evidence, but secondly, we expect both for the reasons assemble said and also for the reasons of the spread biological boundaries between these diseases.
That the psoriasis data have some predictive value for the atopic dermatitis clinical studies.
We determined by the outcomes. The studies were doing at the moment textbook Saddam the two questions on clinical what are we going to measure in atopic dermatitis relevance of leasable schools and easy.
Duncan McHale: So Duncan, two questions on clinical. What are we going to measure in atopic dermatitis, the relevance of lesional scores in easy measures, and then would we move to once-a-week dosing with these two questions?
Measures and then would we move to once a week dosing with the two questions.
Duncan McHale: Yes, with regard to the clinical endpoints, we will, you know, we're measuring easy score at an IGA. They're well-documented.
Yes with regard the clinical endpoints, we will you know we're measuring EASI score at an idea that well precedented kinetics of response to atopic dermatitis quicker than psoriasis. So we expect to see responses within these clinical scores across the 28 day period. So those are going to be the key endpoints.
Duncan McHale: The kinetics of response to atopic dermatitis is actually quicker than psoriasis, so we expect to see responses within these clinical scores across the 28-day period. So those are going to be the key endpoints for us. With regard to the dosing period, I think what is probably more important, rather than thinking about an unusual dosing period, which is once a week, the intent here is that EDP-1815 or another monoclonal microbial that works in atopic dermatitis or psoriasis will be dosed daily. However, what it looks like we've got is a forgiving therapy, so that means that individuals can So from a patient perspective, that's a really important aspect. It makes it very patient-friendly. So rather than thinking about once a day or once a week, this will be a daily therapy, but it will be a forgiving therapy. So for those of us who forget the odd dose, it will not get rid of the clinical effect.
For us we've got the dosing period, I think what is probably more important rather than thinking about an unusual dosing period is once a week.
The intent here is that every 18 15 or another monoclonal microbial works in atopic dermatitis, a psoriasis will be dose daily however, what it looks like we've got as a forgiving therapy. So that means that individuals can forget the odds dose and that will.
Not abrogate the clinical response from patient perspective, that's a really important aspect. It makes it very patient friendly so rather than thinking about once a day. This once a week this will be a day therapy, but it will be a forgiving therapy. So for those of US you forget the dose it will not get rid of the clinical effect.
Very helpful. Thank you.
Nassan: Very helpful, thank you. Thank you. As a reminder, ladies and gentlemen, to ask a question at this time, that's star, then one. Our next question comes from Chris Howerton with Jefferies. Your line is now open.
Thank you.
As a reminder, ladies and gentlemen to ask a question at this time that Star then one.
Your next question comes from Chris Howerton with Jefferies. Your line is now open.
Great.
Operator: Again, congratulations on the data, and thanks for taking the questions. I think, you know, a lot of them have been asked at this point. But maybe on the psoriasis data, you know, did you notice any body region effects? Like, were there certain areas that seemed to be affected more or less than others? And in addition to that, maybe you could help us understand how the focal lesion for the LSS score was initially determined. And then I also have one other question.
Again, congratulations on the data and thanks for taking the questions. I think you know a lot of than had been asked at this point, but.
Maybe on the psoriasis state.
Did you notice any body region effects like was there are certain areas that seem to be affected more or less than others and in addition to that maybe you could help us understand how the focal lesions for the Lss score was initially determined and then also had one other question.
Chris Howerton: So, as you're straightforward, so as the non-clinical CEO, I will answer just because they're straightforward questions.
So as you straight forward so as a nonclinical feel I will answer just because the straightforward question. So.
Simba Gill: We did not see any particular body area specificity or anything along those lines. We're not reporting on it in any more detail right now, but the answer is no. And then the primary lesion was chosen by the principal investigator at the time of enrollment in the study, and in general, they picked the most severe lesion as a general principle.
We did not see any particular 40 area specificity or anything along those lines, where we're not reporting on any more detailed right now the balances.
No.
And then the primary lesion was chosen by the principal investigator at the time of enrollment in the study and in general they picked the most severe lesion.
General principle.
Simba Gill: Okay. Okay, great.
Okay. Okay, Great and then I think obviously had a lot of discussion with respect to the new formulation and I'm thinking about that and I guess my two questions with respect to that would be you know how are you thinking about translation of dosing prime the current formulation to the new formulation.
Chris Howerton: And then, you know, obviously, there was a lot of discussion with respect to the new formulation and thinking about that. And I guess my two questions with respect to that would be, you know, how are you thinking about translating dosing from the current formulation to the new formulation, particularly, I think, in Cohort A of your planned psoriasis Phase 2a trial? And then the follow-up to that would be, is there any significant difference in terms of cost of goods you would expect between the two formulations or differences in processes that would make one or the other more or less amenable to CMC under GMP conditions?
Particularly I think in cohort.
Your planned psoriasis phase two a trail.
And then the follow up to that would be is there any significant change difference in terms of cost of goods you would expect between the two formulations or differences in processes that would make one or the other more or less amenable to CMC under GNP conditions, Yeah, Let me take it from a vessel relative first and I'll, let Duncan and so the question in terms of dosing trial.
Simba Gill: Yeah, let me take it in reverse order. I'll take it first, and then I'll let Duncan answer the question in terms of dosing translatability. So, again, just going up a level on your question, Chris, related to the cost of goods. I actually appreciate it, actually, because one very important point we've always emphasized is that our goal is to develop effective, safe, oral, convenient, and affordable medicines. We're able to make that last claim, which is somewhat unusual for a biotech company for a number of reasons.
Great ability. So again, just going off of level on your question, Chris related to cost of goods appreciate it actually because.
One very important point, we've always emphasized is our goal is to develop.
Active safe oral convenient and affordable medicines, we're able to make that loss claim.
Somewhat unusually for a biotech company for a number of reasons one is linked to cost of goods.
Duncan McHale: One is linked to cost of goods, so we're already at a stage where we can develop our products within the range of small molecules, very unusual for a biotech platform that is this potentially transformative if we compare ourselves, for example, to cell therapies, cell and gene therapies at the other end of the spectrum. So our cost of goods, whatever the formulation is, will be very low. The new formulation certainly offers the potential, because we have something, as I said, that's 30-fold more potent in preclinical studies, to drive an equivalent effect with up to a 30-fold less active ingredient, which would have knock-on consequences on the cost of goods and drive it even lower. But we're not overly concerned about the cost of goods at this stage. It may help us in terms of... and so on in terms of driving patient compliance with less and less tablets, for example. But we're not worried about the cost of goods. It would be an advantage to have FEDPA. Duncan, do you want to do this about diversity and transparency?
So we're already at a stage, where we can.
Extrapolate to likely cost of goods at scale.
Within the range of small molecules.
Very unusual for biotech platform that is this potentially transformative if we compare ourselves for example, the cell therapies.
Selling gene therapies that the other end of the spectrum. So our cost of goods whatever the formulation is will be very low.
The new formulations certainly offers the potential because we have something as I said, that's 30 fold more potent in preclinical studies to drive equivalent effect with up to 30 fold less.
Active ingredient, which would have a knock on consequences of cost of goods and drive even lower but we're not we're not overly concerned about a cost of goods at this stage. It may help us in terms of.
Formulations and so on in terms of driving to patient compliance with less and less tablets. For example, but we're not worried about cost of goods. It would be an advantage having said that.
Dr. Do you want to the dosing translatability in terms of the dosing translatability for the phase two study we used the same total cell count.
Duncan McHale: In terms of the dosing translatability, for the Phase 2 study, we used the same total cell count for each formulation, so the total cell count's the same, and we used two different formulations, and we used the proposal to use the high-dose dose that we used in EDP1815-101.
For each formulation so to tell us out cancer say.
We use the two different formulations and we'll use the proposal minutes use the high dose.
Dose that Weve used in ATP 18, 15 101.
Okay, Okay, great and maybe if you don't mind, but maybe I just missed heard but I I felt like you said that you provided an update on 15 or three today did I hear you wrong I just wanted to double check that.
Chris Howerton: Okay. Okay, great. And maybe, if you don't mind, Siva, maybe I just misheard, but I felt like you said that you provided an update on 1503 today. Did I hear you wrong? I just wanted to double check.
That.
Simba Gill: There is an update in the press release, so just a quick summary of that. Essentially, what we've reported today is that we have completed enrollment in the cohort of patients with microsatellite stable colorectal carcinoma, a reminder that those are late-stage patients who have failed all previous therapies. And a reminder that late stage metastatic renal cell carcinoma is, I'm sorry, colorectal is otherwise non-immunologically responsive, and there are no effective treatments, unfortunately, today. We have not seen any clinical responses that are evident.
There is an update in the press release.
So just quick summary of that are essentially what we reported today.
Is that we have completed enrollment all the cohort of patients with microsatellite stable colorectal carcinoma. A reminder, that those are late stage patients who have failed all previous therapies.
I never mind.
That.
Late stage metastatic renal cell carcinoma is.
Oh, sorry, colorectal is otherwise known immunologically responsive and I know effective treatments. Unfortunately today, we have not seen any clinical responses that are evident.
Simba Gill: We did see several patients in the cohort who experienced extended stable disease, and we've also observed cellular infiltration biomarkers, which we took from biopsies in the relevant patients after monotherapy with EDP-1503, which are consistent with the preclinical observations we saw with EDP-1503. A reminder that it's a combination study. There's a monotherapy run-in window of two weeks from time of diagnosis, and then the patients go on a full combination study. So when we look in that monotherapy window, we biopsy at time of diagnosis, we biopsy again after the monotherapy run-in, and we can look at relevant data there. So we continue to monitor patients in this cohort, and you can expect further updates as we go forward. The other update we made was that given the newly approved treatments for triple negative breast cancer, which you'll be familiar with, we're anticipating that the majority of triple negative breast cancer patients that we recruit as we go forward will have relapsed following prior PD-1, PD-L1 therapy, so a similar type of dynamic to the PD-1 relapse cohort that we're already recruiting as well. So those were the updates. We remain on track for further data release in the first half of 2020, Chris.
We did see several patients in cohort we've experienced extended stable disease.
And we've also observed cellular infiltration biomarkers, which.
We've taken from biopsies in the relevant patient off to monotherapy with ETP 15, or three which are consistent with the preclinical observations we saw.
With ATP 15 of three a reminder, that it's a combination studies as a monotherapy running windows two weeks.
Some time of diagnosis and then the patients go on full combination study. So when we look in that monotherapy window, we biopsy atomic diagnosis biopsy again after the monotherapy running and we can look at.
Relevant data that so we continue to monitor patients in this cohort.
And.
You can expect further updates as we go forward.
The other the update we made was that given newly approved treatments for triple negative breast cancer.
Would you be familiar with were anticipating the majority of triple negative breast cancer patients that we recruit as we go forward, we'll have relapse following prior PD one PDL one therapy. So the similar type of dynamic to the PD, one relapse cohort that were already recruiting as well. So those were the updates we were.
Remain on track for for the release of data in the first half of 2020 Chris.
Chris Howerton: Okay, all right. Well, thank you very much for the clarification, and I'll hop back in the queue. Thanks. Thanks, Chris.
Okay, all right well. Thank you very much the transition clarification excuse me no I'll hop back in queue. Thanks, Thanks, Chris.
Chris Howerton: Thanks, Chris.
Operator: And again, ladies and gentlemen, that is star then one if you would like to ask a question at this time. I'm showing no further questions in queue at this time. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Thank you very much, everyone.
I think and ladies and gentlemen that is star then one if you would like to ask a question at this time.
I'm showing no further questions in queue at this time.
Ladies and gentlemen. This concludes today's conference call. Thank you for participating you may not very much or thank you.