Earnings Transcript for KLDO - Q1 Fiscal Year 2020

Operator: Ladies and gentlemen, thank you for standing by. And welcome to Kaleido Biosciences Conference Call and Webcast. At this time, all participants are in listen-only mode. I would also like to remind you that this call is being recorded for replay. I will now like to turn the conference over to, Amy Reilly, Kaleido's Vice President of Communications and Investor Relations. Please go ahead.

Amy Reilly: Thank you, operator, and good morning, everyone. Welcome to Kaleido's conference call and webcast. Press releases from this morning and a short presentation relating to this call are available in the investors and media section of our website. With me for today's call are Mike Bonney, Executive Chair of Kaleido; Alison Lawton, President and Chief Executive Officer; Dr. Kate Knobil, Chief Medical Officer and Head of R&D; and Will Duke, Chief Financial Officer. After our prepared remarks, we will open the call for questions. Before we begin, let me remind you that on today's call, we will be making forward looking statements covered under the Private Securities Litigation Reform Act of 1995. These statements may involve risks and uncertainties that could cause actual results to differ from expectations and are described more fully in our filings with the SEC, which are also available on our website. In addition, all forward looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. As you may be aware, Kaleido does not typically hold conference calls concurrently with quarterly financial results. However, given the number of topics to review today and their timing with quarter end, we decided this is the most appropriate forum for discussion. Going forward, we intend to host calls and webcast as appropriate based on news flow and clinical data. I will now turn the call over to Kaleido’s Executive Chair, Mike Bonney.

Mike Bonney: Thank you, Amy, and good morning to everyone. First, our thoughts are with those affected by the COVID-19 pandemic. And we are grateful to offer the healthcare workers and those that support them for their selfless efforts to support patients during this challenging time. It is important to note, that the safety of patients, healthcare professionals and our employees remains our top priority during these challenging times. On the call this morning, Alison and Kate, our Chief Executive Officer and Chief Medical Officer and Head of R&D respectively will discuss one of the most exciting and compelling opportunities, I've had the privilege to be part of in my nearly 40 years in the biopharmaceutical industry, the initiation of the COVID-19 clinical program, utilizing our product candidate KB109. The aim of the clinical program is to determine if this MMT KB109 can alter the course of the disease in a newly diagnosed mild to moderate cohort of patients infected, KB109 specifically are well-suited for this endeavor. Product platform in KB109 specifically are well-suited to this endeavor. We are thrilled to be part of a worldwide effort to better understand and moderate the course of this drug data in the fourth quarter of this year, hurls a broader move to explore the impact of various MMT’s on diseases involving immune and inflammatory pathways. Another product candidate from our library, KB295 will be studied in a clinical trial of ulcerative colitis. We expect data from that clinical trial in mid-2021. This new set of strategic priorities adds to our work in UCD and had encephalography with KB195 and KB174, respectively. Now over to Alison for more details on the rationale and study design for these exciting new clinical trials. Alison?

Alison Lawton: Thanks, Mike. COVID-19 -- unprecedented global impact on health and healthcare facilities. We continue to adapt our work to help prioritize safety of employees, patients, and clinical staff. And we understand the need to study sites to limit certain activities in light of the ongoing pandemic. We are fortunate with our product platform and efficient discovery and development, that Kaleido has both the opportunity and flexibility in responding to these developments. And in fact, we're uniquely positioned to advance the number of pipeline programs, for which we expect to deliver data over the next 18 months. The burden of COVID-19 pandemic evolve and there remains an opportunity for inspectional studies in patients with mild-to-moderate disease, a population which represents the majority of those infected. There is also a need for a convenient, orally administered, well-tolerated product that has the potential to augment the patient's own immune system to fight the immune-mediated pathology of this disease, and avoid more serious complications of the infection and proper civilization. We are initiating two non-IND controlled clinical studies of our MMT KB109 that are designed to evaluate the effects of Supportive Self-Care plus KB109 compared to Supportive Self-Care alone in patients with mild-to-moderate COVID-19 infection who are not hospitalized. The program includes both a multi-center study of approximately 350 patients and the second study of approximately 50 patients, which will also evaluate the composition and metabolites of the patient's microbiome. In both studies, patients will be randomized to either receive Supportive Self-Care, the control group or Supportive Self-Care plus KB109 for two weeks and then we'll be followed for three weeks. These studies will include assessments of clinical outcomes, health care utilization, and biomarkers of the inflammatory response that may also help inform the potential of KB109 in other viral respiratory and bacterial infections. We look forward to initial top-line results from the multi-center study in Q4 of this year. KB109 highlights the flexibility of our MMT platform. MMTs like KB109 are designed to drive the function and distribution of the microbiomes existing microbes in order to decrease or increase the production of metabolites and through advantage or disadvantage certain bacteria in the microbiome community. MMT candidates are targeted, synthetic glycans that are orally administered, have limited systemic exposure, and then selectively metabolized by enzymes in the microbiome set. These characteristics of MMT enabled an efficient clinical development path, which allows us to move candidates rapidly from discovery into clinical studies under regulation supporting research with food. Strong scientific rationale and data generated to-date with KB109 has the flexibility of this path has enabled us to move quickly into an area of high unmet medical need. I will now turn the call over to Kate Knobil, our Chief Medical Officer and Head of R&D for additional details on the COVID-19 clinical studies and the scientific rationale behind this new program.

Kate Knobil: Thanks, Alison. We are delighted to be collaborating with the University of Massachusetts Medical School and Center for Microbiome Research on our COVID-19 program, along with a number of other clinical centers in the United States. As you've just heard, the two studies will enroll approximately 400 outpatients with mild to moderate COVID-19, who will be randomized to either, Supportive Self-Care or Supportive Self-Care plus KB109 orally for two weeks, followed by three weeks to follow-up. In addition to assessing safety and tolerability, patients will monitor objective measures, such as temperature and oxygen levels, and participate in telemedicine visits with clinicians. We will also be collecting data on clinical outcomes, healthcare utilization and biomarkers of the inflammatory response that may help inform the potential of KB109 and other respiratory viral infections, and more broadly on the impact of MMTs on the immune system. The study of approximately 50 patients has a similar study design, but will also evaluate changes in the composition and metabolic output of the patient's gut microbiomes. The data and scientific rationale for evaluating KB109 and COVID-19 are compelling. This infection has been associated with activation of an inappropriate inflammatory cascade, which in some patients can cause an abnormally aggressive immune response that can lead to pneumonia and respiratory failure. Increased short chain fatty acids, which are created by fermentation of glycans by the gut microbiome have been shown in preclinical models to influence immune pathways and mitigate immune pathology associated with severe respiratory viral infections, including reducing mortality from lethal influenza virus infection. These studies have also demonstrated that short chain fatty acid producing taxa induce virus specific CD4 and CD8 T cell and antibody responses involved in the reduction of the severity of viral infection, as well as influencing macrophage functionality to mitigate neutrophil-mediated tissue damage. There are also human data to support the role of short chain fatty acids in reducing the impact of viral infections. In patients undergoing Hematopoietic Stem Cell transplants, who have contracted respiratory viral infection, including coronavirus. The presence of short chain fatty acid producing taxa has been associated with a significantly reduced risk of progression to lower respiratory tract infections, which could have significant morbidity in this patient population. MMTs, our novel glycans that are synthesized to enable precise modulation of the taxonomic composition of the gut microbiome, as well as its metabolic output. Specifically, MMTs promote a beneficial short chain fatty acid profile in the gut and promote the growth of taxa that have the potential to support the hosts ability to mount an appropriate immune and inflammatory response, while also preventing an over aggressive hyper-inflammatory state up to and including cytokine storm. KB109 was selected for evaluation in the COVID-19 clinical program, based on its demonstrated ability ex-vivo to increase the production of short chain fatty acids, as well as promote commensals while reducing pathogenic bacteria. We're looking forward to the initial topline data from this important program in the fourth quarter of this year. Alison, back over to you.

Alison Lawton: Thanks Kate. With the priority that KB109 re-forces on the COVID-19 program, Kaleido has elected to pause the tour of clinical study of KB109 in patients colonized with multidrug resistant pathogens. We are evaluating next steps for pathogens program, including a future potential clinical study in a patient population higher risk of infection, such as in patients undergoing hematopoietic stem cell transplant. Beyond KB109, we're expanding our efforts with our immune mediated and inflammatory diseases. To further understand, the potential application of our MMT platform. We plan to initiate a clinical study, evaluating a new MMT candidate, KB295, in approximately 30 patients with mild-to-moderate ulcerative colitis or UC. UC is linked to microbiome dysbiosis and microbiome restoration has been shown to the clinical remission and patient. Short chain fatty acids are consistently observed as down regulated in UC patients. Clinical studies administering uneven glycan have demonstrated an improvement in activity UC associated with an increase in short chain fatty acids. KB295 has shown an ability to increase production of short chain fatty acids, while also reducing the presence of inflammatory bacteria such as enterobacteriaceae also linked to UC. Patients in a single site study will be evaluated over 66 days of treatment, and 14 days of follow-up. We will be looking at safety and tolerability as well as impact on the Simple Clinical Colitis Activity Index. Exploratory endpoints includes changes in microbiome taxa, short chain fatty acid levels in stool, and serological biomarkers of inflammation. We've been working closely with the European sites of study and incorporating remote monitoring into the designs and along with the recent IRB approval of the protocol, we are confident we have -- we will have the topline results in the middle of 2021. Turning now to KB195, which is currently being evaluated in a phase 2 clinical trial called UNLOCKED in patients with urea cycle disorder, who are inadequately controlled on standard-of-care. Given limitations on patient visits and the impact of COVID-19 on new patient enrollment, we now anticipate that data from this study will most likely be available in the second half of 2021. More than 20 sites are currently activated in eight countries and we have submitted an amendment to expand the eligibility age criteria for enrollment patients age 12 instead of previously 18, and up to the age of 70, instead of previously 65. With respect to our KB174 program in hepatic encephalopathy, we are ready to initiate the next clinical study in patients with this disease. However, the study initiation is dependent on partnering the program and the resolution of COVID-19 impact at trial site. In addition to our clinical programs, we have a number of preclinical programs where we expect a clinical-ready, lead MMT to identify in 2021. This will position us well for either potential partnerships or to begin new clinical program. With our immuno-oncology program, our goal is to identify MMT candidates that stimulate the targeted therapeutic response to immune checkpoint inhibitors in response to preclinical models. We are collaborating with Gustave Roussy, a leading center for oncology immunotherapy in Europe and anticipate the selection of lead compounds based on data from our preclinical work in Q4 of this year. We also plan to have preclinical data from validated models of additional immune-mediated diseases that will identify new clinical ready lead MMT candidates in the first half of 2021. And we continue preclinical work for our cardiometabolic and liver disease programs are on track for results from validated models in Q4 2020. Before we take questions, I want to mention that we ended the first quarter with $53.8 million cash on hand and we continue to manage our operating expenses in line with our pipeline priorities. And as a result, we extended our cash runway further into the first quarter of 2021. The next 18 months are very important for Kaleido, as we continue to translate promise of the microbiome’s solutions for patients. We look forward to key upcoming data milestones, including clinical results for KB109 COVID-19 study in Q4, results from our KB295 study in UC in mid 2021 and our phase 2 clinical results from our KB195 study in UCD in the second half of next year. Now I'd like the operator to open up the call for your questions.

Operator: Thank you. [Operator Instructions] Our first question comes from the line of John Newman with Canaccord. Your line is now open.

John Newman : Hey, guys. Good morning. Thanks for taking my question. It's very interesting. I wondered if you could talk to us a little bit more about what you've learned regarding the inflammatory pathways associated with COVID? And how your asset 195, -- excuse me, 109 can be affected there?

Alison Lawton: Yes. Good morning, John. It's Alison. So, great question. I think Kate covered it a little bit in her comments, but I'll ask her to comment some more. Just to summarize, you know, there is a number of pieces of evidence in preclinical models showing the link between the microbiome and short chain fatty acid production. And also just to remind you that short chain fatty acid production is a result of fermentation of glycan in the gut and the link between this and different immune pathways in infections associated with viral respiratory infections. So Kate maybe you want to talk to us a little bit more about the evidence that we have. And then we can comment on KB109 characteristics.

Kate Knobil : Yes. Thanks, Alison. And thanks for your question. We alluded to a lot of the data that we've been looking at recently looking at the insulins of short chain fatty acids in short chain fatty acids, producing SCFA in the gut in preclinical models, and also in humans. So just to reiterate; in preclinical models, we've seen in the short chain fatty acids or the factor that produced produce them has had a positive impact on the pathology that occurs after influenza virus or RSV in preclinical models, and actually has reduced the mortality associated with lethal influenza virus infection in mouse models. It's -- we've also seen that high fiber diets in these mouse models reduce the pathology and the subsequent inflammatory reaction in the mice, as well as I mentioned earlier, the function of CD4 and CD8 positive T cells and macrophage function. The inappropriate activation of these pathways can also cause increased neutrophil activity that can cause tissue damage, which has also been mitigated by searching fatty acids. In humans, the data are really interesting in that, in-patients undergoing hematopoietic stem cell transplants, who have been infected with these respiratory viruses, there's been a decrease in the progression of those infections to lower respiratory tract infections. And I think that's really important, because in these really vulnerable patient populations, we want to mitigate the activity and the sequelae of this inappropriate immune reaction that we've seen with COVID and potentially improve the outcomes of these patients and decrease hospitalization. So there's -- we find these data really compelling for the program. And we're looking forward to seeing the results of this study.

Alison Lawton: And just to add one more comment, just to remind you that KB109 is, we've shown in our ex-vivo screen, that it increases the production of the ratio of short chain fatty acids, as well as the proposed driving down the presence of pathogenic bacteria. And so for that reason, we're very excited to have the opportunity to conduct a study and look at how KB109 can really help the patient's own immune system to prevent the pathological implications with the COVID-19 infection.

John Newman: Okay. Great. Thanks. And then just had a question on the Phase 2 study for KB195, obviously, the entire industry has been affected by COVID-19, in terms of running clinical programs that's been difficult for everyone. Just curious with 195 program, wondering when you might be able to activate some of the sites that you have set up and just kind of curious as to how that might seeing forward?

Alison Lawton: Yes, it's a great question, John. And obviously, all clinical types have been impacted by COVID-19. And I think that the safety of patients is obviously the priority as far as not bringing patients in the hospital and clinical sites where they could be at risk of acquiring the COVID-19 infection. So as you can imagine, the enrollment of patients in our study has suffered as a result of that. So we're working closely with the sites to make sure that as they start opening up, we can start to enroll patients again. I want to remind you that we actually have approval now across 10 different countries. And we have more than 20 sites that we're enrolling and patients that will work closely with as they say, as they start to get back on to some level of normality. And so right now, we are anticipating approximately a six months or more delay in enrollment of that study, but we'll be monitoring that closely as the sites get up and start again.

John Newman: Great. Thank you.

Operator: Thank you. Our next question comes from the line of Terence Flynn with Goldman Sachs. Your line is now open.

Terence Flynn: Hi. Good morning. Thanks for taking the questions. I was just wondering, on KB109, if the current two trials could support a potential approval for definite COVID or if you'd -- if additional trials would be required. And then, maybe you could outline the magnitude of the benefit across the various endpoints that you're hoping to show, in terms of thinking about next steps. And what would be an ideal profile for the drug? And then, any insight on total cost of the program? Thank you.

Alison Lawton: Okay. So I hear three questions in there, Terence. One, on the potential approval, so, let me start there. And what I would say is we are ready for a number of different possible routes for, depending really on the clinical results that we see. We do plan to have Pre-IND meeting with the FDA, while these trials are ongoing, so that we have different options depending on the results. I would say that could be anything, for example, from expanding the current clinical studies, if we see some signals but we decided we want to add more patients. It could be working through and ensuring that IND is filed ready to initiate a Phase 3, clinical study. What I would also say is, given the safety profile of KB109, if we see signs that have any signs that look like, there's a benefit in these patients. It's a very important patient population to target and avoid these people from needing to be hospitalized. So, we would be ready to work with the FDA, at that point and with the potential of opening up an Emergency Use Authorization. So, any one of those, routes could be a possibility, depending on the results that we see. I'm going to hand over to Kate to talk a little bit about, what results we're looking at, as far as what we would anticipate being important trends.

Kate Knobil: Yes. So, we're measuring a number of end-points in the study. From clinical endpoints, patient measured endpoints, as well as biomarkers of the inflammatory response. And so, if we see a trend in the right direction in the clinical response, whether it'd be hospitalizations or even the percentage of patients showing a low oxygen level, or if we see a mitigation of the inflammatory response, we would view this as very positive and very helpful for us to move forward with the rest of the program. The other thing is that, we will get data from this program and that will also inform on the capability of KB109, working more broadly, not just in COVID-19, but potentially in other respiratory virus infections, as well as for the impact of MMTs on inflammatory diseases more broadly. So that's what we're hoping to see. And, we hope to have these data very quickly.

Alison Lawton: Yes. And so coming back, just to summarize, again, Terence on the on the opportunity, if we see any benefit, obviously, there's a lot of discussion about, is there going to be a second wave of COVID-19. What about other potential respiratory viral infections. And certainly, if we see a benefit from this clinical study and things moving in the right direction, we will be ready and able to work with the FDA for that process move forward. And that also ties in, I think, with your last question around costs, because it links directly to manufacturing. And just to remind you, again, that KB109, like all of our MMTs, it's a synthetic glycan, and we actually use small molecule like processing in our manufacturing. So it's very easy to scale. In fact, with KB195, sorry, our lead program, of course, we've already shown that we've been able to scale efficiently, when we did that with our contact manufacturer, Thermo Fisher in six months, we scaled that production. So we're confident we can scale manufacturing and the costs are going to be right in line with kind of small molecule, typical pharmaceutical costs. Mike, I don’t know if you want to add any additional comment to that.

Mike Bonney: Thanks, Alison. And appreciate the question, Terence. Look, as Kate mentioned in the prepared remarks, this is a controlled study, but it's also open-label. So we'll be able to monitor progress as this goes. And that, I think, will provide a lot of clarity as we interact with both the FDA and make decisions around scaling up beyond this initial trial, to have supply of 109 available. So it's an appropriate design from a patient safety standpoint. It also affords us the opportunity to monitor what kind of response we're seeing, and if it looks positive, that's just articulated on the clinical and/or the biomarkers of immune response. We'll be in a position then to work with our partners to start pre-production, if you will, before the final study data are available.

Alison Lawton: Yes. Thanks Mike.

Terence Flynn: Thank you.

Operator: Thank you. Our next question comes from the line of Matthew Harrison with Morgan Stanley. Your line is now open.

Connor Meehan: Hi, all. This is Connor on for Matthew. So just a couple from us, you touched on briefly a couple of them. But could you just comment on current enrollment status for the UCD trial? And I guess, you mentioned that, maybe you're likely pushing out enrollment by six months. But we were just wondering if you could provide any insight on how enrollment stands at present. And then, just on the COVID trial is there any sort of margin of improvement that you'd be willing to guide on in terms of any of the endpoints you mentioned, that you'd need to see to bring forward? And then, just lastly, can you comment briefly on the profile of pretreatment status of the mild to moderate UCD patients in the new KB295 study? Thank you.

Alison Lawton: Thanks, Conner. I’ve got three parts, and I just want to clarify it. So the first question is around enrollment of UCD. Let me address that first. And then I'll come back to your other two questions. So in the enrollment in UCD, we're not providing details at this point of how many patients have been enrolled. And we're guiding on six months, that's what we're anticipating as far as the site's being able to come back online and start enrolling. And, of course, the patients that we have enrolled, and we have data on so far, will be added to the pool of the additional patients that we plan to continue to enroll. I do want to also just remind -- I will mention again, that we've expanded enrollment with an amendment to expand the age group, so that we are confident when we start that enrollment, it should go smoothly. The second question, I have Conner is around the margin of improvement in the different clinical symptoms. And I think you know, it's really difficult to say any single one that we would expect to see certain cutoff as far as improvements. I think that, like many of these clinical studies, it's going to be looking across the broad range and as the FDA would say, looking at the totality of the evidence and seeing trends in the right direction for many of those different things, including, I think, importantly, the biomarkers of inflammation, along with trends in some of the clinical signs and symptoms that we're going to be recording. And then the third question I have, I'd actually asked you to repeat these costs, because I heard you mentioned KB295 in UC, but I wasn't completely clear on the question, and I apologize, I just realized, I've been calling you Carter instead of Connor.

Connor Meehan: No worries at all. I get it more often than you might think. Thank you. So we're just wondering on the pretreatment status of patients that you plan to enroll in the UC295 studies?

Alison Lawton: Okay. I'll ask Kate to Kate to comment on that one. Thanks, Connor. Got it right that time.

Kate Knobil: So these are patients who are not yet on biologic therapy, so they can be on 5-ASAs or aminosalicylate or agents like that, but not as severe to require biologic.

Connor Meehan: Understood. Thank you.

Operator: Thank you. Our next question comes from the line of Jessica Fye with JPMorgan. Your line is now open.

Unidentified Analyst: Hi, good morning, guys. Thanks for taking our question. This is Daniel [ph] for Jessica Fye. On the COVID-19 studies, can you elaborate -- can you walk us through the decision to evaluate clinical outcomes following two weeks of treatment. What gives you the confidence that those two weeks of treatment is sufficient to feed into the clinical benefit?

Alison Lawton: Yes, sure. Kate, do you want to comment on that?

Kate Knobil: Yes, so we specifically, not only are looking at the two weeks of treatment, but also previously followed, because we know that the course of COVID-19 can be several weeks. What we wanted to do is to make sure that we treated patients during the more inflammatory phase of their disease. And so, we're going to be looking at those inflammatory markers, both after treatment and during the follow-up and also looking at their recovery and whether or not they require extra care. So, I think five weeks is going to be enough for us to be able to see the difference.

Alison Lawton: And I would also add that we know without MMT that we see a change in the microbiome, the production of the microbiome metabolites of interest, very quickly of the starting dosing. And so, in that two week period, we would certainly anticipate seeing a change in the short chain fatty acid profile that we're looking for to impact the immune system and the two weakest spot is, what we also know about the cause of the disease as far as that's a critical period, from testing before patients may end up in the hospitals. And so with the goal, again, of treating in that period to avoid the consequences and avoid patients from going into the hospitals, which is where the real need is in the system, I think, we have confidence that KB109 for that duration of treatment has the opportunity to shown effects.

Unidentified Analyst: Got it. Thanks. On the KB174 program, with prior expectations for studies towards the second half 2020, which now seems to be contingent upon finding a partner, is it fair to say that you've already initiated partnership discussions? And why now instead of waiting after getting more data and if could elaborate, what type of partnerships are you looking for?

Alison Lawton: Yes. So, you were cut off just as you started that question, but I think it relates to KB174 and hepatic encephalopathy program. So, as you know Daniel, we had very positive results in a clinical study that we reported at the -- I think it was in December now or early January, I forget the time has gone by so quickly. But that was in cirrhosis patients, where we showed that we were able to reduce the production of ammonia by the microbiome, which was a very important study to show with KB174, as well as showed the safety of it. As a result, we had a number of parties interested in following up on discussions. And we are continuing those potential discussions with partners. And at this point, we believe that that's the best path forward. I don't want to comment any further at this point around speculating what that may look like. Mike, I think you may have a comment to add here as well.

Mike Bonney: Yes. Thank you, Alison. Just wanted to raise -- remind everyone that given the current crisis that we are in, this decision really is one of convenience in that, it is given our framework, a lot of uncertainty what's going to happen with COVID-19 and the developed world. So -- right, so we all acknowledge that there's uncertainty here. It wouldn't be possible to enroll patients in this study currently, that we have designed this next study, simply in order to protect these patients with failing livers from undue exposure to COVID-19. Given that, plus the interest that has attended to partnering this program subsequent to the delivery of the data in the cirrhotic patients that Alison identified, it just made sense to us to gate the start of the study which we're very excited about, on achieving this partnership. And that also will allow the -- hopefully the healthcare system to start rebounding to the point where it's safe for patients with failing livers, who are otherwise not having an acute illness, to come into a center and be started in the study and monitored appropriately and so forth.

Unidentified Analyst: All right. Thank you. And one more question on 295, once the assessment was the impact on simple clinical Kaleidos activity index. Why not also look at the -- the lifetime male score? Thank you.

Alison Lawton: Okay. Kate, would you like to comment on that for us?

Kate Knobil: Yes, so there are a number of scores out there that we could use. The simplified activity score is actually well-correlated with a male score. And so we feel confident that it'll be a very good instrument for us to use in this study.

Unidentified Analyst: All right. Thank you very much for taking our questions.

Operator: Thank you. Our next question comes from the line of Gbola Amusa of Chardan. Your line is now open.

Unidentified Analyst: Hi. Good morning. This is Sam Lee on behalf of Gbola. Thanks for taking my questions. And I have a couple of questions and a follow-up. And some of them actually answered a little bit, already. But number one, can you provide some color on the rationale behind the protocol amendment for 195? Expanding the range from -- age range from 12 to 70? To 12 to 70, I'm sorry, from 18 to 65, is that COVID-19 related? And two; for the Phase 2 Unlocked Trial in KB195 in UCD, do you find that the COVID-19 pandemic is disrupting the collection and/or the quality of the endpoints in anyway? In other words the fasting plasma ammonia and the 24 hour plasma ammonia area under the curve endpoints?

Alison Lawton: Okay, thanks -- thanks for the question. So, first of all, let me start with your question around the age range for the protocol for the unlocked study. It has always been our intention to expand the age range. As you probably know, a number of patients with UCDs involve and include children and adolescents and infants. And so, as we've collected sufficient data required, we've had the opportunity to submit the amendment and expand that age range. So that was always our intention. And it's just fortuitous that your life as far as timing ready or enrolling that broader age group, once we are able to start enrollment again at the clinical site. With regards to the collection of end-points, plasma ammonia, for example, as you can imagine, this is one of the issues with patients coming into sites, and really a collection of blood samples. We've been doing a lot of work in looking at how we can do more remote monitoring and visits and collection of blood samples. And so, all of that has been part of our consideration and thinking about getting the study up and running again, as soon as the sites can be started. As you can imagine, in the COVID-19 environment and the clinical studies, there are many different options in looking at kind of nurses, doing a home visits instead of asking patients to come in to site, those types of things.

Unidentified Analyst: Right, of course and I guess, follow-up on that, for these clinical programs. In addition to that, what other measures are being taken to keep the trials running? You mentioned, maybe potentially nurse visits and such, but would the patient still need to visit the sites at all? And had there been any FDA discussions to adjust the trial design and if so it’s a hustle?

Alison Lawton: So, maybe I’ll ask Kate to comment further on any adjustments to it. There has not been any discussion with the FDA to adjust the trial design, other than the amendments that we have made to expand the age range for enrollment criteria. But Kate maybe you want to talk about some of the works that we've been doing to facilitate the patients enrolling, once we get up and start it again.

Kate Knobil: Yes. And just to reiterate, to make this study as easy on patients as possible. We started out the study with as much remote visits, as many remote visits as we could, because we knew that, that could potentially be a burden. And we're currently looking into ways to provide even more remote monitoring as we open up. So we will be looking at whether or not there requires any further conversations with the FDA. But we know from guidance that these kinds of changes are well within the realm of things that we can do. I just wanted to -- the other thing is that you asked a question about the quality of the endpoints that we're collecting; there's been no impact on the quality of the endpoints that we've been measuring in this study due to COVID-19. I just wanted to make that clear.

Alison Lawton: And maybe I'll just make one more comment again, because we have clinical sites across 10 different countries. We have the opportunity for different sites to start at different times, at different countries and at different phases of the COVID-19 pandemic.

Unidentified Analyst: Got it. And one more final question, in terms of the non-clinical programs in Immuno-oncology on cardio-metabolic liver diseases. You didn't mention in guidance that they should still be on track, but I'm just wondering how you guys are facilitating the bench work in terms of continuing it during the pandemic? How you're adjusting?

Alison Lawton : Yes. No. It's a great question. And we have worked very closely with our partners, both the stuff we see, who did close down for a little while in Paris. And we know that they're planning to get up and started again. We've been working very closely and coordinate with them, and our other laboratories, who've been doing this work, we've also initiated some animal work at other sites. As China was coming back online much faster than some of the other countries, we took the opportunity to make sure we had backup plans and animal work starting in China, so that we could ensure we're on track here. So, I think, with the understanding of where we are, working closely with our partners and contractors in the labs on this, as well as, knowing that the good stuff we see, labs are coming back online, we have confidence that we can deliver this data still in Q4 of this year.

Unidentified Analyst: Great. Thank you so much for taking my questions.

Operator: Thank you. This concludes today's question-and-answer session. I would now like to turn the call back to Alison Lawton for closing remarks.

Alison Lawton: Thank you, and thanks for some great questions there and for joining us on the call this morning. While the first quarter posed unexpected and unprecedented challenges for us, as it did for most companies, I have to say I'm very proud of the team and their flexibility and dedication and commitment to our science, as well as ensuring that our clinical trials and development programs have been able to continue to evolve. And I'm particularly excited about this opportunity that we have as the part of the broader endeavor, to better understand the course of COVID-19, and how we might moderate the course of the disease with the goal of easing the burden on the healthcare system, and the hospitals, as well as, of course, potential future serious viral respiratory infections more broadly. So I'd like to conclude by thanking the patients and their families, our investigators and clinicians who've been involved in all of our clinical studies, as well as our great team here at Kaleido for making it all possible. And have a great day everybody. Thank you.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.