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Edited Transcript of TBIO.OQ earnings conference call or presentation 31-Jul-19 12:00pm GMT

Q2 2019 Translate Bio Inc Earnings Call

Aug 12, 2019 (Thomson StreetEvents) -- Edited Transcript of Translate Bio Inc earnings conference call or presentation Wednesday, July 31, 2019 at 12:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Ann Barbier

Translate Bio, Inc. - Chief Medical Officer

* Ronald C. Renaud

Translate Bio, Inc. - President, CEO & Director

* Teri Babine Dahlman

Translate Bio, Inc. - VP of Corporate Communications & IR

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Conference Call Participants

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* Charles Anthony Butler

Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research

* Eun Kyung Yang

Jefferies LLC, Research Division - MD & Senior Equity Research Analyst

* Geoffrey Craig Porges

SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst

* Joshua Elliott Schimmer

Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst

* Yigal Dov Nochomovitz

Citigroup Inc, Research Division - Director

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the interim results from Phase I/II clinical trial of MRT5005. (Operator Instructions) As a reminder, this conference call will be recorded. I would now like to introduce your host for today's conference, Teri Dahlman. You may begin.

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Teri Babine Dahlman, Translate Bio, Inc. - VP of Corporate Communications & IR [2]

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Good morning, and thank you for joining us. With me on the call today are CEO, Ron Renaud; Chief Medical Officer, Dr. Ann Barbier; Chief Technical Officer, Mike Heartlein; Chief Scientific Officer, Richard Wooster; and Chief Financial Officer, John Schroer.

On today's call, Ron will make some introductory and summary remarks, and Ann will review interim results from our ongoing Phase I/II clinical trial of MRT5005 in patients with cystic fibrosis. At the end of the call, we will open it up for questions, at which point Richard, Mike and John will also be available.

Before we begin our formal comments, let me remind you that during today's conference call, we will be making forward-looking statements that represent the company's intentions, expectations or beliefs concerning future events. These forward-looking statements are qualified by important factors set forth in today's press release and the company's filings with the SEC, which could cause actual results to differ materially from those in such forward-looking statements. Information discussed on today's call is accurate as of today, and we do not intend to necessarily update the specific information in the future.

I would now like to turn the call over to Ron Renaud.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [3]

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Thank you, Teri, and thank you, all, for joining us today. This morning, we will be discussing interim results from our ongoing Phase I/II clinical trial of MRT5005 in patients with cystic fibrosis.

As our first clinical stage program, this is an exciting milestone for our company. We also believe that this is a significant advancement in the messenger RNA field as MRT5005 is the first messenger RNA therapeutic to be evaluated for its potential to treat a genetic disease.

To start, I'd like to say that while the data we will review with you today is based on small patient numbers and a single dose, these results are an early positive signal that represents important progress in the development of MRT5005 and a significant achievement by the team here at Translate Bio.

As many of you know, cystic fibrosis is caused by mutations in the gene that produces the cystic fibrosis transmembrane conductance regulator, or CFTR protein. MRT5005 is designed to treat the underlying cause of cystic fibrosis by delivering messenger RNA encoding fully functional CFTR protein to the lung epithelial cells through nebulization. Because it uses the body's own cellular machinery to produce CFTR protein, it is designed to treat all patients with cystic fibrosis, regardless of genetic mutation and including those with limited or no CFTR protein.

Today's interim results, the first clinical investigation of an inhaled messenger RNA therapeutic, summarize the single-ascending dose portion of the clinical trial. The multiple-ascending dose portion of this trial is ongoing with data expected in 2020.

I would now like to turn the call over to our Chief Medical Officer, Dr. Ann Barbier, to share additional details about this interim dataset. Ann?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [4]

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Thank you, Ron. As Ron just mentioned, today is certainly an exciting day at Translate Bio as we are here to review the interim data from our ongoing first-in-human Phase I/II clinical trial, evaluating single- and multiple-ascending doses of MRT5005 in patients with cystic fibrosis. Again, this is the very first clinical investigation of an inhaled messenger RNA therapeutic.

With this in mind, we're also looking forward to discussing how we plan to use this data to advance this program with the goal of developing a new and innovative treatment option for all patients with cystic fibrosis.

On today's call, we will review results that summarize the single-ascending dose portion of the MRT5005 clinical trial in 12 patients through 1-month follow-up post treatment.

Before diving into the data analysis, I'd like to start with a quick overview of the study. The randomized, double-blind, placebo-controlled Phase I/II clinical trial of MRT5005 was designed to enroll at least 32 adult patients with cystic fibrosis who have baseline percent predicted forced expiratory volume in 1 second, or ppFEV1 value, between 50% and 90%.

For the remainder of today's call, I will refer to ppFEV1 as simply FEV1. The original trial design included multiple parts, Part A to assess single-ascending doses in 12 patients; Part B to assess multiple-ascending doses in 12 additional patients; and Part C to evaluate 4 additional patients in each of the 2 highest tolerated dose levels identified in Part B, including bronchoscopy. The primary end point of this trial is to assess the safety and tolerability of single- and multiple-escalating doses of MRT5005 administered by nebulization to adult patients with cystic fibrosis. FEV1, which is a well-defined and accepted end point measuring lung function, is also being measured at predefined time points throughout the trial.

Now, we will move on to discuss the Phase I/II clinical trial results from the single-ascending dose portion of the trial. The results summarize interim data from 12 adult patients with cystic fibrosis, who received a single dose of either MRT5005 or placebo. Dosing cohorts were comprised of 4 patients, 3 receiving active drug and 1 receiving placebo. The patients who received MRT5005 were assigned to 1 of 3 dose groups: 8, 16 or 24 milligram. In terms of patient demographics, this trial primarily included patients with the most common cystic fibrosis mutation, F508del. Of the 12 patients in the single-ascending dose part of the study, 11 had at least one copy of the F508del mutation. One patient did not have an F508del mutation and was considered nonamenable to CFTR modulator treatment.

For protocol, patients who were taking certain approved CFTR modulator treatments were allowed in the study and able to continue on that medication. The protocol called for patients to have been on stable treatment with this medication for at least 28 days prior to the screening visit and to remain on it for the duration of the study at a stable dose.

As such, in our study, 7 of the 12 patients were using CFTR modulator treatments. Across the different dose groups, the average baseline FEV1 ranged from 53.3%, with a standard deviation of 7.2 to 79.2% with a standard deviation of 7.1.

Next, I would like to review the safety, tolerability and pharmacokinetic data. There were no treatment-emergent serious adverse events and all treatment-emergent adverse events were considered mild to moderate. The most common adverse events through day 29 were cough and headache. MRT5005 was generally well tolerated in the 8- and the 16-milligram dose groups. 5 patients, 3 of whom were in the 24-milligram dose group, experienced transient, mild-to-moderate febrile reactions. These events occurred approximately 4 to 10 hours post dose, were characterized by fever and symptoms such as headache, fatigue, chills or nausea and were treated with medicines, including acetaminophen and NSAIDs and/or an anti-emetic. The symptoms resolved within 24 hours, and all patients were discharged from the study center on day 2 as planned. We have not seen febrile reactions in our animal studies. However, they are not unprecedented as similar reactions has been reported in earlier gene therapy studies in patients with cystic fibrosis.

These 5 patients with febrile reactions also were the only ones who had detectable messenger RNA and/or lipid in their blood, albeit at very low levels. We will continue to monitor and evaluate whether there is a causative relationship between the 2 observations, but this may actually support our belief that the LNP encapsulated messenger RNA is crossing the mucus layer. The fact that we have seen febrile reactions primarily in the high-dose cohort will help us to refine the doses in our ongoing and future studies, which I will talk about in more detail in a few minutes.

Moving on, I'd like to discuss findings related to lung function in these 12 patients. Again, FEV1 was assessed at predefined time points throughout the trial to measure changes in lung function, including at least 2 points prior to dosing; day 1, day 2, day 3, day 8, day 15 and day 29.

Let's review the 3 dose levels and their FEV1 measurements. Patients in the pooled placebo group and the 8-milligram dose group did not show a marked improvement in FEV1. In the 8-day period, after dosing, the 3 patients in the 16-milligram dose group experienced maximum FEV1 increases of 11.1%, 13.6% and 22.2% for a mean maximum increase from baseline of 15.7%, with a standard deviation of 5.8. Of the 3 patients in the 16-milligram dose group, 2 were on a stable modulator treatment regimen for at least 28 days, while the third had a genotype that is considered nonamenable to CFTR modulator treatments. Of the 3 patients in the 24-milligram dose group, through day 8, one patient experienced a maximum increase from baseline in FEV1 of 21.4%, while 2 patients did not show a marked increase in FEV1.

We recognize these patient numbers are small, and this is a single dose of MRT5005 and the primary trial -- or the primary end point of this trial is safety and tolerability. However, we are encouraged by this interim data set and pleased that in several patients, mainly in the 16-milligram dose group, we observed increases in FEV1 in the 8 days after treatment were higher than one would expect to see based on the known variability of FEV1. We believe that the observed increases from baseline in FEV1 and the time frame in which they occur support the mechanism and suggest that MRT5005 is crossing the mucus layer in these patients and enabling the production of functional CFTR protein.

We were also encouraged to see increases from baseline in FEV1 in a patient with the genotype considered nonamenable to CFTR modulators as well additional increases from baseline in patients who are already taking CFTR modulators.

Finally, building on the insights gained from the single-ascending dose data, we are proposing certain protocol changes in this ongoing Phase I/II clinical trial. As previously discussed, the original trial design includes multiple parts; Part A to assess single-ascending doses; Part B to assess multiple-ascending doses; and Part C to evaluate additional patients with bronchoscopy.

Since the 16-milligram dose showed an early signal of possible lung function improvement and was generally well tolerated, we are planning to amend the clinical trial protocol and expand our dose range around this dose level. Therefore, in the single-ascending dose portion of the trial, we are proposing the addition of a 20-milligram dose cohort of 4 patients. Also in the ongoing multiple-ascending dose portion of the trial, we are planning to add 12- and 20-milligram dose cohorts with 4 patients each. The latter dosing cohort will be contingent on successful completion of the 20-milligram single dose cohort and an acceptable safety profile in the lower multiple-ascending dose cohorts.

We no longer plan to evaluate a 24-milligram dose group in the multiple-ascending dose portion of the trial. The originally planned Part C of the clinical trial, which included bronchoscopy, is expected to be redesigned into a Part B expansion to instead focus on the enrollment of additional patients at dose levels of interest in the multiple-ascending dose part of the study. Given the positive signal we have seen in this interim analysis, we believe that expanding the clinical data set with more patients at select dose levels will provide more useful information than we would have obtained from the bronchoscopy.

The Phase I/II clinical trial of MRT5005 was originally designed to enroll at least 32 adult patients with cystic fibrosis. After accounting for the planned changes in trial design, we expect to enroll up to 40 patients. As required, we plan to submit these protocol changes to the FDA. We anticipate sharing results from the additional single-ascending dose group as well as data from the multiple-ascending dose portion of the trial in 2020.

In summary, we are pleased with the data we've collected and analyzed so far, and we are confident that these planned protocol changes will be beneficial to the progress and continued success of the trial.

From the very start, our goal has been to develop a drug that treats the underlying cause of this terrible life-shortening disease. Despite significant advances and treatment options, there remains a critical unmet need for cystic fibrosis patients, whose genetic mutations are nonamenable to CFTR modulators.

At Translate Bio, we believe messenger RNA therapy represents a potential new approach to treating all patients with cystic fibrosis, and we look forward to results from the multiple-ascending dose part of the study next year.

We want to especially thank our clinical investigators and their staff, the Cystic Fibrosis Foundation and the patients who have participated and are continuing to participate in this clinical trial. We anticipate sharing additional analyses from this interim data set at the North American Cystic Fibrosis Conference in the fall.

And with that, I will turn the call back to Ron.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [5]

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Thank you, Ann. As I believe you can tell from Ann's review of this data set, we are encouraged by the results we're sharing with you today. We acknowledge that this is single dose data in a small number of patients, but we believe that the marked increases in FEV1 observed demonstrate a positive signal supporting MRT5005 as an inhaled messenger RNA therapeutic in cystic fibrosis. These interim data have guided our decisions to refine the dosing regimen in the ongoing study, and we look forward to data from multiple-ascending dose portion to continue to inform our development strategy.

Future studies will, of course, depend on the multiple-ascending dose data. But we're already thinking through various clinical trial designs beyond this Phase I/II study. We're excited to contemplate the key role that MRT5005 could potentially play in the treatment of patients with cystic fibrosis.

Our team has dedicated more than 10 years to pioneering messenger RNA as a therapeutic. Since the inception of our MRT platform in 2008, we have been at the forefront of this field and have demonstrated many critical milestones in messenger RNA drug development, leading to this one.

From early on, we established a goal of developing a lipid-nanoparticle encapsulated messenger RNA that could be inhaled via nebulization. These interim results represent the tremendous wealth of knowledge and expertise behind this effort and are a critical step toward our goal. These data also indicates the potential of messenger RNA therapeutics for the treatment of lung diseases and provides increased confidence in our pulmonary delivery platform, supporting the planned expansion of our strategy related to lung targets and the continued advancement of our earlier-stage programs beyond cystic fibrosis.

Building on this news, we look forward to making progress in several key areas, which include continuing to enroll patients and progress through the multiple-ascending dose portion of the ongoing Phase I/II clinical trial, validating and selecting new drug candidates for lung diseases and presenting additional MRT5005 data at the upcoming North American Cystic Fibrosis Conference in Nashville this fall. We believe our messenger RNA therapeutic platform has great potential to help patients suffering from debilitating genetic diseases, and we remain focused on continuing to achieve our milestones.

We look forward to keeping you updated on our progress throughout the year.

And last, but certainly not least, on behalf of the team here at Translate Bio, I would like to echo Ann's sentiment and extend our most sincere gratitude to the investigators, the CF Foundation and the patients who are participating and have participated in this clinical trial. Thanks to your courage and your commitment to innovative research, we are one step closer to potentially developing a treatment for patients with limited or no disease-modifying treatments available today. We thank you wholeheartedly.

And with that, let's open it up to your questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Geoffrey Porges with SVB Leerink.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [2]

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Congratulations, everybody, on certainly the most interesting data we're going to hear about today, I think. Lots of questions. But Ann, could you talk a little bit about, first of all, your explanation for the one responder that you saw, who seemed to be responding at the highest level of the 16 milligrams. So the one responder at 24 milligrams. Could you tell us what happened to the 2 nonresponders at 24 milligrams? And then could you confirm whether the higher response is at 16 milligrams were in patients who are on concomitant CFTR modulator. And then was that combination a [potentiator corrector]? Or was it just [potentiator]? And then could you describe in a little bit more specificity, the blinding of the patients and the study site level, exactly how complete was the blinding?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [3]

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Let me take these questions separately. The first question is, why does it appear that there is only one -- where is there only one patient in the 24 milligrams who showed an increase in FEV1 compared to 3 in the 16-milligram dose group. These are very small numbers, and it's a single dose. So we believe that this data set is really too limited to start to attempt to draw any conclusions about dose responses. So more data will be gathered in the multiple-ascending dose study. And I think at that point, and also in the expansion cohort, I think that's where a clearer picture of that aspect of the effects will start to emerge.

Your second question was about the 3 patients with an increase in FEV1 in the 16-milligram dose group. Yes. For privacy reasons, I cannot tell you which patient had which genotype and which concomitant medication had what FEV1 increase, but we were very pleased to see that in that 3-patient group, we had both subjects with concomitant medication, a CFTR modulator and one without a background medication that had an increase in FEV1.

With regards to the blinding, I can tell you that the drug was prepared in the hospital pharmacy in a nebulizer, was then labeled with tamper-resistant tape and then was brought to the dosing room with a continuous chain of custody, and dosing happened under constant supervision by a member of the staff and the nebulizers were not opened, were not -- the tamper-resistant tape was not broken until after the nebulization, and that's only by a separate member of the staff, an unblinded member of the staff who was kept separately from the study staff who administered the treatment.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [4]

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Geoff, this is Ron. I would just add. If you recall, the study parameters and the eligibility requirements, per the protocol, patients who were taking certain modulators. So for example, if they were on [orcanbe] or [somedeco], they were actually allowed in the study as long as they had been on those drugs for at least 28 days prior to screening and stable on that treatment.

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Geoffrey Craig Porges, SVB Leerink LLC, Research Division - Director of Therapeutics Research, MD & Senior Biotechnology Analyst [5]

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Okay. Great. Can I ask one more question? I really appreciate all the additional color. Ron, you've talked previously about weekly dosing, but it does look as though the effect was really peaked at day 2 or day 3 and then waned by day 8. Do you still feel confident about a weekly dosing schedule? Or are you going to explore different doses, either in the MAD or in future studies -- different frequencies, I mean.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [6]

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Yes. So it's a good question, Geoff. I think for the purpose of this study -- remember, this is our safety and tolerability Phase I/II study. So as Ann mentioned, we're going to add an additional dosing cohort to the single-ascending dose and then some additional cohorts to the multiple-ascending dose. I don't -- I think we're going to still keep it with the once weekly dosing. I think we're -- it's probably too soon to say what we're going to do in terms of dosing adjustments beyond that. But I think we're satisfied with what we're seeing right now. But we'll have, after the study, I think, full flexibility to explore, as I mentioned in my prepared remarks, a number of different either potential approaches or combinations or even dosing schedules.

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Operator [7]

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And our next question comes from Yigal Nochomovitz with Citi.

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Yigal Dov Nochomovitz, Citigroup Inc, Research Division - Director [8]

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Just settling on the last question. With the attenuation that you see at day 8, is that consistent with the half-life of CFTR in epithelial cells?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [9]

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Well, it is certainly consistent with the preclinical data that we have gathered in our animal models where we do start to see a fast expression of CFTR and then it reaches a maximum and then it tails off a little bit. Humans are not animals. So this was one of the questions we wanted to investigate in these first studies, and the multiple-ascending dose studies where 5 weekly doses will be given, I think will give us a clear answer on whether some kind of a steady state is reached, whether we should consider adjusting the dosing regimen. So the data will guide us on this.

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Yigal Dov Nochomovitz, Citigroup Inc, Research Division - Director [10]

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That's helpful. And just -- I wanted to ask a couple of questions on the low level of mRNA and lipid that you saw in the blood. Could you clarify whether you saw this preclinically? And if you're able to actually quantify what those low levels are? And how long did you see the mRNA and lipids persist in the blood post dosing?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [11]

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In the human study that we're discussing today, I can tell you that the levels that we saw both on messenger RNA and lipid were very, very small, just above the level of quantification. And it was typically observed at the time points of 8 hours after dosing and early the next day and then the signal disappeared. So this does appear to be related to the acute phase of delivering drugs -- the drug, we believe, is delivered effectively, goes through the mucus, goes to the epithelial cells and ends up in the blood. So it's an indirect way. Well, actually, it's a pretty direct way, I believe, of illustrating that the drug can get through the mucus and can get to its target, but it does appear to be short-lived in the study we have done so far.

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Yigal Dov Nochomovitz, Citigroup Inc, Research Division - Director [12]

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And then just one more for me. Three of those patients that you saw the mRNA and lipid in the blood group of 24 milligram dose, could you say which -- of the other 2 patients, what dose were they at?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [13]

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I don't think we can give that level of granularity at this point.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [14]

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Yes, we're not going to disclose that level. We'll have additional details from this. Remember, we're going to present the full interim data set at the NACFC in the fall.

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Operator [15]

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And the next question comes from Josh Schimmer with Evercore ISI.

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Joshua Elliott Schimmer, Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst [16]

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Maybe you can help -- the signal from the 16-milligram dose cohort to benefit at 8 hours, is that rapid timing consistent with a drug effect, and as to the late pulmonary exacerbations at day 25 and 27. I imagine you're thinking of those (inaudible) drug related given the timing. And then a third question is, how do you conceptually think about adjusting for some of the baseline imbalances in FEV1 between the dose groups?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [17]

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Let me take the questions separately. I think your first question was the maximum effect seems to be at day 8. Was that your first question?

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Joshua Elliott Schimmer, Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst [18]

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There's a benefit at 8 hours a day 1 measures, 8 hours post dose. So curious as to whether that's -- rapid timing is consistent with the drug effect.

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [19]

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In the preclinical data, we have certainly seen that expression of CFTR protein could be observed after 2 hours. So the time course makes sense. When you look at individual patient data, you do see that not in every patient the effect is at its strongest at [day] 8. As a matter of fact, that's when you start -- typically when you start to see it and then it waxes and wanes over the period.

Your second question, I think, has to do with the base -- the pulmonary exacerbations and were they considered not drug related. The answer is, yes. They were not considered drug related, and there were actually mild pulmonary exacerbations that were treated with oral medications, did not require hospitalization for IV treatment.

And then I think your third question was about the baseline FEV1. Well, this is a very small study. We enrolled the patients that volunteered for the study. In future studies, we will have more patients to evaluate this. But again, this is a safety and tolerability study. So any type of stratification or balancing out of baseline was not appropriate for this type of design.

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Joshua Elliott Schimmer, Evercore ISI Institutional Equities, Research Division - Senior MD & Equity Analyst [20]

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Maybe a couple of quick questions. Was there any change in cough or sputum production throughout the study? Was that something that was captured? And then for the MAD study, will you expect results in 2020? Any greater granularity or estimate when within 2020 those results might be available first half, second half or by quarter?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [21]

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Cough was the most frequently noted adverse event. But again, that is what you see in nearly all cystic fibrosis studies. So we did not interpret this as any particular signal. As far as further updates, those will come in 2020. That's what we're anticipating. But more precise guidance on that cannot be given today.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [22]

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Yes, Josh, this is Ron. We'll have more guidance on that, probably later in the year. As Ann mentioned in the prepared remarks, we're going to be adding some additional cohorts in the single ascending -- an additional cohort in the single-ascending dose and a couple of cohorts in the multiple-ascending dose. We will increase the patient numbers in the study. So I think for us to try to pinpoint when in 2020 we'll have that data is probably a little premature at this point.

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Operator [23]

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And our next question comes from Eun Kyung Yang with Jefferies.

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Eun Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [24]

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Congrats on encouraging data. So based on your comment, is it reasonable to say that there is no discernible difference between the patients who are on CFTR modulator which is not a modulator?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [25]

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With this very limited data set, I think it would be premature to draw any conclusions about differences or comparisons between those 2 types of patients.

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Eun Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [26]

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Okay. And then the pulmonary exacerbation, you said it's not drug related. Then is it related to lack of efficacy in the 2 patients who did not respond?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [27]

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No. These are cystic fibrosis patients. They have pulmonary exacerbations from time to time. As far as we were able to ascertain, these 2 pulmonary exacerbations that were observed were just in the course of these patients' disease, not related to drug, not related to efficacy.

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Eun Kyung Yang, Jefferies LLC, Research Division - MD & Senior Equity Research Analyst [28]

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Okay. And the last question, can you comment on what the inhalation or delivery time for 8 milligram and 16 milligram?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [29]

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So for 8 milligram, it's about 45 minutes. For 16 milligram, it's about double that, 90 minutes, 9-0; and for 20 milligrams, it's about 2 hours and a quarter, it could vary a little bit, but that is...

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [30]

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24 milligrams.

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [31]

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Yes, for the 24 milligrams.

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Operator [32]

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And our next question comes from Tony Butler with Roth Capital Partners.

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Charles Anthony Butler, Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research [33]

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Two questions. Ann and/or Ron, when you're looking at the patients at 24, and you've made the decision to discontinue 24 and you commented that you thought it was too premature to make a dose relationship, which may be obviously true. I'm curious what led to the decision to eliminate 24 now and maybe not even potentially go higher to, say, 28. So that's one. And the second question is, the 12 patients, forgive me for not knowing this, did they give re-randomized on the MAD portion? Or do they have an option to do that? And/or would they simply stay on their existing dose, assuming they do have that option?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [34]

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Okay. So the first question is why not continue with the 24, why not try a somewhat higher dose? Well, the reason here is based on the fact that 3 patients at 24 milligrams had febrile reactions. That's a very clear signal. It was not a particularly worrisome signal because the fever was mild to moderate. It was transient. The patients were fine the next day and were discharged, but it is still a pretty clear signal. On top of that, it is not an unexpected signal. This falls clearly in what is known of this field when you include messenger RNA in gene therapy and CFTR together. So that to us was enough data to conclude that there was really no value in moving above that. Again, at 24 milligram, we started to see drug -- messenger RNA and/or lipid appearing in the blood, which is again an indication of more than sufficient delivery. The drug is ultimately intended to be a local treatment, and it's not really intended for systemic delivery. So between those 3 data points, the signal well established in the field and evidence of sufficient delivery, there appear to be no value in continuing to increase the dose. And this was, of course, discussed with safety advisers, including the Cystic Fibrosis Foundation, and I believe everybody was unanimous on the proposed change.

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Ronald C. Renaud, Translate Bio, Inc. - President, CEO & Director [35]

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Tony, I would also add to that, given that the data that we see in the 16-milligram group, that also supports our conviction that it's probably unlikely that we're going to need the 24-milligram group at this point. And that's why we're going to add the different -- the additional data sets to hopefully add some patient numbers and support what we saw in the 16-milligram group.

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Charles Anthony Butler, Roth Capital Partners, LLC, Research Division - MD, Senior Equity Analyst & Head of Biotechnology Research [36]

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I appreciate that very much. It's very helpful. But what about the existing 12, will they roll over?

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Ann Barbier, Translate Bio, Inc. - Chief Medical Officer [37]

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No. Every subject in this study, the part that we're reporting on today received a single dose. And then in the multiple-ascending dose, we will look at additional separate distinct patients. This is a safety and tolerability study, one of the goals is to expose distinct individual unique patients to the new treatment modality.

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Operator [38]

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(Operator Instructions) Ladies and gentlemen, this concludes our Q&A portion of today's conference. I'd like to turn the call back over to your host.

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Teri Babine Dahlman, Translate Bio, Inc. - VP of Corporate Communications & IR [39]

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Thank you. Again, we're excited to share these results with you today. Thank you for joining the call. We're in the office and available if you have any questions, feel free to reach out.

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Operator [40]

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Ladies and gentlemen, thank you for attending today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.