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Edited Transcript of VRP.L earnings conference call or presentation 5-Nov-19 1:00pm GMT

Nine Months 2019 Verona Pharma PLC Earnings Call

Nov 9, 2019 (Thomson StreetEvents) -- Edited Transcript of Verona Pharma PLC earnings conference call or presentation Tuesday, November 5, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Jan-Anders Karlsson

Verona Pharma plc - CEO & Executive Director

* Piers John Morgan

Verona Pharma plc - CFO

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Conference Call Participants

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* Julian Reed Harrison

BTIG, LLC, Research Division - Analyst

* Lucy-Emma Mary Sarah Codrington-Bartlett

Jefferies LLC, Research Division - Equity Analyst

* Vasiliana Vireen Moussatos

Wedbush Securities Inc., Research Division - MD of Equity Research

* Xiaodong Zhang

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

* Zhilin Long

Joh. Berenberg, Gossler & Co. KG, Research Division - Associate

* Kimberly Minarovich

Argot Partners, LLC - MD

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Presentation

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Operator [1]

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Hello, ladies and gentlemen, and welcome to the Verona Pharma Third Quarter 2019 Conference Call. (Operator Instructions) As a reminder, this call is being recorded.

I would now like to turn the call over to, Ms. Kimberly Minarovic, Managing Director, Argot Partners.

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Kimberly Minarovich, Argot Partners, LLC - MD [2]

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Thank you, Lisa. Good morning or afternoon, depending on which time zone you are in, and welcome to today's call to review Verona Pharma's results for the 3 and 9 months ended September 30, 2019. With me today is Jan-Anders Karlsson, Chief Executive Officer, and Piers Morgan, Chief Financial Officer.

Earlier this morning we issued a press release detailing these financial results as well as clinical developments. A copy of the release can be found in the Investor Relations tab on the corporate website www.veronapharma.com.

On today's call, Jan-Anders will first provide an update on the clinical development of the company's lead candidate, ensifentrine. Piers will then review the company's financial results for the 3 and 9 months ended September 30, 2019. We will then open the call to your questions. As a reminder, the conference call is being recorded and will be available on Verona Pharma's Investor Relations website shortly following the conclusion of today's call and can be accessed for the next 30 days.

During the call, the team will be making forward-looking statements, and we remind you of the company's safe harbor language. All statements that do not relate to matters of historical fact should be considered forward-looking statements including, but not limited to, statements regarding ensifentrine as a first-in-class product candidate; the timing of clinical trials of ensifentrine and trial results; and an end-of-Phase 2 meeting with the FDA; the treatment potential of ensifentrine; the value of ensifentrine for COPD patients who remain symptomatic and uncontrolled despite treatment with current available medicine; and the potential for certain formulations of ensifentrine to address larger markets and expand the commercial opportunity of ensifentrine, partnering, further development and commercialization of these formulations and the company's plans to explore these formulations in cystic fibrosis and asthma.

These forward-looking statements are based on management's current expectations. These statements are neither promises, nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from our expectations and expressed or implied by the forward-looking statements. Any such forward-looking statements represents management's estimates as of the date of this conference call. While the company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change.

With that, I will now turn the call over to Jan-Anders. Jan?

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [3]

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Thank you, Kimberly, and thank you to our participants for joining us today. It's my pleasure to update you on the clinical progress that we have made during the quarter. So 2019 is a busy year with a number of important value-creating clinical milestones. Today's update will naturally focus on the new exciting data with the dry powder formulation of ensifentrine, as well as ongoing studies with a nebulizer formulation.

As a reminder, ensifentrine, or previously RPL554, is a unique, first-in-class dual PDE3 and PD4 inhibitor with both bronchodilator and anti-inflammatory properties that we believe will increase lung function, reduce symptoms and improve quality of life in millions of patients with chronic obstructive pulmonary disease, or COPD. We believe that ensifentrine is truly differentiated from existing COPD medications as it is able to further improve breathing and reduce symptoms in patients already on maximum standard of care treatment dose that have run out of treatment options.

Ensifentrine is currently in Phase 2b clinical development for the maintenance treatment of COPD, a disease that is progressive and life threatening with no cure. In the U.S. alone, the medical costs related to COPD are predicted to rise to $49 billion in the next year, 2020, and the World Health Organization, or WHO, predicts that COPD will become the third leading cause of death globally by 2030.

We believe that ensifentrine has the potential to be the first novel class of bronchodilator in over 40 years with a differentiated profile. This would be a breakthrough for a large number of patients who remain symptomatic with a deteriorating lung function despite being on maximum standard of care bronchodilator therapy. That is a combination of the 2 different types of bronchodilators that are available today at the same time. Treatment options for COPD patients are limited with a lack of innovation, particularly for the more severe population. These patients urgently need better treatments.

Our clinical data continue to support the efficacy and tolerability of ensifentrine. And in September this year at the European Respiratory Society Congress in Madrid, we presented positive results from the Phase 2 study of the dry powder inhaler, or DPI formulation, in COPD patients, and it was very well received. All primary and secondary lung function endpoints were achieved in this randomized, double-blind, placebo-controlled crossover study evaluating efficacy and tolerability of twice daily dosing for 7 days of this novel DPI, or dry powder formulation, in 35 patients. These data were first announced in August this year.

The primary endpoint measuring peak forced expiratory volume in 1 second, or FEV1, which is a standard measure of lung function, corrected for placebo showed dose-dependent improvements over baseline of 102 milliliter to 260 milliliter for the 4 doses tested, which were 150 microgram, 500 microgram, 1,500 and 3,000 microgram. These are substantial improvements in lung function, they're clinically meaningful and statistically highly significant.

Secondary endpoints were also met in the clinical trial, including statistically significant improvements in average FEV1 over 12 hours. This average FEV1 over a 12-hour period on Day 7, together with a robust trough data, demonstrated durability of the effect during the full dosing interval and are supportive of twice daily dosing of ensifentrine also in this formulation.

Ensifentrine in the DPI formulation was indeed very well tolerated at all doses with an adverse event profile similar to placebo, and the safety profile was also comparable to that observed in prior studies with nebulized ensifentrine.

In addition to this trial with a DPI formulation, we are conducting a Phase 2 dose ranging trial to evaluate the pharmacokinetic, or PK profile, efficacy and safety of ensifentrine delivered via pressurized metered dose inhaler, or pMDI, in patients with moderate-severe COPD. The pMDI trial as randomized, double-blind and placebo-controlled 2-part design. Recruitment in this new case study has unfortunately been slower than expected, and we anticipate reporting data from the first part of this trial in the first quarter of next year, 2020, and final data mid-next year.

So these data with a prototype dry powder formulation support ensifentrine's potential to be delivered via handheld device. As most patients with COPD and asthma use the more convenient perhaps DPI and pMDI devices for their medications, we believe the availability of ensifentrine in these inhaler formats could greatly expand the market potential for ensifentrine to the millions of COPD patients who prefer to use such devices. An estimated 5.5 million COPD patients in U.S. alone use either DPI or an MDI device, and the market was valued at approximately $9 billion last year, 2018. To maximize the commercial value of a DPI or pMDI formulation of ensifentrine, our strategy is to partner further development and commercialization.

For the more severe COPD patients, our market and payer research showed that nebulized delivery is a very common route of administration, especially in the U.S., where approximately 1,200,000 patients remain symptomatic with a deteriorating lung function despite taking maximum doses of currently available standard of care medicines. Few treatment options remains for these severe patients, and there are few, if any, new treatments in development for them.

Our clinical data, so continue to support a very strong effect of ensifentrine on the symptoms of COPD. In October this year at the CHEST Annual Meeting in New Orleans, we presented further positive symptom data obtained with a broad range of assessment tools from our 4-week Phase 2b trial with nebulized ensifentrine in COPD. This data would expanded on symptom data first announced in March this -- March last year, excuse me -- showed significant and progressive improvements in COPD symptoms.

We are very pleased that our second 4-week Phase 2b dose ranging clinical trial to evaluate the efficacy and safety of ensifentrine in patients with moderate-severe COPD is progressing to plan. We initiated this trial in May 2019, and October this year enrollment was completed in this 416-patient clinical trial, some taken at 46 sites in the U.S. Patients receive nebulized ensifentrine at 4 dose levels, including a low dose of 0.375 milligram, 0.75 milligram, 1.5 and 3 milligram or placebo twice daily for 4 weeks. The trial is designed to evaluate the tolerability and efficacy of nebulized ensifentrine as an add-on to inhaled tiotropium, a long-acting antimuscarinic, or LAMA, commonly used to treat patients with COPD.

The primary endpoint of the study is improvement in lung function as measured by peak FEV1. Key additional endpoints include other lung function measures, as well as measurements of respiratory symptoms and quality of life by different patient-reported outcome tools.

So the main purpose of this study is to present additional dose ranging information to the FDA in an add-on setting with ensifentrine and one long-acting bronchodilator. We expect a positive dose-dependent bronchodilator, or FEV1 response. While though earlier studies indicate that the dose response curve is relatively flat, and so the lowest dose may still have an effect on lung function.

This study complements the earlier Phase 2b 4-week 400-patient study successfully completed in a different setting last year. And following the completion of the second Phase 2b study, we plan to conduct an end-of-Phase 2 meeting with FDA in the first half of 2020, and thereafter commence a Phase 3 clinical program to evaluate ensifentrine for maintenance treatment of symptomatic COPD patients.

Based on the very positive preclinical and clinical data with ensifentrine to date, and the outcome of the FDA meeting, we plan to conduct 2 regulatory pivotal Phase 3 trials and a 12-month safety exposure. We expect to conduct the studies in COPD patients with no background treatment and in patients using only 1 bronchodilator. And FEV1 could be an important endpoint for a broad label. We expect a Phase 3 program to be significantly derisked as it is based on the 2 Phase 2b studies just discussed. Separately, we plan to conduct an additional market positioning study for physicians and payers in more severe patients with dual and triple COPD therapy. We expect to start both the 2 Phase 3 regulatory trials in 2020, next year.

We believe that these upcoming development and regulatory milestones are important value-creating events, feeding directly into the commercial value of ensifentrine both in a nebulized formulation, as well as in a handheld inhaler formulation.

I will now turn the call over to our CFO, Piers Morgan, to provide a financial overview.

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Piers John Morgan, Verona Pharma plc - CFO [4]

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Thank you, Jan-Anders, and hello everyone. I will provide a brief recap of our financial position for the third quarter of 2019. Also, please refer to the press release that we issued this morning, which has also been filed as a 6-K with the SEC. This release includes unaudited financial results inclusive of income, balance sheet and cash flow statement for the 3 months ended September 30, 2019.

Given that we are headquartered in the UK, our financial results are in British pounds. For your convenience, we have included a translation to U.S. dollars using the noon buying rates of the Federal Reserve Bank of New York on September 30, 2019, which is GBP 1 to 1.2305 U.S. dollars in respect to certain key figures.

Turning to the income statement for the 3 months ended September 30, 2019, our operating loss for the 3 months ended September 30, 2019, was GBP 13.9 million, or $17.2 million, compared to GBP 6.8 million for the third quarter of 2018.

The loss after tax for the third quarter 2019 was GBP 10.1 million, or $12.5 million, compared to GBP 2.3 million for the prior year period. This represents the loss of 9.6 pence per diluted share, or a loss of $0.952 per ADS for the third quarter ended September 30, 2019. And this compares to a loss of 2.2 pence per diluted share for the prior quarter.

The total comprehensive loss is calculated as follows. Research and development costs for the 3 months ended September 30, 2019, were GBP 12.0 million, or $14.7 million, compared to GBP 5.3 million for the prior year period, representing an increase in expenditures of GBP 6.7 million. The cost of clinical trials increased by GBP 6.4 million compared to the previous year, reflecting 3 clinical trials of ensifentrine ongoing compared to 2 clinical trials in the 3 months ended September 30, 2018. The majority of the clinical trial costs in the third quarter 2019 related to the ongoing Phase 2b 4-week study in 416 patients, which Jan-Anders described earlier.

General and administrative costs for the 3 months ended September 30, 2019, were GBP 2.0 million, or $2.4 million, which is an increase of GBP 0.6 million compared to the GBP 1.4 million in the third quarter of 2018. The modest increase is primarily attributable to increases in the costs of commercial market research, the salary costs and insurance.

Finance income for the 3 months ended September 30, 2019, was GBP 1.2 million, or $1.5 million, which compared to GBP 3.3 million for the same period last year. The decrease in finance income was primarily due to a decrease in the fair value of the warrant liability due to a lower share price compared to the prior period and a foreign exchange gain of GBP 0.7 million on cash and short term investments.

Finance income in the 3 months ended September 30, 2019 include GBP 0.4 million in relation to the decrease in the fair value of the warrant liability due to a fall in the company's share price compared to GBP 2.6 million finance income in relation to the decrease in the fair value of the warrant liability in the prior period. Finance income also included a GBP 0.7 million foreign exchange gain on cash and short term investments in the 3 months ended September 30, 2019, compared to a GBP 0.5 million gain in the prior period.

Finance expense was GBP 50,000, or $57,000, for the 3 months ended September 30, 2019, compared to an expense of GBP 30,000 for the 3 months ended September 30, 2018.

Taxation for the 3 months ended September 30, 2019, amounted to a credit of GBP 2.6 million, or $3.2 million, compared to a tax credit of GBP 1.1 million in the prior year. The credits are obtained in our qualifying research and development expenditure. And the increase in the credit amount was attributable to our increased expenditure on research and development compared to the prior period, including a change in the mix of qualifying expenditure.

We entered into the third quarter of 2019 with GBP 41.1 million, or $50.5 million, in cash, cash equivalents and short term investments, which comprised cash deposits having a maturity of more than 3 months.

Our net cash used in the operations for the 9 months ended September 30, 2019, was approximately GBP 24.5 million compared to GBP 13.1 million used in operations in the first 9 months of 2018. The increase in cash used in operations primarily reflects increased research and development expenditure.

We expect that our existing cash, cash equivalents and short term investments will more than enable us to fund our operating expenses and capital expenditure requirements through the end of our Phase 2b development in nebulized ensifentrine for the maintenance treatment of COPD, and our proof of concept studies with both handheld DPI and pMDI inhaler formulations of ensifentrine for the treatment of COPD patients.

And with that, I'd like to turn the call back to Lisa and open it up for the question-and-answer session.

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Questions and Answers

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Operator [1]

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(Operator Instructions) Your first question comes from the line of Lucy Codrington with Jefferies.

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Lucy-Emma Mary Sarah Codrington-Bartlett, Jefferies LLC, Research Division - Equity Analyst [2]

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Just a couple for me. The first relates to the recruitment for the MDI study. I don't recall that being an issue for the DPI study, so I just wondered if you can give us some more detail as to why recruitment's been slow. And then secondly, if you could just give us an update of where you are in terms of the CMC for the handheld devices and any other studies that might need to be done prior to any partnership deals for those. Thank you.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [3]

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So on the MDI, it's disappointing. It started as being done in 2 centers in UK. One of the centers we've used before, and I've actually exhausted the patient pool, quite surprisingly, and that's why it's taking a little longer to recruit into this study. It's a center-specific question, and it takes longer to go to different centers and restart again. So we think this is a short delay, nevertheless disappointing. DPI study was run in U.S., and there are more patients obviously available and quite the different system also for including patients in clinical trials. So that ran very well. And our other study, the ongoing Phase 2b study, is of course also being run in U.S. And as you know, we completed enrollment in very short time, so we're extremely pleased with that study and how it's going. Your other question was around CMC. So we have prototype formulations for DPI and the MDI. Prototype means they work very well in a capsule-based device for the DPI and of course the standard canister for the MDI and we have long stability now. So that looks good. What one would have to do is for a dry powder formulation, adjust it specifically to a partner's device. And that will be extra work, but of course, we cannot really do it until we have a relationship in place because all of them have different or slightly different devices. On the MDI side it's a little different. The main supplier of MDIs in the world I believe is 3M, at least commercially available for us. And that would be down the same canister in any type of MDI device, so that's more straightforward. I think we absolutely, as I said before, we need to have the data from the DPI and the MDI studies available before we start any partnering discussions, unless of course we have anything else ongoing. So we are waiting for the MDI data to be able to provide opportunities for those companies or partners that prefer to use DPI devices, and at the same time perhaps having conversations with those that would prefer to work more with MDI devices. So that's where we are. And during the next 6 months, I'm sure we'll have more clarity on this front.

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Operator [4]

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Your next question comes from the line of Adam Walsh with Stifel.

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Xiaodong Zhang, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [5]

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This is Edwin Zhang on for Adam. Thanks for taking the questions. For the Phase 2b nebulized intervention dose ranging studies about to read out I guess in December, do you need to see dose-dependent effect to support the Phase 3 trial next year? That is my first question. On the primary endpoint we use peak FEV1. What is the view from regulators on the importance of other endpoints, for example, trough FEV1? Thank you.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [6]

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I think on the nebulized study that's going, the 4-week Phase 2b study, we expect it to read out around year-end, so early as before or just after. You noticed that we already completed a study, so of course we have now a cleanup in the database completion, et cetera. So around year-end is the guidance on that. Do we need to see a dose-dependent effect? I think ideally we'd like to see an element of that. It's not necessary. I think FDA has a tendency to select the lower dose available in such a study if at all possible. And I think we would like to look at all the data from of course the ongoing study, but also previous studies and make a robust conversation and argument of course to FDA why we then depending on the data believe one dose is better than another dose. And it will be a conversation. The good thing with ensifentrine is that we really have a well-tolerated compound. We don't think there is any of the doses that we use today that have any particular safety concerns, or already even FDA or regulators, as far as we know, have any particular issues. While they want to push the lower dose, if at the same time the safety is not a concern, I think at least we'll make an argument to find a dose that we believe will be the most relevant for moving forward into Phase 3 studies. And then you asked related to this also about peak effects and other measures of lung function. In all our studies, as you know, of course we use peak effect for easy primary endpoints in terms of measurement. It's very simple and straightforward and little discussion. Of course we're also measuring average FEV1, so around a peak several 2, 3, 4 hours throughout the whole day, throughout 24 hours, and we look at trough effects. And we look at all dose effects and select dose that we think are most appropriate. For FDA for a dose ranging study, we think that we can choose any of those parameters and have a productive conversation with FDA. And remember, this is a first-in-class. It is a new product and it has different properties. We are just talking about the lung function measured by FEV1 here. What we think is the most important probably aspect of the company, so of course the anti-inflammatory effect and the symptom improvement, which patients have every day. And if we can make a difference in that respect, I think we have a very attractive product actually for patients, especially those that we think are already treated with a lot of drugs, or maximum treatment even, and where perhaps a completely new mechanism of action can make a difference for patients. That would be very attractive, and that's what we think we have in our differentiated compound.

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Operator [7]

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Your next question comes from the line of Liana Moussatos with Wedbush Securities.

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Vasiliana Vireen Moussatos, Wedbush Securities Inc., Research Division - MD of Equity Research [8]

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Are you in any kind of discussions with companies that are interested in the DPI formulation? And you ended Q3 with GBP 41.1 million. What's the runway? And do you think that the Phase 3 is more likely to start in the second half of next year than the first half?

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [9]

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So first of all, we have a policy of not really discussing ongoing or tentative discussions with other companies. I think that is appropriate. We believe the dry powder formulation is actually very attractive. It is a prototype, and of course, we need to perfect it. But even so, we found very actually surprisingly large effects on FEV1 in COPD patients that we reported out in Madrid, and that was noticed. And we also had a very nice 12-hour duration on FEV1 area under the curve I mentioned as trough, and we believe that's what will make it a very nice twice a day handheld treatment for many more patients than the nebulizer perhaps. So that's interesting, and we believe that's a way forward. On the runway, perhaps Piers you want to comment on that?

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Piers John Morgan, Verona Pharma plc - CFO [10]

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So the runway, we didn't provide a forecast on it, and it will slightly depend, the current cash flow side depends on the precise timing of the start of the Phase 3. But we think it will take us through into the beginning of 2021 based on our existing cash resources.

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Vasiliana Vireen Moussatos, Wedbush Securities Inc., Research Division - MD of Equity Research [11]

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And do you think the Phase 3 for COPD will start in the second half of next year?

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [12]

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Yes, sorry. So yes, I think it's -- we have data coming around year-end. FDA has very long lead times, as you know, for Type C meetings, end-of-Phase 2 meetings. It's probably around 70 days after applying for such a meeting. I think we will be into the second half of next year before we start the Phase 3 studies, actually.

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Operator [13]

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Your next question comes from the line of Tom Shrader with BTIG.

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Julian Reed Harrison, BTIG, LLC, Research Division - Analyst [14]

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This is Julian on for Tom. Thanks for taking my questions. First, beyond your end-of-Phase 2 meeting with the FDA, just wondering if you could briefly talk about any steps you've taken or plan to take in the near future to prepare for the pivotal program of ensifentrine and how much bearing the I guess ongoing Phase 2b add-on study could have on the final designs with these trials.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [15]

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Yes, thank you. Thank you. So that's a very important question because we had in mind to say something. I think we really see the value of the compound for many of the COPD patients that really have few alternatives. And as I said earlier, there are all many of those patients out there, millions in U.S. only, and there's very little new innovative drugs in this space for these patients. Ensifentrine may be one of them. So clearly to aim for those patients, we are having a two-pronged approach. One is to design a Phase 3 program that gives us an optimum opportunity to have a regulatory approval. And the second part of it, and I come back to the first in a second, is really to design a program that also makes it easier for patients and physicians and pulmonologists to understand how to use ensifentrine and where to use it the best. So those are 2 aspects. The first aspect on is basically 2 pivotal trials. And we have spent a lot of time, of course, with KOLs and advisors and ex-FDA advisors on outlining a program that we believe have a good chance of reaching primary endpoints in a positive way and also minimizing the number of patients that we believe we need to have in this program for regulatory approval in U.S. and then of course globally. I think that program, with the data that we have already in hand and the data coming from the ongoing study, we understand pretty well the statistics -- we will understand the statistics around it and also the other aspects of how to run this program in the most efficient way, including U.S. patients and also dose from abroad, of course. The other aspect of the regulatory approval, and we believe we will get the regulatory approval with a broad label for maintenance use in COPD, because that's the label many of the drugs, if not all of them, most recently have achieved. And that would allow us to commercialize ensifentrine in essentially all lines of treatment in the U.S. and also use publications for promotions by sales reps, et cetera. That would be an interesting and attractive positioning, but we would want to enhance it by also reconfirming in new trials, longer and larger trials than we did before that actually ensifentrine really has the ability to add significant and meaningful lung function improvement in patients already on maximum treatment. And in U.S. there are millions of those patients on dual and triple therapy that reduce -- still have a declining lung function, still are very symptomatic and are really reaching out for something new and different. And that's where we believe that our studies and ensifentrine really can make a difference in these patients. So that's what this is leading up to. Slightly long answer. I hope that explains the strategy. And of course, it's based on the collective data that we have gathered and wisdom from the team, but also from the community and KOLs.

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Julian Reed Harrison, BTIG, LLC, Research Division - Analyst [16]

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Okay, thank you. That's very helpful. And then on the partnership front, just curious about the relative interest levels you're seeing in the MDI and DPI formulations. Is there one of the 2 that you're more excited about? And would you view this as both being a single partnership opportunity, or could you envision them being partnered separately since within large pharma my understanding is some lean towards MDI and others prefer DPI.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [17]

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I think for the same indication, and we don't really talk much about partnership unfortunately, but certainly, the DPI and the MDI devices could only be partnered with one company, as far as I understand it. At the same time, you would need to find a different, completely different indication if you want to split it out. That might be possible in the future somehow, but at this moment I think we just want to gather enough data to show the comparative data from the 2 different devices, and also hopefully, as we are seeing with a DPI, that we have 2 attractive proposals for treating patients that really want to get the different bronchodilator and anti-inflammatory effect than what's available today. And then it's, as you say, then it's up to different companies with different preferences for different devices. And of course we want the broadest possible discussion with as many partners as possible when we're all done.

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Operator [18]

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(Operator Instructions) Your next question comes from the line of Patrick Trucchio with Berenberg Capital Markets.

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Zhilin Long, Joh. Berenberg, Gossler & Co. KG, Research Division - Associate [19]

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This is Iris Long on for Patrick. Thanks for taking the questions. So just a follow up on the Phase 3 study for the approval of the nebulized formulation. You mentioned that you anticipate to run 2 Phase 3 studies. I'm just wondering how many patients do you believe you have to enroll for each of the study. And then also based on the sub-analysis data that generated so far, do you anticipate to have -- to stratify the patients enrolled, or otherwise would you need to limit enrollment criteria? Thanks.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [20]

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I think the, to be specific on the Phase 3 studies, we will be waiting for the ongoing study to read out to fully understand the statistics and the number of patients that we need in each treatment group. In principle, we believe that it would be most appropriate to do a comparison between placebo and 1 dose of ensifentrine. And as we discussed before, a dose that of course we would have to agree with FDA and where we think we have good arguments for selecting a dose that has both bronchodilator and anti-inflammatory effects in COPD patients. That will be, as you allude to, across various subgroups of patients on background or no background treatments and also on different degrees of severity, et cetera, that you could maybe study separately and both statistically and clinically look at this in different groups. I think that discussion is also requires the readout of the ongoing study before we can finalize that. Before and of course after we have the agreement with FDA, we'll of course publish in much more detail exactly what the plans are, the dose is, and how we intend to go about the recruitment in various countries, et cetera. But it's a little premature until we have the data readout around year-end for the ongoing 4-week study.

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Zhilin Long, Joh. Berenberg, Gossler & Co. KG, Research Division - Associate [21]

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Okay, thank you. That's helpful. Just a follow-up. Do you think that the placebo-adjusted improvement in FEV1 that ensifentrine will have to demonstrate from the Phase 3 trial, just from the regulatory approval perspective and from the payer perspective, I'm wondering what should we think about the endpoints here.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [22]

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I think, yes, it will have to be placebo or active comparator. Right now we are leaning towards a placebo comparison in a U.S.-powered study. I think the endpoints that we are looking at will have to be around FEV1. Different endpoints that have been used has been trough FEV1 or a 12-hour area under the curve FEV1, and of course, a number of important secondary endpoints that we think will also be relevant, especially as we believe we have a compound that's particularly important as an anti-inflammatory to reduce symptoms in patients. So we have already, as I said, in the Madrid meeting earlier this year and also in a meeting at CHEST, we presented data around symptom improvement with ensifentrine from our 4-week study. Shorter studies are not so meaningful, but the 4-week study, the symptom improvement on many of the different scales that we used in that study was really quite impressive and clearly met the minimally clinically important difference. So it was thought to be clinically meaningful by physicians and KOLs. And I think that aspect we will also make sure that we capture in an appropriate way so that we can use it maybe in a label and certainly in publications later on that we of course want to share with the physicians and pulmonologists. And this is all built up to provide a strategy for informing decisions and KOLs on how to use ensifentrine in the right group of patients where we also believe that there is a big commercial potential for RPL554, ensifentrine. And of course we are talking about patients already on therapy that really need something new and different. And that's what we will build up the Phase 3 program to deliver.

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Operator [23]

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At this time, there are no further questions. I would like to turn the call back over to Mr. Jan-Anders Karlsson.

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Jan-Anders Karlsson, Verona Pharma plc - CEO & Executive Director [24]

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Thank you, Lisa. So 2019 is an important year, obviously as we talked about, for Verona Pharma. We have a number of we think significant value-creating clinical milestones before we go into an end-of-Phase 2 meeting with FDA, and obviously the start of Phase 3 regulatory trials with nebulized ensifentrine for COPD next year. We believe the broad set of data that are obtained with nebulized ensifentrine to date, including then the ongoing Phase 2b study and our plan for the regulatory Phase 3 trials, will improve our chances of achieving an attractive label for ensifentrine. The nebulized and handheld formulations of ensifentrine with its unique bronchodilator and anti-inflammatory properties have the potential to provide further treatment alternatives for millions of COPD patients that are symptomatic, that have run out of treatment options. We believe that providing different formulations of ensifentrine for these different needs of COPD patients will significantly enhance ensifentrine's commercial potential. We look forward to catching up with some of you over the coming weeks at conferences in New York and London. And I also wanted to thank you for joining us today. We appreciate your continued support. Look forward to updating you on clinical development progress with ensifentrine. And finally, thank you, operator. That concludes today's call. Have a good day.

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Operator [25]

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You're welcome. This concludes today's conference. You may now disconnect.