Good afternoon, ladies and gentlemen. Thank you for standing by. Welcome to today's Summit Therapeutics Fourth Quarter and Fiscal Year Ending January 31 2019 Conference Call. At this time all participants are in a listen-only mode. There will be a presentation followed by a question-and-answer session. [Operator Instructions] I must advise you that this conference is being recorded today, the Wednesday 27th of March 2019. I would now like to hand the conference over to your speaker today, Richard Pye, Vice President of Corporate Affairs. Thank you and please go ahead, sir.

Thank you. And welcome to everyone joining us on the call to discuss our financial results for the fourth quarter and fiscal year ended January 31, 2019 and our operational progress. Earlier today, we issued a press release summarizing this information. If you have not had a chance to review, this is available on our website at www.summitplc.com. Our Chief Executive Officer, Glyn Edwards, will provide today's prepared remarks and our Vice President of Finance, Melissa Strange will join for the question-and-answer session. Before we begin our discussion, I’d like to remind listeners that we will be making forward-looking statements during this call. I refer you to our filings with the Securities and Exchange Commission for a description of the risks and uncertainties associated with these forward-looking statements and an investment in Summit Therapeutics. While we may elect to update these forward-looking statements at some points in the future, we specifically disclaim any obligation to do so, even if our views change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to today. I’d now like to turn the call over to Glyn for an overview of our year and more recent corporate activities. Glyn?

Great. Thanks, Richard, and welcome everybody, and thank you all for joining us today. This past year has not been without these challenges, but we've emerged as a leading antibiotics company. As all of you know, we announced disappointing but clear results from our Phase 2 trial in Duchenne muscular dystrophy in June of last year. The rigor with which we conducted the trial and our team's thorough analysis of the data allowed us to definitively conclude that ezutromid was not benefitting patients. As a result, we pivoted to focusing solely on the other core part of our business, our innovative antibiotic pipeline. Infectious diseases are one of the few areas in medicine where we have the potential to cure patients. Unfortunately, cures are becoming harder to achieve with today's available antibiotics due to the rise of antimicrobial resistance or AMR. And so, there is a huge opportunity to discover and develop new, innovative antibiotics and meaningfully improve patient outcomes. Our approach is to develop new classes of antibiotics against new bacterial targets. And this is rare in the antibiotics space. In addition, our innovation spans beyond the discovery of our antibiotic candidates through development and commercialization. Our plan for success in an area where commercial failures have been prominent is to identify the patients whose infection is optimally treated by our new antibiotic to generate [technical difficulty] is the optimal treatment for patients and physicians and also use those same trials to generate economic data for payers. And we believe this plan could help drive rapid uptake of our new antibiotics which are being developed to become tomorrow's standards of care. Obviously, innovation in science is key here. Starting with antibiotic discovery enables us to identify and optimize new mechanism antibiotics. Over many years of exposure, bacteria have developed…

Thank you, sir. Ladies and gentlemen, we'll now start the question-and-answer session. [Operator Instructions] Thank you. Your first question comes from the line of Hartaj Singh of Oppenheimer & Company. Please ask your question.

Great. Thank you. Thanks Glyn, thanks everyone for the question. I just had a couple of questions, Glyn, on the Phase 3 programs, which is good to see them going now in ridinilazole. It's interesting to know Summit saying that about one-third of the CDI patients either don't have a cure or don’t maintain. So, could you just sort of talk a little bit about how your primary and your secondary endpoints are structured? And what are some of the clinical readouts that could help you, I guess, gain this of underserved patient population? And then, maybe just to drill a little bit more into the health economics data that you're going to be capturing, how that -- will that be part of the label or is that something that you'll start discussion with payers, assuming the trial is positive? And then, I got just a quick follow-up on the gonorrhea program?

Sure. Thanks, Hartaj. And I understand you're flying to India. So, I appreciate you delaying your departure to talk to us. So, approximately a third of patients that we talk about that’s generally and in today's presentation, you can divide that into two parts. There is the first relatively small proportion of 8% to 10% who do not get an initial cure from treatment; and then, depending on the trial, there's about a quarter of patients, 25%, varies up to as you know, 30% of patients who have a recurrence. And so, when you put those two things together, you get about a third of patients that either don't have a cure or the cure is not sustained. And if you remember, from our data and also from the public data, these recurrences happen pretty quickly. The peak recurrence is about 14 days and the numbers I've just given of about 25%, having a recurrence with vancomycin is measured at the 30-day period. So, that gives us a significant number of people who have a poor outcome. And it means with a better drug, as we believe ridinilazole is, you can, with a reasonable number of patients, expect to show superiority over that, if you have a better drug. So, our primary endpoint, as you know, is sustained clinical response. So, you need to be cured at the end of treatment and then not have a recurrence in the in the next 30 days. We have a whole host of secondary endpoints. But, the ones I'll really focus on, looking for not inferiority on the initial cure, looking at the recurrence rates. But we also look at recurrence not just at 30 days, we look at 60 days and 90 days, so we can look at the longer term follow-up of these patients. So, those are the sort of clinical endpoints of real focus. You asked about the health economic outcomes, we don't expect that those will be included in the label. But, they are of key importance for the payers and when they look at their cost models. And so, length of hospital stay, these are actually key metrics. It's very expensive to be in hospital. If we can reduce hospital stay, that's important. And readmission rates are really very important. And they're not just important for the cost of the hospital; you have to cover the overall treatment cost of the patient. There also a metric used in overall performance measures for hospitals. And hospitals can be penalized a significant part of their overall Medicare, Medicaid fees, if the readmission rates rise above a certain threshold. And while readmission rates across the whole hospital are driven by a number of things, readmission rates of the CDI is something they can probably do something about. So, it's one of the measures that with a drug like ridinilazole, you can actually have an impact on. So, we think these will be very powerful drivers for the adoption of the ridinilazole.

That's great. And I know 2018 was a tough year with DMD, but it's really -- I really know, that has been extremely interesting to me to see two very robust Phase 3 trials and sort of all of this data that you're accruing that you're starting is exciting for me. On the gonorrhea candidate, one question I have is, I know that Scott Gottlieb has left the FDA. But, FDA has changed in the last few years; it's been more thoughtful about bringing candidates to the market hopefully sooner rather than later where they show where there is a high unmet need with good clinical data. Is there any way or pathways whereby you could fast track or speed the gonorrhea candidate to market, depending on the data of course. And if so, what could they be or is that really less likely in the infectious disease division? And again, thank you so very much.

Yes. So, actually, I’ll answer this more broadly for all our development candidates coming after ridinilazole. And that is that there is a really high unmet need here. And there are pathways to getting faster approvals and faster clinical trials. And that's what we're looking very hard at, not just for the gonorrhea program but also for our ESKAPE pathogens. The U.S. introduced this LPAD system for high unmet need areas of key interest, hasn’t had a great success so far. And it's -- one of the examples is Achaogen trying an LPAD route for their bloodstream infection with Zemdri. But, they didn't deliver on the trial that they'd agreed with the FDA. So, I think it's unfair to sort of cast any kind of aspersions on the process itself, as I don't think that's a blue chip example. So, I think there is an accelerated pathway through. And there is also some things that companies can do to learn from the cancer space and particularly when we're looking at more precision antibiotics. And if you're looking at antibiotics, the target at particular organism, then I think there are some learnings we can take from the switching cancer therapy from broad spectrum chemotherapy to more targeted agents. So, yes, we're working very hard to try and come up with innovative development pathways, which will give a faster throughput and also result in superiority claims that mean that physician will be able to identify group of patients, which the new drug should be the standard-of-care. So, I think, there is a lot of innovation that we can put into development here with these new and narrow spectrum new mechanism of action products. And certainly all the indications are that the regulatory authorities, both in Europe and particularly in the U.S. would be amenable to those faster development pathways.

Glyn, actually just one other follow-up, just to that specific point. So, if there is a high correlation in terms of preclinical and clinical data on efficacy and safety, unless you say again the Phase 1 and you do something analogous to Phase 1/2b cancer trials where you do safety and efficacy at the same time while you're doing dose ranging. And I'm not suggesting that's what's going to happen with the gonorrhea or the ESKAPE pathogens. But, if you were to go something analogous to that, could you actually start getting favorable feedback from regulators in your early stage development about a faster track or do you think in this division, it’ll still take more time for them to sort of give you visibility of how quickly you can get to market? Again, thank you.

I think, you will get more feedback. I think, what you can't do is compare the oncology division today with infectious diseases today. Infectious diseases are starting 15 years behind. So, I think it'll be a big improvement on I think of what we've seen from traditional antibiotic development for traditional broad spectrum agents, I think you have to have a targeted agent, you have to have a specific group of patients for whom you're developing. But, I do think we will get feedback and we will be able to shorten some of these development times, provided you got an agent that's truly innovative and group of patients where there's a high unmet need.

Thank you. Your next question comes from the line of Tim Chiang of BTIG. Please ask your question.

Hi, Glyn. You mentioned outcome studies. What's the possibility that you might be able to work with some of the U.S. hospitals to also potentially expedite enrollment of your Phase 3 studies? I think, in your Phase 2 study, you had about 100 CDI patients recruited, around 30, 35 sites in North America. Could talk a little bit about just how many sites you’re going to enroll in North America for the two pivotals? Is there a chance enrollment could be faster?

Yes. That's a good question. I’ll be able to answer that later because we have an investigator meeting in the U.S. for our U.S. site this weekend. But, the guidance we’ve given on enrollment has been placed on the average enrollments across the last three large Phase 3 studies in CD that we're looking at approximately this population. So, that's the cadazolid study, the surotomycin study and bezlotoxumab studies. And if we look at the enrollment per site per month, we’ve used the same average rate that those have done, and that's how we’ve come to giving you this guidance. Worldwide, there are going to be about 300 sites involved in these studies, and about a third of those will be in the U.S. Although we expect about half the patients to come from those sites because U.S. sites in previous studies have proved to be good enrollers as we do that. Now, it is possible, we will be able to enroll faster than that because all three of those studies were effectively going on at the same time. So, there were three big Phase 3 programs trying to enroll from the same sites at the same time, whereas today as we sit there, there's only us as a large Phase 3 study in this particular patient population. But, I think we should stick with the guidance. Now, let's review where we are in, at the end of the year once we’ve got a chunk of enrollment under our belt. And we can see what the actual enrollment rate is. So, I do think there is a possibility to enroll faster, but I’m not going to change our guidance until we’ve got some experience. But, the sites are well motivated where we've got a good turnout in our meeting in Texas at the end of this month -- this week, sorry. And I think the signs are really good and we're looking forward to getting this study done as fast as we can.

Glyn, just one follow-up. I noticed that you -- on clinicaltrials.gov, you sort of list out the key secondary outcome measures. Are some of those secondary outcome measures more important for the hospital community? Of course, the primary outcome measure is certainly very important. But, can you just talk a little bit about what other outcome measures hospitals are going to be looking for as you enroll patients and complete these two pivotals?

Yes. I think, we discussed that a little bit with Hartaj's comments. And everyone, all the stakeholders, patients in particular are going to be interested in the primary endpoint, because it captures the essence of the unmet need. Are we curing patients and are managing to sustain that cure? That's what patients want to know and that's what the physicians will want to know on behalf of the patients. Now, that's a composite endpoint, and no one to then break that down and look just to make sure that we’re getting the initial cures as well as the reduction in recurrence rates. So, I think the key secondary endpoint is going to be this cure. After that, I think interest diversion, the payers start getting interested in things like the length of hospital stay and readmission rates, because they have a direct financial impact on the profit or not, but they'll make from the individual patient, whereas, I think the patients are going to be interested in -- and the doctors are going to be interested in well is this sustained response continued over the longer period, is it the 60 or 90 days that those really help. From a scientific point of view, we're also going to be interested in some of the microbiome measurements that we make, because the basic hypothesis though, I think we've demonstrated really well through developments is the reason we're getting this superior performance in terms of the recurrence is that this is a very narrow spectrum agent and that we have a minimal impact on the microbiome. And so, there still be a large elements of microbiome in this. And the data from that should really help us about the science behind that. And as you know, we continue to publish really interesting data from our Phase 2 study, including recently some interest in terms of biology. So, the whole scientific reason why the drug performed so well is emerging from the Phase 2. And we expect to get many more publications and more data from these secondary endpoints in the Phase 3. But, I don't think any of these secondaries count unless you meet the primary endpoint. And if we’re superior to vancomycin on the primary endpoint, that's going to be the biggest driver of patient uptake and hopefully allow us to become what we should be, which is the standard-of-care for the frontline treatment here.

Thank you. Your next question comes from the line of Joseph Hedden of Rx Securities. Please ask your question.

Good afternoon. Thanks for taking my questions. Just one on the gonorrhea program. Being as the rise of so called super gonorrhea strains, it's kind of attracting quite a lot of media attention. Is that, do you see an increasing in the competitive landscape? Are there any other kind of candidates out there, are they looking to kind of capitalize at the moment. And also just one on the ESKAPE program, I was wondering when we might see a first candidate in the clinic for that? Is there anything you could say about that?

Yes. So, there are other drugs in development for gonorrhea. The two most advanced GSK’s gepotidacin and then there's the Entasis drug as well which is being developed by GARDP. So, they are ahead of us in development, but not without their issues. And there are some earlier stage ones as well. So, as with a number of these things that it's not without that competition. The acute problem with gonorrhea is there's nothing else approved. And what would normally happen is the World Health Organization would announce that resistance rates have reached the point where we need to switch to the next one. And unfortunately, there is no next approval. So, we really, as society, desperately need, not just one new drug to come through but we need one followed by another, followed by another in due course, because resistance will come to these drugs. We have the advantage of being a totally new mechanism of action. And we think that's fundamentally puts us in a strong position, should the drug be successful in its development program. We had a number of questions about the super gonorrhea. And from -- a patient who's got super gonorrhea, obviously, it's really important that they are able to have a new treatment that solves that. But, we see the opportunity by new mechanism of antibiotics, not just to treat to be the last line of the treatment for these multiple resistant cases. We really see that with new mechanism, narrow spectrum agents, we have the opportunity to become standard-of-care and equally potent against the non-resistant and the resistant strains. And we think that's the opportunity to develop further gonorrhea product and also as we look in the ESKAPE pathogens too.

Thank you. The next question comes from the line of Yun Zhong of Janney. Please ask your question.

Hi. Thanks for taking the questions. So, on the gonorrhea program, and I believe the Phase 1 is on track to be imitated in the second half of this year, and wonder whether there would be any efficacy signal or activity signal in addition to safety and tolerability from the Phase 1 study. And then also, upon positive data, and this might be redundant to a previous question, but is the pathway still a typical Phase 1 followed by another Phase 3 to confirm the efficacy in patients, and what about the timeline, if you have considered anything about the timeline? Thank you.

We're not giving any guidance about timelines including whether it will be Phase 1 followed by Phase 2, Phase 3 or it will be a more abbreviated one. But, I’ll just refer that there is a lot of innovation in development possible with these now spectrum agents. But, we have to look at our data. We have to have a discussion with the regulatory authorities and then, we'll announce what the detailed plan is. I think, whatever your plan is, the initial patients will be or the initial first in man is likely to be focused on safety that I think with all these drugs, there is a potential to do Phase 1/2. We're not confirming that that will be the case with these and whether we'll be merging patients into the healthy volunteers. But, we're exploring all these opportunities, because the opportunity -- there is a great economic benefit that you can get to market more quickly. There is a great value proposition, if you can start getting patient data sooner. And obviously from the patient's point of view, if we can get these new antibiotics into widespread use that is going to have a massive impact for human health. So, can't confirm exactly what the plans will be for this year, but we're certainly actively looking for all these drugs, that ways that we can accelerate the development path and be very innovative about the way we do that.

And a quick follow-up question. Are you able to disclose what kind of milestones are required for you to get the remaining £2.5 million grant payments please?

Hi, Yun. Yes. We guided that we need to get through to the end of Phase 1 in order to receive the full money from the CARB-X grant to gonorrhea. And we have more details in the 6-K filing made; we guide you to have a look at those.

Thank you. And our next question comes from the line of Gary Waanders of Bryan Garnier. Please ask your question.

I have a couple, if I may. The first one is, can you comment at all on any observed resistance to 571 in gonorrhea in the preclinical setting? And the second is more about the strategy of superiority versus non-inferiority. And I wonder -- while I completely the argument, I wonder if you could comment on the statistical burden in terms of trial size that you need to for the superiority compared to non-inferiority. Thank you.

Yes, two good questions, Gary. So let's take the first one first. Obviously, we're not in patients with 571, but one of the huge advantages of a new mechanism is that while there may be some organisms that have developed mechanisms that get round older mechanism antibiotics, it's the first time they’ve been exposed to this. And so, effectively, for all of clinical strains that we've tasted in vitro so far with 571, we see virtually identical potency. And that's with comment on guidance [ph] strains, if I dare say, with strains and resistance to one particular antibiotic or with the super gonorrhea strains that are multiple resistant including we've actually tested this against some of the strains that have made the headlines for the difficulty of being treated here in the UK. So, we see virtually identical potency across all those. And that's just a function of the new mechanism. And there are traditional ways of measuring propensity to resistance, which involves serial passage, as you know, and we selected a candidate in 571 that that shows extreme resistance to developing any resistance in the organism. That's not to say that resistance will never develop if the drug gets to market. But, it doesn't seem to develop rapidly in serial passage. So, we are very optimistic about it, both in terms of its potency and its ability to get round current resistance mechanisms. Obviously, there is a number of steps before we get into the clinic as we need to complete the stocks [ph] package and all these kinds of things. But so far, it looks really promising. And I didn't write down your second question, because I thought I’d remember it. I’ve completely forgotten it.

It was regarding the statistical burden for non-inferiority versus superiority?

Yes. So, it's a really good question. And I think, the answer is, if you've got something that a treatment that is currently working pretty well, let's say 90% cures in patients, then showing non-inferiority, there is probably the way you would go if you had a new treatment. Because to show any statistical superiority on something that's 90% effective, we see it in cardiac treatments. You need tens of thousands of patients to do that. But, if like C. diff, you have an endpoint where the current treatments are giving say 60% positive outcome, then there is room to show superiority in any manageable number of patients. So, part of what we need to do when we’re selecting what trials to do and what drugs to develop is to look at those areas of high unmet needs. If current treatments are working pretty well, there isn't an unmet need; you shouldn't be developing drugs against them. And one of the great powers we have with the Discuva platform is we're able to choose which organisms to go for and we’re choosing those organisms where there's either a high or a growing unmet need. So, we may not be able to do superiority studies in -- with every development. But, unless you can -- unless there's an unmet need, unless there is something where you can show your drug satisfies that and this is better in some respect, it may not be your primary endpoint, then why are you developing it? So, we will be choosing those indications where there's a critical problem at the moment. And that's -- that'll be our focus.

Thank you. [Operator Instructions] And your next question comes from the line of Julie Simmonds of Panmure Gordon. Please ask your question.

Thank you. Just wondering, in terms of the ridinilazole trial that is ongoing at the moment, are you happy about the rate at which the new sites are opening? Clearly, you've got your U.S. investigator meetings this weekend. But, in terms of sort of site, trial site, is that all progressing as planned?

Hi, Julie. Thanks for calling in. Yes, we are, and this is a truly global study. And we have -- we're getting our regulatory approvals in and sites opening, we're really quite pleased with that. I evaded the question earlier about recruitment rates, and we don't intend to give a blow by blow rate, but obviously you can't recruit until you’ve got the sites opened. So, that's the first stage and we're pretty pleased with that. Our focus has been the U.S. We opened the U.S. first. If you look at other C. diff studies, which is different to many other infectious disease actually, the big recruiting sites, the higher recruitment rates have been in the U.S. And that's why we’ve really focused our initial activity on getting the U.S. open first and getting the U.S. sites opened first. But, other countries are coming along. So, the approval for [indiscernible] place is the day before yesterday. So, yes, the rates -- the other sites are coming on, as planned, and we're pretty pleased with that.

And just switching to gonorrhea product. Clearly, you've got 571 and then another behind that. Is the reason that one is on hold because you won't find out more information on 571 or is it purely financial? And if that's the case, is there possibly of getting non-dilutive funding for that one as well, or do you think sort of used up your opportunity in gonorrhea because of the 571?

No. Actually, there is opportunity to get non-dilutive funding for the other program. But, one of the great things about the Discuva platform is we have a whole host of potential new antibiotics for other things. And I think over time, the world will need another mechanism after the 571 mechanism. But, we, in terms of our priorities, we would rather get several antibiotics out of our ESKAPE program before we started putting effort into the next gonorrhea program. We will do that, and it is actually progressing, but not with great alacrity because our focus is on other infections where there is we think a higher unmet need.

Thank you. We do have further question. Do you wish to take this?

Absolutely, we do. Yes.

Thank you. Your next question comes from the line of Dewey Steadman of Canaccord. Please ask your question.

Hi. Good morning and thanks for squeezing me in. I just had a quick question on meeting [ph] coming up in the coming weeks, what presentations should we be watching for at the conference? And what do you think will be most critical to advancing the Summit story going forward at the conference?

You must have a webcam over my shoulder, because I was already to tell everybody on this call exactly what was coming up at meeting. [Ph] But, Richard, kicked me on the shins and said there is an embargo and I'm not allow to do that. But the abstracts are going to be public and we'll be able to show that in about a week’s time. So, I'll be able to do that, but I encourage you to look at the abstracts in about a week’s time. And I think you'll be excited as I would be as I nurse my bruised shins.

Well, thank you. And I'm looking forward to reading those next week.

Thank you. There are no further questions. Thank you for participating, ladies and gentlemen. You may now disconnect. Speakers, please stand by.