Arrowhead Pharmaceuticals - Earnings Call - Q4 2017

Transcript

Speaker 0

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals Conference Call. Throughout today's recorded presentation, all participants will be in a listen only mode. After the presentation, there will be an opportunity to ask questions. I will now hand the conference call over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead, Vince.

Speaker 1

Thanks, Liz. Good afternoon, everyone. Thank you for joining us today to discuss Arrowhead's results for its fiscal twenty seventeen fourth quarter and year ended September 3037. With us today from management are President and CEO, Doctor. Christopher Anzalone, who will provide an overview of the quarter Doctor.

Bruce Given, our Chief Operating Officer and Head of R and D, who will discuss our near term clinical candidates and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financials.

Speaker 2

We will then open up the

Speaker 1

call to your questions. Before we begin, I would like to remind you that comments made during today's call contain certain forward looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than statements of historical fact, including without limitation, those with respect to Arrowhead's goals, plans and strategies are forward looking statements. These include statements regarding our expectations around the development, safety and efficacy of our drug candidates, projected cash runway and expected future development activities. These statements represent management's current expectations and are inherently uncertain.

Thus, actual results may differ materially. Arrowhead disclaims any intent and undertakes no duty to update any of the forward looking statements discussed on today's call. You should refer to the discussions under Risk Factors in Arrowhead's annual report on Form 10 ks and the company's subsequent quarterly reports on Form 10 Q for additional matters to be considered in this regard, including risks and other considerations that could cause actual results to vary from the presently expected results expressed in today's call. With that said, I'd like to turn the call over to Doctor. Christopher Anzalone, President and CEO of the company.

Speaker 2

Chris? Thanks, Vince. Good afternoon, everyone, and thank you for joining us today. 2017 has been an enormously productive year for Arrowhead as we moved forward from the very difficult decision in 2016 to discontinue development of prior generation drugs, ARK-five twenty, ARK-five twenty one and ARK AT that utilize the EX1 delivery vehicle. That decision moved us from a clinical stage company with two Phase II candidates and one Phase I candidate to a preclinical stage company overnight.

In addition, at that time, we had not disclosed much about our new platform and had not given guidance on timelines for getting back into the clinic. Understandably, there's a lot of uncertainty for investors about where Arrowhead was going. We were clearly on our heels, but the real medal of a company only makes itself known in the face of adversity. As we look back on what we accomplished and forward to what is to come, I'm extraordinarily proud of this company. We are on pace to file two CTAs to begin clinical trials during the next two quarters.

These are for ARO AAT to treat alpha-one liver disease with a CTA planned in Q1 twenty eighteen and ARO HBV as a potentially curative therapy for chronic hepatitis B infection with a CTA planned in Q2 twenty eighteen. We think the insights gleaned from our prior programs in HBV and alpha-one liver disease represent real competitive and strategic advantages and should enable us to move with speed and precision once the clinical programs begin. We are also on schedule to file three additional CTAs in the next twelve months. These are for ARO APOC3 and ARO ANG3 to treat hypertriglyceridemia and ARO Lung1 against an undisclosed lung disease target. All three are planned for CTA filings around the end of twenty eighteen.

In addition, our two cardiovascular collaborations with Amgen are moving forward rapidly. One which was previously called ARO LPA against the target lipoprotein A or LP, has been formally nominated as a clinical candidate and which is now referred to as AMG eight ninety by Amgen. We anticipate that this may enter the clinic sometime in 2018. The Amgen deal was announced in September of twenty sixteen and Arrowhead received $56,500,000 in upfront payments and initial equity investment. And we are eligible to receive an additional $617,000,000 in potential milestone and equity payments.

So we plan to go from zero clinical programs to five or possibly six over the next twelve months. I don't believe I have ever seen any biotech company do this. The table is now set for a potential breakout 2018 and 2019 as the makeup of this company changes dramatically and we see how these drug candidates perform in patients. Let's now unpack this a bit and take a look at these programs. First, they're all built on a new platform.

In September, hosted an R and D Day to unveil the new targeted RNAi molecule or TRiM platform that builds on more than a decade of research at Arrowhead on actively targeted drug delivery vehicles. We view TRiM as an evolutionary step for the field of RNAi delivery. The TRiM platform retains the maximal activity of prior generation technologies but moves towards structural simplicity that offers several advantages. These include: one, simplified manufacturing and therefore reduce costs two, multiple routes of administration including subcutaneous injection and inhaled administration. And three, potential for improved safety because smaller molecules with reduced metabolites may reduce the risk of intracellular accumulation.

Also the TRiM platform does not rely on DPCs so we expect substantially wider safety margins than we had in previous generations. ARO AAT is a good example of what we believe TRiM can do. It appears to be more potent than ARC AAT and provides a longer duration of activity, but we expect a significantly better safety profile. In addition, much of what we learned from the ARK AAT program gives us confidence in ARO AATs. First, potency of ARK AAT, our previous generation compound, in nonhuman primates was predictive of potency in humans.

Should this hold for ARO AAT, we would expect monthly or even less frequent dosing to provide near complete suppression of hepatic sources of AAT. Second, knockdown in healthy volunteers was similar to knockdown in patients. If this holds for ARO AAT, we could predict proof of concept, at least as it relates to activity, early in Phase I. Similarly, our experiences with prior HBV programs have guided many of our plans and expectations for ARO HBV. We have always believed this, that a sufficiently potent and well tolerated RNAi based therapy could enable S antigen seroclearance and functional cure of chronic hepatitis B infection which has been elusive for other drugs and mechanisms.

Our case for the potential importance of ARO HBV toward this goal has strengthened last week when we presented new data at the HepTAR conference from the ARK-five 20 open label extension study. Specifically, we showed that fifty percent of patients in the follow-up study or two of three E antigen positive and two of five E antigen negative patients have achieved a sustained host response after receiving ARK520 treatment in combination with entecavir characterized by continued reduction of multiple HBV viral markers including S antigen and coinciding with an increase in ALT indicative of host response. So what does this mean and why should you care? Well, goal has been to silence everything the hepatitis B virus makes and thereby enable the body to overcome immunosuppressive forces and control the virus on its own. ARK-five twenty appears to have done something that enabled the host to fight the virus on its own even after ARK-five twenty was withdrawn.

And this is a big deal. It is the first clinical evidence that an RNAi based approach can lead to the type of favorable sustained host response that we have always believed is possible and in fact critical if a functional cure is to be reached. If this was in fact a marker of the immune system being reawakened then it bodes very well for ARO HBV. When considering these results in the context of ARO HBV keep in mind that ARK520 was a suboptimal therapy in part because it could only silence gene expression from CCC DNA. This leaves continued production from viral DNA that integrated into host DNA unchecked.

And we have demonstrated that integrated DNA can be a major source of S antigen production. Therefore ARK520 was fighting the virus with one arm tied behind its back. It was only targeting one source of immunosuppressing S antigen. Importantly, ARO HBV may be substantially more active against S antigen than ARK520 since it was designed specifically to hit all viral mRNA transcripts from both CCC DNA and integrated DNA. We also have reason to be optimistic about our newly announced hypertriglyceridemia programs, ARO ANG3 and ARO APOC3.

Angiovoyant three and apolipoprotein C3 are validated targets that are independent risk factors for cardiovascular disease and they are not effectively addressed by traditional therapies. In addition to large cardiovascular market opportunities, these targets are associated with smaller orphan indications as well, providing multiple regulatory pathways and market approaches. This flexibility is important in part because it offers strategies that could involve partnering or keeping candidates in house for internal development. Finally, we believe that our new lung programs represent a fundamental leap forward for RNAi generally and for Arrowhead specifically. In multiple animal models we have been able to deeply silence lung targets via inhaled administration.

This capability is a good example of the flexibility of the TRiM platform and addressing lung targets will open a host of new opportunities. Once we validate the first program whose target remains undisclosed, we view the lung targeting TRiM technology as a franchise unto itself. We will provide additional details on the initial program as well as more data in 2018. With that overview, I would now like to turn the call over to Doctor. Bruce Given, our COO and Head of R and D.

Bruce?

Speaker 3

Thank you, Chris, and good afternoon, everyone. Chris mentioned that ARO AAT and ARO HBV are on pace for CTA filings during the first two quarters, and then we anticipate having up to three additional CTAs before the end of twenty eighteen. These are all very exciting programs for us. Today, I wanna focus just on ARO AAT and ARO HBV since they are our current lead programs and are on pace to get into the clinic shortly. I will go over two areas for each candidate.

The therapeutic rationale for the target and select data that provides us with confidence in the candidate's potential. Let's start with ARO AAT. Alpha one a trypsin or AAT deficiency involves a genetic mutation that causes the AAT protein to be misfolded and thus not properly exported from hepatocytes. This causes two downstream issues for patients with this disorder. First, AAT protects tissues from inflammation and damage.

Patients that have the misfolded protein have low circulating levels of AAT, which can lead to early onset lung disease. Second, since the protein is not properly exported from the liver, it accumulates and then aggregates into polymers and globules inside the cell. So the lung disease is due to deficiency in functional AAT, but in the liver it's a storage disease. There are approved protein replacement therapies for the lung disease, But at this time the only option for treating the liver disease is transplant. There are estimated to be around one hundred thousand potential patients in The US and possibly more in Europe with alpha-one antitrypsin deficiency.

Based on those numbers, it qualifies for organ disease designation but it is one of the more common rare diseases. RNAi as a mechanism is very good at halting the production of an individual protein. So we think alpha one liver disease, is clearly caused by the accumulation of the misfolded mutant AAT protein, is a very attractive therapeutic target. We have done extensive work with the transgenic mouse model that produces the human z mutant protein, which is the one we care about. Unfortunately, this model recapitulates several aspects of the human disease well.

The mice have problems secreting the z protein, but they do get some out of the circulation just like humans. The z protein and hepatocytes forms polymers and globules. Their livers get inflamed and they develop hepatocellular carcinoma as a result. We completed separate studies in which we intervened early in disease progression during mid stage and then also in older mice that had started to develop hepatocellular carcinoma. We really wanted to confirm that RNAi was the right approach here.

In young mice, we demonstrated that we could virtually eliminate their monomer production, and they had less polymer and globules just eight weeks later than they had at baseline and substantially less than mice that had gone untreated over the eight weeks. The liver is doing what we would hope. In older mice that already have a lot of globules in their liver at baseline, when treated for thirty two weeks, their livers moved a long way back towards normal. They had minimal to moderate globules but much less. They also no longer had compressed nuclei which were present at baseline and which were seen in mice treated with placebo.

Treated mice also had no inflammatory cells. When we studied older mice, we also saw significant benefit from treatment. The liver architecture of treated animals improved and they had a clear reduction in hepatocellular carcinoma. These results provide us with confidence that RNAi based therapy like ARO AAT has a lot of promise against alpha-one liver disease. In addition to the work we've done in mice, we have also looked at knockdown of circulating AAT in primates and we also have clinical experience with our prior generation compound ARC AAT.

In primates, ARO AAT led to a reduction of circulating AAT of over 90%. Keep in mind that about 10% of AAT is produced outside the liver, so we believe 90% knockdown represents near full suppression of the liver produced protein. The duration of effect in primates was long, which may enable a monthly, bimonthly or even longer dosing interval. As Chris mentioned, we intend to file a CTA for ARO AAT in Q1 twenty eighteen. We are excited to get back into the clinic and we've designed an innovative first in human study that is intended to generate single dose and multiple dose data rapidly in one study.

We will discuss this design in further detail when the study is initiated. Now to HBV. There are estimated to be between two hundred and three fifty million people chronically infected with HBV and it is a difficult to treat virus for which curative therapies have been elusive. HBV is clearly a global health problem that needs to be addressed. The current standard of care involves nucleotide and nucleoside analogues or NUCs that inhibit reverse transcriptase.

This class of drugs is very good at reducing circulating virus but does almost nothing to improve functional cure rates over patients who receive no treatment at all. Many experts believe that HPV infection remains chronic because in addition to fully formed viral particles, the virus produces a large excess of viral proteins that silence the immune system and prevent the body from exerting immune control. At Arrowhead, we sought to develop a therapy that reduces the production of all HBV gene products including pre genomic RNA, polymerase, the core protein that forms capsid, surface antigen, e antigen and the X protein. We believe deeply reducing everything that HBV produces may allow the body's immune system to reconstitute, leading to a sustained host response and ultimately a functional cure of HBV. I'm sorry here, I just lost my place.

Here we go. In fact, we recently presented some follow-up data on ARK-five twenty that we think represents the first clinical evidence that an RNAi based approach may lead to the type of favorable sustained host response that we have always believed is possible. Just like other difficult to treat viruses, HBV will likely require a combination approach. So how do we see a central role for an RNAi therapy like ARO HBV? Because we attack the entire transcriptome and that's most important to us I think, any other direct acting HBV drugs are going to be enhanced by RNAi because we reduce the inputs.

We reduce the stress on these drugs and we have already seen synergistic effects with NUCs. Also RNAi has been the only way to date to address s antigen coming off of integrated DNA. So from our perspective, anybody who wants to have the best possible chance of achieving a functional cure better have an RNAi in their combination regimen. I recently had the opportunity to present some select preclinical data on ARO HBV. Notably three doses of ARO HBV monotherapy in wild type plasmid HBV mice led to reductions in HBV DNA of 3.44 logs and both S antigen and E antigen dropped below the level of quantitation.

This represents reductions of greater than three logs and greater than 2.2 logs respectively. In addition, Arrowhead created a mutated plasmid HBV model that eliminates the HBX trigger site to simulate HBV patients with high levels of integrated HBV DNA relative to cccDNA. In this model, a single dose of ARO HBV led to a reduction in s antigen of 2.95 logs. The duration of effect was long and s antigen was still reduced by approximately two logs at eight weeks following the dose. This is highly encouraging and ARO HBV was very active in these models.

We plan to file a CTA by Q2 twenty eighteen and like ARO AAT, we intend to generate as much single and multiple dose data as we can in our first in human study. Importantly, we intend to include HBV patients during phase one in the multiple dose ascending portion of the study. As with ARO AAT, we will provide further detail when the study is initiated. Now I'd like to turn the call over to Ken Myszkowski, ARO Head's CFO, who will review our financials. Ken?

Speaker 4

Thank you, Bruce, and good afternoon, everyone. As we reported today, our net loss for fiscal twenty seventeen was $34,400,000 or $0.47 per share based on 73,900,000.0 weighted average shares outstanding. This compares with a net loss of $81,700,000 or $1.34 per share based on 61,100,000.0 weighted shares outstanding for fiscal twenty sixteen. Revenue for fiscal twenty seventeen was $31,400,000 compared to $158,000 for fiscal twenty sixteen. The increase is driven by the upfront payments received from our collaboration agreements with Amgen.

During fiscal twenty seventeen, we have recognized revenue for all but $5,300,000 related to the Amgen agreements and we expect to recognize the balance in fiscal twenty eighteen. Total operating expenses for the year ended September 3037 were $68,400,000 compared with $81,900,000 for the year ended September 3036. Net cash used in operating activities in fiscal twenty seventeen was $23,900,000 compared with $64,400,000 for fiscal twenty sixteen. Our R and D expenses declined from $41,500,000 to $31,700,000 primarily due to discontinuation of our previously of our previous clinical candidates in November of last year, although closedown expenses continued into the fiscal second quarter. Salary and payroll expense also declined due to the workforce reduction we put in place after the discontinuation of our previous clinical candidates.

General and administrative expenses also declined primarily due to a reduced professional services expenses. Turning to our balance sheet, our cash and investments totaled $65,600,000 as of September 3037 compared to our cash balance of $85,400,000 at September 3036. The decrease in our cash and investments balance reflects cash used in operations of $53,900,000 and $7,800,000 of capital expenditures, primarily related to the build out of our new research facility in Madison, offset by 42,500,000.0 in cash received from Amgen consisting of $30,000,000,000 upfront payment for ARO LPA and $12,500,000 in additional equity investment. Our common shares outstanding at September 3037 were $74,800,000 With that brief overview, I'll turn the call back to Chris.

Speaker 2

Thanks, Ken.

Speaker 3

As you can see, we've had an

Speaker 2

incredible amount of progress throughout 2017. We believe that 2018 is set up to be transformational. Transition on to the TRiM platform has been rapid and we expect to file CTAs for five drug candidates in calendar twenty eighteen where we believe we have strong competitive advantages. We are clear leaders in alpha-one liver disease and expect to be the only company with a clinical candidate against this manifestation of alpha-one antitrypsin deficiency in the first quarter of twenty eighteen. We are clear intellectual leaders in chronic HBV and expect to be once again development leaders in RNAi treatment of HBV.

We believe that RNAi will become a backbone therapy for HBV and we plan on being back in the clinic in the second quarter with what we see as the first RNAi therapeutic with a real chance of enabling functional cures. We are leaders in RNAi for cardiovascular disease and believe that Amgen, with the candidate we developed, will be the first company to use RNAi against LP in humans. Similarly, we expect to file CTAs for ARO ANG3 and ARO APOC3 by the end of twenty eighteen and that we will be the first company to use RNAi against angiopoietin three and apolipoprotein C3 in humans. We are also now leaders in RNAi for lung targets. This opens a new chapter for us and enables us to go after diseases in ways no other company is capable of at present.

We expect to file a CTA for our first lung candidate by the end of twenty eighteen and believe we will be the only company with a viable approach to using RNAi against lung diseases with inhaled administration. This is certainly a lot, but given our nonclinical data and experience in AAT and HBV, we feel comfortable with these aggressive plans. It is also safe to assume that we will continue to build our pipeline in 2018 and that we will go after additional high value disease targets where new therapies are badly needed by patients. Our ability to create new potential medicines outstrips our ability to develop them all into marketed products, at least for now. Therefore it makes sense to do more collaborations like we did with Amgen last year for some of our programs.

The world has seen how fast we were able to move over the past twelve months and that the TRiM technology may be optimized to address a variety of target tissues. So we believe we are well positioned to attract high quality partners to maximize the number of products we can ultimately get to patients. It has been a very productive 2017 and we look forward to an exciting 2018. I would now like to open the call up for your questions. Operator?

Speaker 0

Our first question comes from the line of Catherine Zhu with William Blair. Your line is now open.

Speaker 5

Hello?

Speaker 2

Hi, Catherine.

Speaker 5

Hi. Hi. Good afternoon. Thank you for the call. I have a few questions.

First, I'm just wondering, given the very interesting data that you saw with the a r a r c five twenty, do you think we would need to in the future, you would need to stop treatment to get the immune response, or you just keep treating until you drive everything down to zero and then remove to see a response? Or do you think that during the treatment period, you would see that response? And my second question is, what is the timing of the approval concept for ARO AAT and ARO HBV, are we going to see the proof of concept data in 2018? And lastly, on the safety side, apparently, this is most important for the new platform. Can you comment on any incremental information you can provide?

I understand that there was very good therapeutic large safety margin in the acute tox study. Any incremental information since then on the GLP tox and and and other safety aspects? Thank you.

Speaker 2

Okay. So help me let me know if I forget any of the three here. So with respect to the first question about needing to stop treatment with ARO HBV to see a sustained host response? The answer is we don't know. That's a good question.

That was certainly not the intention for ARC-five twenty. We had to discontinue that program and so we were able to follow a handful of patients after that. But we'll just have to see. We think that ARO HBV is going to be a powerful drug here because it's going to it's designed to knock down S antigen coming off of both CCC DNA as well as integrated DNA. So it's got a shot of knocking down S antigen in a more effective way than ARC-five twenty.

We'll just have to see if that bears out in humans. And if that's the case, the goal right now is to continue to treat and to bring that S antigen down as well as X and other antigens to a level where the body can take over. So that's our plan right now. Could it be that the body needs that jolt of removing therapy? It's possible.

But we just don't know the answer to that at this point. And so right now we're just going to the plan is to dose for a certain period of time and then see what we see. The second question is our call relating to proof of concept data for HBV and AAT. I don't think we want to give too much guidance on that at this point just because we don't know when we're going to start dosing. Once we file those CTAs we'll let you know.

And then once we start dosing patients we will also let you know. Once we're actually dosing patients I think we can give more granular guidance about when we think that we can start to have data. So I think it's best for us just to wait until that happens and then we can talk about it. As Bruce mentioned, I think we've got really good potential protocols there that would give us early readouts. But we need to ensure that those protocols are approved by regulators and that we can start at a reasonable time.

We'll let you know as soon as we know on that. And then the final one with respect to safety, we don't have anything more to say at this point. We do expect a much wider safety margin with the new TRiM platform than with DPCs. We are in GLP talks right now and so once that's finished we'll get into the clinic and see where we are. But we certainly do expect a good wide safety margin with that whole platform.

Speaker 0

Our next question comes from the line of Elmer Burrows with Cantor. Your line is now open.

Speaker 6

Good afternoon, gentlemen. I was wondering maybe if you could help me to understand what is it in the new design that makes this version of the RNAi against HBV more efficacious against even integrated DNA.

Speaker 2

Thanks, Elmer. Bruce, do want to walk through where the sequences are here, at least broadly?

Speaker 3

Yeah, sure. So, you know, Elmer, this is an overlapping transcriptome, you know, at the at the three prime end, but the the X protein is is quite short. And in ARC five twenty, both of the the RNAi triggers were both, you know, targeted in that x region. Now that turns out to be the region that's frequently lost during integration. So in in ARO HBV, one of the triggers is still in that x region, but the other trigger is quite a ways upstream in the s region and in in that that part of the of the DNA that is, you know, almost always preserved during integration.

So, you know, it's, you know, it's that's it's that second trigger being quite safely out of that x region that gives us confidence that that ARO HBV, you know, should also knock down the integrated source of us. And in fact, we we created an animal model to try to, you know, test that hypothesis as best as we could and and that that model gave very good knockdown of the of the s antigen even when the X trigger was essentially, you know, taken out of the picture.

Speaker 2

Very good. And let me just underline one thing, Eleanor. And I know you recognize this, but I want to make sure it's clear to others who are on the call. So when we developed ARK five twenty, the world didn't appreciate the importance of integrated DNA as a source of S antigen. Just wasn't clear.

We discovered that again as you know. And so just by rotten luck we had both of our sequences in ARK520 that were in a region is often lost during integration. Now it turns out that was actually fortuitous because it enabled us to understand this whole new biological force within the virus. But the downside of course was that we were only knocking down one part of produced S. And so now ARO APV, if it works as designed, it's not going to have that floor.

With ARK520 we can knock down only so much that was coming off of CCC DNA but it still left this floor that's being produced by integrated DNA and now the floor is gone. And so it will be interesting to see how much knockdown we're able to get with ARO Anyway so I think that is important to understand.

Speaker 6

Yep, thank you very much for that. And so Bruce if you compare the data that you just presented at HempDOT, the mice data, was the data with five twenty as impressive as this was? If you

Speaker 2

had the So genetic

Speaker 3

for the wild type you know, DNA model, it was very similar, I would say, between ARC five twenty and ARO HBV, although that's a model that's purely indicative of c c c DNA. At that time, we had not created this mutant plasmid model to, you know, to knock out that, you know, our x trigger. So we did not have anything comparable with ARC five twenty. We didn't know to to build that. So, you know, this is but I think with respect to, you know, c c c DNA, you know, derived transcripts, you know, this this would look very similar, I would say, to what was achieved with ARC five twenty.

Speaker 2

Yes. And and also keep in mind, we're talking about s here, and we think s is important. But we know that the other gene products are important as well. And so it's important to point out that we're not just knocking down S, we're knocking down, as we mentioned in the prepared remarks, we think everything this virus is producing. And one of those important ones is X antigen.

Gilead has done some very interesting work that suggests a real importance for X antigen. We think that any RNAi therapy that does not knock down X is going to do it at its peril.

Speaker 6

Okay. And Bruce, in the long term follow-up data that you also presented, the five twenty, I think the RNAi product was given four to seven times or four to nine monthly infusions. At what point was entecavir stopped, or was it continuous?

Speaker 3

So entecavir used in these patients. So they they started at, you know, when they got their first dose of r five twenty, and they are still continuing today of entecavir.

Speaker 6

Got it.

Speaker 3

So that has not been discontinued.

Speaker 6

Okay. Okay. So that probably didn't have an impact on, triggering the host response?

Speaker 3

No. Historically, you know, historically, the the NUCs really do very little for antigenemia. And, you know, the in those rare cases, of course, where where they do give seroclearance, which is extremely rare, then you see the antigenemia fall. But for the most part, the NUCs are well known to not be very helpful, especially with respect to surface antigen.

Speaker 6

Okay. And just a last question to Ken. Ken, how do you envision the cash burn changing now that you're moving back into the clinic with potentially five programs by the end of next year?

Speaker 4

So if you look at our history of our cash burn, this past year we spent about $56,000,000 excluding CapEx and the year before that was probably about 10,000,000 additional when we were heavier into the clinic. So if you look at our historical cash burn when we were in the clinic and expect to see some increase there in 2018.

Speaker 6

Okay. Thank you very much, gentlemen.

Speaker 2

Thanks very much.

Speaker 0

I'm not showing any further questions in queue at this time. I'd like to turn the call back to Chris Anzalone for any closing remarks.

Speaker 2

Thank you all. Happy holidays and we wish you a Happy New Year and we look forward to seeing you in 2018.

Speaker 0

Ladies and gentlemen, thank you for your participation in today's conference. This concludes the program and you may now disconnect. Everyone, have a great day.