Arrowhead Pharmaceuticals Inc (ARWR) 2018 Q1 法說會逐字稿

Ladies and gentlemen, welcome to the Arrowhead Pharmaceuticals conference call. (Operator Instructions)

I will now hand the conference over to Vincent Anzalone, Vice President of Investor Relations for Arrowhead. Please go ahead.

Thanks, Amanda. Good afternoon, everyone. Thank you for joining us today to discuss Arrowhead's results for its fiscal 2018 first quarter ended December 31, 2017. With us today from management are President and CEO, Dr. Christopher Anzalone, who will provide an overview of the quarter; Dr. Bruce Given, our Chief Operating Officer and Head of R&D; and Ken Myszkowski, our Chief Financial Officer, who will give a review of the financials. We will then open up the 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 provide any -- or 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-K 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 Dr. Christopher Anzalone, President and CEO of the company. Chris?

Thanks, Vince. Good afternoon, everyone, and thank you for joining us today.

It's been a short time since we held our last earnings call for fiscal 2017 year-end, but we have already made substantial progress toward our goals for 2018. It was gratifying to see how far we've come in the last 12 months and exciting to see where we are expecting to accomplish in 2018. We are positioned to go from 0 to 5 clinical programs in 12 months and I want to applaud the hard work of all the smart, talented and driven folks at Arrowhead who are making this possible.

Let's begin with the primary goals we have for calendar 2018. They are: one, complete dosing of our Phase I/II study of ARO-HBV; two, complete dosing our Phase I study of ARO-AAT; three, organizing R&D to discuss the new pulmonary platform; four, execute a business development collaboration; five, file a CTA for ARO-APOC3; six, file a CTA for ARO-ANG3; seven, file a CTA for our first inhaled pulmonary program, ARO-Lung1; and eight, present data at appropriate scientific conferences.

All our programs are based on our TRiM platform, which utilizes ligand-mediated delivery and is designed to enable multiple tissue targeting while being structurally straightforward. It is a product with more than a decade of research at Arrowhead using targeted drug delivery vehicles for RNAi.

TRiM technology enables Arrowhead's RNAi therapeutics to retain the maximal activity achieved with prior generation technologies, but with a more structurally straightforward molecule that offers several potential advantages. These include simplified manufacturing and, therefore, reduced costs; multiple routes of administration, including subcutaneous injection and inhaled administration; potential for improved safety; and a promise to bring RNAi to tissues outside the liver, which would represents a big leap forward for the field and a substantial competitive advantage for Arrowhead.

For more comprehensive presentation on the TRiM platform, you can view the webcast recording and R&D Day that we hosted in September 2017, which can be found on the Investors section of the Arrowhead website.

One significant benefit of the TRiM platform is that it allows us to move very fast from an idea to an optimized clinical candidate as demonstrated by the speed at which we were able to advance our 2 lead candidates. ARO-AAT is our second-generation subcutaneously administered candidate for the treatment of alpha-1 antitrypsin deficiency liver disease and ARO-HBV is our third generation subcutaneously administered clinical candidate for the treatment of chronic hepatitis B virus infection.

We went from restarting our preclinical models and designing new triggers at the end of 2016 to selecting final candidates, manufacturing drug supply, completing GLP tox studies and filing CTAs just 12 months later. The ARO-AAT filing was a quarter ahead of guidance and the ARO-HBV filing was 2 quarters ahead of guidance. This was the result of monumental effort by our R&D organization, but also related to our technology and our corporate culture. The TRiM platform allows us to start and advance new product development programs with extreme precision and we are relentless in our pursuit of speed. We look for every opportunity to shave days, weeks and sometimes even months off the development time lines.

Since filing our CTAs, we've had positive interactions with the review committees for both the ARO-AAT and ARO-HBV programs and only a few questions have been asked. Drug will be available at the sites in March and we believe we are on track to begin dosing this quarter, although, of course, this will require final regulatory and IRB approval.

For both candidates, we intend to use fixed dose levels as opposed to dosing on a milligram per kilogram basis. We hope this will simplify the process for pharmacists at the sites and reduce the risk of dosage error. It ultimately, may also give opportunities for simplified commercial dosage forms such as prefilled syringes or other option that make it easier for patients and physicians to administer the products.

We have a good amount of experience with these diseases from our prior preclinical programs that spanned 17 countries and included more than 300 human subjects receiving over 800 dose administrations. Our relationships with influential investigators throughout the world remains strong. This is partly due to the high quality science that underlies our candidates and our proven ability to effectively manage complex clinical studies.

For both candidates, the first-in-human studies will evaluate safety, tolerability, pharmacokinetic and pharmacodynamic effects. For ARO-AAT, the pharmacodynamic measure will be the reduction of serum alpha-1 antitrypsin levels. For ARO-HBV, we intend to assess all measurable viral markers, including s-antigen, DNA, RNA, e-antigen and correlated antigen in chronic HBV patients.

Now let's turn to the other programs in our pipeline. During our R&D Day last year, we talked about our expanded cardiometabolic pipeline, which includes ARO-APOC3 and ARO-ANG3. ARO-APOC3 is designed to reduce production of apolipoprotein C-III or apoC-III, which is a component of triglyceride-rich lipoproteins, including VLDL and chylomicrons, and is a key regulator of triglyceride metabolism. Elevated triglyceride levels is an independent risk factor for cardiovascular disease and severely elevated triglycerides in patients with familial chylomicronemia syndrome or FCS can result in acute and potentially fatal pancreatitis. ARO-ANG3 is designed to reduce production of angiopoietin-like protein 3 or ANGPTL3, the liver-synthesized inhibitor of lipoprotein lipase and endothelial lipase. ANGPTL3 inhibition has been shown to lower serum LDL, serum and liver triglycerides and have genetic validation as a novel target for cardiovascular disease.

Both apoC-III and ANGPTL3 appears to be well-validated targets and could be of interest to large pharmaceutical companies with resources to run large pivotal cardiovascular studies and, ultimately, market such drugs. We believe that ARO-APOC3 and ARO-ANG3 will be the first RNAi candidates against these targets to reach the clinic and that we will have certain advantages against other potentially competing modalities. As such, we believe we are well-positioned to attract good partners for these programs when the time is right to enter into collaborations. We should be on track to file CTAs by the end of 2018 for both programs.

We are also moving forward with disease targets outside liver, the first 2 of which are ARO-HIF2, which is being developed for the treatment of clear cell renal cell carcinoma, and ARO-Lung1 against an undisclosed lung target. ARO-HIF2 is moving toward a planned CTA in 2019 and ARO-Lung1 has a planned CTA around the end of 2018.

We have not disclosed much about our lung targeting programs. We have generated some very promising data showing that after inhaled administration, we can achieve substantial knockdown of lung express targets with long duration of effect. We can foresee a host of new diseases we can attack and multiple targets for each of those diseases. As such, our TRiM-based pulmonary platform feels like a franchise unto itself. This could enable us to drug certain targets in a way that no other company is currently capable of. Needless to say, we see substantial value creation opportunities here.

Our goal is to have an R&D Day around the middle of the year to discuss that program in more detail and reveal our first disease target. We are really excited about this and we will provide more information about the R&D Day presentation in the coming months.

Having a highly reliable technology platform like TRiM gives us far more product development opportunities than we can currently move forward ourselves. Because of this, one of our key strategic priorities is to seek development partners for some of our programs and retain global rights for others. As I mentioned, we see ARO-APOC3 and ARO-ANG3 as potentially attractive partner programs at some point and we see the pulmonary platform as target-rich for collaborators as well.

In 20 -- in September 2016, we signed our first partnership and collaboration agreement for the TRiM platform with Amgen. That deal covered 2 cardiovascular candidates: One against lipoprotein(a) or Lp(a), which is referred to as AMG 890 by Amgen; the second, which we call ARO-AMG1, is against an undisclosed target. We are thrilled to be working with a company like Amgen and both of these programs are progressing well.

ARO-F12 is another candidate intended as a partnering opportunity. It is designed to reduce the production of factor XII, which may provide benefits in both thrombosis and hereditary angioedema. We previously had it listed on our pipeline chart as available for partnering. We will discuss ARO-F12 with interested parties, but we do not currently have a development partner and we do not intend to initiate clinical studies on our own so we have removed it from our pipeline. We will provide updates if this changes.

We see partnering as a way to maximize the value of our technology. It allows us to focus our internal development resources on our lead candidates and also gives exposure to additional high-value opportunities that may be beyond the reach of a small biotech company. In addition, partnering can be an important source of capital that can supplement our need to access the capital markets.

That leads me to our recent equity financing with gross proceeds of $60.4 million. This was a very successful oversubscribed transaction that accomplished several important goals. It strengthened our balance sheet so that we can move our pipeline to key milestones that could represent significant value catalysts. The stronger balance sheet also puts us in a better negotiating position should additional business development opportunities arise. The equity raise also gave us a much improved institutional investor base. Since we discontinued the ARC-520, ARC-521 and ARC-AAT clinical programs in 2016, we have been substantially under-owned by institutions. We still have a lot of opportunities to bring in new funds, but this financing was a good first step toward rebuilding a long-term support of shareholder base.

With that overview, I'd now like to turn the call over to Ken Myszkowski, Arrowhead's CFO, who will review our financials. Ken?

Thank you, Chris, and good afternoon, everyone.

As we reported today, our net loss for the quarter ended December 31, 2017 was $13.2 million or $0.18 per share based on 74.8 million weighted average shares outstanding. This compares with a net loss of $12.1 million or $0.17 per share based on 71.4 million weighted average shares outstanding for the quarter ended December 31, 2016.

Revenue for the quarter ended December 31, 2017 was $3.5 million compared to $4.4 million for the quarter ended December 31, 2016. Revenue in each period relates to the recognition of the upfront payments received from our collaboration and license agreements with Amgen. Of the total upfront payments of $35 million, all but $1.9 million has been recognized as revenue to-date and the remainder is anticipated to be recognized over the next 9 months.

Total operating expenses for the quarter ended December 31, 2017 were $17.3 million compared to $19.3 million for the quarter ended December 31, 2016. This decrease is primarily due to the discontinuation of our previous clinical trials in late 2016.

Net cash used in operating activities during the quarter ended December 31, 2017 was $14.7 million compared with net cash provided from operating activities of $10 million during the quarter ended December 31, 2016. The key driver of this change was the $30 million upfront payment received from Amgen in 2016 associated with our ARO-LPA collaboration and licensing agreement.

Turning to our balance sheet. Our cash and short-term investments totaled $50.7 million at December 31, 2017 compared to $65.6 million at September 30, 2017. The decrease in our cash is primarily driven by cash used in operating activities.

In January 2018, we completed an equity financing issuing 11.5 million shares, which resulted in $56.8 million of net cash proceeds to the company. This financing, along with our existing cash and short-term investments, provided us with more than $100 million of liquid assets which will allow us to continue to advance our pipeline through the clinic for many quarters. Our common shares outstanding at December 31, 2017 were 74.9 million.

With that brief overview, I'll turn the call back to Chris.

Thanks, Ken. We have great expectations for 2018 and believe that the company you will see this time next year will be substantially different than the one you see today. We believe that we are the fastest and most innovative company in the field and, because of this, we are at the door of disruptive opportunity to change medicine and public health in a variety of areas. To both new and existing investors, we think we can accomplish a lot together and we sincerely thank you for joining us.

I would now like to open the call to questions. Operator?

(Operator Instructions) And the first question comes from the line of Katherine Xu of William Blair.

Well, congrats on the rapid progress. But I just want to ask maybe if you could elaborate how come the -- you could beat your guidance by that much with the CTA filing and also how the tox studies had been going, including the GLP tox. Currently, that's a very important part with safety on the TRiM platform that people are concerned about.

Bruce, do you want to take that?

Sure, Katherine. We sort of had to play perfect baseball, so everything had to go kind of flawlessly with the tox program, everything had to go flawlessly with the manufacturing program. And because of that, I think we -- in the end, you had to set a guidance, not necessarily expecting perfection. We, of course, internally -- most people, when they give guidance, they necessarily mean kind of the end of the quarter. I think with our AAT guidance, we were thinking that maybe we would be submitting our CTA sometime in January or so. And with HBV, we were thinking maybe in the April time frame. And we're just -- we're able to execute in such a way that we were able to beat those guidances with both of those CTAs going in essentially between the middle and the last half of December of last year. But we pushed hard to get those in early because we wanted to get into the queue for evaluation early in 2018. We felt that even delaying into January, we ran the risk of not making it into the first set of evaluations by the IRB and regulatory authorities. So it was worth it to us to really push people very hard and do a lot of work in parallel instead of in series. And by doing that, we were able to achieve and produce extraordinary results.

Then the tox observation so far?

Well, we're comfortable with them. The final arbiters of tox are always the IRBs and the reviewers from a regulatory perspective. But we felt comfortable with our submissions and we continue to feel comfortable, but we tend not to give detailed review of our GLP tox and that's pretty true usually in the industry as well, I think.

But we can tell you broadly, look, our confidence in these drugs weren't changed by the GLP tox findings. It was consistent with what we expected.

Yes. We weren't surprised.

And then, is it fair to expect some proof of concept data from both the AAT and HBV programs towards the end of the year and potential partnership deals for the -- for some other programs during 2018?

So we're not prepared to give guidance on proof of concept data yet because we still have not yet started dosing patients. Let's get final approval by the IRBs and final approval by the regulatory agencies. Let's start dosing patients. And at that point, I think we could -- we'll be better positioned to give good firm guidance. It is our hope, as I mentioned earlier in the prepared remarks, that we can finish dosing both of those studies in calendar 2018 and so just give us some time on this and let's -- and we'll provide guidance once we start dosing.

Sorry, what was the other question?

Partnerships.

Partnerships. Yes, similar there. Look, I think that we have a good chance of getting important collaboration done this year, but you really can't give guidance on that because that's out of our control. I think what is within our control, you're building up this TRiM platform, demonstrating that it is active and that it appears to be well-tolerated. We're doing all those things and we feel good about it. And I think that we have some targets that are potentially interesting to partners. And so everything we can do, we're doing. And now we'll just see if we can bear some fruit this year. It is certainly our hope that we could do that.

Our next question is from the line of Keay Nakae of Chardan.

With respect to potential partnerships, especially for the cardiovascular patients, is the numbers you disclosed from the Amgen partnership, is that what we should be thinking about is you're able to partner those given the fact that you expect to file the CTAs around the end of this year?

Yes. I appreciate the question, but not one that I can answer. A, I don't -- here's what I think. I think that apoC-III and ANGPTL3 are good targets. I think they're good validated targets that should be of interest to Big Pharma and that they could be attractive targets for partners. I believe that. When can we get a partnership done? Can we get a partnership done? I don't know the answer to that. And so speculating on timing of that is just -- is not something that I'm going to do at this point. Similarly, I really can't speculate on should that happen. I really can't speculate on what the economics would be. Some of that will depend upon the time of partnership, of course. The longer we hold on to these, potentially the more valuable they could be. So there are just too many variables there, unfortunately, to really speculate.

(Operator Instructions) Our next question is from the line of Madhu Kumar of B. Riley FBR.

So my first question relates to the apoC-III program. So looking at the indication space for apoC-III, how much do you think you would pursue, the kind of orphan indications that some of your competitors have gone pretty far down the development pipeline in right now versus the kind of a bigger ticket cardiovascular indications?

Yes. So let me take a first crack at that. One of the things we like about apoC-III is that it gives us multiple regulatory pathways. If we were to hold on to this for ourselves, it would clearly make more sense for us to focus on orphan indications, whereas if a partner were to take this, it may make more sense to go after the large cardiovascular markets and go ahead and invest in a large outcome study. So I think, ultimately, which route we take will depend upon who takes us forward, I think.

Okay. And remind me, did Amgen -- were they shown C-III and angiopoietin-like 3 as part of the partnership?

No. No. So we started talking to Amgen quite some time ago about Lp(a) and about the undisclosed target. That was before we had any program in ANGPTL3 or apoC-III. So these are relatively new.

And one last. Remind if I missed this. Would there be 520 or 521 data kind of follow-on data at EASL?

Yes. I think we may see some 520 data. I don't think we're going to see 521 data just because that study really got stopped so early. What data we had got presented, I think it must have been EASL last year when we presented what data we had, but it was quite sparse. Enough to be very tantalizing, but we don't have more 521 data sort of hiding out someplace. We pretty much showed everything we had.

And at this time, I'm showing no further questions.

I'd like to turn the conference back over to Chris Anzalone for closing remarks.

Thanks very much everyone. Thank you for joining us on our call today and we will see you next quarter.

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