Halozyme Therapeutics Inc (HALO) 2015 Q4 法說會逐字稿

Good afternoon, and welcome, to Halozyme Therapeutics fourth quarter 2015 financial results conference call.

(Operator Instructions)

As a reminder, this conference call is being recorded. It is now my pleasure to introduce your host Jim Mazzola, Vice President of Investor Relations at Halozyme. You may begin your conference.

Thank you, Brandon, and good afternoon, everyone. Welcome to Halozyme's fourth quarter and full-year 2015 conference call. Following market close today, we issued a news release with a summary of our results and posted a short slide presentation to accompany this call. You will find both on the investor page at Halozyme.com.

Leading our call today is Halozyme's President and Chief Executive Officer, Dr. Helen Torley, who will provide an overview and update on our business. Then Laurie Stelzer, our Chief Financial Officer, will review financial results for the December quarter followed by a Q&A period. Also with us for today's call is our Dr. Athena Countouriotis, our Chief Medical Officer.

Before we begin today, let me remind you that during this conference call we will be making forward-looking statements. The Company's actual results may differ materially from those expressed in or indicated by such forward-looking statements. For a description of risks, please refer to our quarterly and annual filings with the SEC. Now, let me turn the call over to Helen.

Good afternoon, everyone, and thank you, for joining us today. Let me begin with what I think are the three takeaways for today's call. Firstly, regarding our financials, we finished 2015 in line with our guidance, well-financed for 2016 plans and with strong momentum in both pillars of our strategy.

Secondly, in our oncology pillar, where our lead product is our investigational new drug PEGPH20, we are on schedule to initiate our pivotal Phase 3 study in pancreatic cancer patients next month, and it remains our goal to expand our ongoing clinical trials in additional tumor sites in the second half of this year in support of our objective of demonstrating the pan-tumor potential for PEGPH20. We now have eight studies in process between the Company, clinical collaborations and investigator sponsored trials and we are making the appropriate investments we believe today to realize the full future potential value of PEGPH20.

Thirdly, we've got strong momentum in the enhanced pillar of our strategy tube with an enviable list of six global partners, four royalty generating product approvals with launches in 48 countries, and four new products entering the clinic just in the last four months. I think this may be the most underappreciated part of our story as it continues to create value and serves as a key differentiator for our business.

For additional details in our progress, I will start on slide 2, with an overview of our strategy. We operate the business and make investment decisions in two strategic pillars. The first pillar is our oncology business with our investigational drug PEGPH20 at the core. Our PEGPH20 temporarily degrades hyaluronan, which is a glycosaminoglycan, or chain of natural sugars in the body, that can accumulate around certain tumors and can constrict the tumor vasculature.

In animal models, we've demonstrated that degrading hyaluronan, or HA, reduces tumor pressure, increasing the blood flow and thereby, the access of cancer treatment into the tumor. And we're currently studying PEGPH20 in pancreatic, non-small cell lung and gastric cancer patients, but we see broader potential of pick-upability for its use in multiple tumor types and in combination with immuno-oncology agents, monoclonal antibodies and chemotherapies.

Now, we're working oncology is funded in part by the second pillar of our strategy, which is centered on our licensing agreements with marquee partners which includes Roche, Baxalta, Pfizer, Janssen, AbbVie, and most recently, Eli Lilly. These partners co-formulate or co-administer their therapies with our enhanced technology platform, which temporarily degrades HA under the skin and that enables larger fluid volumes or molecules to be delivered with a subcutaneous injection or on a less frequent dosing schedule. Both the enhanced and PEGPH20 are based on our proprietary rHuPH20 enzyme.

Our revenue's driven by product sales, milestone payments and royalties. For the fourth quarter, revenue increased 72% year-on-year, to $52 million, which included a $25 million upfront license fee from a global collaboration and licensing agreement we announced in December with Lilly. Royalty revenue of $9.5 million reflects sales of partner products in the third quarter of 2015. Our royalties increased 15% from the third quarter of 2015, and 136% year-on-year from the fourth quarter of 2014. These results closed a record year for Halozyme, with revenue of $135 million, a 79% increase over 2014.

Now with that summary, I'll provide more detail on the progress we've made this quarter in our oncology pillar. Our clinical study of PEGPH20 is making excellent progress and continues to generate strong support from investigators. This month we closed enrollment in our Phase 2 study, stage 2 of Study 202, in metastatic pancreatic cancer patients with 133 patients enrolled in the United States. We project being able to provide mature progression-free survival and response rate results from this study in the fourth quarter and we would expect to report additional details at Medical FOR A in 2017.

Moving on to our preparation now for our Phase 3 trial, I'm pleased to report that our partner, Ventana, submitted an investigational device exemption, or IDE, earlier this month to the FDA for the companion diagnostic. This represents another important milestone towards a start of our Phase 3 study. The IDE seeks approval for the use in a clinical study to collect safety and effectiveness data in support of a final regulatory approval of the companion diagnostic.

Ventana and Halozyme have been in an ongoing dialogue with the FDA regarding the assay, methodology, scoring algorithm, cut point and analytical study designs. We believe we have alignment with the FDA on these key elements. And if the FDA has no comments following a 30-day review period, the diagnostic is cleared for use in the Phase 3 trial and patient screening for high HA may begin based on clinical protocol driven biopsies.

The data we presented in January in the Phase 1 data from Study 202 using the Ventana diagnostic and which supports the Phase 3 design is shown in slide 3, and an overview of the Phase 3 study design is shown in slide 4. Study 301 will be a 420 patient global double-planked placebo controlled randomized trial of patients with stage IV pancreatic ductal adenocarcinoma who will be prospectively identified and included based on high levels of HA.

With input from a type-B meeting with the FDA in March 2015, and scientific advice from the European Medicines Agency last July, we're proceeding with two primary endpoints; progression-free survival and overall survival. We plan to conduct an interim analysis from the target number of progression-free survival advances reached. Based on the interim analysis, the data monitoring committee will have the option to recommend we stop the study based on efficacy, continue it to the target enrollment of 420 patients, increase enrollment of up to 570 patients for the final overall survival assessment, or stop the study for futility.

If the progression-free survival data shows a significant benefit in the PEGPH20 treatment arm and both the overall survival and overall risk benefit are supportive, these data may form the basis for marketing application in the United States and a conditional marketing authorization in Europe. Now, I am pleased to also report that we are track to dose the first patients in Phase 3 study next month. Approximately 200 global sites have agreed to participate in this study. Our US investigator meeting occurred earlier this month and site startup visits are now well underway. These are important steps, as upon completion of these site visits, patients may initiate screening activities.

Turning to our rest of world plans. Earlier this month, we also received protocol approval in 11 European countries under the voluntary harmonization procedure and we continue to submit protocols in additional countries. Our plan is to initiate sites in the rest of world locations beginning early in Q2, and to reach our target of more than 90% of the centers ready to start screening patients by the end of the year.

I'm very excited by the strong support we're seeing for the study and the excellent progress we are seeing in our startup plans. Once we initiate the study and establish the enrollment trajectory, we intend to provide periodic updates upon achievement of key milestones, such as when the first patient is dosed and with a target number of US and rest of world sites are ready to screen patients.

As we execute on our Study 301 plans and complete Study 202, we're taking steps to improve our overall readiness to seek approval for PEGPH20 at the earliest possible timeframe. While we do not believe a filing based on Study 202 is likely, we will be prepared for that possibility should the data be supportive. If the data were supportive, we would seek FDA input regarding an accelerated approval pathway and believe that having the Phase 3 studies 301 underway would be helpful. We see this as an appropriate approach given we have a targeted therapy in a patient population with a high unmet need. Now as a reminder, Halozyme remains blinded to the efficacy data from Stage 2 of Study 202, and it is our plan to analyze the data using the Ventana companion diagnostic to identify the high HA patient population when the target number of events has been achieved, which we project will occur in the fourth quarter of this year.

Now, while we are farthest along in our study of PEGPH20 in pancreatic cancer, our preclinical model support the potential for PEGPH20 in a broad range of solid tumors, and it's our goal to demonstrate this pan-tumor potential. Slide five shows our currently active and planned clinical trials. As we've communicated, Halozyme is conducting two separate additional studies to evaluate the pan-tumor potential of 4PEGPH20. Each study has an all comer dose escalation Phase, followed by a dose expansion Phase in which only high HA patients will be enrolled.

Our Primal study is evaluating PEGPH20 in combination with docetaxel in locally advanced and metastatic non-small cell lung cancer patients who did not respond adequately or lost their response to a platinum based regimen. It is designed to identify the dose and safety of PEGPH20 plus docetaxel.

In addition to the Primal study, we're in very good position to adapt to the changing landscape in the treatment of non-small cell lung cancer with our Phase 1B study of PEGPH20 in KEYTRUDA, or pembrolizumab. The PEGPH20 plus pembrolizumab trial will enroll relapse refractory stage IIIB and stage IV non-small cell lung cancer patients who have been treated with at least one platinum-based regimen, or recurrent locally advanced or metastatic gastric adenocarcinoma patients who have failed at least one chemotherapy regimen. We're currently in the dose escalation portion in both combination studies to determine the maximum tolerated dose of PEGPH20.

And just as a reminder, the design of the dose finding portion is similar in each trial, where if three patients complete a dose cohort without a dose limiting toxicity, or a DLT, in the first 21 days, escalation to the next dose level occurs. If a patient in a cohort has a DLT, three additional patients are enrolled. And if there are no additional DLTs, escalation to the next dose level may occur. If there are two or more DLTs, the maximum tolerated dose is considered to have been exceeded and additional patients can be evaluated at the lower dose.

Now, let me provide an update in the progress of each of our trials. In the Primal study, after experiencing dose limiting toxicities at three micrograms per kilogram of PEGPH20, we have decreased the dose and continue to enroll patients at the 1.6 microgram per kilogram dose level. We've also submitted a protocol amendment to regulatory authorities to evaluate intermediate doses of PEGPH20 between 1.6 micrograms per kilogram and three micrograms per kilogram. Selection of the right dose to take into the dose expansion Phase, where we will evaluate both efficacy and tolerability, is one of the most important decisions we will make and we feel it's important to evaluate these additional dose levels.

With the KEYTRUDA study, since enrolling in the first patient in November of last year, we're now awaiting completion of follow up on the first dose cohort at 1.6 micrograms per kilogram. If no DLTs occur, we project moving to the next dose cohort of 2.2 micrograms per kilogram in the late March timeframe. It remains our goal to advance to the dose expansion Phase of both the Primal and KEYTRUDA studies in the second half of the year pending the number of dose escalation cohorts required in each study. And as a reminder, we will be selecting for high HA patients in the dose expansion Phase of both studies and evaluating larger cohorts of patients for efficacy as well as tolerability at the maximum tolerated dose of PEGPH20.

And finally on this slide, we have our planned clinical trial with our collaboration partner, Eisai, to evaluate HALAVEN, or eribulin, in combination with PEGPH20 in first line HER2 negative high HA metastatic breast cancer patients. Since announcing the collaboration last July, we have finalized protocol with Eisai, a contract research organization has been selected and we estimate a study start in the second quarter of 2016.

As a reminder, this will be a Phase 1B-2 clinical trial to explore whether PEGPH20 in combination with HALAVEN can improve overall response rate as compared to HALAVEN alone. Including our Phase 2 study in pancreatic cancer patients, we now have a total of eight studies in process between the Company, clinical collaborations and investigator sponsored trials, representing the investments we're making to realize the full potential of PEGPH20.

Now, let me turn to -- move to slide 6, for a discussion of the second pillar of our strategy, our ENHANZE platform. Our ENHANZE platform is in its best position it's been at any point in the Company's history. We have six marketing partners generating milestone revenue, four product approvals generating royalty revenue, four new products in the clinic that have the potential to generate future milestones and royalties, and two potential new indications for existing approved product in development.

Since December of 2014, in just 14 months, we have doubled the number of collaboration partners and generated revenue from these initiations of more than $60 million, including the notable addition of Lilly in December. Since October, our partners started dosing in four separate Phase 1 trials, resulting in an additional $7 million in milestone payments to Halozyme. These include clinical trials involving Pfizer's rivipansel for vaso-occlusive crisis in sickle cell patients, Janssen's anti-CD38 daratumumab for multiple myeloma patients, AbbVie HUMIRA to help reduce the number of induction injections at higher doses, and the most recent example came earlier this month when Pfizer dosed the first subject in a Phase 1 trial evaluating the safety, tolerability and pharmacokinetics of bococizumab, an investigational PCSK9 inhibitor using our enhanced platform.

A couple of brief updates on the studies. The Pfizer study with bococizumab is designed to explore optimizing the delivery and frequency of injections and its initiation triggered a $1 million milestone payment. In addition, Genmab indicated in their fourth quarter update in the study of daratumumab with ENHANZE has progressed with the first dosing cohort and is currently dosing patients in the second cohort.

In combination with these recent milestone payments, we are pleased with the value potential that is unlocked as our partners progress in the clinic and ultimately, commercialize these therapies, benefiting a greater number of patients and securing additional and potentially substantial future royalty revenue for Halozyme. Among the reasons for our success with the ENHANZE is the platform can be used in combination with a variety of other drugs and is applicable across many therapeutic categories.

The value proposition on slide 7 includes lifecycle management with the opportunity to prolong the exclusivity period for the combined product and the ability to reduce dosing frequency and duration by taking drugs from an IV to subcutaneous formulation or allowing higher volumes to be infused at one time. Now today, we benefit from sales of Roche's Herceptin SC and MabThera SC in countries outside of the United States, and from Baxalta's HYQVIA in the US and Europe.

As Roche indicated during the most recent quarterly call and as shown in slide 8, Herceptin SC is now available in 48 countries and its sales now account for approximately 40% of the total Herceptin sales in Europe. This update reflects its launch in new geographies and growing market shares. Roche also said that MabThera SC is now launched in 12 countries representing approximately 30% of sales in these markets for the treatment of patients with non-Hodgkin's lymphoma.

Baxalta's HYQVIA, which was launched in the US in October 2014, combines immunoglobulin fusion 10% with our rHuPH20 and is indicated for adults with primary immunodeficiency or PID. PID is a chronic condition and HYQVIA is the only once a month subcutaneous treatment for adult patients. The PID market is expected to reach $3 billion in sales by 2020, with subcutaneous therapies representing more than 50% of the market.

In their fourth quarter report, Baxalta indicated that HYQVIA is experiencing strong uptake and a very favorable reception by patients and physicians with annual run rate sales now approaching $150 million. More than 50% of US HYQVIA patients are converting from competitive therapies and approximately 25% are newly diagnosed patients.

We're very pleased with the progress and momentum to date and it only serves to motivate us to achieve more across a wider set of collaborators and in a wider range of therapies. With that update, I will now turn the call over to Laurie to discuss our financial results for the quarter in greater detail. Laurie?

Thank you, Helen. I will begin on slide 9, where you'll see that revenue for the fourth quarter was $52.2 million, compared to $30.4 million for the fourth quarter of 2014, driven primarily by the $25 million upfront license fee booked when we signed the Lilly agreement, offset by the $15 million upfront license from Janssen in 2014, as well as another strong year-over-year increase in royalty revenue. Our revenue is primarily comprised of royalties, bulk sales of rHuPH20 for use in manufacturing collaboration products, and HYLENEX product sales.

During the quarter, royalty revenue totaled $9.5 million, an increase of $1.3 million sequentially from last quarter, and $5.5 million above the fourth quarter of last year. The year-over-year increase came largely from higher sales of Roche's Herceptin SC during the third quarter. Bulk sales of rHuPH20 totaled $9.3 million, HYLENEX product sales totaled $4.3 million, and other collaboration revenue totaled $29.1 million, which includes the $25 million license fee from Lilly.

Turning to slide 10, for our more detailed breakdown of our P&L. Cost of product sales was $8.4 million in the quarter, compared to $6.1 million in the prior year. This increase in manufacturing costs primarily reflects our increase in product sales to partners. Research and development expenses for the fourth quarter were $27.7 million, compared to $19.7 million for the fourth quarter of 2014, a continuation of the planned increase we have discussed for several quarters to support our growing clinical and manufacturing activities for PEGPH20.

Selling, general and administrative expenses were $10.6 million, compared to $8.4 million for the fourth quarter of 2014. The increase was primarily due to personnel expenses including stock-based compensation for the period. Overall, our operating expenses increased by $12.5 million from the fourth quarter of 2014, which as we said last quarter, was anticipated as we ramp investments in our expanded clinical program and pull forward some manufacturing expenses.

Net income for the quarter was $4.3 million or $0.03 per share, compared to a loss of $5.3 million or $0.04 per share in the fourth quarter of 2014. Cash, cash equivalents and marketable securities were $108.3 million at December 31, compared to $123.7 million at September 30, and $135.6 million in the fourth quarter of last year. Our financial results for the full-year were in line with the 2015 guidance that I provided in August, with revenue exceeding guidance due to the license fee from Lilly that was booked in the quarter.

On slide 11, you will see our full year result of net revenue $135.1 million against our guidance range of $110 million to $115 million, operating expenses of $162.5 million towards the lower end of our $160 million to $170 million guidance range, net cash burn of $27.3 million against our $20 million to $30 million guidance range. The $25 million cash payment for the Lilly upfront license fee was received in January 2016. And our year-end cash balance cash balance of $108.3 million against our guidance of between $105 million to $115 million does not include the receipt of the $150 million financing nor the $25 million cash payment from Lilly.

Looking ahead, we enter the year well-financed for our 2016 plans through the $150 million non-dilutive royalty back debt financing we completed in January. Our ability to finance the Company in this manner is another differentiator of our business model with a healthy enhanced franchise supporting our investment in a promising oncology franchise.

We provided guidance for 2016 last month that is summarized on slide 12. On the revenue line, I want to reiterate that our guidance of $110 million to $125 million does not forecast new ENHANZE partner initiation payments. In 2015, we had $48 million in one-time payments from the initiation of our agreements with AbbVie and Lilly. Excluding these upfront payments, our 2016 guidance reflects an underlying revenue growth of 25% to 40%.

For operating expenses, we are guiding to a range of $240 million to $260 million, reflecting the ramp required to support initiation of our Phase 3 clinical trial in pancreatic cancer patients and expansion of our clinical programs to study the pan-tumor potential of PEGPH20. We expect spending to be evenly spread through the year, meaning operating expenses should consistently be at or above $60 million per quarter beginning in the first quarter.

And finally, our cash flow including the cash from financing is expected to be in the range of $35 million to $55 million, with our year-end cash balance to be $140 million to $160 million, including the $150 million cash raised in our royalty back debt arrangement and the $25 million Lilly upfront received in January. With that, let me turn the call back to Helen who will provide some closing comments.

Thank you, Laurie. As you just heard, we have strong progress across both pillars of our strategy and we believe that in any market environment our business model is an important differentiator and driver of value for our investors. During the quarter, we took significant steps forward in our pancreatic cancer program and continue the exploration of PEGPH20 in a wider array of tumor and therapy types. While at the same time, we have yet another quarter of important milestones in our ENHANZE pillar with continued confirmation of commercial progress through the growing royalty revenues and four new products entering the clinic.

I remain very optimistic about the investments we're making in both pillars to deliver even greater value for the future. And I would like to close as ever by thanking our growing employee team here at Halozyme for their continued hard work in advancing the programs and supporting our partners. We're now ready to take questions. Operator, could you please open up the call?

(Operator Instructions)

Jessica Fye, JPMorgan.

This is Ryan on for Jess. Appreciate you taking our questions. So you gave a little bit of an update with where you are at with primal and the KEYTRUDA combo study, but is it possible that we would be able to see any data from those two studies later this year?

Thank you, Ryan. Let me just address that. As we mentioned in the prepared remarks, we're really at this point in time in our dose escalation portion. But we do project being in the dose expansion portion in the second half of this year.

That's going to be the key part of the study, where we will be looking at HA high only patients and we'll be looking at the target dose we want to study for efficacy. And so it really is going to depend on when we feel we have a robust number of patients in that dose expansion portion at the right dose only in high HA patients. So stay tuned, but that sequence of events that will occur and trigger us for when we were able to report efficacy.

Great, thanks. And I guess the second question is, you talked about how you are not you wouldn't use the data from study 202 necessarily, as a basis for filing, but could you walk us through a scenario in which you would -- that data would be potentially strong enough for you to consider taking that forward to the FDA?

Thanks, Ryan. As I mentioned, we have not discussed this with the FDA, so any decision to do that would depend on the FDA. But I can say, that what it would be looking for would be a very strong efficacy profile and that strong risk benefit in a targeted population. So we do think that it's a low probability scenario. We do questions on it which is why we mentioned it today, but that would be the scenario. We would want to talk to the FDA before we would even proceed with that path.

Great. Thanks for taking my questions.

Andrew Peters, UBS.

Hi, thanks for taking my questions and good afternoon. I guess a couple here. First, just on the Phase 3 data and how you described overall survival if data is supportive. Just to help frame that, when you described the stage 1 data that we have seen so far as supportive? Or would you expect to need to see additional benefit given that in stage 1 of a good chunk of patients came off drug?

Yes, thanks Andrew. I will ask Athena to address that. But you are absolutely right, the data that we've looked at in stage 1, about 40% of patients did get their therapy discontinued prematurely because of the clinical hold. Athena, would you address that question for Andrew?

Hi, Andrew. I think the first thing I would start with is that the Phase 3 really was built off of our strongest data set from the Phase 2, which was progression free survival. Remember, the phase 3 has two primary endpoints for both PFS and overall survival and what we should previously was an improvement in the PEGPH20 arm in terms of the median overall survival and clearly the PFS difference.

And that it's been repeated with the Ventana analysis. Clearly, the Ventana analysis still has a strong hazard ratio at 0.48 for progression free survival. Helen did mention at JPMorgan that we did discuss the overall survival just in her remarks and that there is a continued benefit in the PEGPH20 arm that is a narrower difference than what we showed previously but it is still supported.

Okay. And then, maybe a question just on guidance. Can you breakout what are the contributors of the guidance this year and how the royalty revenue growth fits into that? Just trying to understand the split between new partnerships and milestone payments and things like that versus your expectation for the ENHANZE royalties.

I will ask Laurie to address that.

Hi, Andrew. On our guidance, we guided to $110 million to $125 million on revenue for 2016. And as a reminder, that does not include any new ENHANZE partnerships.

And so for year-over-year comparisons, we did receive $48 million in upfront payments between AbbVie and Lilly in 2015. And so, when you strip that out and look at the underlying growth rate, our guidance is growing between 25% and 40% year over year. We haven't historically broken out royalties specifically. So to that specific question, but we do expect to see royalties continue to increase year-over-year.

Charles Duncan, Piper Jaffray.

Hi, guys. First of all, congrats on a great year of progress.

Thank you, Charles.

You are welcome. It's notable.

So let me first ask you about PEGPH20. I am intrigued with the idea of very capital efficient route to the market but I'm not counting on it. Relative to enrollment in 301 by year-end or say roughly, early next year, approximately how much of that trial will be enrolled when you would be making a decision on the results of 202?

Thanks for the question, Charles. As I mentioned, we're just at the stage now having had a very successful US investigator meeting and as I speak, sites in the US are getting their site initiation visits to start screening. In the second quarter, we will start the European sites. And so, we don't have specific data I can project off the moment to know what the enrollment is going to be by year-end.

But what I can say is that our focus is on getting all of these sites up and running and screening just as quickly as possible. And so, once I have a little bit more detail on having the sites and the screening and the enrollment rate, I am going to be in a better position to give an estimate of how many patients are likely to be enrolled by the end of the year. It's a little premature to be able to do that.

(Operator instructions)

Arlinda Lee, Canaccord.

Hi, guys. Thanks for taking my question. I guess maybe on the primal and pembrolizumab combination trials, you guys -- I am glad that you guys are still on track to go into those phase 2 portions of the clinical trial. Can you maybe clarify what kind of precipitated the dosing amendments?

Thanks, Arlinda. And just to say that we're still in the phase 1, 1B portion of the study where they contained both dose escalation and then dose expansion at the select dose before in primal. In particular, moving into the phase 2 portions. So I just wanted to clarify that.

The amendment that we have elected to do for primal is really just focused on the fact that there was a big jump between the 1.6 microgram per kilogram dose and the 3 microgram per kilogram dose. And having experienced the dose limiting toxicity at the 3 microgram per kilogram dose, we felt it was appropriate to amend the protocol to look at some interim doses between 1.6 micrograms and 3 micrograms per kilogram. Because from our animal models, we know that there's a dose response based on the dose of PEGPH20 with docetaxel and we feel we haven't adequately explored it by just looking only at 1.6 micrograms and 3 micrograms per kilogram.

Okay, great. Thanks very much. And then, I am intrigued by the idea and I know you've indicated that it's a low probability, but can you please clarify on the suggestion that you could potentially file it on study 202 if it was I assume extremely positive? Is this for only the part 2 portion, the 133 patients that you -- I mean enrolled subsequent to the clinical hold and are these only HA high patients by the Ventana definition?

So for the stage 2, it actually is still on all comers study. But our plan is to analyze the data and we are blinded to efficacy at this point in time using the prospectively defined Ventana cut point. The database that the FDA would want to look at if this data was to be supportive, would include all of the patients in study 202, as the FDA will want to understand the overall risk benefit.

But if there is any potential past here, it would be based on the stage 2 patients, the high HA patients in stage 2. And the other data, however, would all have to be supportive towards the risk-benefit profile of PEGPH20. But I'll just say again, we get questions on this. We will be ready for it but as you said at the start of the question, it still remains a very remote possibility that this data would support an accelerated approval. But we will be ready for it in the event that the data does turn out to be supportive and the FDA feels there is a path forward.

Okay, great. Thanks very much.

Charles Duncan, Piper Jaffray.

Thanks, guys for taking the follow up. It's probably a question for Laurie. On the guidance, I understand it doesn't include any new ENHANZE partnerships. That said, could it include additional milestones from current partnerships? And secondarily, is it possible that you could sign additional ENHANZE partnerships this year? Is that one of your goals?

I'll answer the question on additional ENHANZE partners. Charles, it continues to be something that we explore. We believe there are other molecules out there that may benefit from the ENHANZE platform. It's always hard to predict if and when, but I can tell you our business development team continues to work hard at that. Laurie, do you want to answer what's in the guidance with regard to milestones?

Sure. Charles, thanks for the question. So our current guidance certainly does include our estimate for milestones with our current partners as they progress products through the clinic. Again, I can't be specific about what those are, again, respecting that our partners haven't given any public information as to when they would achieve certain milestones. But to the extent we foresee that, we would have included those in the guidance.

Thanks, Laurie. That's helpful. Appreciate it.

Jon Eckard, Barclays.

Hi, guys. This is Brian on for Jon. Just two questions. Curious about whether you guys have mentioned this, I may have missed it. But the lung cancer data that you plan to present for PEGPH20, how do we expect to see the data to be presented with regards to the HA cutoff? Are there certain prespecified thresholds in that trial?

Let me ask Athena to address that and just to say that at the moment in the study, in the dose escalation portion, it is all comers. But when we move into the dose expansion, we do plan to use an HA cutoff. Athena, do you want to talk about the approach we're taking.

Hi, Brian. Let me just back up, as Helen was just saying. Remember, the dose escalation phase is all comers, so we're not looking for HA status at this point. We're projecting it will move into dose expansion to second half of this year. And that's really the cohort where he believe we could present potentially more data in regards to one, patients would be selected for HA, but two, it will also at the maximum tolerated dose of PEGPH20. So it really is a more appropriate data set to discuss a bigger efficacy and safety data set.

Having said that, to address your HA cutoff question, we are working with Ventana. We're looking at available commercial tissue in the lung cancer space. Remember, this is also relevant for our other programs. The pan-tumor potential also explores gastric cancer and breast cancer. So we're looking at not only commercially available tissue with outcomes data as well as tissue micro-arrays to further optimize the cutoff that we'll be using in all three of those indications based on our pancreatic cutoff.

Great, thanks a lot. And with regards to the recent growth in Herceptin SC and MabThera, I am just curious about what markets are still waiting for reimbursement, especially with regards to MabThera?

Yes, Brian, that really is information you would have to get from Roche. We are limited to what they've stated publicly and when they gave their last updates, they didn't provide a list of specific countries that they were reimbursed in. And so I am not in a position to be able to answer that.

Okay. Thank you very much.

Thank you.

(Operator Instructions)

Dr. Torley, there are no further questions at this time. I will turn the floor back to you for closing comments.

Thank you, everyone. I think as you've heard, we had a very strong year in 2015. We are very pleased with the momentum with which we have entered 2016, and we look to providing you with further updates as we make continued progress in our PEGPH20 program as well as our ENHANZE platform. Thank you so much for joining us today. Goodbye.

Ladies and gentlemen, this concludes today's call. You may now disconnect your lines.