Pacira BioSciences, Inc. (PCRX) CEO Dave Stack on Q2 2021 Results - Earnings Call Transcript

Pacira BioSciences, Inc. (NASDAQ:PCRX) Q2 2021 Earnings Conference Call August 3, 2021 8:30 AM ET

Company Participants

Susan Mesco - IR

Dave Stack - Chairman and CEO

Charlie Reinhart - CFO

Roy Winston - Interim Chief Medical Officer

Conference Call Participants

Daniel Busby - RBC Capital Markets

David Amsellem - Piper Sandler

Christopher Neyor - JPMorgan

David Steinberg - Jefferies

Anita Dushyanth - Berenberg Capital

Andreas Argyrides - Wedbush Securities

Greg Fraser - Truist Securities

Serge Belanger - Needham & Company

Gary Nachman - BMO Capital

Tim Chiang - Northland Capital

Operator

Good day, and thank you for standing by. Welcome to the Q2 2021 Pacira BioSciences, Inc. Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded. [Operator Instructions]

I would now like to hand the conference over to your speaker today, Susan Mesco, Head of Investor Relations. Please go ahead.

Susan Mesco

Thank you, Dawn, and good morning, everyone. Welcome to today's conference call to discuss our second quarter progress. Joining me as speakers on today's call are Dave Stack, Chairman and Chief Executive Officer; and Charlie Reinhart, Chief Financial Officer. Additional members of the Pacira executive leadership team are also here for our question-and-answer session.

Before we begin, let me remind you that today's call will include forward-looking statements based on current expectations. Such statements represent our judgment as of today and may involve risks and uncertainties. For information concerning risk factors that could affect the company, please refer to our filings with the SEC, which are available from the SEC or our website.

With that, I will now turn the call over to Dave Stack.

Dave Stack

Thank you, Susan. Good morning, everyone, and thank you for joining us. We are taking a new approach on today's call and will limit our prepared remarks to a few key highlights, allowing us to take more time for your questions.

We made terrific progress in the first half of 2021, with momentum growing in the second quarter. Second quarter revenue of $135.6 million notably ramped up our bottom line, with adjusted EBITDA coming in at $50.3 million, both record levels for a single quarter despite ongoing COVID-related challenges within the elective surgery markets.

All market dynamics point to the strong momentum continuing for the remainder of 2021 and beyond, reinforcing our outlook for growth over the next 5 years with expectations for EXPAREL annual sales growth percentages in at least the high teens, gross margins improving to the mid-80s and modest increases in operating expenses. These key trends should allow Pacira to deliver operating margins that exceed 50% within 5 years.

I'll start with a quick update on the lawsuit filed against the American Society of Anesthesiology, seeking damages and the retraction of 3 articles published in their journal, Anesthesiology. This process is in the early stages, and our next step will be moving towards discovery to advance this case towards a resolution. While the timing is on exactly how this will play out is difficult to predict with any level of certainty, I can tell you that we are confident in our position that the publications are maliciously false and misleading. This was laid out clearly in the declarations on our website.

We have not seen any material impact with EXPAREL's value proposition continuing to drive strong demand. At the same time, we cannot allow these faults and misleading publications to be referenced as fact on a go-forward basis.

Turning to the rollout of EXPAREL in pediatrics. We are now several weeks into the launch, and it's going even better than we anticipated. As you know, we deployed a thoughtful, gated approach to the launch targeting KOL influencers. This has proven to be a winning formula as we are seeing a high level of acceptance from prominent thought leaders.

For example, EXPAREL use is rapidly expanding in scoliosis surgery, which is one of the most expensive, invasive and painful orthopedic procedures. Spine is a tightknit group of like-minded surgeons who are highly motivated to minimize exposure of children and teens to opioids given the population's elevated risk for persistent opioid use. We have been delighted with the high level of receptivity and enthusiasm from prominent thought leaders who are providing a rapid transfer of best practice for establishing EXPAREL-based protocols as the new standard of care, specifically in the near term through presentations at local and national pediatric meetings.

Medical education is a core component of our pediatric strategy. Our team is successfully securing the engagement of thought leaders from top children's hospitals. We are partnering with the top echelon of early adopters to deploy the education across their networks and spheres of influence using programs like fellowship training, ask-the-expert panels, technique workshops and awareness campaigns.

These key influencers are also generating data using EXPAREL in a broad range of procedures at leading institutions around the country, such as Reid E. Children's, Texas Children's, Scottish Rite and the Shriners Hospital systems.

We are now broadening our launch initiatives to our full customer-facing team and expect to trigger a chain reaction within the pediatric community that will ultimately shift EXPAREL-based multimodal protocols to the standard of care for this vulnerable patient population, replacing pumps and catheters-based pain management.

The pristine safety profile of EXPAREL will continue to be the hallmark of our positioning across all pediatric and adult settings. This is validated by the over 8.8 million patients treated in the United States since launch. The pediatric indication and label further underscore the safety of our DepoFoam platform, which does not have any of the toxicity and safety warnings we have seen within the package inserts for other drug delivery technologies, specifically in the pain space.

Shifting gears to women's health, COVID has escalated the need for many breast, plastic and oncology surgeons to expedite discharge for their patients. With EXPAREL, they are now able to meet the needs of women who demand an opioid-free experience and who don't want to stay in the hospital overnight, while simultaneously optimizing their care experience through better pain management using EXPAREL-based ERAS protocols.

C-section adoption continues to grow and OB/GYN surgeons and anesthesiologists are leading the charge for evolving protocols to minimize opioids and provide new mothers with a better recovery experience after C-section. Looking ahead, we see this opportunity gaining additional traction as society meetings returned to in-person settings to bring hands-on education and training to life.

Turning to the lower extremity block. In May, we support -- we reported top line results from our STRIDE study. STRIDE was designed to evaluate EXPAREL as a single acting local analgesic with no preoperative multimodal therapy in the study design to bridge upfront coverage for EXPAREL, which differs from real-life practice. While the study did not achieve its high hurdle for the primary endpoint, we view the results as a highly valuable opportunity to work with the FDA on defining a pathway for adding a 96-hour indication to our label. We are preparing to meet and discuss the STRIDE study and our lower extremity nerve block strategy with the FDA in the third quarter.

The design of the follow-on studies is underway. We believe these studies can be executed seamlessly as STRIDE gives us a strong foundation. We are currently planning a study evaluating a popliteal sciatic nerve block in patients undergoing bunion surgery. We will only use those sites from STRIDE that were successful and followed appropriate protocol and technique.

We are also initiating a Phase III adductor canal field block study to provide specific package insert guidance for dose, volume, use of bupivacaine and administration technique. We intend to launch these studies in the second half of this year. Keep in mind that as far as our 5-year plan, the STRIDE outcome does not materially impact our outlook as we believe this is roughly a 15- to 18-month delay in achieving a lower extremity nerve block indication in the United States.

Internationally, we remain on track to launch EXPAREL along with iovera° in Europe in October of this year. The EU launch will focus on only these markets where we can secure pricing that closely aligns with the price in the United States. COVID has caused a tremendous backlog for orthopedic procedures in Europe with waiting lists as long as 2 years. In addition, the typical length of stay in Europe is several days. These dynamics provide an optimal opportunity for both EXPAREL and iovera°.

The Pacira portfolio will be positioned to enable rapid recovery after surgery to address the EU market's high interest in accelerating recovery times and discharge to increased surgical throughput and address the post-COVID elective surgery backlog.

For EXPAREL, our initial focus will be regional anesthesia protocol adoption in shoulder and total knee arthroplasty. For iovera°, we will begin by targeting painful osteoarthritis as well as total knee arthroplasty. We envision iovera° playing a key role in the long-term pain management, especially as surgeons and anesthesiologists work through the significant waiting list for elective procedures.

Importantly, our broad efficacy label, which covers EXPAREL administration via infiltration, field blocks and both upper and lower extremity nerve blocks along with a superior safety profile, give us a clear competitive advantage in Europe where iovera° is already approved. To remind everyone, EXPAREL is approved for a lower extremity nerve block in Europe.

We recently expanded our global footprint in one of the fastest-growing international markets, Latin America through our partnership with Eurofarma. The Eurofarma team has considerable scale, expertise and relationships to support EXPAREL expansion. Our initial focus will be on Argentina, Brazil, Colombia and Mexico. Eurofarma will be taking a lead in securing EXPAREL regulatory approval as well. We have our first steering committee meeting next month to begin laying out our detailed strategy and time lines.

To cover iovera°, continued sales growth and an expanding customer base underscore the growing level of interest in our educational and commercial programs taking hold and highlight this novel cold technology and its ability to deliver drug-free and surgery-free pain control that endures for several months. Our PREPARE study is proceeding according to plan and set for readout later this year or early 2022.

Our iovera° registry is underway and will capture real-world evidence in TKA procedures in leading centers of excellence. In addition, we will roll out a Generation 2 iovera° platform later this year, and our development team has successfully developing additional smart tips that will utilize the same handheld device with separate smart tips for low back pain procedures and specific spine procedures.

Our clinical development team is also moving to the next cohort of our subarachnoid program for spinal administration and a depo dexamethasone asset for particulate-free inflammation therapy. We remain very active in the business of development front, having invested in both musculoskeletal and chronic pain spaces in the first half of this year.

Looking ahead, we continue to advance these two key franchises with a focus on knee and spine continuums of care and bridging to chronic pain. We plan to use the combination of strategic investments that support promising early stage platforms, like GeneQuine and Spine BioPharma, and end licensing our acquisition transactions to build auto pipeline of innovation.

In closing, we feel great about where we stand today and the market dynamics that we are seeing for both products. We will continue to build on our growing momentum and remain highly confident in our growth outlook. Looking ahead, we fully intend to lead the way by expanding the use of EXPAREL and iovera° and by investing in novel innovative technologies that are synergistic with our goal to bring non-opioid pain management and regenerative health solutions to patients in need.

With the experience and expertise of our management team, dedicated employees and over $650 million in cash, we are excited about the short-term and the long-term future for Pacira to improve patient care. With that, I'll turn the call over to Charlie to cover a few key topics.

Charlie Reinhart

Thank you, Dave, and good morning, everyone. On the financial front, we continue to deliver outstanding results with the second quarter coming in at record levels for the top and bottom lines. EXPAREL utilization continues to fuel this growth with average daily sales coming in at 178% of prior year for the second quarter and 120% for the month of June.

To remind you, in June 2020, EXPAREL returned to year-over-year growth following the peak impact of COVID in April and May. As we look ahead, we believe the robust 20% year-over-year growth rate achieved in the month of June is a strong indicator that EXPAREL growth is back to pre-COVID growth trends, consistent with our expectation of growth rates in at least the high teens over our 5-year planning horizon.

With regard to gross margins, we continue to project gross margin improvement of 1,000 basis points over the next few years, with EXPAREL gross margins reaching at least 85%. This will be achieved through the combination of lower cost manufacturing capacity and steadily expanding volumes.

For manufacturing, yesterday, we were excited to announce a key milestone ahead of schedule with the FDA's commercial approval of our 200-liter batch manufacturing unit located in our U.K. facility. We expect to start selling commercial product manufactured by this unit later this year. This will deliver another uptick in gross margins in 2022 when we begin selling significant 200-liter inventory. We expect margins to exceed 85% once our 200-liter suite is primarily responsible for supplying EXPAREL.

Projected unit costs from the 200-liter batch process are lower than those of the current 45-liter batch units. As we have mentioned in the past, per-unit manufacturing costs from our U.K. facility are comprised of a higher proportion of variable costs, while those from our San Diego facility have a higher proportion of fixed cost. Consequently, sourcing total EXPAREL volume demand from our 3 manufacturing suites in the most economical way will require a bit of balancing because as we take volume out of the San Diego facility, the per unit fixed cost for the remaining units produced at that facility will increase.

With the FDA's approval of the 200-liter process, we have submitted our new patent for Orange Book listing. This product by process patent Manufacturing of Bupivacaine Multivesicular Liposomes claims composition of EXPAREL prepared by our improved process and will take our proprietary position to January 2041.

Over the last 6 years, we have invested more than $100 million in a more efficient method for making EXPAREL in a matter that meets the FDA's rigorous standards for safety and bioequivalents. This new patent is the first deliverable from our comprehensive patent strategy, adding another layer of market exclusivity and underscoring the deep multivesicular liposome manufacturing expertise that we have accumulated over more than 25 years. The EXPAREL manufacturing processes are highly specific and a core competency proprietary to Pacira that we are committed to safeguarding globally. Remember, Pacira is the only company that has ever manufactured a multivesicular liposome at commercial scale anywhere in the world.

Regarding any potential generic EXPAREL, FDA guidance established extremely rigorous hurdles for proving bioequivalence, and this would have to be accomplished without infringing on the Pacira patent state, which now includes another strong patent to consider. This would require a multiyear near decade-long effort to design and construct the commercial scale manufacturing facility that would also require operational licensure and validation prior to any bioequivalent study requirements by the FDA. This is a long and extensive process with little chance of duplicating the EXPAREL pharmacokinetic profile since we have never disclosed our proprietary batch specifications or release assay.

In short, we have great confidence that we'll never be a generic EXPAREL. And given the package inserts we have seen for potential competitors, we believe EXPAREL will remain the branded market leader for many years to come based on safety across a broad range of infiltration, field block and nerve block procedures for both adults and pediatrics. While we are currently not providing 2021 guidance, given the continued uncertainty around COVID-19 and the pace of recovery for elective surgery market, we will continue to report preliminary monthly product sales to share intra-quarter trends with you. We will consider changing this practice as we have more visibility post COVID.

The COVID variance with increasing infection rates and the lack of clarity around soft tissue surgeries delayed by COVID returning to the market in the back half of this year, lead us to the conclusion that providing guidance at this time is not warranted. We remain bullish in our long-term expectation for robust top and bottom-line growth, and we are confident in our 5-year plan, which is on track to deliver revenues that will approach $1 billion for EXPAREL and $200 million for iovera°, gross margin improvement of 1,000 basis points and operating margins that exceed 50% by the end of our planning period.

With that, I'll ask the operator to begin our Q&A session. Operator?

Question-and-Answer Session

Operator

[Operator Instructions] Our first question comes from the line of David Amsellem with Piper Sandler.

Our next question comes from the line of Daniel Busby with RBC Capital Markets.

Daniel Busby

I've got a couple. First, with respect to elective procedures that were pushed out of 2020, can you talk about what you saw during the second quarter in terms of the number of those procedures that came back?

And have your expectations for the second half of the year changed since your last update? I think in the past, you've talked about roughly half of the 4 million warehouse procedures potentially coming back during the second half of this year.

Second, the situation with Delta variant is clearly still evolving, but thus far have you seen any impact on overall procedure volumes or EXPAREL use, particularly in those regions of the country that are most affected?

Dave Stack

Thanks, Daniel. First of all, I mean, we thought that there were 4 million procedures that were not performed in our TAM in 2020. We've -- as we went into the last Q call, we revised the number of patients who we thought would come back for procedures in 2021, 2022 to 3 million, given the number of patients who expired -- really important, the number of patients who no longer had employer-provided insurance. And so we're -- that number was dropped largely because of the environment and some of the things that have happened as a result of the COVID experience.

So far, what we've seen is, in the quarter, very little difference, Daniel, as we went through the second quarter. As we got to the last couple of weeks of July, we did see a little bit of softness in the marketplace. We, frankly, don't know whether that was related to vacations. And we have seen some fairly protracted vacations in the marketplace with folks just saying, 'Look, I've got a huge backlog but my family really needs to get away and spend some time together,' and we certainly all understand that. So we don't know, frankly, whether that's anything related to Delta or whether that's just the July phenomenon that we would have seen under any circumstances.

I mean I can tell you that we've already disclosed, of course, the first couple of months. And July was -- what you would expect for July on a forecasting basis. So I guess the broad answer is nothing material. We are watching some hospitals in certain specific areas, as you mentioned, that are sequestering beds for COVID again. But so far, we've seen no impact on the ASC or the HOPD, which are now responsible for over 70% of our business. So we think that the impact will be muted in any case.

Daniel Busby

Got it. If I could ask one follow-up on capital allocation. You're in the, I'd say, enviable position of having cash investments of almost $650 million and growing. And I realize that your priority is business development. But in the absence of suitable targets and specifically large targets, is there a point at which you start thinking about returning some of that cash to shareholders, whether via share repurchases or perhaps a special dividend?

Dave Stack

Yes. We've initiated that discussion with the Board, Daniel. We haven't made any decisions on that yet. But clearly, our preference would be to create value by bringing in additional assets that benefit from the relationships we have with anesthesiologists and orthopedic guys in spine, et cetera. In the absence of our ability to find those kinds of assets, we are talking to a capital allocation that would return funds back to the shareholders. But we're not there yet, and we have a number of things in business development that we're actively pursuing.

So -- but over time, and Charlie outlined, that we expect that our net income is going to grow quite rapidly as the top line grows. So there may be a point even with some aggressive BD and even with large targets that will be in that position several years down the road. But I don't think we're looking at that in the short term.

Charlie Reinhart

Daniel, don’t forget that in the near term on April 1 of next year, we’ll – we have $160 million of the first convert comes due. So that’s also in our time horizon.

Operator

And your next question comes from the line of David Amsellem with Piper Sandler.

David Amsellem

My apologies for the tech issue before. So just a couple of questions. So first, I wanted to get your latest thinking regarding long-term operating leverage, particularly with Swindon online. And this isn't a question about, say, 2022 guidance, but really more about how you think about the direction not just on gross margins, but also EBITDA margins. Also realize that capital allocation and acquiring other assets is a priority. But ideally, do you have a long-term EBITDA margin target that you'd like to share, particularly now with Swindon online? So that's number one.

Number two is on the foot and ankle study on STRIDE, and I apologize if I missed this. So you've talked in the past about another study. Can you just go into more detail on what you think you need to do to sort of get over the hump, so to speak, regarding that o to 96-hour endpoint, if indeed that is still going to be the endpoint going forward? Just help us understand your thinking on next steps on that program.

Dave Stack

Sure. And David, let me start by saying we don’t intend on this call to give long-term net income guidance, and I’ll try not to do that actually. But we think we’re in a very strong position. We have to start out with gross margin, and I’ll ask Charlie to give any comments he has here in a second. But if margins improved to something over 85% and we think that we’re in a position where, frankly, we’ve disconnected the generation of additional revenue from the traditional way of just calculating a percentage of gross sales, is all of the expense items.

So we think that our R&D budget stays in the area of $60 million to $70 million with everything that we know is currently in the BD pipeline as well as EXPAREL and iovera°. SG&A, there’s some additional short-term expense in there associated with the legal action against the Anesthesia Society, but that’s a short-term issue. We will only add a nominal number of additional reps on an annual basis. And so we’re thinking something in the 5% to 6% range of increases on an annual basis.

So when we get to the bottom line, the net income, as we said in the script, will be over 50% over the 5-year planning period. That could modify to the upside, depending on what we find in the BD world. If we don’t buy anything, it will clearly be higher than that. But what we’re planning now is that we believe that we will be successful in some of these BD efforts, we will have some access – some capital allocated there.

But if you think that – if you take our numbers out to $1 billion for EXPAREL and $200 million for iovera°, you calculate a gross margin in the 85% range for both products. You keep G&A or R&D relatively steady, you would nominally increase SG&A, you will come to your own conclusion about where the net margin is. And that leads us back to Daniel’s question about some type of a special distribution to shareholders or something because we will be generating a lot of cash.

On your second question relative to STRIDE, it was a bit of a false scenario that we – that was set up by the FDA, that there was no additional multimodal therapy that was used in addition to EXPAREL for that first 12 hours. In the new trial, we will accommodate that. There’s actually 2 trials, David. One is going to be the traditional foot and ankle trial, where we will use an additional therapy that will bridge the first 12 to 18 hours, and we will still extend out to 96, we believe, and 96 will be the primary endpoint here.

We also are doing an adductor canal trial largely because we want to put a specific knee trial for this field block into the package insert, with some specific instructions around dosing. But we also expect to have a similar duration of activity. And there, the marketplace is very much form the ERAS protocols around a multimodal strategy. And so we’ll do the same thing.

I think the market is a little bit confused why we didn’t do anything for those first 12 hours in this trial. And really the only opportunity that the FDA gave us for lower extremity nerve block here in the United States was either to do a non-inferiority trial, which would have meant we had over 600 patients in that trial, or study EXPAREL alone for the first 12 to 24 hours. And they now know what we knew then that we do need a multimodal design for those first 12 hours, and then EXPAREL is at full strength and takes us out to 96.

Operator

Your next question comes from the line of Christopher Neyor with JPMorgan.

Christopher Neyor

Thanks for the questions. First one is on [indiscernible] nerve block. So following up on kind of the earlier question, I'm interested in what feedback you've heard from physicians and KOLs on the STRIDE study and specifically on the 12 to 96 hours of pain reduction. And you referenced 15 to 18 months deferral in time line, so what's underpinning that view? And what are the key hurdles for getting this indication across go live at this point?

Dave Stack

It's just a matter, Christopher, of just getting the trial done. We will meet with the FDA. They can clearly see now that there is some additional therapy needed in the additional 12 hours post the surgery, and we'll go back with those protocols. We have successful sites that were in STRIDE. Those sites remain available to us. They are very modest changes to the case report form, into the CRM and to all the other stats programs, et cetera, that are very time-consuming in getting these things up and running. So we expect to have this trial up and running in a very short period of time here.

And it's -- the only thing that keeps us from having this thing be successful is to get the patients through a site that is going to abide by the protocol and not make -- not have protocol violations, which were the problem with the other STRIDE -- with the most recent STRIDE study. So we think 15 to 18 months would be aggressive under normal circumstances. But we think given this scenario, where we've got the same sites -- well, not all the same sites, but the same sites that did the trial correctly, and frankly, were responsible for the 0.03 primary -- the statistically significant primary endpoint in the beginning of the trial at the interim analysis.

So we have great confidence that we know how to do this. It will be a minor adjustment to the protocol. And we will separate out the sciatic for the lower extremity nerve block and then the adductor canal block for the knee and do 2 separate trials that will give us adductor and lower extremity. We don't know, frankly, whether the FDA then would use that to give us a broad label for the lower extremity. But if we have foot and ankle and knee, basically, we've got the vast majority of all the procedures covered, so it will be very much like brachial plexus for the upper quadrant, right? It's not a broad label, but it basically covers all the procedures. So no harm, no foul.

Christopher Neyor

That's helpful. And then a second question on iovera°. So how -- specifically on kind of the uptake curves over the next 12 to 24 months. How do you think about the size of opportunity relative between knee and osteoarthritis? And just what are the key drivers kind of building out this market near term?

Dave Stack

Yes. It’s surprising to us, to be candid upfront, that there is great interest in the anesthesia community around using iovera° for OA pain. So what we purchased from MyoScience really all were primarily related to knee. So if you look at the PREPARE trial, it’s using iovera° several weeks before the procedure to get the patient out of the wheelchair or going up and down stairs, et cetera. So we bring a better patient to the OR, then use EXPAREL for the pain storm of the TKA procedure itself. And the PREPARE trial is measuring functional outcomes, how does that patient do in PT, do they have better long-term prognosis as they go back to work. And a lot of these questions, frankly, Christopher, are being driven by self-insured employers, who want to know how does this impact.

So we’re spending the money and what do we get for our dollar. And how does this patient come back to us? Are they better than they were before? Are they the same as they were before, and we’ll try and answer all those questions in PREPARE. There’s a number of different ways that you can affect the use of iovera°. The anesthesiologists are using a long needle with a single larger ice ball, and that’s typically done under imaging. The sports medicine folks and the ortho folks are largely using the Trident needle, which is 3 probes, and the ice ball forms at the end of each of those probes. Those are typically done under – with anatomical landmarks and so they’re not using imaging. And that requires a number of injections, generally 3 or 4 or not injections, different administrations, where the 190 needle, in many cases, it’s just a single ice ball forming because they’re actually looking at that rate on the ultrasound.

So it’s total knee arthroplasty as a procedure. And the primary selling right now for our field force is osteoarthritis of the knee for patients who won’t get surgery or can’t get surgery because during COVID they went from ASA 3 to ASA 4. We’ve also – have a lot of special situations, people that want to dance at their daughter’s wedding, people that are going on vacation with their family and they want to have more mobility. Just people have belonged to a country club that aren’t playing golf or tennis, because their knees hurt. All of those kinds of things are coming into play.

So generally, the 200-liter – or the $200 million guidance is largely reflective of just those procedures. On a go-forward basis, I mentioned that we’ve got a separate tip that we have great confidence will have – will be an effective several months treatment from media branch block pain, low back pain, 14 million Americans. We’re also looking at very specific spine procedures, working with spine surgeons and spine anesthesiologists who have been the people that have actually driven a number of these protocols and are working with the prototypes on how we address the pedicle and how we actually administer these products.

There is a lot of activity now and great interest, frankly, in spasticity. Looking at spasticity in kids, specifically was from some of the Shriner physicians. Currently, they’re using Botox, which is administered on a trimester, on a 3 times or 4 times a year basis under general anesthesia. We think we can improve that with cold. We’re looking at rib fracture and cardiothoracic procedures. So there’s a number of opportunities outside of the knee, OA and shoulder, OA and foot and ankle, OA and the risk. So all of those things lead us to believe that this could be a very big product if we catch a couple of breaks and if we can really be very specific with the way we engineer these tips to address these specific situations.

Operator

Your next question comes from the line of David Steinberg with Jefferies.

David Steinberg

I have a couple of questions. The first one is on the backlog of procedures, Dave. I know that you've talked about 3 million to 4 million backlog. I was wondering if you could give us some sense of the cadence. Do you think most of them could be finished this year? Or do you see a high percentage moving into next year?

And then speaking of cadence with your -- with the approval of the Swindon manufacturing facility, perhaps Charlie, you could help us with there obviously is going to be some gross margin improvement going forward. And now that this facility is approved and you're going to launch later this year, how we should think about the cadence of the improvement this year and next year and the year after for margins?

Dave Stack

Thanks, David. Let me -- I'll take the first one and turn it over to Charlie. So if we -- what's happening in the marketplace now, David, is a lot of what we're seeing in terms of catch-up in the marketplace is the orthopedic procedures. So if we go to most of the ASCs now, you'd see an OR schedule that is mostly hips, knees, spine. And the reason for that, of course, is they're not only highly painful, so you have a very motivated patient population, but they're very profitable. And so they're expensive procedures. And so the insurance companies are very aggressively moving these cases towards the ambulatory surgery centers and the HOPDs.

And so that combination of highly motivated patients and insurance carriers, both self-insured and commercial, as well as CMS, frankly, are moving those patients towards the ambulatory surgery center where EXPAREL does very well. So that's really been the strength of what we've seen so far. That's driven largely, by the way, by the fact that an orthopedic surgeon or a spine surgeon has a decade-long relationship with a patient, which is really quite different than a primary care patient who needs a hernia or a hemorrhoid or something like that. And so we're seeing that marketplace consolidate itself again with patients going back to those -- to their primary care doc and then being referred.

Many of those procedures, David, are ending up in the hospital and the hospital elective surgery department primarily because the ASCs and many local environments are just in a position where they don't have to take low-profit margin procedures yet. So as we catch up with the orthopedic procedures, we believe that we'll start to see more of these soft tissue procedures come into the ambulatory surgery market, but we think that a lot of what will happen when the hospitals get back to elective surgeries, that they're going to be stuck with these lower-margin procedures that they tried to move out of the hospital through their ambulatory surgery strategies in the first place. So that will be quite an interesting phenomena to watch as we get through the rest of this year.

We're clearly not going to catch up all 3 million this year, David. I think if we get into the 1.5 million, 1.6 million range, we'll be in a pretty good spot. And so we think that there's still going to be something like 1 million plus of these procedures that carry over into the early part of 2022. The question that we talk about all the time is if you had a hernia or if you've had a hemorrhoidectomy or something like that it's approaching 2 years before you have an opportunity to get those procedures filled, whether it's insurance or facility availability or whatever, are those patients going to have that surgery? We think the answer to that is yes, but it's not as clear cut the joints and the spine.

Charlie, you want to jump in for gross margin?

Charlie Reinhart

Sure. I'd be happy to. So David, at this point, with the first 200-liter unit becoming commercially available, we'll start to use that. You know that we have 45-liter batch process units in both the U.K. and San Diego. So as volumes continue to grow, as we're projecting in our 5-year plan, we'll start to more fully utilize the 200-liter. We'll use the 45 kind of for the backup. Hopefully, in the future, we'll have DepoFoam-related pipeline products. So some of the 45s, probably the San Diego 45s might be used for both pipeline product and to manufacture smaller batch sizes for rest of world, you've seen.

We're also developing a second 200-liter unit in San Diego, which we hope comes online kind of end of '24, early '25. So by the end of our 5-year planning horizon, it's quite possible that EXPAREL's U.S. product is all 200-liter product, which would be really great. And at this point, our best estimate is that the gross margins will improve a couple of percentage points each year for the next 3 or 4 years as we drive towards those goals.

David Steinberg

Just have a follow-up question, vis-a-vis your new competitor. And if it's already been asked, I apologize. We were on a previous call. But I assume some P&T discussions have now happened since the Heron drug has been approved. I just curious, you're on many of these formularies, have you found any instances where you've been knocked off the formulary due to the Heron product? And if so, why would that be given that your label is much broader than theirs?

Dave Stack

Not one, David. So I don’t have any – I don’t have – I have no response to the second part of the question. We don’t have one.

Operator

Your next question comes from the line of Anita Dushyanth with Berenberg Capital.

Anita Dushyanth

Could you sort of talk about like the procedures that are sort of where EXPAREL is being used in the pediatric market now and which other procedures it could possibly expand to?

And kind of along the same lines as far as the European launch, what are some of the procedures that are likely to use EXPAREL as the early adopters? And then I have a follow-up.

Dave Stack

Thanks, Anita. I'm going to ask Roy Cleland -- Roy Winston has been much closer to the pediatric procedure market, so I'm going to ask him to cover that in one second. In the European market, we're focusing largely on knees and shoulders. It's where there is the greatest backlog. And we've got a unique opportunity here where the national health system, the payer, the government payer is working with different groups of surgeons around the country in the U.K. to try to expedite the -- addressing this huge backlog of procedures that they've got.

So we're working with these folks, sharing our ERAS protocols with them, in many cases showing our -- using -- having our surgeons talk to these folks and anesthesiologists talk to these folks about how are we doing same-day surgeries, how do our patients walk out of an ambulatory surgery center 3 or 4 hours after a total knee. So it makes the most sense for us to go to those procedures with both iovera° and EXPAREL.

So in Europe, we'll focus on those, then we'll move that out to spine and hips as we move forward and then work our way backwards into the soft tissue procedures, largely because of the pain profile and because of the really desperate need given in the U.K. right now, it's a 27-month wait for a total knee arthroplasty. So we think we've got an opportunity that will take us several years and needed a cleanup on the front end of this. And so that's where we're going to focus when we launch.

And we're well into the prep for that now educating these guys and sharing protocols, et cetera.

Roy, would you -- could you give a need some specifics about which procedures are leading the way with peds and where they're headed?

Roy Winston

Sure, Dave. Happy to. And Dave did mention at the beginning that we did a very tight-controlled launch. We stuck to pediatric idiopathic scoliosis because number one, that's where a lot of our data was; in. And number two, it's an area of great need. You have these kids that have these massive back surgeries. They're usually between the ages of 10 and 16, and they use a lot of opioids and have a tremendous amount of pain.

So we launched there and we found a very rapid uptake to where the -- really the key opinion leaders were rapidly adopting. And from there, there has been quite a bit of expansion. For instance, some of the Shriners hospitals now. And you got to keep in mind that 80% of pediatric drug use is off-label to begin with. But in lower extremity, they're finding that it's just such an advantage to be able to give kids a block with EXPAREL instead of using catheters like they used to or plug them into a PCA device. So we're finding a very rapid uptake in areas where kids are currently being served by either IV opioids or catheters. And these are large reconstructive orthopedic procedures.

But there are also big abdominal procedures and large thoracic procedures. Really all these large painful procedures. And the thing that we are finding, not only among the spine surgeons, but even among the pediatric anesthesiologists, it's a small, tight-knit group. We have a lot of people doing quality improvement studies now looking at EXPAREL, major institutions across the country that are beginning to use. And I think in pediatrics, we expect the trend to continue, because I feel like it's one of those things where the motivation is really just to provide the best possible care for patients and that's all that the pediatric surgeons and pediatric anesthesiologists think about. And I think that's what's led to the very quick uptake.

Dave Stack

Yes. And so Anita, very specifically, right, the orthopedic procedures Roy was referring to, club foot, for example, a significant number of places that are experimenting with burns, appendicitis is called out as one that one center is using a lot of product in. Store economies, GI, GU. So -- and what they're really looking at is a lot of the evolution of what we saw in adults. But given the -- all of the experience we have now, there's a number of places where there's very significant interest in getting these kids out of the hospital. And if they were staying in the hospital largely to control pain with opioids or with a PCA pump and they weren't certain that they could keep the catheter in overnight, now they're using EXPAREL and so there's a lot of interest in that as well.

Anita Dushyanth

That was very helpful. And then just one question related to the expenses. I know you are kind of not providing too much guidance on that. But I just wanted to know like with the additional steady starts in the lower exit procedures and then the launch in Europe, can you sort of give some color on how we should think about increase in the expenses in the second half?

Dave Stack

Yes. So for R&D specifically, we think that the $60 million, $70 million that we’ve told folks that they can count on with the current portfolio, plus what we know about in BD, is a good number. On the sales side, we are hiring a contract sales organization. And so we will have some additional resources. But frankly, not anything that would cause us to dramatically increase the budgets for those marketplaces.

Actually, Anita, the rest of ‘21 looks very much like the back half of 2019, if you wanted anything that was more specific in terms of what the numbers are. The only outlier really in everything we’re doing now is an increase in the G&A line as a result of some material spend in the legal action against the American – the Anesthesia Society. Outside of that, the back half of ‘21 is strikingly similar to the back half of ‘19.

Operator

And your next question comes from the line of Andreas Argyrides with Wedbush Securities.

Andreas Argyrides

This is Andreas Argyrides on for Liana Moussatos. Two quick questions here. First, regarding iovera°, you've previously guided it to be a potential $200 million product opportunity in 5 years. How much of that comes from outside of the U.S.?

And then as a follow-up to the pediatric question just now. If you guys can just remind us what the outlook there is? And if there's such a rapid uptake, is it potentially to exceed the -- I believe you must have guided to like $100 million?

Dave Stack

Yes. So outside the United States, we're looking for iovera°, we have signed a license agreement for Canada and we are launching in October into Europe. And if you roll those numbers together, you get something in the neighborhood of in the $70 million to $80 million range in the planning period. I'm sorry, Andreas, can you tell me what the second question was? I was writing down the first question and I missed the, beginning I'm sorry.

Andreas Argyrides

Yes. Just on the pediatric opportunity. You previously guided, yes, like $100 million. Just if you could comment on that.

Dave Stack

Yes. No, thanks. That’s a really good question, actually. So we guided against the TAM for adults. And we – so we were basically using extending orthopedics, extending many of the soft tissue procedures, et cetera. What we’re finding is a much broader desire to use the product in things like burns. And still in GI, GU, I think we’re in pretty good shape. But there’s a lot of pediatric procedures that were not in our adult TAM. So I think it’s safe to say today, especially given the pace of the adoption that $100 million, from my expectations at least, would be on the low side of where we’re going to end up over the 5-year planning period.

We haven’t come up with anything specifically. We haven’t guided to anything higher than that. What we’ve looked at is the time line to $100 million. And so I would say, increased confidence in the $100 million number, and that’s probably conservative given everything we know now.

Operator

Your next question comes from the line of Greg Fraser with Truist Securities.

Greg Fraser

I got on late, so I apologize if you already covered this. But did you comment on EXPAREL sales in July?

Dave Stack

We did not. No, we did not, other than to say it looked like July. And so given the guidance that we've talked to about high teens and those kinds of numbers, Greg, nothing that would be surprising.

Charlie Reinhart

Greg, this is Charlie. I think the way I'm looking at it is for the couple of months in Q2, the relationship between '21 and '20 just didn't make any sense because of COVID. And now June kind of crossed us over because at this point, June '20 was -- we had bounced back from COVID. And so now starting in June, we're now looking at year-over-year comparisons. So I think what Dave is saying is that July was another good month, but it was -- it will compare favorably to last July, but we'll release the actual numbers next week.

Greg Fraser

Got it. Okay. Two key growth drivers for EXPAREL is in the brachial plexus nerve block indication and TAP blocks, I'm curious how you would describe where you are in the penetration curve for those indications. I guess would you say it's still early days for growth?

Dave Stack

Brachial plexus is – Greg, it clearly was not so much just brachial plexus, it was really the I point for regional anesthesiologists to have some experience with EXPAREL. So shoulder and rotator cuff is leading the way. I would say, fourth or fifth inning with that indication. But I think that would be a bit shortsighted, because really, their success there has led docs to use EXPAREL and a number of other brachial plexus procedures or procedures where a brachial plexus block would be appropriate but not a place that they ever would have thought about using EXPAREL before, right?

So in the past that they were going to do, say, a carpal tunnel surgery or an elbow or a risk surgery, they would have wanted an infiltration protocol just for the use of EXPAREL in that procedure. Now that they’ve seen the effectiveness across the whole quadrant based on a brachial plexus nerve block, you see guys expanding the use of EXPAREL in that – with that regional anesthesia procedure. So I think that we’re, say, 4^th to fifth inning, which you’re talking about, specifically rotator cuff and shoulder surgery, I think it’s probably more like the bottom of the 2^nd if we’re talking about how brachial plexus is going to change the way regional anesthesia is used to address pain control in the upper quadrant, if that makes sense.

It’s pretty much the same story in TAP. TAP was something that folks were doing before EXPAREL was called a rescue TAP and so they waited for patients to wake up in pain. And then they would do the TAP hoping to get the patient through the first postsurgical night. Now we see TAP leading the way and increasing the confidence of the anesthesia and the surgery community to try these regional blocks. And so TAP is still really important to us as it relates to C-section, et cetera.

But what we’ve seen as a result of the success with TAP is blocks like the ESP block, the erector spinae block, which is useful in the scoliosis procedures that we were just talking about. And patients or physicians are now using it in a number of different procedures. So I think if you’re talking about TAP specifically, it’s probably, again, fourth inning. This is a 9-inning game I’m referencing, by the way. And if you’re talking about ESP, the rapid expansion of pecs block and PENG blocks and a number of different ways that the anesthesia community is learning how to use non-opioid, long-acting regional anesthesia blocks, it’s probably more like the top of the 3^rd.

Operator

Your next question comes from the line of Serge Belanger with Needham & Company.

Serge Belanger

I had 2 questions. The first 1 is a follow-up on a prior question related to ZYNRELEF. The competitors made it pretty clear that they'll be targeting the TK segment. Just curious if you've seen anything so far? It maybe too early given they only launched the month, but maybe if you're expecting any impact even if just transitory.

And then second question is related to one of the graphs in your slide deck. I think it's slide #9. The one that compares the external sales data on a weekly basis to volumes in elective surgeries. We've seen EXPAREL really outperform the elective surgery volumes. And that outperformance, I think, really increased in June. Just curious how we should think about that if it's an indication of EXPAREL's growing role in the ASC or it's really just related to how the claims data are coming in.

Dave Stack

Yes. Let me take the second one first, Serge, because I think you raised an important point. So it is a compilation of claims data. So it does normalize over time. right? So the delta of 6 weeks from now is never going to be as great for last week for 2 weeks ago, for example, as the delta in real time, right? So we have real EXPAREL data, and we're comparing that to a compilation of claims data that will change as those claims data come in.

What we've seen is that even in a normalized procedure, EXPAREL is 10-plus points higher than the elective surgery market. So when the elective surgery market is normalized plus/minus very small amounts against the pre-COVID surgery line, we still see that EXPAREL is doing materially better than that. And I think that's what we've seen with the numbers, and that's what we expect to see. Again, driven -- it is driven to some extent by the move to ambulatory surgery and the move to hospital outpatient departments from insurance companies insisting on those sites of care and the lack of tools that would be available to some of these physicians for pain control in the hospital that are just not available in these same-day surgery environment.

But I think as much as anything else, docs are starting to see that they can do lower, no opioid surgeries now. And they're seeing, especially in the peds market, that they don't need to use a pump in a catheter. They don't have to worry about whether that catheter is going to fall out or dislodge or whatever. And so I think there is a base of increasing confidence in the use of EXPAREL for several days with a single administration. In that light, I think you see some more confidence from the STRIDE study. Yes, we missed our primary endpoint, but having a p-value of 96 hours has real value to these doctors in the marketplace, and we're seeing that as well.

So I think the curves will normalize and EXPAREL will still be 10-plus points better on a normalized basis than the claims data for the elective surgery market in general.

Your question regarding the Heron product and knees. The only feedback that we've had is the product is very sticky. It's very difficult to use. It changes color rapidly and the docs weren't ready for that. And you can't put it through a laparoscope. We haven't heard anything good, I guess, is what I would say.

In the package insert, that's -- yes, in the package insert, the pain score stays in the neighborhood of 7 through 72 hours. So different than some of the verbiage that we've heard in the marketplace, we can show the physicians the FDA-approved package insert, which suggests that the pain score never gets to anything like the pain score that was achieved in the PILLAR trial with EXPAREL. So I -- there is very modest trial use. I don't expect it to have any impact on EXPAREL over time. Any follow-ups, Serge? You good?

Serge Belanger

No, I’m good.

Operator

Your next question comes from the line of Gary Nachman with BMO Capital.

Gary Nachman

Also on the competitive dynamics with Heron's product. If it is used in some fashion, do you think they'll be able to get any sort of penetration in the ASCs? Or are you expecting to really dominate that portion of the market? So discuss if there were some barriers there based on your experience with uptake in the ASCs.

Dave Stack

Well, Gary, honestly, the only reason -- the only reason, and I think even they would admit this, that anybody would use Zenrolefis because it's less expensive than EXPAREL. In the ASCs, routinely EXPAREL is reimbursed. So there would be -- if somebody was going to try it only because it was cheap, that opportunity wouldn't exist because both are going to be reimbursed. In fact, recently, CMS increased the reimbursement of EXPAREL from $1.29 a milligram to $1.33 a milligram. So big customers who have contracts with us can actually purchase EXPAREL at a slight discount to the reimbursement that they get from CMS. And we routinely see the commercial payers and the self-insured payers follow CMS' lead.

And so I think of all the places that you might use this product, the least that we're worried about is an ASC, because there is -- it's a narrow label, you can only use it for a few things. I think the package insert is really damaging not only the safety section but the data that shows that it's 70 to 36, 48 and 72 hours, the pain score is still hovering around 7 in a total knee arthroplasty, that is just not acceptable there Gary. So like I said, if somebody was going to use it because they were trying to save a couple of bucks, if it's reimbursed, it's reimbursed, that -- even that option falls away. So I just don't see it.

Gary Nachman

Okay. And then just a follow-up on EXPAREL. Just comment a little more on the trends you're seeing in C-section that you just referenced in the previous question. Are there certain types of hospitals that are driving most of the adoption thus far? Or is the uptake more broad-based? And any change of how you view that opportunity at this point?

And then I'll just squeeze in one last one. What types of deals have you been most focused on recently? Would they likely be similar to spine in iovera°? Are you considering anything much more significant at this point to diversify the portfolio more rapidly and further leverage the infrastructure, especially now that you have a competitor in this space?

Dave Stack

Yes. Thanks, Gary. So women's health, it's no surprise, Gary, that it's the big institutions -- the big women's health institutions that are most interested in providing a short-term stay. We see that in a number of different places. We see moms who are really interested in -- it's not so much opioid sparing, it's how do I minimize the exposure of the mom and the baby to any possibility of being in a COVID environment. And we're starting to see private equity firms and some OB/GYN groups around the country building out birthing centers.

And our involvement there is, generally, we get a call and they're looking for a same-day enhanced recovery after surgery protocol, which takes us into all kinds of curious areas like how do you discharge the baby on the afternoon, right? Because there's no pediatrician standing around in a birthing center or in a place that -- so the problems, the hurdles that we have to overcome are more tactical around you change the way that a C-section would be handled so significantly that you have to really construct a way that you can discharge mom and baby a relatively short time after.

So you can see that there's real interest in moving these gals out of the hospital as quickly as possible or not putting them in the hospital at all. And that's largely born in the big cities where you've got aggressive centers. It's also borne, frankly, in the southeast, in Tennessee, Alabama, Arkansas, where big hospital chains would tell you that they lose money on every C-section that they do. These are largely involved in some type of social services payer system, and those payer systems just don't support the mandate for 3 days. And so they're trying to change those regulations that say that those gals can stay in the hospital for up to 3 days and have free access to opioids, largely driven by the finances associated with treating that patient population. So again, it's a bit of a different reason to try to shorten the length of stay, but it has the same outcome from a provider perspective.

Your last question relative to BD, Basically, what we've said, Gary, is we don't have any philosophical or emotional reason that we wouldn't do a big transaction. We have plenty of access to capital given our current scenario or situation. So we would love to do something that further enhances our ability to address our infrastructure opportunities and our relationship with all of these big physician groups, et cetera, we just haven't found the right deal yet.

And I think we are price-conscious. We're not going to do something silly. But we will do that deal if we find it, and we can justify the price and make sure that we're creating value for shareholders. There's no reason why we wouldn't, Gary.

Operator

And your next question comes from the line of Tim Chiang with Northland Capital.

Tim Chiang

Dave, could you talk a little bit just about this recent patent that you guys were issued on EXPAREL? How important is this [495] patent? And sort of comment on just what additional IP you plan to put around EXPAREL. That would be great.

Dave Stack

Yes. Thanks, Tim. Hugely important. As background, our IP was -- our Orange Book listed IP was going to expire on December 24 of this year. So now the current patent will extend out to 2041. it's associated, Tim, with observations that were unexpected as we've gone into larger processes, but also in ways that we've improved the manufacturing process for EXPAREL. And so we think as it relates to the manufacture of multivesicular liposomes that, as you know, are very difficult in the first place, we've further tightened the specs and the opportunity for anybody to be able to make a generic EXPAREL as it's outlined and the points to consider from the FDA that it would have to be an exact duplicate.

It also, Tim, to answer the second part of your question, there are additional product and process opportunities, like our current Orange Book listed patents that have been filed with the PTO. And I think probably most important of those is the new IP gives us an opportunity to also have new IP associated with a new assay. So we released EXPAREL against a proprietary assay. And having an improved proprietary assay that tightens the specs around what a generic would have to look like and never telling anybody what those specs are or what this assay is, I think, makes this pretty much impenetrable in terms of a patent estate around EXPAREL.

Operator

I will now turn the call back over to Dave Stack, Chairman and CEO, for closing remarks.

Dave Stack

Thank you, Dawn. I’d like to thank you all for participating in today’s call. We look forward to keeping you updated on our progress. Next up with us is the Wedbush Conference next week. Thanks all. Stay well. Goodbye.

Operator

Thank you for participating in today's conference call. You may now disconnect.