Helping Others Conquer The Mountain

Posted February 8th, 2017 in Patients | Leave a comment

Snow sports are a passion of mine; almost any day up on a mountain is a great day. By combining this passion with a bigger purpose, I’ve recently tapped into a true vein of inspiration, integrating both my professional and personal life in a wonderful, unexpected way.

Indeed, helping address the needs of patients is what gets many in the biomedical research community out of bed in the morning. The biotech sector’s shared mission is to discover new therapies and advance them to patients as quickly as possible. Yet, surrounded by all the cool scientific advances, actual patients often get forgotten. First-hand engagement with individuals that are dealing with the medical conditions we seek to address is often missing. But it shouldn’t be.

Recently that has changed for me: I volunteered this winter season to be an adaptive ski coach with New England Disabled Sports (NEDS) at Loon Mountain. The experience has been nothing short of inspiring.

NEDS has a simple but powerful mission: “through sports, to change lives affected by disabilities. ” The organization and its 200 or so coaches provide nearly 3000 lessons each year to student-athletes with a range of disabilities, including physical, cognitive, hearing or visual impairments.

I’ve primarily focused on coaching students with physical disabilities, and in particular those that require them to use one of several kinds of bucket-style sit-ski’s, e.g., a mono-ski or bi-ski of various configurations depending on the degree of independence of the student (and how much the coach needs to tether or steer the device). This type of equipment is frequently used for individuals with multiple sclerosis, spinal cord injury, Duchenne’s and other muscular dystrophies, cerebral palsy, spina bifida, stroke, traumatic brain injury, neuromuscular diseases, and other conditions where lower or upper extremities are compromised. Many of these conditions are the ones our biotech community is engaged in trying to address with new therapeutics and regenerative medicine.

Over the past few months, it’s been a real privilege to work with individual student-athletes facing down these conditions and their respective disabilities. To share some of the inspiration I’ve felt, here are six themes that I’ve learned working closely with these student-athletes so far this season.

  1. Attitude is everything: never accept the word “never”. Most of these students or their families have heard people say the word never, but to their credit they largely refuse to listen to it. As a new coach, I learned this right away. My first lesson was with Colleen, a wonderful and courageous teenage girl with spina bifida, who had recently had spinal tethering surgery and was wheelchair-bound. That didn’t stop her from wanting to learn how to independently bi-ski, with a totally positive can-do mentality. A few weeks later I worked with another teenager, Nico, similarly only a few months out from a spina bifida-related surgery, who was super eager to improve. Every chairlift ride he would ask me what he could do to get better on the next run. The look on his mother’s face as he skied down the slope on the last run with us was overwhelming. Or take nearly 9–year old Logan, who was born with a rare condition called hereditary spastic paraplegia; a totally fun, upbeat kid with a great attitude about life. Trading his crutches in for a bi-ski, he can truly rip turns down the mountain faster than the majority of skiers. As Zig Ziglar said, “Your attitude, not your aptitude, will determine your altitude” – even more true in the mountains.
  2. Changing the context can unleash unexpected strengths. Physical disabilities are often easy to see, which frequently leads to a range of (mis)perceptions from onlookers. Take Chris, a 67-year old who’s been battling primary lateral sclerosis (PLS), a neuromuscular disease, for the past decade; his speech and ability to walk are significantly compromised, presenting in a manner similar to stroke. He certainly doesn’t look or sound like a skier today. But his lifelong passion for the slopes couldn’t be kept down; with the help of other NEDS coaches over the last decade, he’s become a very capable athlete in a bi-ski, independently carving S-turns down the blue slopes all over the mountain. To watch Chris ski, you’d never know he was a patient with PLS. I saw the same from Debbie, a 55-year old woman with multiple sclerosis, that I had the pleasure of coaching for a morning a few weeks ago; while wheelchair-bound on land, on the snow she was a super-fast, very aggressive skier who loved to take her bi-ski right up to the edge of the trail (and scare the coaches tethering behind her!). When you move an individual with disabilites into a different context, like onto the slopes of the mountain, amazing things often happen.
  3. The excitement of adrenaline and the wind on their face. Adrenaline is one of the most basic human hormones: key to the fight-or-flight response, it’s also a trigger for thrill-seeking excitement, along with its cousins, the positive endorphins. To varying degrees, everyone wants to enjoy the rush of adrenaline from time to time. Students with disabilities, even those that can’t participate actively in skiing down the mountain, are no exception. I’ve enjoyed guiding a wonderful 22-year old young man with cerebral palsy, Ryan, down the slopes; hearing him vocalize his excitement as we carve down the mountain in a sit-ski is a sure sign he’s having a blast. The thrill of the slopes is an absolute joy to share with him.
  4. Finding confidence and purpose through community. Adaptive ski programs like NEDS create a great environment for student-athletes with disabilities to grow, and to increase their broader life confidence through their activity and achievement on the mountain. The story of 20-year Sam, who also has cerebral palsy, is a great example: he’s been involved in NEDS for 15 years and truly loves skiing with the NEDS community, having grown up with many in the program. With the confidence that in part he’s gained through this experience, he’s now become an intern at the Massachusetts state house this year. He’s a great young man, and I’m fortunate to have been out there with him a few times this season. Other students with disabilities in the NEDS program have now grown up to become coaches themselves, assisting the rest of us with coaching the next generation of younger athletes – bringing broader purpose to their lives and others.
  5. Quest for independence, one turn at a time. While not every student can become an independent skier, the lessons and equipment chosen are tailored to facilitate as much participation in the sport that a student’s condition allows. Take JB, a fun-loving 9-year old boy with Duchenne’s, whose gloves have green and red tape on them; moving down the slopes the coaches holler out a color, and JB does a great job of shifting his weight by reaching with that arm to initiate the turns in his bi-ski. Another athlete, Courtney, has progressed from a tethered bi-ski to independent snowboarding over the past couple years as her recovery from TBI continues; we had a great time boarding together a couple weekends ago. Having a student-athlete “own” as much of their snow sports experience as possible, exerting increasing amounts of control and independence on the slope, helps further reinforce confidence both on and off the mountain.
  6. Summiting personal mountains transcends age. In my very short tenure as an adaptive coach, I’ve now worked with student-athletes that span nearly 65 years of age: from Chris, mentioned above, to a little toddler named Mack, who is just 3-years old. Mack, who has cerebral palsy, did a number of runs in a tethered bi-ski with us one morning and ended each one with a huge smile. His excitement reminded me that skiing is indeed a lifelong sport; it’s one of the few that you can do over the span of decades. Grandparents can actively ski with their grandkids, as my parents have done with my kids. Gravity works the same on our mass regardless of our age. But coming back to NEDS, individuals of all ages have their personal mountains to climb – and I’m lucky to be part of a program that helps many of them reach their peaks.

As you can probably tell, I’ve been totally inspired by the NEDS adaptive program.  It’s a fantastic group, and it’s a privilege to be a part of it. A big thank you to the NEDS staff and experienced coaches for bringing me onto the team.

Many of the individuals I’ve helped coach already benefit from important medicines discovered and developed over the past few decades, such as autoimmune therapies, anti-inflammatory agents, epilepsy drugs, or anxiety medications, etc. But they also greatly benefit from being recognized as far more than just patients; in fact, I’m hesitating to call them patients here, as these are wonderfully-engaging individuals and families trying to push themselves to be the best they can.

It’s also clear to me that even with similar physical disabilities, the unmet needs of individuals are often very different. In biomedical research, we often think of these clinical conditions at the population-level, yet there’s broad heterogeneity not only in how their symptoms present, but also of how these individuals think about their symptoms relative importance.

This leads many in biotech and clinical research to often miss important real-world, everyday needs and goals that many of these individuals have – like wanting to conquer the mountains, both the literal and figurative ones, in their lives.

NEDS, and adaptive sports programs like it, help them reach that goal.

 

Postscript request: New England Disabled Sports (NEDS) is a 501(c)(3) not-for-profit organization, providing adaptive sports instruction to students of all ages and abilities. It is through the generous donations of individuals, corporations and foundations that so many student-athletes living with disabilities are able to enjoy the mountains.  Please consider a donation through the website or through the link here.

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Seven Important Policy Agenda Items For BioPharma

Posted January 31st, 2017 in General Venture Capital, Pharma industry, Science & Medicine | 1 Comment

President Trump’s tenure as the 45th POTUS has begun with even more fireworks than most pundits predicted – protests, marches, bans, and lots of other drama. The coastal Twitter/Facebook bubbles are exploding with anger and rage, while the Trump populists in the “other” America are celebrating. Seems like the country has gone crazy.

Crazy also means unpredictable, which is a bad thing for investing. Long-term allocations of capital, especially illiquid pools like venture and private equity, require a some degree of predictability around the rules of the game.

Predictable business environments are critical for a healthy long-term investment climate.

Predictable environments are those were long-term scenarios are definable with some guardrails, and where investments can be made with some confidence about the future regarding the key strategic inputs: product forecasting, capital access, talent expectations, regulatory clarity, tax rates, stable national security, adequate infrastructure, etc…

This is particularly true for R&D-intensive fields like biopharma and venture capital investing, where we take a 10+ year view of the world and make bets around high risk innovation.  For us, as with many other long-term sectors, a “predictably good” forward view would certainly be great, but even “predictably bad” is better than the insidious effects of chaotic uncertainty. At least with “predictably bad” policies we can plan accordingly, hedge our forward views, and accommodate a set of potential realities.

Unfortunately, right now, we’re in a climate strongly biased to uncertainty – as it’s unclear where the Trump administration and new Congress will take us on a series of policy issues. They don’t appear to be taking tips from any prior playbook, especially not the “free-market” GOP version. Further, Twitter enables a level of impulsiveness in some that exacerbates the unpredictable. Hopefully, as the dust settles, we’ll begin to have clarity on the business environment we’re in – but hope isn’t a strategy.

Recently, NVCA Chairman and Menlo Partners managing director Venky Ganesan said “If you’re not at the table, you’re on the menu.”  This is certainly true. We can’t sit on the sidelines for four years hoping things work out. We need to engage both Congress and the Administration and “focus on staking out positions” of importance to us.

In that spirit, here are seven policy areas that I think are crucial for the health of the innovative biomedical sector over the next decade, especially for early stage biotech investing. Many of the future medicines of the next few decades will depend on the health of the latter. Getting clarity on these will aid in the predictability of various future outcomes for our sector.

None of these issues will be surprising to readers, but given Trump’s meeting with Pharma CEOs today and his comments, it’s a good time to articulate these issues. Importantly, these are my personal views – I’m not speaking for BIO, PhRMA, NVCA, or even Atlas – though most of these issues will resonate with those groups.  Apologies in advance for the length; for those unable to tolerate the rambling nature of the prose, just read the boldface for the Cliff Note version.

Seven policy areas:

1. Encouraging drug pricing reform that promotes a healthy innovative biomedical sector. In principle, this means maintaining our market-based pricing model that rewards innovation and reflects the value of medicines; confidence in knowing that future medicines will be rewarded is central to the biopharma sector.

In practice, though, there are a number of reforms needed to address the “astronomical” pricing issue. As a response to the EpiPen crisis in the summer, I’ve previously outlined my thoughts on drug pricing (Innovators vs Exploiters: Drug Pricing and the Future of Pharma). Like others, I’m deeply disturbed by the egregious pricing actions from Exploiter firms, that take advantage of regulatory loopholes to create artificial monopolies and jack up prices. And I’m also disappointed with the irresponsible addiction to high biannual price increases that some Innovator companies have developed over the past decade. I think industry self-regulation is an important part of the solution, and leaders like Allergan CEO Brent Saunders have taken strong positions on this issue. I share Brent’s concept of a “social contract” entirely, which is in line with Roy Vagelos’ view of the industry’s relationship with society thirty years ago. Beyond self-regulation, we need to see a few things, reiterating just three from that August post, to create a long-term sustainable pricing approach:

  • Encouraging and accelerating generic competition. Anathema to some in our industry, I’m a firm believer that when acting in good faith and in accordance with patent law, generic competition is a resounding good for our sector. We need to ensure there aren’t artificial monopolies, or stalling tactics (e.g., pay-2-pay, delaying biosimilars), which presumably requires reducing some of the regulations at the FDA to ensure more generic manufacturers and their products are approved. Generic competition reduces prices and makes room for rewarding the next generation of great medicines.
  • Increased transparency on how healthcare costs, including drug prices, flow through the system. Actual healthcare costs in the US are opaque, and drugs are no exception. Until these become more transparent, list prices in our sector will remain lightning rods for public outcry. Given the entrenched interests, this may require legislative action.
  • Incentives and support for value-based pricing models. Effective drugs deliver enormous value to the system: improving and extending patient lives, keeping our workforce healthier, and reducing the costs of other components of the healthcare system. Creating the right incentives for “value-based pricing” models to emerge will also drive the adoption of personalized precision medicine: getting drugs to patients most likely to respond. Policies to support this approach, and guidelines for how these should be framed, are in discussion now (here).

2. Supporting the FDA’s continued embrace of innovation. Over the past 10 years, many of us believe the FDA has moved from being an obstacle to innovation to being a genuine facilitator. Numerous initiatives and guidelines have enabled this: Critical Path, Accelerated approval, Fast Track, Breakthrough Therapy Designations, etc… Many of these were part of the numerous renewals of the FDA User Fee Act since 1992. While there are certainly specific product examples where I might argue with an FDA position, in general the FDA has embraced the idea of bringing compelling medicines to market faster. From pre-IND guidance meetings through pre-approval Advisory Committees, the FDA has a series of touchpoints with innovators as they develop new medicines. The results are clear: a number of approvals in recent years only spent 4 years in clinical testing, far fewer than the historic average. And over 200 new medical entities have been approved since 2011. The FDA is the world’s leading regulator on many metrics (like speed to approval).

There’s much talk in Washington these days about Peter Thiel’s views and “unleashing the Silicon Valley mindset” onto the FDA. While there’s much to like in some of these ideas (e.g., enabling digital health, better genomic integration into care, technology playing a bigger role in understanding real-world drug performance, etc), the concept of eliminating the bar for efficacy for approval is troubling and fraught with unintended consequences.

First, we already have something akin to this – it’s called the Accelerated Approval Program. Drugs can be approved without clinical efficacy, but with benefits suggested by the right movement in a surrogate biomarker. The approvals under this program are conditional: if future confirmatory trials fail, the drugs are taken off the market. This seems to me to strike a good balance for some diseases with large unmet needs. Efforts to enhance or broaden Accelerated Approvals or related initiatives could be beneficial and are worth considering in a balanced way. But not having some indication (i.e., surrogate biomarker) of a drug’s effectiveness prior to approval isn’t appropriate.

With regard to “right to try” experimental medicines for dying patients, we already have this too.  It’s already authorized for the terminally ill under compassionate use by the FDA and is supported by most companies; this is just largely just sentimental legislation rather than a materially different process, and despite passing in lots of states has only impacted a small number of patients (here). Efforts to improve the process would be welcomed, but this won’t fundamentally improve patient outcomes.

Second, a world without efficacy requirements puts both patients and the eventual payor (taxpayers) at risk. Without data on efficacy, understanding the risk-benefit of a new medicine is impossible even for trained physicians, much less so for the majority of patients. Further, who is going to pay for drugs that aren’t proven to work? Without the FDA’s stamp of approval, this bar simply punts the evaluation to the payor world, who will have to enact their own “efficacy inside” metrics for how to pay and price these. And since Medicare is the 800-lbs gorilla of the payor world, the unintended consequence of this supposedly libertarian idea will be more direct engagement of Medicare in explicitly setting price in the US. In a world where patients take medicines, physicians prescribe, and payors pay – it’s not clear to me how a “Yelp for Drugs” version of the FDA, that depends on individuals engaging in a price/value discussion at vast scale, would work. How can “value-based pricing” be established without objective data from clinical studies (including real-world studies)? The plural of a Yelp anecdote is not data. Instead, it’s a slippery slope and ends up looking like the mess in the supplements world: individual consumers reading snake oil testimonials and paying for their own “at risk” pills by judging the crazy claims for themselves. No wonder almost none of the supplements have been shown to definitively add value.

Part of the FDA’s role is to accredit the approval of new medicines with a common standard of efficacy and safety.  This standard, along with the EMEA and others around the world, is an important demarcation of medicines proven to add real value to patients – and this standard is a big part of how the healthcare payor system justifies the payments to either insured individuals or collectively taxpayers. Continued FDA reform to facilitate more innovation is a great aspiration, as there are always things to improve, but damaging the FDA’s standard of approval – its weighing of the benefit-risk of any new medicine – would be bad policy.

3. Make American businesses more globally competitive through corporate tax reform. It shoudn’t be news to anyone, but we have the highest corporate tax rate in the world, and we tax ex-US earnings of US headquartered businesses (unlike other countries). This makes US businesses less competitive on the global stage. Reforming this tax rate permanently, enabling the repatriation of both past and future ex-US earnings, will spur investment in US businesses. Capital trapped offshore today can be used to fund R&D, set up collaborations, acquire new products, among other things; by extension, this flow of capital back to the US will be good for the R&D-stage venture-backed biotech sector as a whole.

It’s worth noting that the Irish didn’t have much of a Pharma sector until they created an attractive tax rate, which gave them a competitive advantage. I’m not advocating a race to the bottom on corporate tax rates, but I’m keen to see ours become more competitive. Though I dislike tax inversion deals, I don’t think they are nefarious acts; they are a rational response to an abnormally high and punitive tax structure in the US, as I described when the Pfizer-Allergan deal was nixed (here, creating an unpredictable precedent, I might add). Seems clear that if we made our tax rate competitive with other major markets, we’d fix the inversion issue instantly and make US businesses more competitive with their global peers. As I understand it, the new administration is pushing forward with proposals along these lines.

Another element of tax reform I would encourage the new administration to consider would focus on R&D-stage, loss-making businesses: reforming Net Operating Loss restrictions. Ensuring that R&D-stage companies can take full advantage of the capital they’ve sunk in the ground is important. A market-driven policy here could include “tradable NOLs” from loss-making R&D-stage companies: creating liquidity and funding by selling the tax deductions of their NOLs to larger companies. I’ve been advocating for these since 2011 (here). Further, R&D tax credits have been used elsewhere to good effect (e.g., Australia, Canada, France), and could benefit US-based biotech startups. These are pro-growth, pro-innovation policies that should be embraced in a bipartisan way.

4. Ensuring we are funding the basic sciences to maintain our R&D leadership in the world. Funding for the National Institutes of Health (NIH) is critical to both advancing the basic science required to make the medicines of tomorrow, and to maintain the global scientific leadership of our academic institutions. NIH funding was severely constrained in the past, not even pacing with inflation, and this has creating a challenging funding environment for investigators young and old (here, here). As noted on the NIH website: “From FY 2003 to 2015, the National Institutes of Health (NIH) lost 22% of its capacity to fund research due to budget cuts, sequestration, and inflationary losses.” This needs to be resolved with long-term budget commitments to the NIH and related research institutions: Make American Biomedical Research Great Again.

In addition, in recent years, the NIH budget has shifted increasingly towards translational sciences: discovering and developing new drugs, supporting academic high throughput screening centers, experimental therapeutics facilities, clinical trials, etc…  While I think these have been a net positive, I do think the pendulum has swung too far and needs to shift back to basic science in order to ensure that work on fundamental discoveries is adequately supported. Commercial endeavors, like startup biotechs and larger pharma companies, are designed by nature to be translational vehicles for many of these basic discoveries. Lastly, continued support for the principles embedded in the Bayh-Dole Act, which was fundamental to the rise of biotechnology, is critical: it’s the responsibility of those who get funding from the NIH or other groups to ensure their new discoveries are appropriately “technology transferred” into the private sector.  It’s the only way that inventions can become marketed innovations. Policies that reinforce this would be a positive for our sector.

5. Reinforce the criticality of strong intellectual property law and its importance in global trade. Patents are the backbone of what we do: without patent protection, we wouldn’t have the innovative pharma sector nor the medicines it has created. We need to maintain and strengthen policies around intellectual property. The patent reforms in 2011-2013 that moved the US from first-to-invent to first-to-file helped to harmonize global patent systems, and were important for removing uncertainties around patent filings (policies making the world more predictable!). As we’ve seen with the recent PCSK9 patent issues, IP can be very contentious – and potentially affect drugs getting to patients. Whatever the specific outcomes of that case are, and I don’t claim to know the details, we do need to ensure that policies and court judgements continue to support innovators and defend the patentability of new discoveries.

And with whatever trade agreements the new administration pushes forward, we should ensure that IP protection is a core part of them. Further, these trade agreements need to better address the differential global drug price issue around patented, branded agents: the US shouldn’t be subsidizing the rest of the developed world (as mentioned here previously).

6. Support a pro-immigration policy for attracting and retaining the world’s best-and-brightest. As this has been the subject of enormous public outcry in recent days, I don’t need to say much here as it’s all been said (here, here). Our sector relies on talent flows from across the globe. A timely January 2017 Nature article, “The new face of US science” highlights that 52% of the 69,000 biomedical researchers in the US are foreigners, either as non-citizens working here or naturalized foreign-born citizens. Our own portfolio is similar: of the biotech boards that I currently serve on, more the 60% of those CEOs are immigrants.

Although the #immigrationban Executive Order “only” targets individuals from six ISIS-linked countries, the principle here matters greatly: we lose the war for talent, and let the terrorist win the upper hand, if we start down the slippery slope of restricting the flow of people into the US inappropriately. The global, diverse nature of our workforce is paramount. Predictable, legal paths for abundant skilled labor to enter the country, as both students and workers, is critical for a sector reliant on global talent pools. Broader pro-immigration reform is also an important broader element of policy.

7. Lastly, if the Affordable Care Act is going to be repealed, it must be replaced with a viable alternative. Regardless of your views as to whether it should be repealed at all, it seems likely that in a Republican-led Congress with a Trump administration this could indeed happen. From a practical perspective, insisting on a simultaneous “replace” will be important so that access to medicines are maintained for those reliant on Obamacare for insurance and those with prior conditions (among other things). I’m not a policy wonk, so won’t weigh into the specifics here, but the biopharmaceutical sector should come out strongly in support of maintaining key elements of the healthcare coverage found in Obamacare.

I have a personal view that we should scrap the employer-based care model entirely as an artifact of 1940s labor laws: an individual market for health insurance, across state lines and with national market competition around the different types of offerings, feels like a far better solution. Coupled with things like HSAs and different coverage plans, we’d see far more diversity in the offerings and experiments in how best to deliver cost-effective health coverage. Further, I’ve always hated the idea of my employer choosing the health plan that was right for me. Lastly, leaving the employer-based model frees up job mobility for individuals wanting to become entrepreneurs or move jobs, but are afraid of losing insurance coverage. Enough of my dreaming though, as getting any consensus on more radical reforms would be like watching a horde of hungry Congressman try to grab a greasy pig.

Whether or not you agree with the new administration, it’s the current reality that we as a biopharma sector have to deal with it. Trump was elected to make changes by one-half of America, whether the other-half likes those ideas or not. He’s got a Republican Congress to work with, so we should expect a lot to happen.

Because of that, as noted before, we can’t sit on the sidelines.

We should, of course, become more active in our collective civil discourse, and engage publicly around issues of importance to us. Freedom of speech, and of protest, are important rights as Americans – and are also responsibilities when we have issues that deeply concern us.

But we also need our industry leadership to stake out our sector’s agenda, and try to work constructively in Washington to champion policies that will be supportive of the long-term health of the innovative science-based biopharma ecosystem. As others have said, we don’t have to agree with the Trump administration on every issue, but we need to try to facilitate positive policies – especially those with bipartisan support. The above seven policy areas represent my personal view of some of the issues worth staking out related to biopharma. I know many of our industry’s leadership are engaged on a number of these topics, and I appreciate their efforts.

Lastly, it seems good counsel for any new administration, at least from a business strategy perspective, to become predictable quickly – dispel the uncertainty around policy changes and reduce the entropy of government – both of which can drive out long-term investors. Persistent unpredictability would significantly damage US business. Long term resource allocation and risk mitigation, the two critical levers in any business strategy, are much more effective when the future scenarios can be framed with some predictability. The future is never known, but pro-growth environments are almost always ones with low uncertainty and reasonably predictable policies. Hopefully Trump’s advisors are impressing this upon the President (and his Twitter account).

This issue around predictability is especially true for those of us in the venture space trying to create new startups and make long-term illiquid investment decisions.  As early stage biotech investors, it’s our job to create and fund new drug discovery startups that we hope will make the medicines of tomorrow.  For those companies we launch in 2016, if we’re lucky, we should have positive early clinical data by the next inauguration… what will be world be like then?

It’s up to us to do everything we can to shape it.

 

 

 

 

 

 

 

 

 

 

 

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