BioDelivery Sciences' (BDSI) Hosts Investor
`and Analyst Event on BUNAVAIL Launch
`and Pipeline (Transcript)
`
`Sep. 6, 2014 12:10 AM ET | About: BioDelivery Sciences International, Inc. (BDSI)by: SA
`Transcripts
`
`BioDelivery Sciences International, Inc. (NASDAQ:BDSI)
`
`Investor and Analyst Day Conference Call
`
`September 05, 2014 12:00 PM ET
`
`Executives
`
`Mark Sirgo - President and CEO
`
`Richard Soper - American Society of Addiction Medicine
`
`Kent Hoffman - Diplomat of the American Board of Addiction Medicine and the American
`College of Osteopathic Family Practice
`
`Al Medwar - Head of Corporate Development and Marketing
`
`David Acheson - VP of Sales and Managed Markets
`
`Drew Finn - Head of Product Development
`
`Mark Sirgo
`
`Good afternoon everyone. I am Mark Sirgo, I am the President and CEO of BioDelivery
`Sciences International, of course better known as BDSI, our trading symbol on NASDAQ. We
`are very pleased to have you with us today. This has been a very exciting year for the company
`thus far with the approval of BUNAVAIL in June. The second positive pivotal trial for
`buprenorphine chronic pain product partnered with Endo which we announced in July and more
`recently the positive directional read we had on our Phase 3 pivotal trial for Clonidine Topical
`Gel based on the interim analysis.
`
`So, a lot of good things going on, nothing more exciting however than the upcoming launch of
`BUNAVAIL, which is our treatment for opioid dependence. What I would like to do now is kind
`of walk you through our agenda and along with some objectives that we hope to achieve here for
`you today.
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`RB Ex. 2047
`BDSI v. RB PHARMACEUTICALS LTD
`IPR2014-00325
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`Before I do that, I would like you to spend a minute looking at our forward-looking statements.
`In terms of our objectives for the meeting, I would like to provide you with details around our
`marketing and sales efforts for our upcoming launch of BUNAVAIL and the types of metrics
`that you can expect to see from us going forward in terms of measuring our products post launch.
`
`Hopefully these presentations today around BUNAVAIL will give you confidence and show you
`our confidence in not only our preparedness for this launch but also the overall success of
`BUNAVAIL going forward.
`
`Our second objective will be to give you an update on our pipeline particularly buprenorphine
`for chronic pain and clonidine.
`
`And then thirdly, I would like to make sure that you leave here understanding the value creation
`we believe we have behind our portfolio going forward and particularly the upside case.
`
`So let me briefly walk you through our agenda for today. After my opening comments, we will
`ask Dr. Richard Soper to come up. He will speak to us on the treatment of opioid dependence.
`Dr. Soper is Board certified in Addiction Medicine. He has been practicing Addiction Medicine
`for 22 years. He is currently Chief of Addiction Medicine for the Center for Behavioral Wellness
`in Nashville, Tennessee. He also serves in a number of capacities at the American Society of
`Addiction Medicine including being one of the directors.
`
`We will then turn our transition to Dr. Kent Hoffman. Dr. Hoffman also Board certified in
`Addiction Medicine and Family Medicine. He has been practicing Addiction Medicine for the
`past 10 years and has served as one of our investigators in our BUNAVAIL 201 study which was
`our safety study. And I think he recruited about 25% to 30% of the subjects in that trial, so he has
`got hands on experience with our product. He also serves as a Team Physician for the Orlando
`Magic.
`
`Dr. Hoffman will be followed by Al Medwar, Al is our Vice President of Marketing and
`Corporate Development at BDSI. And he will review with you the marketing, how we’re going
`to market BUNAVAIL and all the materials associated with that and then we’ll ask David
`Acheson, our Head of Sales and Managed Markets to present to us really the construct and the
`alignment of our sales force as well as the managed markets review of where we are with
`BUNAVAIL. And then Dr. Andrew Finn will come up and review our pipeline for you. I’ll do a
`quick wrap up and then we’ll proceed to the Q&A and hopefully we’ll have about 10 or 15
`minutes to do that.
`
`In terms of some housekeeping items, we’ve provided file cards at all the tables so you can
`please write down any questions if you might have for us or for our speakers and we hope to be
`able get to those at the end of today’s session. We will also be present afterwards to answer any
`questions we may not be able to get to you during the course of the presentations. Also due to
`competitive reasons it may not be possible to answer all of your questions, but we’ll do the best
`that we can during the time that we have here today.
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`Also I want to remind everybody that this session is webcast and it will formally concluded at 2
`PM for those that are watching here via the web. So with that in mind I’m going to now ask Dr.
`Richard Soper to step up and please kick this off for us. So thank you again for being here.
`
`Richard Soper
`
`Thank you Mark. It’s a pleasure to be here. Nashville Tennessee is known amongst financial
`circles and various other entities as for profit center for medicine or mecca as (Bill Morris) [ph]
`calls it. Addiction is an area that we also are very involved with. I don’t know how many of you
`all do the due diligence but we have the honor of being second place to Alabama. Alabama
`writes 148 opioid prescriptions per 100 capita per year, Tennessee only writes 142, West
`Virginia writes 138, Mississippi is 136, Louisiana it's about 132. So if you’re listing on
`geographically locating as you know a fairly strong concentration in the south. The lowest of our
`50 states is Hawaii 52 prescriptions per 100 capita.
`
`Last year there were 256 million prescriptions written in our country for opioids. As you know
`there has been some reclassification of a couple of those opioids recently and so like you push
`the blue on one sided pop on the other side, most of the people that suffered from this chronic
`medical disorder do have created inventive ways to find other access. What is opioid
`dependence? Opioid dependence can go by many terms and definitions it’s pretty much easily
`narrowed down to its medical diagnosis is characterized by the individual's inability to stop using
`opioids even though that would be their preference and that’s what they would like to do
`objectively in their best interest, they’re not able to.
`
`Addiction, what is addiction? I use the mnemonic TTC, what I mean by TTC? TTC is time,
`tolerance, consequences. More and more of my time is spent during the time, do have enough
`where am I going to get the next? Does anybody else have some? Who has some financial
`resources that I can use or some fixed property? All day long all I’m doing is thinking about it.
`
`Tolerance, I need more I need more on that. I’m not giving you for it necessarily anymore but I
`need more just to make sure that I’m not suffering from the withdrawal symptoms or the Clinical
`Opiate Withdrawal Scale, which we objectively gauge in which Kent is going to talk about.
`
`Consequences, despite negative consequences, I’ve lost my job, I’ve lost my marital partner. I've
`been intervened on by my professional society or by my colleagues and I still continue to use.
`This is an national academic it’s not going away. We won’t talk about the politics of our U.S.
`Government protecting the poppy fields we have in Afghanistan with our U.S. Army, but in 2010
`they were related more than 16,000 deaths directly related to opioids representing a little over
`300% increase in 10 years that number is still linear and it is still increasing. More than 200
`million and this number was in 2012 SAMHSA, Substance Abuse and Mental Health Services
`Administration report, which will be coming out in about three weeks as privilege to help write.
`This number is now up to about 2.5 million in 2013 that use or required or needed treatment for
`opioid dependency. Total use the SAMHSA report was showing national drug health survey that
`it's about 25 million of our population; these numbers are skewed way to the low end.
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`I’m absolutely certain, I’m sure Kent is, I’m sure most of other colleagues that I discussed things
`with management regionally these numbers are governmental numbers as we all know they
`usually skewed conservatively. Opioid analgesic is responsible for more deaths in this country
`then auto accidents, suicides or the combined cocaine and heroin overdose. And that numbers
`also influx as we know as we tightened down on and as we increase our regulatory constraints on
`prescription opioids, there is prevalent easy access to street opioids.
`
`In particular and I know I’ve got a lot of slides I will try to do this quick. Last year in Nashville
`this past summer, our ED, our emergency room department at Vanderbilt had 86 encounters with
`individuals below the age of 18 for heroin overdose. My friend Larry Gentilello who is in-charge
`of the emergency room department at Dallas, Parkland, who is now retried, told me three years
`ago watch out for this Rich, it’s coming. You can buy black tar heroin rolled up in a marijuana
`paper on the playgrounds at our schools in Dallas for $0.50 that’s now the reality in Nashville.
`Efforts to use opioids, we can go back to late in the 90s when all of a sudden pain became the
`fifth vital sign and the push from that commercial pharmaceutical houses for opioids to be
`considered as absolutely appropriate necessary.
`
`In October a little bit over 10 years ago now, 2002 FDA approved buprenorphine products for
`use for opioid addiction. The Drug Abuse Treatment Act of 2000 identified for the first time in
`our country that you did not have to go to a federally approved governmental clinic, you could be
`treated in the privacy of a physician’s office as long as the physician obtained certain credentials
`for your opioids dependency.
`
`Buprenorphine as far as is positive, it has a lower abuse potential. Methadone is a full new
`receptor agonist. Buprenorphine is a partial. We’ll talk about it in a minute who is definitely
`better safety as far as opioid deaths from overdose methadone where there is form a pain clinic
`or methadone clinics have a right at 7 per thousand buprenorphine right now is right at 3.
`
`Some of the negatives, there is low efficacy of the current products on the market. We’ll talk
`about that and how BUNAVAIL I think clinically is going to significantly shift that. The taste
`again an opportunity for new products to hit the market and then some of the clinical side effects,
`which are also opportunities.
`
`I mentioned earlier buprenorphine is a partial new which is the receptor side in the nervous
`system that opioids go to, there is also kappa, delta and lambda. We won’t go into some of that
`pharmacology Mark and some of our other speakers are much more experts in pharmacology
`than myself.
`
`Maximal effects have a ceiling effect. There is a certain amount of buprenorphine which upon
`reaching that level because of its long-half life in the body anything above that level really has
`no additional impact.
`
`There is some slight respiratory depression effects and in fact if you discontinue abruptly rather
`than a gradual taper under physician’s care there can be side effects and consequences. The
`agonist effects again increase lineally as I mentioned earlier.
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`DATA 2000 Act allows qualified physicians as I mentioned. Initially when it came out, it limited
`the number of patients a physician could see to 30. There was a lot of talk internally among some
`of the governmental agencies regarding what would this product do when it reaches the market
`and that was predominately the reason for the limitation. And some of the data that came over
`from France and the reason why the product here had naloxone as I am sure some of you all
`know also had impact on why the limitation. Shortly after that it was altered to 100. I’ll go into
`some details about the status of that situation as it is currently in our country.
`
`We have to attest that we will refer patients to higher level of care if necessary that we’ll refer
`them for counseling if necessary. The data is a little low but it’s still very similar. As far as
`physicians this is from 2010. Less than seven days used physicians say effective for about 32%.
`More than a month 74% of physicians felt that buprenorphine was an effective product to use for
`opioid dependency. And it’s at least that and that’s with the current products that are on the
`market.
`
`Today anesthesiology news came out. Anesthesiology news mentions into FDA approval of the
`product that we are here to asses today BUNAVAIL. I can tell you my colleagues both in
`Nashville and around the country are anxiously wanting additional tools in their toolbox to help
`with this medical condition. We can expect hopefully that patients will be compliant and that
`patients have some motivations to be in treatment and that they agree that they will be reviewed
`for treatment options along with buprenorphine. Some of the clinical dynamics I hope you go
`over currently. The patient treatment is a comprehensive plan as the DATA 2000 Act mandates,
`you have to refer patients for guidance and counseling if you’re not doing that in your own
`office, you should is the word that’s operatively used in that act.
`
`Whether or not and if and I do in my own practice bring in family or significant others for
`support, discuss with the individuals’ their mental health, their physical health, their relationship
`health, their financial health because all those are impacted by opioid dependency. Some of the
`challenges with current therapies we’re going to talk about and as well Kent will talk about the
`outcomes whether or not and if we are improving again treating addiction is hopefully saving
`lives and it’s hopefully decreasing the amount of abrupt as we seen catastrophic outcomes it can
`happen with individuals like Philip Seymour Hoffman.
`
`Medication treatment opportunities again, we are limited right now with what we have to treat
`opioid dependence and one of those opportunities that this product and others have is to provide
`significant paradigm shifts in what we are currently limited to. As far as being on the current
`formulary, the administration options are definitely limits and then also not being discrete and
`again the taste of the current options.
`
`Persistence of Buprenorphine and naloxone tablets and again this is part of the reason the film
`came out have been disappointing, 48% after one month you see still compliant with therapy and
`this data also is a little older, its 2008, if we were current, I think you would see this graph
`increased but it would still be a slope over the six to 12 months. Optimally we’re retaining right
`now somewhere around in my practice about 70% after a year I think nationally it’s somewhere
`between about 50% and 60%.
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`This is not necessarily only involved what the dynamic is with the patient but it’s also some of
`the physicians in the way that physicians have been trained and the way that physicians have
`developed their report with their patients.
`
`Surveys, this was just done this spring, the data is not even out publicly yet. The National
`Alliance for Advocates of Buprenorphine Treatment surveyed a little over 600 individuals, about
`half male and female and 37% of them mentioned that they had used opioids recreationally
`initially, 50% mentioned that they were having to pay currently being on treatment with
`buprenorphine because they had no private insurance. I’m from one of those states, over 50% of
`our population is uninsured, we’re one of those states that decided not to go into the Affordable
`Care Act and expand Medicare is still influx with that as we all know in several other states in
`our country.
`
`27% of the individuals that we surveyed so they’ve received buprenorphine without prescription,
`it is on the street, it’s been available now for right at 13 years in our country. Surveys initially as
`well also show that about one and four felt that the current buprenorphine therapy medication
`formats were a nuisance. They had to refrain from talking and swallowing. They experienced
`significant clinical side effects like constipation, like Aphthous or oral ulceration of the gingival
`like an unpleasant after taste, all of which I think we’re going to see this product has different
`presentations.
`
`[indiscernible] abnormalities, again that are mentioned by patients, about half of them
`experienced dry oral cavity, accumulation or excess salvation, some gum abnormalities as I
`mentioned earlier and about one in three take it in private so they don’t anyone to know that they
`are taking it and they realize they have to be in private because literally there is a rich well to
`dosing right now with the film in particular or the tablet which is even more crude. Its sublingual
`under the tongue, you have to hold your chin down to try to prevent swallowing as much as you
`can and holding your chin down after it’s melted for at least 10 minutes. After that and before
`that you don’t want to have any nicotine use because it’s a vassal-constrictor and you don’t want
`to be eating or drinking anything after to try the continue absorption it’s still vary -- it is not
`efficacious, about 20% at best of the film at the tablet is absorbed by our patients.
`
`How do we improve access to care? That’s part of what we’re also faced with challenging as I
`mentioned earlier briefly tell you that the DATA 2000 Act, this is a political year, we know there
`is an election this November, but there is a significant conversation and dialog going on, on the
`Hilary Washington and amongst professionals regarding moving those numbers of the
`limitations of the DATA 2000. There are insufficient physicians writing, we know that about
`80% of the prescriptions for buprenorphine are written by 20% of the physicians that are waived.
`
`We also know that a little over 60% of the buprenorphine is east of the Mississippi. As you’ll see
`a national map represented I think it’s Dave or Al in their presentation later, the number of
`physicians are also mostly east of the Mississippi, why? I can’t really tell you other than there is
`just different dynamics.
`
`A need for physician linking with ancillary services, if I’m in primary care, if I’m an OB/GYN
`and I have a patient and I do have waiver and I’m writing Suboxone or buprenorphine then I
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`might need to have someone else I am referring my patients to for their guidance or their
`counseling.
`
`Many of my referrals with young ladies when they’re in their reproductive years, when they
`become pregnant are from OB/GYN because they don’t want to deal with that, it is a little more
`labor intensive for the doctor.
`
`Our current limitations, Senator Carl Levin who is retiring as well as Senator Schumer here from
`your own state have significantly increase the conversation both that the office of National Drug
`Control Policy, which is in the precedence in the White House and our planning to introduce
`legislation as well as a couple of the U.S. representatives to raise the number.
`
`SAMHSA CSAT Center for Substance Abuse Treatment and Substance Abuse and Mental
`Health Services Administration are in direct conversation with us at American Society of
`Addiction Medicine, The American Academy of Addiction Psychiatrist and other entities the
`American Osteopathic Academy of Addiction Medicine. There will be legislation introduced,
`this doesn’t have to be a legislation move, it can be done internally as the 30 to 100 was done,
`within CSAT and SAMHSA. The legislation that’s being considered and the verbiage that we’ve
`currently come up with and what ASAM supports is that we will have a gradual phasing and we
`will raise the number over 100 if the individual positions have certain qualifications. We don’t
`let podiatrist do invasive cardiac procedures nor should we let individuals -- I think I’ll try that it
`might supplement my income.
`
`So if you’re boarded in addiction medicine, if you’re certified my American Society of
`Addiction medicine, if you have certain hours of continuing medical education, if you have
`waiver then if you have been practicing for x number of months or years with no one to
`outcomes, the number right now being tossed around is you will have raise, your limit will be
`raised to 250. After a year potentially you’ll be able to apply for and then have the number raised
`upon that. If you don’t have any of those credentials I mentioned you can still get your waiver
`which is an x number to your DEA and you’ll be held at 30 as currently are. And then you can
`raise actual 100 if you’ve met the additional qualifications.
`
`To shift for a minute to BUNAVAIL as I mentioned earlier I think this is going to not be a need,
`this is not sublingual delivery. Again you’ll hear more from Kent about this but the unique
`delivery system. It is a buckle placement and again by a buckle placement there is a double layer.
`So the medication is absorbing into the mucosa and it is not coming into the old cavity. So we
`get rid of those aphthous ulcers, we get rid of that bad taste, we get rid of that I can’t talk, I have
`to keep my chin down. So lot of the short comings of the current products are being addressed
`with BUNAVAIL.
`
`Its discrete, I can still talk, I could have one in right now on my cheek and be talking with you.
`The efficacy of BUNAVAIL numbers are conservative from BDSI. The numbers that I have
`seen its over 50% absorption. As I said earlier current suboxone buprenorphine products is about
`20%, 25% at best. So that provides, I am hopefully going to be able to use and the products that
`they’re planning on bringing out are significant lower in milligram, I mean do the numbers. If
`you currently got a patient on 16 milligrams a day, and I can increase the efficacy of this product
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`I can drop him immediately to 8, not only a cost savings but he’s getting the same amount of
`buprenorphine delivered. Twice the bioavailability of suboxone.
`
`I’ll throw another in for you on the features of this. This has come into market at exactly the right
`time.
`
`I got a text message I could read to you on my phone that I got from a patient yesterday. All my
`patients have my mobile phone number, because in addiction it doesn’t operate between 9 AM
`and 5 PM. A patient sent me a text message yesterday, I saw her yesterday in my office,
`yesterday afternoon. Dr. Soper I am CVS, they don’t have any suboxone. They say they can’t get
`any in. And I was just at Walgreens who told me the same thing. And I am not talking about the
`2 milligram, the 4 milligram or the 12 milligram, they’re always short. Zubsolv is always short,
`in my area of the country.
`
`So supply and demand again back to basic economics. I asked last night to one of BDSI
`executives here at the table. Can you meet the demand? Physicians want this product on the
`market; patients are interested in this product on the market. For us as we talked about the side
`effects lower constipation, obviously if it’s less medication that’s been absorbed orally is less GI
`track consequences. Use as I mentioned to me newer patients, I am absolutely going to put it on
`my table with Zubsolv, Buprenorphine generic and Suboxone and maintain the attachment
`between myself and my patient that we develop treatment plan together. We talk about what
`options.
`
`Your formulary will only approve Zubsolv, so that’s our only option. You private pay that’s
`right, we can do any one of these. There is also now a new product BUNAVAIL on the market.
`Current patients, pregnant females absolutely that’s a possibility. Stable long-term patients,
`Nashville is known as sort of the music city, I have a huge number of my patients that are
`professional entertainers. And I could tell you sometimes there in situations where it is
`impossible for them to sit for 30 minutes and not say anything or do anything. With the current
`medication formats that are available.
`
`Questions we’ll have later I hope, I hope some of this was informative to you all. Thank you for
`coming.
`
`Kent Hoffman
`
`I am Kent Hoffman and I don’t have as many slides. Richard has already done all the heavy
`lifting, so my job is going to be easy. If you think it’s a cool job being the team physician for a
`national -- an NBA basketball team, it is, but actually this is my passion. What I love to do is
`addiction medicine. And by the way I do this -- I wear my family practice hat for the magic just
`in case you are wondering. But what I get to do in addiction medicine is help people get their life
`back. I get to give them back their son, their daughter, their husband, their wife and help people
`get their lives back and get them on track. I’ve seen miracles happen in my addiction practice
`every day. And there is nothing more rewarding in medicine than that and that’s why I do this.
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`So is it fun working with the magic? Absolutely. Have I’ve seen miracles happen there?
`Absolutely not. So that’s what I will tell you for sure. What BUNAVAIL is going to allow me to
`do if it’s going to take that same wonderful molecule buprenorphine in a better delivery system
`and allow me to help these patients even more. So it’s pretty simple.
`
`This is the problem as Richard mentioned earlier. It’s a huge problem. And why do we include
`patients treated for opioids for pain? Because about 20% of Suboxone sales is estimated are for
`pain. It’s written off label, okay? And this number is huge. The number is going to increase --
`well this number actually will shift and starting down with that orange balloon at the bottom
`which is grossly underestimated, the numbers I’ve heard more recently are somewhere around
`800,000. All these balloons from the bottom line up will get larger once the schedule three to
`schedule two change happens with hydrocodone, because all of a sudden these patients who call
`in on Friday afternoons, because they are short on their hydrocodone medicine and they call a
`doctor’s office, these patients can no longer have these prescriptions called in. That’s easy for a
`doctor to do.
`
`My medical assistants come with a list of patients you need medications, it’s Friday Afternoon,
`they know the weekend is coming and patients routine they call in. It happens. So they call me,
`now they give me a list of five medications they need to be called in. Now a few of those are
`pain medications, those can’t be called in any longer after this rule change takes place. Now
`those have to be written out and the patients have to come in and pick them up and they can’t be
`refilled. All of a sudden that’s going to start to bring these issues to a forefront and there will be
`in the doctor’s space so to speak.
`
`So these numbers have start to increase and all of a sudden more of those patients on Friday
`afternoons will be opioid dependent and be referred. And we’re going to have more
`buprenorphine patients. So entered within the delivery system, once again the same grade
`molecule, a much better delivery system and I think we will see why.
`
`Again it’s a buckle film that goes inside the cheek, placed for one to two seconds and one of its
`interim BioLayer is a MucoaDhesive, call it cheek glue if you will and it’s very easily used, it’s
`pleasant tasting, about two thirds of the patients found that it was pleasant or very pleasant to
`taste. The patient can immediately swallow and talk, that’s a big difference from holding your
`jaw down and forward for anywhere from five to 20 minutes. Again I have a practice where
`many of my patients are professionals. They don’t have time to sit there for 20 minutes with their
`head down for this medication to dissolve and absorb underneath their tongue. They can swallow
`and talk, again it adheres in seconds, it’s very discrete. Nobody will even know that you even
`have medication in your mouth. It’s a very efficient delivery system. Once again about a 50%
`bioavailability, it’s slightly higher than that, but we will say 50% because it’s easy to remember.
`So it’s about a 2:1 when it comes to when you are taking Suboxone dose versus BUNAVAIL
`dose.
`
`So the clinical study as it was mentioned earlier, I was involved in the clinical trials with
`BUNAVAIL, so I have a great amount of experience at teaching patients how to use the film,
`seeing what the results were, seeing what the transition from patients established on Suboxone to
`BUNAVAIL which is what the studies were about. These are the comparator of BUNAVAIL to
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`Suboxone as far as the blood levels and the half-life. And as you can see that mimics it very
`closely as far as rapidity of onset as well as the concentration in the blood, BUNAVAIL being
`the green line. Now if it has placed the bioavailability where is the rest of that medication go in
`the case of Suboxone, down into the GI track. And in fact what we saw is this will become more
`importantly to run and I will mention why. So approximately if you are taking 8 milligrams of
`Suboxone, you have 2 milligrams that's absorbed, about 25% absorption and 6 milligrams going
`on into the GI track. We have new receptors all over our body not just in our brain also in the
`gut. And so in the case of BUNAVAIL you’ve got 2 milligrams being absorbed and 2 milligrams
`going to the CNS and then 2 milligrams into the GI track.
`
`So the objectives of the study were to determine the safety and tolerability of BUNAVAIL over a
`three months trial, determining the dosing conversion from patients that were already established
`and stabilized on Suboxone over to BUNAVAIL. But 250 patients who were anywhere on
`between 8 milligrams and 32 milligrams daily dosage of Suboxone, these patients were assessed
`for symptom checklist at the beginning and end of the study. The COW scale, which is the
`clinical opioid withdrawal scale it looks at things like heart rate, sweating, agitation, ability to sit
`still, piloerection, which is goose bumps, GI disturbances, diarrhea, cramping, things like that, all
`basically so the higher the score the more withdrawal of patients in. Also oral exams were done
`where we’re actually turning by a dentist on how to do these oral exams looking for erythema,
`ulcerations, any kind of abnormalities in the oral mucosa.
`
`What we saw is that the proportion of the patients that had a urine positive test were non-
`prescribed opioids was extremely low at 8% I can tell you from clinical practices, that’s
`extremely low. The patient retention was 80%, almost 80%, throughout the year, three months
`trial, which is a great rate. Among the patients the baseline in COW score dropped from pre-
`dosing to post-dosing from greater than 13, which is a pretty uncomfortable patient in a
`significant amount of withdrawal down to less than 1.1, which is a very calm, very pleasant
`patient to deal with, essentially in no withdrawal.
`
`Now one of the other things we founds, well I mentioned about that 6 milligrams with Suboxone
`going down into the gut and only 2 milligrams with BUNAVAIL, we saw a 68% decrease in
`constipation so that 4 milligrams of buprenorphine that isn’t going down into the gut created lot
`less constipation. And actually we saw a great -- this huge release or relief of constipation. And
`although patients may not mention constipation when they come in, they’ll just deal with it on
`their own. In fact, what we found in the tail end of the study is that patients certainly mentioned
`it once it was relieved and once they no longer had and didn’t have to take whether it was
`metamucil or miralax or a variety of other remedies on a daily basis.
`
`The other thing that personally I didn’t expect was that we actually found the oral exams from
`the beginning of the study to the end of the study got better. These patients were placing one or
`more inter-oral BUNAVAIL patches in their mouth every day in some cases I had patients
`placing three of these in their mouth and their oral exams actually got better. So if there was
`erythema that they’re beginning with, it wasn’t at the end, et cetera, et cetera but we didn’t see
`any irritation of the cheek or mouth in general.
`
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`So here what I mentioned earlier is you see how well accepted in the open label study
`BUNAVAIL was, both as far as in ease and use. Ag