Marinus Pharmaceuticals, Inc.

Q4 2022 Earnings Conference Call


spk_0: where do you ever want to welcome to the emeritus pharmaceutical fourth quarter and full year two thousand and twenty two financial results of business up they call at this time all participants are to listen only mode after the speakers presentation there will be a question and answer session if you have a question for thought that time you may press star one that's not my pleasure to introduce your hosts saucer do money alice senior vice president of help it affairs and investor relations
spk_1: look ahead thank you and good afternoon with me for baroness are doctor scott brown theme chairman and chief executive officer pretty schaefer cheap commercial officer doctor joe houlihan chief medical officer and steep and still chief financial officer and chief operating officer before we begin i would like to remind everyone that some of the statements were making today are forward looking statements under the security flaws these forward looking statements involved substantial risks and uncertainties that could call or clinical development program future result performance or achievements to differ significantly from those expressed or implied by such forward looking statements these risks and uncertainties of and risks associated with our business or described in the company's report filed with the securities and exchange commission including for a ten k ten to and ha i will melt now in the coal over to our
spk_2: chief executive officer scott bronstein thank you saucer and welcome to our call in twenty twenty two we continue to make important progress advancing our oil and i began absolute programs driven by the cross functional commitment of the mayor and his team at the forefront of our achievements was the landmark us approval of the ptolemy in march and the subsequent commercial launch in late july he told me represents the cornerstone of are rare ability franchise and it's us approval validates our belief in the potential to connect flown differentiated mechanism of action and our ability to grow the commercial franchise importantly we are pleased to report or first full quarter of sales which are reflecting robust demand and give us proponents we are meeting the needs of this underserved patient population christie would provide further details on our commercial progress including to launch of metrics and an update on pair coverage in parallel with our first product launch we made significant progress advancing or broader clinical pipeline including our second generation formulation program and are to critically important pivotal trials for both the ivy an oral franchise we remain focused on expanding the value proposition of connects alone for a rare epilepsy and believe that a second generation formulation is important piece of that puzzle we are pleased with the early data we have seen in our seas one dosing studies which joe will discuss shortly and look forward to seeing this program advance to the clinic in a very short period of time and with a focus investment we now see a new and expanded pathway for the world the next phone franchise although it is early we are also on track to replicate this developmental success with the second generation or the formulation furthermore we believe that the adjustments me to support recruitment and enrollment in the phase three raise trial in refractory status epileptic kids are trending positively and we been met with enthusiasm by a growing number of participating site just this month i've met live with kinda to gators some tampa baltimore and boston and they are highly motivated to participate give a medical need in this life threatening condition the protocol in them and had been fully implemented and topline result continue to be expected in the second half of twenty twenty three i would like to also acknowledged that the other ivy programs really to and or for european registration and reset in establish that it continued to press forward while all three trials progress we will continue to focus our primary efforts honorees the us pivotal program and have begun the commercial investments that we believe can help drive a successful us launch let's move on to the current world franchise we are working closely with the psc community and will continue to read awareness around the fees three trust tsc clinical trial which is now recruiting in the us in europe with additional site activation expected over the coming weeks and months in can the israel italy belgium australia and china last week marriage is participated in a panel discussion hosted by the tlc alliance and we will use these types of worms to continue to educate the community about this clinical trial one that we believe it's first of it's kind in a highly refractory psc population as we have learned with cdt advocacy and tolerability or key attributes to success in the refractory epilepsy population and we are confident that changes to the tight treason schedule give us the maps more opportunity for a successful fees three outcome we remain on track to disclose topline that in the first quarter of twenty twenty four i would like to provide an update on the status of this is tommy marketing authorization application in europe we submitted are day one twenty responses to the in a november we received the day one a report including a list of outstanding issues in january the list contained a number of major objections including or choice of regulatory starting material which is expected to be the biggest hurdle in bringing this medicine to patients in europe the formulation of the me recently approved in the us contains the same starting material the cgmp is expected present his opinion on the a a in the second quarter of twenty twenty three we remain committed to working closely with the in a the advocacy community and our partners at orion corporation to advance this important medicine there remains a broad global opportunity for the next alone we announced the collaboration with to nature biotechnology november twenty twenty two for the development and commercialization of good next alone in china tunisia has moved quickly on the regulatory front and as a result of our combined efforts we plan to include chinese sites within the trust a c trial development plans are also under way to maximize the artist the opportunity we continue to explore additional x us commercial alliances including the mena region and japan and expect to expand the commercial footprint of the tommy in twenty twenty during before handed over to chris the i want to share some exciting news we received a notice of allowance from the us patent and trademark office on march first for additional claims related to our clinical therapeutic regimen for the treatment of status epileptic is using i began excellent this would be our second newly issued patton for the ivy franchise we believe be allowed claims will strengthen our ip portfolio in our status epileptic is program additionally as many of you know see said he opens joining the organization nearly two years ago has played an integral role in the launches the tommy help strengthen our balance sheet and has been an important contributor to our strategic planning established himself as a leader within the organization and has driven a number of important agreements and taking over as chief financial officer i am pleased to share that the will now be taking on the expanded role as chief operating officer in addition to his responsibilities as the fo finally we are pleased to announce the appointment of christine silverstein to our board of directors and audit committee in january christine bring the deep capital markets background and extensive expertise in corporate strategic planning business development compliance and or it's management for financial and strategic acumen combined with her experience neurology and rare diseases maker an outstanding addition to the board
spk_3: now i would like to turn the call over to our cheap commercial officer chrissy cheaper for updates on the commercial launch of the tommy
spk_1: thank you scott
spk_4: and please to provide you with an update on our continued progress as we execute on the us commercial launch as the tommy
spk_1: as a reminder we launched the tommy on july twenty eight twenty twenty two and generated five hundred and sixty thousand dollar and initial net product revenue and the third quarter and the fourth quarter the first fall quarter following launch the tommy had net revenues of two point three million bringing the total for the fiscal year and
spk_4: did december thirty first twenty twenty two to two point nine million we received over forty completed see detail five deficiency disorder prescription enrollment farms in the fourth quarter of twenty twenty two and over ninety total completed cdt prescription and that farm for the fiscal year ended december thirty first twenty twenty two inclusive of clinical trial patient transition and naive commercial patient we continue to see a steady build of treatment naive commercial patients and a healthy distribution of prescription from centers of excellent large epilepsy centers and local community physician with prescriptions coming from a growing and diverse prescriber base of more than sixty unique account
spk_1: launching the tommy we have been particularly encouraged by the progress the team has made with market access more than seventy five percent of gdp patients with completed enrollment form for able to receive reimburse therapy by the end of twenty twenty two and most of the prescriptions were filled within thirty days or less we are pleased to announce that as of february twenty eight twenty twenty three total payer coverage for the tommy increase to approximately two hundred and twenty million lives including both commercial and government program the tommy has received favorable coverage determinations from thirty five pairs representing close to a hundred and twenty five million commercial live which represents seventy nine percent of commercial plan we expect most of the remaining coverage statements in the first half of twenty twenty three
spk_3: medicaid access has been confirmed in all us states as well as washington d c and porto rico representing approximately ninety five million lives
spk_4: we believe this early success speaks to the strength of our market access and patient services capabilities as well as an appreciation for the unmet medical need and an impact of the disease on cdt patients and their family we continue to see a steady build of treatment naive commercial patients and a healthy distribution of prescriptions from both see always large epilepsy summer and local community physician we are delighted with the response and feedback we have received from the patient community regarding orsini specialty pharmacies white glove approach and dedication to supporting patients and families throughout their treatment journey
spk_3: that's far the average patient maintenance dose is approximately fifty percent above the initial trace windows which is in line with our label and expectation based upon our experience today we have not seen anything in the marketplace that warrants have to change are forecasting structure we have seen a handful of adult and young adult patients being treated consistent with broad uptake and to and above
spk_1: our momentum had benefited from the strength of our digital marketing tools publication strategy and robust education and awareness efforts ahead of and following launch wifi continued study engagement rates on our the tommy patient and health care provider website which confirms the effectiveness of are authentic pay shouldn't centric marketing approach
spk_3: the field interactions are being supported by the launch of our speaker bureau and the execution of a significant number of programs that have been well received with great a tendon
spk_4: we plan to expand as the tommy speaker bureau to add more clinical voices to the cdt treat or community filling a need for peer to peer education of the palm a clinical data tdd diagnostic indicators and the importance of early diagnosis
spk_1: with the solid foundation we have established we are well positioned and extremely excited to grow our promotional strategies in several ways than twenty twenty three
spk_4: the tdd diagnostic journey is one area where we think we can offer meaningful support for health care providers and family and we continue to further our understanding of the current cbd genetic testing and diagnostic paradigm in the us these insightful help inform our next step to support on encumbering the cdb diagnostic journey and determining our expanded offering of education to resources and solution
spk_1: planning has also comments to activate a caregiver ambassador program to share experiences of families who have initiated treatment with the told me and what that experience has meant for their loved one in their families these stories are plan to be incorporated into are branded promotion along with the weapon our theory for the cdt community that off a feature of health care providers who can educate on the clinical profile of the tommy we feel there are many opportunities to continue to grow our brand and we are committed to supporting cdt families and meaningful way throughout the year we are very pleased with our early launch progress and are grateful for the impact we believe we are making on cd patients and families
spk_5: i'll now him mcconnell over to our chief medical officer joe houlihan to discuss our ongoing development program good you christie war everyone listen to the strong commercial progress we've made and twenty twenty two we continue to generate consistent and compelling data good highlighted the potential can actually be differentiated mechanism of action and safety and efficacy play boil to benefit patients including to your open label extension data in she detail part
spk_2: deficiency disorder over the course of the year data from more clinical portfolio were presented a major medical meetings including the annual meetings with the american epilepsy society are critical care society and child neurology society
spk_5: also result of our studies were published and talk to your medical journals including ones neurology and epilepsy
spk_2: most recently results from the face to placebo controlled study of work next alone in pc dh ninety related epilepsy the publishing epilepsy research can actually lead to a greater me and reduction in future frequency compared to placebo who was generally well tolerated
spk_5: if you recall we reduce the scope of this study to a proof of concept for several reasons
spk_2: though the study results did not achieve statistical significance we believe it's important to continue to keep the patient and advocacy community informed about the data generated in clinical trials with can actually now would like to share some exciting updates on a clinical development programs starting with our efforts in developing a second generation can actually i'm pleased to announce encouraging results from our phase one second generation canucks one formulation studies where we recently completed the third and final call work in a single a sending those trial utilizing doses up to twelve hundred milligrams and healthy volunteers we saw a linear dose exposure relationship up to this higher end of the ghosts range and a profile that has the potential for be id dosing with a longer percentage of time at a blood level above the minimum effective concentration
spk_5: the next step is a multiple a sending go study look here repeat be id dosing which will be initiated in the second quarter
spk_2: along with some additional pk modeling una de study will be important for defining dosing in a pivotal clinical trials
spk_5: ideally we'd be able to move straight to face three rather than having to do dose raging in face two
spk_2: the initial clinical indication we will pursue his lungs gusto syndrome a severe form of epilepsy the begins in childhood with neurodevelopmental impairment an intractable a tonic tonic can generalize seizures
spk_5: given the overlapping seizure types and etiologies with other disorders work going actual own has therapeutic potential such a cdn to a c
spk_2: we believe that lgf represent a promising opportunity to address the continue not men need in this patient population we're targeting formalization of the plans for clinical development in the second half of this year
spk_5: we also advancing the development of can actually improved rugs for both oral an ivy administration an oral pro drug candidate has been selected and preclinical development is ongoing
spk_2: and we expect to select a lead ivy candidate shortly moving to a face three trust a few trial and to bruce grosses complex we're pleased to share the we're actively screening and are more patients
spk_5: targeting ninety clinical site predominantly in the us and europe
spk_2: with additional said activations expected in canada australia in china
spk_5: rickard with a high level of enthusiasm in the medical community for this trial
spk_2: and it is paid top line data in the first quarter of twenty twenty four
spk_5: now i'll move on to our i programs a scott mention the protocol amendment for the phase three race trial in refractory status epileptic is has been broadly adopted it our clinical trial sites
spk_2: we're expanding the number of participating race study centers in the us as well as canada and australia the november we held investigator meeting in the us to emphasize the importance to this study for patients and to educate our sights on the updated protocol
spk_5: investigators have expressed considerable optimism about the potential of the amended protocol to allow recruitment of a greater number of eligible patients particularly patients transferred from other centres to study sites or from the emergency room to the i cu we are working closely with site to support timely study enrollment actively monitoring what's working well at a site level in identifying where we can provide additional support for trial recruitment and execution these protocol changes inside engagements are critical to enrolling appropriate patience for the phase three study and replicating the success of the phase two trial
spk_2: in addition members of our scientific affairs and clinical development teams have been on the road maintaining intensive site engagement and responding to questions about the protocol and study procedures meredith scientific affairs has a group fully dedicated to supporting study enrollment and engaging with raised principal investigators and other side personal with these in roman initiatives more sites being activated on a global scale and a reduction in the impact of coburn on health care systems were seeing an uptick in enrollment and remain on track for data in the second half and twenty twenty three as a reminder based on previous conversations with the ft a we expect that a positive race study will be sufficient for filing in the u s
spk_5: there is also the potential for expansion of the age range of eligible patients the trial is currently designed to enroll patients twelve years of age and older however we recognize that there's a high incidence of status epileptic as and children
spk_2: we're currently working with the ft a to determine what information would be required to support the inclusion of patients below the age of twelve and our studies which could expand the pool of eligible patience and further support enrollment
spk_5: as we previously mentioned there is the option for an independent data monitoring committee to conduct an interim analysis when two thirds of the participants approximately eighty two patients have completed the study
spk_2: we will make a determination in the second quarter whether we will move forward with an interim analysis later this year
spk_5: while conduct of an interim analysis often affects the statistical power of a study should continue to follow enrollment the interim analysis for the race study is designed to have a minimal effect on the efficacy outcome of the fully and roll trial we're also happy to share that we have successfully manufactured a modified ivy formulation of gun actual on with a new buffer and expect to incorporate it into the race trial in the second quarter of this year we believe this formulation change will lead to increased products stability and are targeting a shelf life of the least twenty four months
spk_2: registration batches of the modified formulation are expected to be placed on stability shortly
spk_5: planning continues for the race to study and refractory status for european registration which is expected to begin and rolling patients in the second half of twenty twenty three
spk_2: moving on to the face to reset study and establish status epileptic us we remain on track to begin us enrollment this year the first phase of the study is designed to determine the optimal regimen of can actual on for established status and will include up to eight sequential cohorts and five patients each with the results from each cohort used to determine dosing in the next
spk_5: we expect to complete the first cohort by the end of this year
spk_2: we're excited with the momentum of our programs going into twenty twenty three focusing on our late stage clinical trials second generation formulations of gun actual own as well as our continued support for the tommy and d i appreciate the cross functional efforts from our our d regulatory and scientific affairs teams in executing our studies and engaging with the clinical scientific and advocacy communities
spk_6: now i'll turn the call over to steep and steel who will provide you with a financial update
spk_2: thanks show and good afternoon everyone i am pleased to be able to share our financial results for the fourth quarter and oh you're twenty twenty two as well as initial guidance for twenty twenty three before going into our results i like to touch briefly on that was a very active fourth quarter on the financing front in the quarter we successfully completed a follow on equity offering which weighs sixty four point five million of not funding we are very pleased to bring in several new investors to the mariners story as a part of the offering additionally we completed a revenue interest finance thing agreement with the guard helped partners which brought up thirty two point five million up front in return for future payments on us net sales of can actually including the tommy additionally we received a growth up from payment of ten million from tunisia as a part of our development and commercialization collaboration with them for the chinese market the three deals added over one hundred million in cash to our balance sheet which when combined with our existing cash results in a year and twenty twenty two cash balance of two hundred and forty point six million our gas is projected to be sufficient to find our operations into the second half of twenty twenty four inclusive of maintaining the required minimum cash balance of fifteen million required under our credit agreement i'll now move into our financial results in twenty twenty two we recognize product revenues of two point three million and two point nine million the three and twelve months ended december thirty first twenty twenty two as a note this revenue consists of the tommy product sales in the u s separately we recognize barter avenue that one point eight million and six point nine
spk_6: million for the three and twelve months ended december thirty first twenty twenty two respectively as compared to one point five million and six point four million in each of the same period in the prior year
spk_2: our actual twenty twenty two barter revenue up six point nine million was at the bottom of our guidance range of between seven million and ten million we also recognize collaboration revenue up three million in the fourth quarter twenty twenty two related to the upfront payment associated with our agreement with the nature research and development expenses increase to twenty one point four million and seventy nine point nine million for the three and twelve months ended december thirty first twenty twenty two respectively as compared to eighteen million and seventy three point five million for the same period in the prior year the change was due primarily to costs associated with increased during the headcount and clinical trial activity selling general and administrative expenses increase to fourteen point seven million and fifty six point eight million for the three and twelve months ended december thirty first twenty twenty two respectively as compared to ten point six million and thirty seven point three million for the same period in the prior year the primary drivers of the change were increased headcount and commercial support for the u s launch of the tommy for the four year twenty twenty two total operating expenses inclusive of bar in the and as dna were one hundred and thirty six point eight million which was below are guidance of one hundred and fifty million to one hundred and fifty five million and was driven by the timing of certain activities including our a p i on showing initiative in general spend management the company repo or did not losses of thirty four point three million and nineteen point eight million for the three and twelve months ended december thirty first twenty twenty two respectively as compared net losses of twenty eight point three million and ninety eight point eight million for the same period in the prior year as a note the twenty twenty two net loss includes the one time gain of one hundred seven point four million from the sale of our party review voucher and que three twenty twenty two these turtles also include noncash stock based compensation expense of three point eight million and fourteen point nine million for the three and twelve months ended december thirty first y twenty two respectively asked
spk_6: paired three million and thirteen point nine million for the same period in the prior year
spk_2: cash used an operating activities was one hundred and twelve point nine million for the twelve months ended december thirty first twenty twenty two as compared to cash used in operating activities of fifty five point five million for the same period in the prior year where the fiscal year twenty twenty three we are projecting us itami revenues to be in the range of fifteen million to seventeen million and part of revenue to be in the range of eight million to eleven million we project or gap operating expenses and coos of a bastion a and are the expenses to be in the range of one hundred and sixty five million to one hundred and seventy five million of which we expect approximately sixteen million to be noncash stock based compensation
spk_6: the increase in operating expenses is during by several critical incremental activities including the initiation of our a p i on shoring program which as a reminder is seventy percent funded by bardem cnc id investments related to commercial readiness our second race trial for the you market and for your annual vacation of the tommy law in support costs
spk_2: now attorney call back to scotland will provide concluding remarks thanks feed twenty twenty two with a transformational year from the mariners team and we're thrilled to enter twenty twenty three with a strong balance sheet positive momentum advancing are too late stage clinical programs and encouraging the surrounding or second generation product development as always we remain committed to delivering shareholder value and will continue to expand opportunity to serve patients they may benefit from the ptolemy with that i would like to thank our employees for their hard work and dedication to advancing our mission
spk_0: operator can you now open the called to questions
spk_6: certainly at the same again if you do have a question that will be star one on your telephone or here first today from bryant abrahams with rbc capital markets oh hey get good afternoon congrats and all the progress in gratitude stephen expanded role and thanks for taking my question and maybe just up starting on
spk_5: and and se on the and or a study i was wondering if you can elaborate a little bit more on on what you're seeing with regards to some of the add up to the protocol up modifications against with regards to the types of patients going on to therapy
spk_6: the seizure burden on and then i guess your senses know how the pace of enrollments is is is is proceeding now and and your latest thoughts and whether or not
spk_2: if you would potentially take an interim and that had a follow up thanks brian at this has got a job with be the first time the mariners team is all on a conference room together and a long time so i kind of fun maybe i'll i'll make one or two comments and all pass over to joe it was the really the fall of last year when we kind of gave gave a comparison between the early in rome and trends and raised in our feed to data and we'll plan to do that again around the time that will will send the data to the dsm be and so i don't think we can specifically comment on any updates in the in the most recent weeks and certainly as we see in rome may continue to expand either this is a very active process and i think you're gonna have to be patient with us that realistically we you know this is not something we're going to be updating on a regular basis i think from outside perspective is joan i'd both said on the call were really enthusiastic about where we are today teams working hard we're seeing that in the enrollment know the riding generally we feel like we've got the right investigators the right side that are going to jive high quality patients the appropriate patients for the study and and certainly no who were really still focused on patients more than eating who's next treatment would move to general anesthesia and guaranteeing or expecting that will join a low perfumery in the study and i think most importantly we we are still very confident about those type of
spk_5: patients be enrolled joe any other comments you want to make specifically know i'll just have you know yes about seizure burden and so far the seizure burden on in the face three closely replicates the face two and and you know this protocol amendment on should even more closely we'll bring in patients and even more closely replicate the population and face two i'm creations you know there was actually misunderstanding patients who are intubated couldn't come into the trial but there were below about half the patients in the face to study weren't painted on on trial tree
spk_7: and so that's one thing that's gonna facilitate roman have more patience
spk_5: that i'm the amendment will allow more patients coming in on intubation
spk_6: of from transfer in the hospital for me your
spk_8: got it at and then maybe if i could a follow up on the oral are you recently had the publication of the appease the aged nineteen data and eight that eat that you mention
spk_2: can you give us any sense of the potential for reimbursement in that indication and and seventy the interest in amongst additions to the used to tell me there is how much how much expectations for off label use or are baked into your guidance with that beat all upside and a half of going to cute thanks brian we've been pretty pretty open about just reporting cd the numbers overall and and although the epidemiology for pch same kinda very similar from a number sam point compared to tdd in a we've spoken to quite a few physicians in the community and the unmet need is dramatically different there's really only a small sub group of patients who suffer from pch and keanu web intractable seizures so i think we think about it is a much smaller market opportunity we certainly think the face to that in the publication is something that the pairs and compendium can look at and review and see that
spk_9: that day data in the public domain we think that's important we have seen a few spontaneous prescriptions but we don't see that the meaningful part of the prescription story in the near future but certainly nice to know that payers understand that these patients who have retractable pc
spk_2: h nineteen
spk_5: could potentially benefit from the tall me and i think that it's really important than in those rare cases there is access potentially available to them so it's it's really nice to see
spk_0: that's really healthy we have a think we have that you got it right thanks to the questions
spk_10: and again for questions that as fallen at this time we would like to ask that you please limit yourself to one question with one follow up we're here now from june leave with tourists securities
spk_6: i thanks for the updates and for take our questions it's impressive that you're able to provide guidance as such an early stage of the launch what does that reimbursement rate than like and on fourth quarter an overall close the net and welcoming spring terms of reimbursement rate and gross net for the first quarter twenty three and i've apollo yeah huygens the bansal here i'll touch on that the gross tonnage piece are so eat a we have kind of consistently said we expect growth discounts to be in the low twenty percent right around there we still think that the right expectation we're still seeing a process sixty percent or more patients with medicaid coverage we know that the twenty three percent discount separately we have kobe programs for commercial payments on we the sweetest the upside arm in the back half of last year i think our our growth in abductions were around fifteen percent in into for and as that's really and by a few dynamics of having a second half of your life
spk_10: one is simply lot of patients or through the kobe so they don't need as much support for that the other pieces week we simply we didn't have all our access to all state medicaid programs which we now do so now that we expect to have kind of more medicaid patients coming in with the a stabilizing this year around that twenty percent growth and the production
spk_11: great and you know the all centers is and when you do an interim look we have an opportunity to expand the trial or stop or to trial either because advocacy or utility basically trying to understand the goal of the interval for raise taxes
spk_7: yeah the theater room is being done for the potential to stop for efficacy
spk_10: i'm stopping for futility we've been is really hard to demonstrate primary goals whether or not we can stop for efficacy that point
spk_12: by thank you
spk_2: judah our next farm i'm sorry operator live each said a little color june to your question i think when we initially powered the study we had very conservative assumptions about a thirty percent advocacy delta on both primary endpoint we had really very limited data on our key secondary and point and a we continue to be confident that the delta between pussy he bo a will be significantly greater than thirty percent that's our hope and expectation and and certainly now one of the key elements that goes into an interim is our belief that when we look at a key secondaries specifically looking at days in the in the i cu we have the and eighty percent power that interim to showed today or more benefits and so you add those pieces up and i think to jos point gives us a lot of
spk_13: confidence that not only can we hit advocacy at the interim analysis but really showing mean full health economic benefit which is going to be critical for the launch of the drug
spk_0: sorry operator i'll turn back to you
spk_10: no problem woman next to spp securities market men
spk_4: and is rudy on popper marks no sense motive him a question of you can talk about the turn of new patients sars marine to twenty twenty three and for now following tags to fulfill the prescription maybe just walk us through the process and hi there thanks for the question and you know considering the fact that we've seen about
spk_1: thirty new prescription a roman forms in two three and then another fourteen keys for we seem to be very pleased with the progress and continued momentum that we've been living moving to queue for were or scuse me and to cure one with that progress we're are tracking at about forty percent increase in total perscription oh
spk_14: ver que four at that time
spk_4: in can provide o'connor i'm like on our in texas for you the presumption
spk_1: yeah sorry i forgot that that note i apologize for that right now
spk_15: we
spk_14: ah plant around ninety days to get through that prescription for found that process and we're very pleased with the fact that right now we are tracking at around thirty days seventy five percent of our patients right now have received reimburse fair be free trade you for
spk_0: and we continue to see that the moment current telling him moving forward and take your one
spk_16: go this or have a sense for her next from interest i was jeffries thanks to rattle our progress thanks for sharing all these updates
spk_17: did have one clarification question on the the interim analysis on on my summary but i you know i hopefully we captured a correctly is that if you did hit on the interim on it is possible the study completely stop studio overwhelming advocacy
spk_7: on the other scenario would be study continues as is for the final analysis but it may be unknown whether there was a trend as opposed to perhaps the drug not showing any thing is that kind of the right scenario we should be thinking about
spk_18: yeah
spk_19: so if if theres efficacy at the interim
spk_7: the trial you know takes about two months to clean the data and do the analysis that would be conducted by blinded statistician
spk_5: in conjunction with the data monitoring committee
spk_7: if they see efficacy at that point then they'll notify us the decision is made to see whether or not to stop the trial
spk_5: if
spk_7: they do not show efficacy we will know anything not to say continue the trial without modification
spk_2: and then will complete to one hundred and twenty four patients but we won't know anything about the direction of the study the direction of the results it would just be continue without modification and i point out to and i think i said this in the prepared remarks that you know we pay him we don't pay a substantial penalty for doing the inner
spk_16: right to be it's really a minimal effect on the statistical power if it goes to completion and the a bad as one additional clarifier why should we choose to do an interim analysis in that period while the data's being cleaned reviewed by the dsm be we will continue to enroll patients during that period of time we would you those patients important for the overall as heath within the label for the fp a requirement and ultimately we would collect that dataset as well let's assume we on day one we choose to do an interim analysis at a sixty when the dsm be comes back to the company we might have been rolled five ten fifteen or twenty more patients
spk_6: and that would be critical to evaluate that a double blind portion of the study with the final at the a file
spk_5: very clear and thank you so much very clear on as and secondly as a follow up on in terms of that the ptolemy guidance is tina seventy million for twenty twenty three just curious
spk_2: on to accent you guys can share is what kind of assumptions are being baked in eye on the lower and upper and
spk_6: i guess the real question is is is realistic type of guidance or that a conservative one such that you know you can be raised at the year thank you
spk_2: hi under this is steve are all address that question of look we tried to be really reasonable with our assumptions and i think we talk about some of those in the path i think your we feel pretty tight about that the growth and at deductions being in that twenty percent range
spk_6: elite it's still early we just have that one full quarter of launched so far but in a we feel pretty confident when look at a bottle prescribed and we're seeing it just over five on and than a patient population that that that that that's a reasonable number on as we look forward we do think that will increase increasingly over time as patients aids
spk_5: yeah we're seeing a steady builder a patients this isn't a a bowl this situation
spk_6: we know these patients have a lot going on it's a complicated decision a lot factors in arms so we expect to see canada steady build of of patients overtime and then appeal from and attrition standpoint again still very early but using the miracle paid three open label data we know that are sixty percent of patients are still on drug to years
spk_16: there will be some that that will attract where they just won't reach the right
spk_2: although can access own of for other reasons
spk_0: but we think you know for the vast majority that patients katya seventy percent or so
spk_6: are going to are going to stay on the therapy
spk_2: for a long period of time with the on annual attrition more in the single digits after that initial our initial three to six month period so that that should give you kind of the broad outlines how he came to that the fifteen to seventeen million range
spk_7: burger thanks again conrad
spk_5: thank you andrew appreciate the questions
spk_20: and charles dunkelberg cantor fitzgerald have our next question
spk_5: okay super young congratulations on all the progress and thanks for taking our questions i had a question on raise and then really made my main questions are and the second generation can excellent and so just quickly on raise i guess i'm but there's by cannot debate among some investors whether or not of broadly adopted changes in the protocol result in more or less heterogeneous patient population and how do you feel about that relative to the trade off for timing yeah charles struggle him i'm so i don't think it's going to introduce more heterogeneous to navy into the population a day there are the range of etiologies we're seeing so far and phase three we're very closely phase two
spk_2: an and you know the treatment is really more of a final common pathway of status then dependent on etiology although altman patient i'll come obviously depends on the etiology so we don't see that the amendment is contributing more heterogeneity and on the flipside i think the thing as much more powerful with scott mentioned is to change to the protocol that and next treatment the next likely treatment would be ivy anesthesia and that is gonna i think increase the sensitivity to detect a treatment difference on that second and point the pan get us patients again that that are consistent in terms of their severity but also as i mention beer the patients in the face to study yeah and charles i'll add you know that is epileptic is by definition is a heterogeneity a does ease of heterogeneity
spk_5: and as joe manchin the face to there is no evidence that the disease the underlying that it was it all affected by treatment
spk_7: add was an independent predict your of success and i what i loved about the fees to with that we thought every the algae i was a little worried in the face to particularly sites like duke and brigham that see a lot of glioblastoma that we would get a disproportionate number of glioblastoma in the face to and we did it because
spk_5: in real world statuses real is is quite interesting lee has five or six major etiologies and as jo said that's what we're seeing in the face three i think the critical piece that we're spending our energy on is it is really making sure that the protocol and them and still lead to patients whose next step would be gentle and it's
spk_2: visa i think we're very fortunate when patients are screened they are in constant contact with our medical team or medical team is talking to those physician henry bit cabbage who was or lead investigator from the day too many of you know are many of those call doctor guess your magic guess your who wrote the place to protocol
spk_21: all is on many of those call to every one of these patients who are involved in the trial we've not only are aware of but we are in constant communication with those investigators and we continue to believe the quality the patients are far away what we need them to be to really show the value proposition of the judge joe
spk_22: was going to add one common yeah one other thing occurs to me
spk_5: and that is still at the baseline before they're treated we do have a score called the stairs status epileptic as severity score and that also seems to be mirroring the what we saw in face to so that is probably a good measure of heterogeneity more so than than diagnosis the severity of the status is based on you know a number of of clinical factors so that that scores so far looking similar to please to very helpful added colored looking forward to that data is i made his one follow up with regard to the second generation can acts loan really intrigued with said i'm wondering if he could provide any additional color or my you think that could be a be id those saying and then any and
spk_7: he sense in terms of the size of the trial for the phase three in linux gusto
spk_5: so the reason of the first quarter question trousers that we are seeing kinetics with the single those studies that really support the id dosing i mean the goal is to see increased exposure increased a you see
spk_7: and relative to see max and then so we're seeing a good a bump in the a you see with of slower decay of the
spk_2: the plasma concentration and then we'd model the be id dosing the done some you know pharmacokinetic modeling from the single those results and that looks very favorable we're we're see a good i'm
spk_13: minimum plasma concentrations at what we think maybe the target dose and so in one that that that was a limitation is specially in the early
spk_2: fogle epilepsy studies when they gave it twice today does the see men would drop below the minimum effective concentration in fact the modeling
spk_23: we did modeling for both the suspension to current formulation and the reef formulation and giving the suspension be id a would we actually saw similar actual results in love in one of the focal epilepsy studies that them it was reproduced by the modeling know so very comfortable with the marlin with
spk_2: yeah and i only a child that thing you know do he actually been greeted in and maybe study probably not just from what we've seen but i think for us to think about leapfrogging these three having a comprehensive and maybe study understanding how the product dogs with different foods which is
spk_0: so important in a pediatric population and seeing those curves to that will we should we choose to go to phase three we will really be able to my hope would be the target two different blood concentrations as a critical part of that study so again early days that i would think about of these three that has three arms to
spk_2: act active armed and a placebo very similar to what you seem out with epa dialects in for example their ts t study their face three study do you think we we have the ability to have some interesting regulatory discussion to other be a single or single study or two studies at a week or thank you very hard about safety ah as in what would be required from the safety database perspective though more to come on that and we certainly haven't made a final decision i did what we wanted
spk_24: communicate with you this call is that the kinetics or incrementally better than we had hoped for and given that it makes it a a a bit of a morph a a potential to move quickly and to pays three if if we see a consistent signal for net and the study so
spk_25: it is really exciting we're seeing things that this franchise have had never seen with its oil program before and we really are believers have higher blood levels on a chronic bases can can increase the efficacy of that and already very favorable of product so ah thanks to the question please
spk_7: shane it hope we got it all
spk_5: yeah thank you very good great for her next from douglas cell with a seaweed right
spk_7: how does that mean thanks for taking questions just just to clarify on i think he said and terms of the interim analysis on the secondary and point in terms of on he did it prudent in terms of days in the i see you soon with the something that you have
spk_5: subsequently top more comfortable in terms of the powering just get an additional work that you've done on the health economics monitor just understanding how long patients are in the i see you that you feel more comfortable that you will be able to hit that down given the power in numbers for the for for the enjoyment out of
spk_7: yeah mom fact fabulous this is joe on so yes the the short answer is yes we're confident we'll hit on the that he secondary we have a number of healthcare utilization and points are built in one is days and the i see you
spk_5: one of them is actually built into the hierarchy of analyses you know it's a step wise analysis get the first primary of the second primary it too quickly clinical primaries and then that health utilization and point is actually in that hierarchy of analyses so if they all hit
spk_2: that and that healthcare utilization and point is statistically significant that would be considered a substantial level of evidence and of would be appropriate for promotion i'm the energy to be a high level of evidence and so we looked at at the powering assumptions and not just for the primary but for the secondary and that that see helped you udall that utilization and point is time on ventilator due to status epileptic us and that's less founded days in the ice you may be confounded by
spk_26: you know whether there's pressure on beds and so on
spk_27: and so that the time on ventilator and we've gotten advice about this from someone who's very versed in health economics
spk_2: adams role sick is a neurologist in germany is done a lot of work with this and and that is a much will be a much more sensitive and point to look at but we're also looking days in the i see you tom and we'll see what happens on that one i also think you know we have adequate power to show a difference on that as well and the own it i'll add a dog is this is something when we first met with the of the a we thought about powering the study did not really play we we included into into key primary endpoint but we really have the scientific team and i give alex and that he and his team a lot of credit of we spent a lot of time helping us really look at the literature think about where these patients would come out and what we would need to see in terms of an improvement or to win on these key outcomes of to this disc caution before we went to the f t a and and asked to perform an interim our team vetted what we thought we could win on and that drove the end of eighty two specifically of and certainly when we looked at in and of sixty for example we still felt very calm and about the primary but our ability to hit secondaries were significantly lower a power to about fifty percent so that innovating to with the sweet spot from primary and those keys secondary an now even i even at the interim we have ninety percent power on that on the time on ventilator and okay great thank you and then just as a quick ball up the
spk_0: statistics to clarify so if you do the into unlock you would still and roll patients and would ultimately be and be a filing be based on the interim or would it be based on the full dataset
spk_10: yeah our basic assumption today is that it would be based on the interim as the primary label we would collect all of the the blind data we would submit it all so there is a potential in there have been one or two cases we've seen that blind the data included in labeled normally those things are pre negotiated did we wouldn't expect it today but the only the only piece i will mention is that the agency has said if you choose to do an interim remember there is a safety burden and of safety that we would like from the company so we are continuing to not only roll double blinded to to
spk_4: can have an additional number of patients that we can evaluate but should the child be stopped for advocacy on an interim which would be our our expectation or should we take that look we would continue in all probability do keep it open label arm force the that safety collection or use res to as another they knew to collect additional safety as part of our requirements for registration but you know we've had these discussions about what we expect to label look like i think base case is that it would look it will be primarily based on the patients in the interim analysis but that being said we will have double blind placebo controlled data on another set of patients that we certainly would submit to the agency as part of the package makes and right thank you so much yes sir in from operator will move next to jail cell
spk_1: he progress and all of progress and thank you for taking the question have you seen any increase in this study diagnosis or it launches at home be what are the current actors didn't limited denied magnus read have you plan to increase diagnosis and would have more
spk_4: drivers of volume go through the tommy twenty three hi there this is for sale to i'll take the first part of this question so from acidity diagnosis point we do a lot of analyses on usage of the i city ten code across the united states and what we've realized is that are promotional effort has have utilized the code much more and that at the end of twenty twenty two and to twenty twenty three which is supportive of not only identifying these patients coding them correctly and then getting them properly i'm on therapy sell
spk_1: from a diagnosis standpoint that currently as howard triangulating and finding me patients
spk_10: they're currently wheat we have found you know we made up some assumptions on where these patients are being treated or reminds you that there are eight cdt centres of excellence across the united states
spk_0: however we do know that the patients go to these centres of excellence
spk_10: on a limited basis sometime for every sex every twelve months and then there's been more routinely at their home physician
spk_2: so the increase in the diagnostic rates may be limited if you will at the home physician and monday's increased rates at the at the center of excellence
spk_10: the other thing that we know is that in more rural areas patients don't have the capability to get to the centers of active to get to a center of excellence so are the utilizing the code at the best to their capabilities probably not right now though and twenty twenty three we have some efforts to not only be able to educate more it distinctly were increasing our speak
spk_28: or programs we have a very distinct efforts to increase awareness through our patient advocacy partners are ill partners that have patience unfair be to speak to families who have new diagnosed patient so there's a lot plan for twenty twenty three to increase awareness increase education and ultimately get
spk_29: the code use more more specifically the patient population
spk_5: brutus up to take you
spk_2: for her next from brian's forty with baird
spk_5: i get sick more often than not receive on the ocean waters are on thought want to get some some guidance on are your thoughts around interim does sound like you're you're going lot of conquered come that you should be powered based on what you've seen for the next month
spk_7: yeah and from sir i really wanted to get a handle on what sort of don't for assumptions you have the differences between the primary endpoint for a full analysis without the arm up here
spk_17: two
spk_7: the key value on versus the awfully do take the infirmary seems by my calculation of like for example the personal thirty three percent golf on i guess i'm i'm under some i'm having trouble understanding why was non obvious decision to keep the and common is in that case so well my question is what are the factors to consider as to why you would
spk_5: do you pick the ago well do the job
spk_2: thanks brian for the question so the study is well powered
spk_5: we were looking i think we have more data now on the secondary and points they wanted to be comfortable as scott mentioned that it was powered to hit on t key healthcare utilization and points
spk_30: the the assumption about the delta his same
spk_7: the the reason we would
spk_2: decide not to do the interim
spk_5: would be a roman is just gang busters and by the time we got done with performing the annulment alice's the study would be fully and enrolled so there be no reason to do the and on
spk_2: and that and that would be the consideration otherwise we're going to do it
spk_5: now
spk_2: just seemed a little bit into the weeds but there is there's a lot of assumptions you can use to build and infirm analysis how much as you know how much help you spend the interim versus the end there is an alpha spend at the interim analysis however if you look at the actual outcomes on the endpoints the difference between of four point o five have a fully and road study and the and the alpha we would have at the end having performed an interim is a difference in one patient help and so even though there's you know you have to hit a lower p value with the end if it proceeds to the and after an interim he does the actual clinical penalty you pay is very low but the assumptions for the interim are the same thirty percent delta and it still remains well powered
spk_0: let me jump in joe look right now i'm totally with you i don't think we have any expectation that the delta and this study's going to be thirty percent we think it's gonna be potentially forty fifty potentially sixty percent that being said adding in a small thirty one or two patients could potentially do want
spk_10: key things to your eyes you days or other health economic outcomes so in general my buys would be to have more patience in the study to reduce their risk of an outlier joe has reminded me the outlier could come on patient number ninety five or one hundred and five this
spk_31: same way to come a patient number five so we keep that into consideration as well but i a get to this point i think the bigger and certainly gives us a little bit of comfort on outliers more than anything else and really has minimal impact in our view of the primary and
spk_10: point that said i think every time it's site now initiate and treat a patient and get comfortable with the protocol they're gonna be a little bit better on patient number two with three that's normal as and and i think as we saw in the face to that comfort only lead to equally stuff
spk_7: greater success in terms of the utilization of the drugs so there is a comfort level as as our clinicians get into a sweet spot there is an element of sites that are you know activating now and and and starting to get busy that we give them a but you know several months to participate in the study
spk_32: he but yeah don't think any of us are really losing a lot of sleep on the are the key powering assumptions it's it's just a small and always creates some some unknown risk up particularly on the placebo side so nothing more than that i think it's more theoretical and practical
spk_33: but it is to have a lot of data points while the study is ongoing it
spk_5: to what we've shared with you and term the underside understanding baseline characteristics and and not being a surprise by the types of patients being and roll etc so love it it it is it is that that's what we were balancing in and we feel that we're fortunate that we have the luxury of the f a support if we if we choose to take an inner for her now from adjacent butler would say and peace security
spk_7: i think certain questions are just a couple more on the novel formulations
spk_5: first one from the mit data did you expect to have will be updated or to make a meaningful interpretation of the the somnolence
spk_2: the enter sorry incidents and then secondly if you move forward quickly with with the the first reformulated the for formulation into at a phase three trial and out yes how should we think about the utility of the the pro drug and and how you could use that strategically prove it forward thanks god i couldn't comment on the first part about the the someones trees and thanks for the question go and so
spk_34: i i think
spk_2: we do see increases in see max with increasing dose i think the major factor this going to affect the rate of samland is going to be a tight ration rate we've adjusted the tight race rate in the current ongoing c study you can have them low and slow approach start the escalations at a low level and then wrap them up towards the to the net and to the tide ration and i think that's going to be the make major factor of factor affecting somnolent i wouldn't expect you know a detailed read on someones will get some idea from the a d study but these are healthy volunteers and they you know worn on the can and medications they don't have the cognitive impairments and so on neurodevelopmental problems so you don't really takes the clinical trial to get a good idea about that i'm and in terms of the pro drug role of scotch new comment on the pro drug piece of it's sure and linear back up i think i'm on the and lady and muthama jason i'll use this opportunity to share as we have that we continue to feel as though in the blind it's a three tier see study we are seeing improved rates of tolerability lower rate of discontinuation anna and i really think worth joe has done to greet that new tight ration schedule we're seeing what we believe in going to be a meaningful impact in the he study and at the lower doses of our novel formulation it behaves very similar to get axel own so we would expect use the same type of citation almost the identical hydration of for the new formulation certainly when you are absorbing much wardrobe your going to get some bigger see max's but again we believe in a very reasonable fashion via hydration we don't see it as an issue today and and we certainly will get some additional insight on that from from the and they do you study but but we're only doing some mild iterations in the and my and maybe study at the at the twelve hundred milligrams does so i'm it's not truly it's high treason schedule is
spk_0: it's an inmate work for tight race study it's in a may maybe study and to just to be clear

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