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spk_0: hello and thank you for standing by a welcome for abc hosts file sizes reports for the fourth quarter as and year in two thousand and twenty two conference call at the site offices puts on the listen only mode after the speakers presentation there will be a question and answer session the ask the question during the session you need to press saw one one on your telephone and you have been who are automated message advising your hands raised to withdraw your question please for a star one one again
spk_1: i will now like to him the coffin sober to susan that throttle you may begin think it's honda good afternoon and welcome to the opposed by the slightest conflict quoted that financial and operational results for the year end and fourth quarter ended december thirty first two thousand and twenty two earlier today up to issued a press release relating to the east
spk_0: financial result the news release as well as related as the filings are accessible on have to website joining the unsullied call a doctor william gay rights chairman president ceo not the roughly have a hard senior vice president chief medical officer and mr fletcher pain senior vice president and chief financial officer before we proceed i would like to
spk_1: remind everyone that through thick and made during the call will include forward looking statements within the meaning of us and canadian security blood forward looking statements reflect after his current situation for gordon future events
spk_0: not guaranteed to reform and and it possible that actual results in performance to differ materially from the seated expectation they involve known and unknown risks uncertainties in assumption that may cause actual results performance improvements to differ materially from those expressed to learn more about these risks and uncertainties please read the ritz crackers set forth in effort is not returned and your
spk_1: put on warmth and k and as if the in cedar filing or forward looking statements made during for is only as as a date the me after them to take no obligation to revise their update the statements to reflect events or circumstances after the date of this call except as required by law i will now turn the call over duff the rice trim and president and ceo of after oh sciences have the right
spk_2: like this isn't i want to walk their one to our call for the your and and fourth quarter ended december thirty first only twenty two first up about a very quick overview twenty twenty two that about had market has been extraordinarily challenging oppose continued steady march forward with stated our cash way of runway to the end of que one twenty twenty fourth we continued building a talented and experience team we created and began testing a new formulation for looks happen if and most importantly we made significant strides and the development of perspective for the treatment of the khumalo leukemia or hey a ill when it comes to test putnam or cause as we call it i want to emphasize attali differentiated profile having demonstrated the potency to achieve complete remission and very ill relapse refractory a male patients while also being safe and about ah gallery it's extraordinary for an anti leukemic aged to deliver family responses and such an aggressive cancer without causing the typical toxicities of other reasons and today we will unpack both the potency and take the attributes of touch it's also important a highlight the a a male population that has been treated with has been up to date and our phase one to dose escalation and those exploration trial these perfectly third line fourth line of the on having failed the best available approved therapies and in many cases having failed various investigational drugs or prior metacritic stem cell transplants these are incredibly difficult patience to treat and to reverse the disease progression i'll make these patients even more difficult to treat is extreme diversity of holly adverse genetic an effort to have a genetic alterations expressed by their disease if we recall the admiral trawl from just five years ago during which the commercial dose of guilt written in a flip three inhibitor was tested for responses an email the patients were second line offensive had not seen other flip through inhibitors and had not seen net clocks in contrast patients entering our trial are far more treatment experience with half belling probe and at a class sixty percent felling prior treatment with have a meth letting agents or a committees more than a quarter having failed transplants and half of the flip three newton patients having failed prior therapy with a through inhibitor nevertheless cause has delivered responses with convenience wanted early or those thing of tablet across for those levels one hundred sixty milligrams one hundred and twenty milligrams eighty milligram and forty milligrams and no deal tease were observed with any of those acted those levels from mean the taste and from a mutation sensitivity perspective has a shown an unprecedented breadth of activity has delivers responses and flip three wild type patients as well as it doesn't play three mutated patients we also seen responses in a male patients having a very difficult to treat pp fifty three mutations as well as patients with in pm one and flip three commutation a patients having alterations in the the an empty three a ranks one or the ace one splicing factors a ethics how one hand mll jeeps the one of the most interesting observations is the activity and relaxed or factory a male patients with ras mutations mutations in the raf pathway serving an escape mechanism to generate resistance to many other drugs however we've measured a forty two percent overall response rate in patients with ras mutations including a twenty nine percent c r e r h response rate in fact one patient had a mutation and a mutation and ptp and eleven representing a dual mutation and the rest pathway will continue to monitor that response rate and rashmi mutated a male patients this year and determine if ras mutated relapse your factory a male patients may represent a population of heinemann need for future accelerated approval trials a doctor bihar will describe and further detail in a few minutes we wrapped up are highly successful phase one to those escalation hand those exploration trump we traded over sixty patience to date in that trial we've assembled a strong safety data package we selected safe and effective doses for a single agent and drug combination trials we demonstrate the the a pass to dramatically reduce vulnerable marrow blast and a high fraction of patients and to achieve formal responses and we initiated are activate dose expansion study of tusk in a single agent and in combination with fanatic lax and the activate trial this year we will enrich certain patient populations to receive mana therapy so that we can collect data to got our conversations with the ft a to requests and accelerated approval path for test in patients of hi my name in parallel with the activate mana therapy dosing will treat a broad array of a male pace since with a combination of costs less than that o'clock referred to as he has been doublet this has been doublet is being done it to support doublet combination registration trials in second line am ill patients and to serve as a bridge to a pilot study of cause has been hot a have a metal letting agent or the past the and hm a triplet in front line a male patients i'll test clearly can deliver responses as a single agent the ultimate goal and commercial to have success of us or any drug free email will be in combination with other drugs as of this week we have gotten enrollment of a a male patients on the cusp been doublet and we will place additional patients on this doublet throughout twenty twenty three once we can experience with the dublin we plan to initiate the test then hm a triplet and frontline patients the future of a ml therapy will also revolve around cocktails of drugs and harder line to therapy to take patients into deeper permissions such a male cocktails will require the blending of drugs that best conserve broad populations of patients can deliver the permissions and can be tolerated without cardio talk yes these unnecessarily prologue malice oppression and other complicating side effects and that's precisely describes tough test his position to become the ideal partner for addition to the men hm a doubling because of it's convenient as a once daily or agent it's brought activity and safety profile together data to date point tough toward application as a mana therapy for accelerated approval in relapsed refractory email as doublet therapy for accelerated approval and second line email for use and triplett combination and from on patients as well as you use and maintenance therapy and doctor may harm will provide you with additional color these activities momentarily now let me turn briefly to look after them many of you know what as cg eight or six lux as we typically refer to it with our second a pipeline program lux is a clinical stayed small molecule oral flip three and be carney from hitler lucky's ability to target carnitas operative in certain leukemia and lymphoma as let us to develop it impatience with be sell leukemias and bombers and in patients with a a mill we already have are reported that lux administered as our initial first generation or g one formulation deliver to see our and an a a male patient and a cr in a deal c l and former patient demonstrating lux is a clinically agent you also are aware that we developed a new formulation of locks and we call it the g three formulation because it represents the third generation formulation single dose administration's during twenty twenty two and a ml and be some a legacy patients will determine the g three formulation achieved up to eighteen full great absorption than the original g one formulation because the highest dose of the original formulation what's that at nine hundred milligrams we initiated continuous dosing of g three at an team fold lower dose level of fifty milligrams we continue to collect pk and safety data would g three and a a male patients and the preliminary results suggest continuous dosing a fifty milligrams g three dozen they deliver roughly equivalent plasma exposures at nine hundred milligrams of the original t one formulation that was the target we hope to g achieve with the fifty milligrams of g three and next with plane to administer a higher dose a three to determine if it can he can achieve even greater plan and exposure levels we'll keep you posted on our findings and like aware of will report pulmonary data around he r i also want to mention that posts and collaborate as easy as the doctor month you on a while and doctor stephen how just published an article entitled looks at the nypd interferes with limb mediated activation sick and modulator vcr signaling in the palmer and the online journal plos one and which we described the ability of luck to tacked on the be cell receptor pathway at the level of the lc k and l y an early and canucks is and to influence downstream bdk activity this relates the role of lux tacked on be so cancers as well as inflammatory and out immunity processes so please take a look in that the article to get a chance finally we often get ask about potential partnerships for test that him in january during jp morgan week we engage him productive discussions the several big pharma biotech companies that further have to define our priorities and to solidify our clinical plans with us patent it clear what we need to accomplish with the drug that has such an extensive commercial opportunity we were pleased to see the were on the radar these companies and interest in our program is growing the treatment back paradigm for a male is shifting toward tablet and triplet therapy and despite some successes the current combination therapies are somewhat limited by toxicities as i mentioned previously the proven breadth of activity and superior safety profile of to sputnik lend itself to combination therapy potentially as the drug of choice addressing the most sizable markets and am ill and clearly making cars and gives me a perspective big pharma drug the data we generated to date have helped the delay a clinical and commercial plans for test bet them and multiple lines of therapy including at use and doublet and triplet combinations and as maintenance therapy or chief medical officer doctoroff albay heart will speak about our recently initiated activate clinical trial of past that nip and i am ill as a single agent and in combination with veneta plaques as well as our extended clinical plants which include triplet combination therapy
spk_3: he also be available for questions afterwards i now will turn it over to our resident care well our chief medical officer doctoroff albay hard to talk more about our to sputnik clinical plant raf they felt the january we were thrilled to kick out the hiding twenty milligrams a thing at authentic in the minor therapy i am a deactivate phase one to trial at my can you know we have successfully completed joke escalation and of exploration stated that i cut statement you try to being approximately sixty we have tried to end up patients who were heavily exposed to manipulate it in fact a doctor right mention oliver wrapping up the does exploration part of the study with at the pretence that the putting additional patient on the lowest forty milligrams one group because of the ft a product up an advantage i did goes exploration during really did out and about how to products if experience gave it the additional data needed to support our monetary debt collection and the not more out of the safety concern rather as hard higher doses the defendant had shown an apprentice a zebra about since the last forty no up by the late last year we have achieved to pinnacle responded in that low dose group both anna patients with only dated for three including the most recent powering accounting pp fifty three mutation one of the most highly advise thematically me editing importantly this is the second he be fitted a patient that it a t the critical response the first with or the eighty milligram dealt who achieve an unqualified the are at their best response to we look to enroll more these patients with had a poor pugnacity have a great unmet need in the after the trial the activate expansion trial is designed good for monetary activity the patient enrichment a specific in case they define a anal population including that he befitting need patient as well as with three mutated patients with it failed by privately and headers as supported by an f the a fast track designation and a clinically significant response rate today if patient continued and great i that medical need and they believe that the ability to rescue the station and perhaps allow them into if it until transplant now done with have a as day when allows the quicker path registration in addition to being potential accelerated approval patrick defendant treating disagrees will provide critical data to a former contained allen path i am pleased to say that we have begun treating patients in a monitor the i'm at the after the trial in a growing network of clinical fates investigators are engaged in a moment and that this has been red brick in the activated commands and round to spend an author will be headed in combination with inadequate have a fake that regulatory clearance and both and hand allowing acidification moment on the test then combination earlier this week having the catlin combination aren't open is an important events and this represents an attractive treatment option for patients and definition video camera earlier in the course of treatment increasing the likelihood of achieving a of meaningful clinical benefit so what is our timeline for a clinical trials because after they didn't open label trial he will report data when available appropriate for it you will have and the right yeah change and for them but as we usually do that because data collection verification does take time and activated only get up and were shot while this will be an incremental updates he would expect that more complete data that luckily for the monetary the on at the european school him at all of the meeting your face at the end of october industrial portugal expect more data including from the top and combination covert to then be updated ash in san diego in december fell twenty for me three will be a big year for us having to defend defendant in specific genetic we define population you would expect exhibition patient data this year than same way to face the registration fairly for support accelerate approval a doctor i mentioned the or including relax or repatriate our patients with i'll leave it if with three oh yeah fuck all while pie patients that have other adverse mutation exploring fifty and activity in patients with the phantom treatment okay a single agent and in combination with inadequate identify nineveh like unity and other adverse average could lead to other options retaliate for the the paradigm for the treatment of and now increasingly moving toward combination therapy we have to petition to fed and had a preferred aged for damnation and you an earlier line to treat it it our hope and based on data thus far dark vacation and we will move forward defendant in a triplet combination animated thanks dr novel diversion md anderson has been one of the investigative pioneering a combination therapy inadequate is arlene the theater on activate and an eager as we are to see what extent can do in a setting also highly a few comments from doctor harry about the do to do during a recent okay well of it he noted that this drug may be better suited for the company should be the of the development anything we have right now and he was excited about the parent like of mouse depression know the near killed he to date as and he emphasized that a drug like cause we have a position of the to get it at that it actually people found that are treating outcomes about the question clearly you agree wholeheartedly the doctor urban we believe the potency bread and at it would negativity along with the safety profile leg stand up the ideal transferred on a some therapy and scale commercialization on our website because he are projected timeline for ongoing and plan clinical trials and what to think our clinical paying for their hard work execution getting both arms it out to be declared that he other running he certainly look forward to sharing the do with you
spk_4: they'll i like to turn the called over to our cfl fletcher pain for an update on our financial debt leisure thanks wrath and good afternoon on before we start speaking but financials or the interviews to you the newest member of our finance king brooks and son who's a dp and controller a baptists mr ensign has more than twenty years from school and experience in accounting finance corporate development he started this disposition from multiple public and private companies the shenton has a masters and holes and m b a from harvard business school and a masters in accountancy we're pleased to be able to recruit call people like him and we're very happy to have him here at actors let's review the fourth quarter and your in financials as most of you know oh fine actors will take a approach to cash management and always the to prioritize are quite a clinical activities without sacrificing quality of our programs these efforts of extended a cash were wrong my into two thousand twenty four and a cash management policies and actions taken and helpless avoid the financial impact of silicon valley banks out now let's review our cash position we ended to does a tweet to with approximately forty seven million dollars cash cash equivalents and investment a decrease of four point eight million dollars as compared to the previous quarter during the quarter the net loss was a proxy ten million dollars translating into a price mean negative eleven cents per share loss down from twenty four point three million dollar loss from the comparable period in two thousand twenty one and again by an income statement we had no revenues during the fourth quarter of two thousand twenty two richardson development expenses for six point eight million dollars for the quarter down twenty point two million dollars in the same quarter and twenty twenty one research and development expenses for the full year period ended december thirty first twenty twenty twenty eight point one million dollars as compared to forty six million dollars for the compare your periods a decrease of eighteen million dollars that decreased is due to several factors including a twelve million dollar licensing pay a fee paid to harm me for the previous previous year the choir global development rights for to the net which comprise a five million dollars cash payment and seven billion dollars with common shares additionally there were lower costs for lunch program and to five three program as well as well or personnel costs
spk_3: these savings or fantasy offset by costs for the to sept and program that was adopted it doesn't talk to
spk_4: gina expenses or three point six million dollars for the quarter of compared to four point one million dollars for the same quarter of two thousand twenty one june expect this for the twelve month period ended december thirty first two thousand twenty two a fourteen point five million dollars as compared with nineteen point five million dollars for the can pair to period a decrease of approximately five million
spk_2: the decreases primary do a decrease in stock based compensation expenses offset by higher compensation expenses travel expenses and professional fees
spk_0: as of march twenty three two thousand twenty three actors has ninety three million five thousand two hundred seventy eight common shares outstanding more detailed information click on my filings on anchor consider else from it got back ductless thank you flatter as well call for questions please feel free to pose a question to any of us operate if you could please hundred is the first question thank you at this time i like to my everyone how to ask the question to ask the question please press start one one or your telephone
spk_3: and they await for your name to be allowed to withdraw your question please press star one one again please somebody to help you and a roster our first question comes with a lot of matthew low with oppenheimer yaalon is often
spk_2: oh hi guys like they update on to cure for me i'm i'm wondering if it you can kick guide on patient numbers for that october update on yet from the up in a trial and then i'm just curious about them of the comments draft made about the doublet versus the singlet to to that give it up after a i'm just i'm curious if you're if you're concerned that it might be challenging to enroll them mana therapy arm given that there is a double a or have how are you approaching that harry setting out
spk_3: have weeding outpatient from one to the other day thanks matt this is bill i'll i'll start on that that they are neither your second question is really easy dublin vs monetary we've had exceptional uptake i wrap it up take and how i think the the word that are we talked to be argued was risk uptake of the mana therapy we got it up and running first this year has been great enrollment pace and we're just now beginning to enroll the doublet in terms of the year the numbers of patience and on gonna turn it back over to dr bay heart will be careful not to really bracket them too much or try to give yourself raf the at that like that and adjutant thousand and until you're really a point about that in raleigh to both of the the goblet it a given to be more appealing investigators in the monitor be in general that once both arms are open and both options exist will be a random assignment so we are hoping that not only did they get more patient earlier more do the oven for the study but the christian man come on earlier in the course of therapy because the rate that sub accommodation options available to them
spk_5: so we'll focus on both through the end of the year and will give you more clarity
spk_6: when the get to that point it took the numbers a patient add a it's like i said it's hard to put it exact number on it but i would say the roman as a very good and on there certainly will be bad
spk_0: some and reckoning can maybe ten the patient and the my therapy arm and hope for and somewhere between again and twenty patients on that on the debate on by the time that we we are near the end of year
spk_7: right right thanks thank you please stand by for on a question
spk_2: next question comes from milan assume it boy with george jones trading line is okay have you wanna thank you for the up a damn good you give us a little bit more color on the defend to school hot five years
spk_3: enrolling currently between forty eight hundred twenty and then the hundred patient you mention a what fleet is monique happy and tablet god has committed to the right so yeah we have completed the the dose escalation in those exploration trial and nurse or doctor but i'll talk to be hard to give you a break down on their the numbers of patients there and then he can talk about the have to be right
spk_7: ill as if the ash meeting when we had not yet open up today we had i treated sixty patients between the dose escalation and what we call the dose exploration we have treated additional patients in that of exploration arm i primarily the forty milligrams oh several the further characterized by better or for that up to date with opened were we where then the thing at a fair deal exclusively an activated that he became a lightweight would do that
spk_3: at the jokes about that we started after they eat at the mind of their be with hundred twenty milligrams get her that may change it as we learn more about it the decay and and the at a activity of a drag and on the name of eighteen have an answer the monetary biggest thing at the level of activity like that and we have implemented
spk_2: for the combination study eighty milligrams i will be the be starting out and difficult for in college with respect with that been adequate and as always that it off with a dick change because i didn't we receive arm
spk_8: so how are you thinking of presenting the dumb may media our lives second half also are you going to to have
spk_6: love with some the a trial like the traditional know why our response rate theory to come over number of patients treated and alongside even to show how long term if any durably to data from down under oath escalation expansion know part of the trial
spk_0: traditionally we have done that kind of more complete update at a major medical meetings like ha and ash and i get that well that may hold true for ash i do think that ha will be a more incremental updates as a very the may not be that much level a detailed because be the honestly be cut off date for data with an idiot trade about now so we don't necessarily have a lot more to say them we have said earlier this year ago so we will do an incremental updates on the for the highlight of at any activity or issues that arise study ready ha but expected larger data package with another more detail you just described at a later in year
spk_9: have a i got so much you just add that that we will have certain scientific findings had a half or that will be presenting that's the plan as well as some of the or the additional data as you said as we followed some of these patients that have been on the of escalation dose exploration of able to provide that but then doctor they are said you know it's we just started the after the trial and now will present the david that are available it won't be as has huge number of patients by that time and i will present well cap thank you and congratulations on the progress and cushman thank you please stay by for our next question
spk_2: next question comes from line joke and eunice with a see why why a lot of help it the guys get up near they've taken the question so a bill the was wondering maybe if you could do a little benchmark audience about your regulatory plan for the up monotherapy arm in after they talked about you know since it mano your potential accelerated approval self you know based on your internal thoughts regulatory consultants or what have you a new benchmark how many patients do you think you'll
spk_3: ah for the have to a to be happy with and more importantly can you benchmark
spk_2: essentially response rate rcr rate to beat
spk_9: ah boy number of questions there are so first of all i'm not going to go too much on a limb because soon we are gonna be having the into the f t a and we've we've already articulated that to the street are so will be speaking with all the parameters you you just mentioned for the mana therapy as well as the yard the tablet dated that are coming out we want to make sure that as we go to the ft a by then we will have a number of patients that are already on the mana therapy that after the trial make sure that we're doing everything that we should ah determine if there are additional primers we need to measure so that when we go to them with the data later in the year or will have everything that we need and hopefully the date will be supportive of of going toward a of and accelerated approval whether that a mana therapy a tablet you know we'll we'll see how those data merge toward the end of the year and
spk_2: the raf is there anything else you wanted add to that terms of a toy
spk_3: and like a deathbed difficult way to put it i think that we do need to have any new the ft eight really align yourself and depending on what because we agree upon that that change changes going to study but certainly in a hurry to give us that he would be a much smaller study that he would have to do he did a a randomized smoky on study and then also little bit later and years we collect data on the the tablet or we want to be able to go to the ft a present the data there and hopefully i have the ability to move into the triplet trough ah that is your questions you know it doesn't i guess maybe just a little on the us for for the listeners and every one investors in general
spk_2: you know benchmarking you would look at from and advocacy standpoint hell i'd recipe yeah so wrapped you want to that income tax relate relative to the admiral problem and don't think solution yeah get any get that way to view it as a white population are we treating and what advocation my they had from alternative to that it wasn't available and remember the her patients who if they are flicker mutated in i think that do inhibitor be likely been through at least to light the fire therapy for the coming to a third line of the ad in a second line setting with the address
spk_6: study at the early in the interim analysis for gets written in d c r c r h rate like twenty one percent and later that matured especially with the inclusion of patience is best response was measured after transplant but at the point of the in terminology that led to the pool of the drug i was twenty one percent in second line patients largely naive about it
spk_0: therapy so we would argue that a meaningful number in the third line setting will be significantly less than that and perhaps yeah well as have battery or somewhere between have to two that range given that the alternator the station to that point on i've even less effective than they might have been affected by setting at the word ammo study with chemotherapy response rate for cr that eleven percent
spk_10: so that the ballpark that we're working with and what we come down with with the of the i think well well then shape their the scope of the study the five the telling in an effort discussion with that right yeah think a benefit you have the bars is fairly low for that piece population as he said that the many of them will have already failed other flip three inhibitors veneta clarkson and more and more patients that are coming along now in the us are are having a are much more experience with prior drug therapy and so these patients are very difficult to treat so we think the bar will not be exceptionally high or that we also believe we can achieve
spk_2: thank you very much pressure to coming up thank you please say my for our next question alex question comes on the lot of public ten off with fight with sailor a lot of help it hey thank you very much i like the graph below poverty can be like putting yeah hum i think list of questions on to they are putting on was but i wanted as can lock sort of higher level how that fits into ah that freedom tower or how the streets and to your development plan and specifically you know what alexa patient shows that like they were considered patrolling i'm got it ultimately house combinability navy the was five and i'll take so much i think for and ted for the question shall we don't get them many questions on luck anymore a but we're still will ensure still excited by the drug another we have our new formulation and species we got to that next to a higher dose level that that's the plan now and we hope we get her exposures we go into debt and in terms of what we like to do with this molecule me first of all i must say that perspective is our top priority among have
spk_0: among everything and it has to be because it is delivering it's more advanced slippery but prospect of but lox ah as we move forward would love to see if that were getting exposure that we want and that the that the hill burden is also much less cost of goods much less if we continue to see activity in a ml are we have done studies where we put the person and not much together and they are not and peg in a stick they also
spk_11: are we know have different activities against different kind he says so it may turn out to be like some of the other arm
spk_12: indications we have multiple kind a says that he had different patients with different ah different mutation profiles the most likely have waited we likely will move it more toward the up toward the be sell arena and yeah and also toward inflammation and auto merely because we've been as you can tell from the publications will be digging and that area understanding it they're still in need because this drug is different from the other non kobe be became hipsters it has a different set of kind a says it has different activities and we believe that if we're able to combine in francis with the
spk_2: as with some these other drugs that are being developed for the be sell malignancies i like the network like france and stand now we believe we can see real activity there so there are pass fort that do not interfere with tospend that your how did your question yes it does very helpful thank you yeah aren't thank you thank you for a fan i for our next question the next question comes from a lovely watch that of external on of open everyone man for the thanks for take my questions just a couple here and personally i am against some color around early activity that you even mana therapy i'm and after me and then and the rat pathway can you talk a bit more about wait to go at this guy named a wrath correlates with and the other mutations potentially and whether you see nano and kind of therapy potential here
spk_3: toss out thank her thanks rosemary for coming on as all star with isn't the me and maybe doctor a hard one to jump in terms of early activity again it is very early in the after the trial on the mana therapy and as we said in our presley's we're beginning to see what we call had a nickel and how leukemic activity you'll remember we're very conservative and what we say in terms of what we're seeing in the the clinic oh yes if you're ask us how we do see some level of last reductions we're not gonna be you talk about how much your what we're seeing or the number of patients it's just very early that are we seeing hence of activity beginning yes it's early that we are he also asked about the rest mutations are find this one very exciting to pay the truth because
spk_2: many the other drugs out there was there was a major skate pathways for other drugs is the rest pathway of him a we've seen activity crc our ages i mean these are real responses in patients have in rask a rat and also other mutations within the raft pathway so it's a real need that after i don't think people have highlighted enough in a a male because there has been a really good drug to treat these are but i am hoping we get more these patients i'm hoping that we see activity and these patients and maybe this will be
spk_6: another indication that we can look toward as an accelerated approval but the data will have to a point is no stretch i'm on a turnover doctor they harm if he has an additional comments
spk_0: and thought it was led by i think what is exciting that the activity and reputation reputation and relax and really i mean can they get i can they do in the frontline setting even drive like kinetic lacks you can get sponsored and taste for them laughing at but i setting i went to country that with typically were expanded and red color and you agree that require that actually fit at wrigley network so the with the ability to target casey for them and reputation is offending not only get three potentially the factory places that the that he patiently hotline and prevent the development of a different bit a pathway and we're hopeful that it had benefit from and of a population and skills your point about the activity and after they say that start but if point out that patients began rolling out to be in january it takes a month before the first that
spk_3: take bonanza take place and then another month before the confirmatory that he takes place to we get the that at that point out for the earliest patients a world so loud millie say that least observed activity in terms of total blast production from looking at that early look at the diner only but loudmouth more data ran at as you get regular agora how rosemary did we answer questions i guess our thanks for coming on thank you as a reminder ladies and gentlemen that star one one to ask the question please same by for our next question
spk_13: our next question comes on the lot of gregory runs up at rbc e is alpha
spk_0: hi guys it's a nice on for greg congrats on the progress and thanks for taking my question just on paths i and considering the different ml mutations are some population studied and with the data to date and which type are you seeing the most responses and is a follow up in which subtype are you seen greater response to the forty milligrams dosing edge men versus those that require greater exposure slash higher dose for response trust and how my these findings in former yet of regulatory next step thanks so much
spk_14: i could close and but the wrap our given that know jumping on the second i can start a that and a great question i think that that is something that will gary edited ernie out remedy by few things first is facing numbers that even after being sixty playstation you don't necessarily have that many patients any particular genetic subgroup when you open it studied or
spk_4: can we don't have large nominators with which it everyday be highly accurate about a response rate but we do see activity and if patients that have these mutations that we would like advocated you get including an raf it again cp patient the to be fifty three days of the ever get any these are all patients that are predicted to not do as well because it's efforts mutations that they carry and could be subset of population great and medical need to be fair argue that you're right up a operations our population great and that medical need as many are you can't be cured financial therapy they need good way to join stem cell transplant at that point so the wanted interest i think i mentioned and refugee fifty three for three patients that exhausted for three years prior
spk_2: but the maybe others and it may become a nation immigration the matter for example and pm one answered remediation within a reasonable response we did that patient populations well and he added a study by rolling additional basins will will get a coffin if we understand what this response trying to the population he would have it out the rent or to be the final render federal we've reported that it were two responses at that at at that as a whole and very small numbers not really enough to discriminate whether he of what you have enough for some patients but not enough for others and it will have to really look at it became market to define what the optimal doses there even though we're thrilled to see activity at the fourteen identical well said top thank you mexican thank you
spk_3: please and by for our next question it alex next question comes from a lot of john newman mechanical salon is open
spk_2: i got a fixer taken a question as you move forward with the activate study
spk_15: in terms of the potential for accelerate approval do you expect that you'll be focusing on a specific mutational pipe or would you be focusing more broadly thanks
spk_6: yeah a started in doctor be hard to come in like shots coming on and so as we look at them or the pasting tree with mana therapy clearly we want to to enrich for certain these populations at once a doctor be hard mention those that had failed partly through inhibitors others have tp fifty three mutations now the retain some these data with ras will as to investing
spk_0: peters we can try to find patients more like that and hope to get enough of these patients to be able to or to go to the ft and say hey there's a real signal here would like to move forward with accelerate approval
spk_2: but i also want to emphasize the the double it is very important for us because showing the to drug works well and and is well tolerated in combination with with fanatic lax on that was gonna largest into two different pathways one is it gonna position is for the triplet and to go toward for for outline patients and that is ultimately where we want to go and we think it's are drugs gonna be the ideal drug to combine with the other hm events because of the are other reasons that the doctor be hard kick later but it also allows them to decide how to move forward in dublin so we're looking at ways to have the the then pass patients ah for a and hopefully we can design it so that we can have an early look at the data accelerated approval as we are continues to or to web ring patients on for full approval and that the and doublet drop and i'm sure doctor they are consent far more eloquently
spk_0: how would you like that job and yeah i watch added get got me though but i love a that that is it did atmospheric actually that model for like you might get the new in a second my setting same for example with at that that connecticut tablet where you have a failure powered to ventilate meet our overall survival but that include incoming incremental an interim analysis that they could abby compelling enough to seek approval said that is one option with the monitor be of course your entire raid impaired you so you we can be shooting for targets entrees that point now the thanks for gamestop to any talk about those little bit on thank you yeah any other questions john oh i know i gotta or thing thank you
spk_1: i'm currently showing no further questions and lucky
spk_0: alan now like the can call back on the productive rice for closer we much oh i wanna thank everyone for joining us this afternoon and thank you for all the up the interest in have toes the drugs and the data that we're generating or gratified it is we look in the rearview mirror of twenty twenty two and we see the clinical progress of tospend
spk_1: mm strides remaking making to do three formulation of luck
spk_0: yet our eyes now are really looking forward to twenty twenty three and beyond and we're here to eager to share data with you during the yard the coming year again we talked about being able to present data at a conference is but also as the earnings calls as well as and as up making a making meetings so we want to thank our
spk_1: clinical team our investigators are patients for their help and support work we appreciate the support of our shareholders and analyst and will afford to keep you updated on progress rest of your thank you and have a good evening
spk_16: thank you ladies and gentlemen that concludes today's coffee call you may disconnect and have a wonderful day
spk_2: the you hello and thank you for standing by a welcome for abc health file sizes reports for the fourth quarter as and year in two thousand and twenty two conference call at the site offices that sauna listen only mode after the speakers presentation there will be a question and answer session the ask the question during the session you need to press star one one on your telephone and you would be in her automated message a in your hand is raised to withdraw your questions please for a star one one again i will now like to send a cop and sober to susan petrol you may begin thank each honda good afternoon and welcome to the oppose firefighters cop with quoted got financial an operational results for year and and fourth quarter ended december thirty first two thousand twenty two earlier today up to issued a press release relating to the yes result the news release as well as related se si filings accessible on up to the website joining the unsullied call on wmg right chairman president and ceo not the roughly albay har senior vice president chief medical officer and mr fletcher pain senior vice president and chief financial officer before we proceed i would like to remind everyone that certain things made during the call will include forward looking statements within the meaning of us and canadian security blood forward looking statements reflect after the current situation regarding future events you're not guaranteed to reform and and it is possible their actual results in performance to differ materially from the seeded exploitation they involve known and unknown risks uncertainties in assumption that may cause actual results performance improvements to differ materially from those expressed to learn more about these risks and uncertainties please read the risk factors set forth in athens his most recent and the report on forms and k and as the cnc to filing or forward looking statements a during for speak only as as a date or me after them to take no obligation to revise or update the statements to reflect events or circumstances after the date of this call except as required by law i will now turn the call over up the rice trim and president and ceo of after firefighters doctor right like i want to walk in there want to our call for the your hand and fourth quarter ended december thirty first twenty twenty two for shall provide a very quick overview twenty twenty two that about at market has been extraordinarily challenging oppose continued steady march forward with stated our cash way runway to the end of que one twenty twenty fourth we continued building a talented and experience came we created and began testing a new formulation for looks happen if and most importantly we made significant strides and the development of hospital for the treatment of the khumalo leukemia or he a male when it comes to test putnam or tough as we call it i want to empathize attali differentiated profile having demonstrated the potency to achieve complete remission and very ill relapse refractory a male patients while also being safe and well tolerated it's extraordinary for an anti leukemic aged to deliver family my responses and such an aggressive cancer without causing the typical toxicities histories of other reasons and today we will impact both the potency and take the attributes of course it's also important to highlight the a a male population that has been treated with suspicion up to date and are phase one to dose escalation and those exploration trial these typically third line fourth line liner beyond on having failed the best available approved therapies and in many cases having failed various investigation or drugs or prior metabolic stem cell transplant these are incredibly difficult patience to treat and to reverse the disease progression i'll make these patients even more difficult to treat is extreme diversity of holly adverse genetic an effort to have a genetic alterations expressed by their disease if we recall the admiral trawl from just five years ago during which the commercial dose of guilt written in a flood three inhibitor was tested for responses the email the patients were second like of eventually had not seen other through inhibitors and had not seen panetta clocks in contrast patients entering our troll are far more treatment experienced with half belling private network lacks sixty percent felling prior treatment with have a met letting agents or a jamais more than a quarter having failed transplants and half of the flip three newton patients having failed prior therapy with a flipper inhibitor nevertheless tested delivered responses with convenient once daily or those sing of tablets across for does levels one hundred sixty milligrams one hundred and twenty milligrams eighty milligram and forty milligrams and no deal keys were observed with any of those acted those levels from me the taste and from a mutation sensitivity perspective has he shown an unprecedented breadth of activity has delivers responses and flip three wild type patients as well as it doesn't play three mutated patients we also seen responses in a male patients having a very difficult to treat tpp three mutations as well as patients with in pm one and flip three commutation and patients having alterations in the the an empty three a ranks one or the ace one splicing factors a ethics how one hand mll geez the one of the most interesting observations the the activity and relax to factory a male patients with ras mutations mutations in the raf pathway serving an escape mechanism to generate resistance to many other drugs however we've measured a forty two percent overall response rate in patients with ras mutations including a twenty nine percent c r crc r h response three in fact one patient had arrest mutation and a mutation and ptp and eleven representing a dual mutation and the rest pathway will continue to monitor the response rate and rashmi headed a male patients this year and determine if ras mutated relapse your factory am ill patients may represent a popular ocean upon my need for future accelerate approval trials a doctor bay harbor describe and further detail in a few minutes we wrapped up are highly successful phase one to those escalation and those exploration trump we treated over sixty patients to date in that trial we've assembled a strong safety data package we collected safe and effective doses for a single agent and drug combination trials we demonstrated the ability of pass to dramatically reduce bone marrow plat blast and a high fraction of patients and to achieve formal responses and we initiated are activate dose expansion study of task in a single agent and in combination with fanatic lax and the activate trial this year we will enrich certain patient populations to receive mana therapy so that we can collect data to got our conversations with the ft a to request an accelerated approval path for tough in patients of hi my name in parallel with the activate mana therapy dosing will treat a broad array of a male patients with a combination of toss plus phonetic lacks referred to as he has been doublet this has been doubling is being done it to support doublet combination registration trials and second line am ill patients and to serve as a bridge to a pilot study of cause has the has a have a metal letting agent or the post den h i'm a triplet in front frontline a male patients i'll test clearly can deliver responses as a single agent the ultimate goal and commercial success of tell us or any drug free email will be in combination with other drugs this week we have gun enrollment of a male patients on the test been doublet and we will place for additional patients on this doublet throughout twenty twenty three once we can experience with the dublin we plan to initiate the test then hm a triplet and frontline patients the future of a ml therapy but also revolve around cocktails of drugs and already aligned to therapy to take patients into deep permissions such a male cocktails will require the blending of drugs the best conserve broad populations of patients can deliver the permissions and can be tolerated without cardio talks yes these unnecessarily prologue malice oppression and other complicating side effects and that's precisely describes tough tough his position to become the ideal partner for addition to the men eight you made doublet because of it's convenient as a once daily or agent it's broad activity and safety profile together data to date point tough toward application as a mana therapy for accelerated approval in relapsed refractor email as doublet therapy for accelerate approval and second line email for use and triplett combination and front on patients as well as you use in maintenance therapy and doctor may har will provide you with additional color of these activities momentarily now let me turn briefly to look set to them many of you know what as cg eight or six lux as we typically referred to it is our second a pipeline program lux is a clinical state small molecule oral flit three and be ek counties inhibitor luck his ability to target carnitas operative and certain leukemia and lymphoma as let us to develop it impatience with be sell leukemias and bombers and in patients with a male we already have for reported that lux at menace stirred as our initial first generation or g one formulation deliver to see our and an a a male patient and cr in a deal be sealed and former patient demonstrating lux is a clinically agent you also are aware that we developed a new formulation of locks and we call it the g three formulation because it represents the third generation formulation
spk_3: and single dose administration's during twenty twenty two and a ml and be some a legacy patients will determine the g three formulation achieved up to eighteen full great absorption than the original g one formulation because the highest dose of the original formulation was that at nine hundred milligrams we initiated continuous dosing of g three at an eighteen fold lower dose level of fifty milligrams we continue to collect pk and safety data would g three and a male patients and the preliminary results suggest continuous dosing a fifty milligrams g three dozen they deliver roughly equivalent plasma exposures at nine hundred milligrams of the original t one formulation that was the target we hope to g achieve with a pity milligrams of g three and next with plane to administer a higher dosage jittery to determine if it can he can achieve even greater play
spk_17: as an exposure levels will keep you posted on our findings and like aware of will report preliminary data around he op
spk_3: i also want to mention that at posts and collaborators as the doctor month you son of while and doctor steven how just published an article entitled looks at the nypd interferes with liam mediated activation sick and modulator vcr signaling in the bomber and the online journal plos one in which we describe the ability of luck tacked on the be cell receptor pathway at the level of the l c k and l y an early and kind maxes and to influence downstream pdk activity this relates the role of lux tacked on be so cancers as well as inflammatory and out immunity processes so please take a look at him at the article to get a chance finally we often get asked about potential partnerships for test that nip in january during jp morgan week we engage him productive discussions the several big pharma biotech companies that further help to define our priorities and to solidify our clinical plans with us patent it clear what we need to accomplish with the drug that has such an extensive commercial opportunity we were pleased to see that were on the radar these companies and interest in our program is growing the treatment back paradigm for a a male is shifting toward tablet and triplet therapy and despite some successes the current combination therapies are somewhat limited by toxicities as i mentioned previously the proven breadth of activity and superior safety profile of to spend them lends itself to combination therapy potentially as the drug of choice addressing the most sizable markets and am ill and clearly making cars and gives me a perspective big pharma drug the data we generated to date of the silly a clinical and commercial plans for test bed them and multiple lines of therapy including a use in dublin and triplet combinations and as maintenance therapy our chief medical officer doctoroff albay heart will speak about our recently initiated activate clinical trial of has pet nip and a email as a single agent and in combination with veneta plaques as well as our extended clinical plants which include triplet combination therapy he also be available for questions afterwards i now will turn it over to our resident care well our chief medical officer doctoroff albay hard to talk more about our to spend their clinical plant raf they spell in january we were thrilled to kick out the hiding twenty milligrams a thing at at that live in the minor therapy i am at the activate phase one to trial had like of you know we have successfully completed the escalation and does exploration stated that i cut statement you try to approximately sixty we have to try to end patients were heavily exposed to manipulate it in fact a doctor right mention ali we're wrapping up the the expiration part of the study it at the prince get the putting additional patients on the lowest forty milligrams treatment group because of the ft a product up an advantage i it goes exploration during early did out at about how products if experience gave it the additional data needed support our monetary debt collection and a lot more added safety concern rather as hired as a the defendant had shown an apprentice facebook that since the last the forty no gun by the late last year we have achieved to pinnacle responded in that low dose group both anna patients with only dated for three including a nice recent powering accounting pp fifty three mutation what are the most highly adverse fanatic it again importantly this is the second to be fitted with patient that it achieve the critical response the first with the eighty milligram doubt who achieve an unqualified the are at their best response have a to enroll more the stations with had a poor finances have a great unmet need and the after the trial the activate expansion trial is the dining and for monetary activity the patient enrichment a specific education to find a now population including that if if if you need patient as well as split three mutated patients with it failed that privately inhibitors as supported by an f the a fast track designation and a clinically significant response rate today he faced continued am great i let medical need and they believe that the ability to rescue the station and perhaps allowed into if it and for transplant now don't have a faces ecstatic when allows the quick that registration in addition to being potential accelerated approval pathogen to threatening tweeting disagrees with provide critical data to a former contained and path i am police say that we have begun treating patients in the monitor the i'm at the after the trial in a growing network of crackle all investigators are engaged in a moment and that this has been right breast and the activated commands and round to set an author will be kept in combination with inadequate have a fake that right or clearance and both trenton hand allowing a it is your moment on the test than companies and earlier this week having the cat and combination aren't open is an important events and this represents an attractive treatment option for patients and extradition didn't and general earlier in the course of treatment increasing the likelihood of achieving a minute meaningful clinical benefit so what is our timeline for a clinical trials
spk_4: because after they didn't open label trial over point data when available at appropriate for it you will have and up right yeah change in or them as we usually do that because data collection verification does take time and activated didn't get up and were shot while this will be an incremental updates you would expect at more complete data that ugly for the monetary the on at the european toward hematology meeting your fate at the end of october industrial portugal expect more data including from the and combination or two then be updated ash in san diego and teller fell twenty twenty three will be a big year for us having get the defendant in specific genetically define population he would expect exhibition patient data this year than say wait a few industries have any for supporting salary the poodle a doctor i mentioned the including real or regard for in patients with or leave it if with three or we often called while population that other adverse mediation exploring
spk_3: fifi inactivity and patient with the phantom treatment both a single agent any combination with inadequate
spk_4: identify nineveh like kennedy and other adverse average could lead to other options retaliate group the paradigm for the treatment of and l increasingly moving toward combination therapy we have addition to fed and had a her aged for domination and you an earlier lines of treatment
spk_18: it it our hope and based on data thus far dark occasion that we will move forward defendant in a triplet combination animated thanks
spk_4: dr novel diversion md anderson has been one of the investigative pioneering a combination therapy for an likes it or leave the theater and out today and an eager as we are to see what authentic and do in a setting also highlighted a few comments from doctor harry about the can trying to do during a recent k well of it he noted that this drug may be better suited for the combination of you have to development anything we have right now the excited about the current like of mouse depression noted near killed that to date
spk_3: as and he emphasized that a drug like cause we have a position mostly because it is that it few people found that are treating outcomes about the question
spk_4: really he agree wholeheartedly the doctor or that we bleed the potency bread and every weekend activity along the safety profile make better the ideal transfer combination therapy and scale the commercialization what our website you can see are projected timeline for ongoing plan clinical trials and what think clinical paying for their hard work execution getting both arms about to be declared that he other running he firmly look forward to sharing the with you now i like to turn the called over to our cfl fletcher paying for an update on our financial debt pleasure
spk_2: thanks wrath and good afternoon on before we search speaking but financials or the interviews to you the newest member of our finance king brooks and son who's a vp and controller about baptist mr ensign has more than twenty years from school and experience in accounting finance corporate development he served a disposition for
spk_6: multiple public and private companies the shenton has a masters and holds an m b a from harvard business school and a masters in accountancy were pleased to be able to recruit call people like him and we're very happy to have here actors let's review the fourth quarter and you're in financials as most of you know from fine actors with
spk_0: ticket disciplined approach to cash management and always that the prioritize are quite a clinical activities without sacrificing quality of our programs these efforts of extended a cash were way into two thousand twenty four and a cash management policies and actions taken a helpless avoid the financial impact of silicon valley banks fallout now let's review our cash position we ended two thousand twenty two with approximately forty seven million dollars cash cash equivalents and investment a decrease of four point eight million dollars as compared to the previous quarter during the quarter the net loss was a proxy ten million dollars translating into a price mean negative eleven cents per share loss down from twenty four point three million dollar loss from the comparable period in two thousand and twenty one
spk_19: as a delphi an income statement we had no revenues during the fourth quarter of two thousand twenty two
spk_3: richardson development expenses for six point eight million dollars for the quarter down twenty point two million dollars in the same quarter and twenty twenty one research and development expenses for the full year period ended december thirty first twenty twenty one twenty eight point one million dollars as compared to forty six million dollars for the come perry periods
spk_2: a decrease of eighteen million dollars that decreases due to several factors including a twelve million dollar licensing pay a fee paid to harm me for the privy to the previous year the choir global development rights for to set the net which comprise a five million dollars cash payment and seven billion dollars with common shares additionally there were lower costs for lunch program and to five three program as well as well personnel costs
spk_3: these savings were potentially offset by costs for the to sept in a program that was adopted it doesn't twenty gina expenses or three point six million dollars for the quarter of compared to four point one million dollars for the same quarter of two thousand twenty one june expects this for the twelve month period ended december thirty first two doesn't way to a fourteen point five million dollars as compared with nineteen point five million dollars for the compare to period a decrease of approximately five million the decreases primary do a decrease in stock based compensation expenses offset by higher compensation expenses travel expenses and professional fees as of march twenty three two thousand twenty three actors has ninety three million five thousand two hundred seventy eight common shares outstanding more detailed information click on my filings on agora consider else from he got back that lies thank you flatter as well my call for questions please feel free to pose a question to any of us operate if you could please introduce the first question
spk_5: thank you
spk_6: at this time i like to my everyone how to ask the question to ask the question please press start one one or your telephone
spk_0: and they await for your name to be allowed to withdraw your question please press star one one again please bobby two thousand ah q and a roster
spk_7: our first question comes from a lot of matthew beat with oppenheimer yaalon is often oh hey guys thanks they update on a cure for me i'm i'm wondering if it you can a guide on patient numbers for that october update on yet from the up in a trial and then i'm just curious about them in the comments rap made about the dublin or says the singlet to that levin up after a i'm just i'm curious if you're if you're concerned that it might be challenging you enroll and mana therapy arm given that there is a double at our have how are you approaching that are harry sitting out
spk_2: i have weeding out from one to the other day no thanks matt this is bill i'll i'll start on that though they are from that their second question is really easy doublet vs monetary we've had exceptional uptake her wrap it up take and how i think the at the word that are thought to be argued was risk uptake of the mana therapy we got it up and running first this year has been great
spk_3: enrollment pace and we're just now beginning to enroll the doublet in terms of the yard the numbers of patients and are gonna turn it back over to doctor bay heart will be careful not to really bracket them too much or try to give yourself raf the at that like that and adjutant taliban until you're really a point about that and raleigh to both of the the government to give any more appealing investigators in the monetary be in general that once both arms are open and those options exist will be a random assignment so we are hoping it not only did to get more patient earlier more do the at the study but the patient match come on earlier in the course of therapy because the rate the sub accommodation options available to them so we'll focus on both through the end of the year and will give you more clarity on the get to that point in terms of numbers of patient add it up like i said it's hard to put it exact number on it but with a roman has a very good and on there certainly will be out
spk_7: from me you know regulating that maybe ten the patient than the my therapy arm and hope for and somewhere between again in twenty patients on that on the debate on but finally we are near the end of year right right thanks
spk_3: thank you please stand thereby for on a question
spk_2: select question comes from a lot of sumit boy with george jones trading the line is okay have you wanna thank you for the up a damn good you give us a little bit more color on the defend to school hot five years
spk_8: enrolling currently between forty eight hundred twenty
spk_6: and then the hundred fish any mention of what fleet is monique happy and tablet
spk_0: god has committed to the right so yeah we have completed the yeah the dose escalation in dealt exploration trial to her nurse or doctor but i'll talk to be hard to give you a break down on their the numbers of patients there and then he can talk about the have to be
spk_9: right
spk_20: feel as if the ash meeting when we had not yet opened up to date we had i treated sixty patients between the dope escalation and will be called the dose exploration we have treated additional patients in the of exploration arm i primarily the forty milligrams of several the further characterized by better or for up to date with opened where we
spk_9: where then the thing at least ideally exclusively an activated that he became a lightweight would do that at the jokes about that we started after they eat at that amount of their be with hundred twenty milligrams
spk_2: get her that may change it as we learn more about it the decay and and the at a activity of a drug and on the name of to eating have an answer the monetary biggest thing at the level of activity alerts for the we have implemented for the combination study eighty milligrams i will be the and be starting go so we figured for in college with the suspect with that been adequate and as always that it off with a change big muddy that we receive my arm so how are you thinking of presenting the data may media our lives second half also even going to have
spk_3: love with some the activate trial like the traditional know why our response rate rcr rate
spk_2: over number of patients treated and alongside even to show how long term if any durably to data from down and of escalation expansion know part of the trial
spk_9: traditionally we have done that kind of more complete update at a major medical meetings like ha and ash and i get that well that may hold true for ash i do think the a table be a more incremental updates as a their it may not be that much level a detailed because the the if be cut off date for gated with an idiot jade about now so we don't necessarily have a lot more to say that we had said earlier this year ago so we will do an incremental updates on the for the highlight of at any activity or issues that arise is betty ready ha that expected larger data packet with another more detail he is described at a later in the here
spk_2: perfect i got so much you to that that we will have certain scientific findings had a half or that will be presenting that's the plan as well as some of the or the additional data as you said as we followed some of these patients that have been on the of escalation those exploration of able to provide that but then a doctor they are said you know it's we just started the after the trial
spk_3: that will present the david that are available it won't be at a huge number of patients by that time and by will present while cap again congratulations on the progress and cushman thank you please stay by for next question
spk_2: next question comes on land yell and enough with a see why why a of it the guys who up near they've taken the question so a bill was wondering maybe if you could do a little benchmark for the audience about your regulatory plan for the model arm and activates be talked about you know since it's motto your potential accelerated approval self you know based on your internal flawed regulatory
spk_6: consultants or what have you can you benchmark how many patients do you think you'll need for the f a to be happy with and more importantly can you benchmark a
spk_0: essentially response rate or cr rate to beat oh boy number of questions there are so first of all i'm not going to go too much on a limb because soon we are going to be having the into the f t a and we've free for the articulated that to the street ah so will be speaking with all the parameters you you just mentioned for the mana therapy as well as the yeah the dublin that
spk_10: are coming out we want to make sure that as we go to the ft a by then we will have a number of patients that are already on the mana therapy that after the trial make sure that we're doing everything that we should ah determine if there are additional premieres we need to measure so that when we go to them with the data later in the year or will have everything that we need and hopefully the day will be supportive of of going toward a and accelerate approval whether that's a mana therapy a tablet you know we'll we'll see how those data emerged toward the end of the year an raf is or anything else you wanted to add to that terms of a toy
spk_2: and like a deathbed death a good way to put it i think that we do need to have any new ft eight really align yourself and depending on what because we agree upon that that change changes over the study but certainly in hurry to give us that he would be a much smaller study than he would have to do he did a a randomized smoke out that and then also little bit later and years we collect data on the the doublet we want to be able to go to the ft a present the data there and hopefully i have the ability to move into the triplet trough that is your questions you know it i guess maybe just fell little on the you know for for the listeners and every one and investors in general you know benchmarking you would look at from and advocacy standpoint hell and recipe yeah so wrapped you want to the net income tax relate relative to the had no problem and don't think solution yeah get better get that we to view it as in a white population are we treating and what advocation my they had from alternative to that it wasn't available and remember the her patients who if they are flipping mutated in i think that do inhibitor be likely been through at least to light the fire therapy for the coming to a third line of the ad in a second line setting with the address daddy at the early in the interim analysis for gets written and d c r c r h wait like twenty one percent and later that matured especially with the inclusion of patience is desperate response is measured after transplant but at the point of the in terminology that led to the pool of the drug i was twenty one percent and second line patients largely naive about it arabic
spk_21: so we would argue that a meaningful number in the third line setting would be significantly less than that and perhaps yeah well as have battery or somewhere between have to two that range given that the alternator the station to that point on i've even less effective than they might have been affected by setting that the word ammo study with chemotherapy response rate for cr but that eleven percent
spk_10: felt that the ballpark that were working with and what we can down with the of the i think well well then shape their the scope of the study the side the telling in an effort is getting that
spk_2: right yeah i think a benefit yeah but the bars is fairly low for that piece population as he said that the many of them will have already failed other flip three inhibitors veneta clarkson and more and more patients that are coming along now in the us are are having a are much more experience with prior drug therapy and so these patients are
spk_6: very difficult to treat so we think the bar will not be exceptionally high or but we also believe we can achieve
spk_0: i thank you very much pressure to coming up thank you
spk_11: please them by for our next question
spk_12: alex question comes on the lot of public ten off with five with sailor a lot of help it hey thank you very much i like the graph below poverty can be like putting yeah i'm i think list of questions on to they are putting on last but i wanted i can lock sort of higher level how that fits into ah on that freedom tower or how the streets hunting
spk_2: your development plan and specifically you know what alexa people feel like they were considered partnering i'm gonna it ultimately have combinability navy the with five and i'll take so much thanks for and ten for the questions yeah we don't get that many questions on luck anymore a but we're still will ensure still excited by the drug another we have our new formulation and species we got to that next to a higher dose level that that's the plan now and we hope we get term hearts posers we go into debt and in terms of what we like to do with this molecule me first of all i must say that perspective is our top priority among have among everything and it has to be because it is delivering it's more advanced it's slippery but has better but lox ah as we move forward would love to see if that were getting exposure that we want and that the that the the hill burden is also much less cost of goods much less if we continue to see activity in a ml are we have done studies where we put the person and not much together and they are not mpeg in a stick they also we know have different activities against different kind says so it may turn out to be like some of the other
spk_3: indications we have multiple kind a says that he had different patients with different ah different mutation profiles the most likely have waited we likely will move it more toward the up toward the be sell arena and yeah and also toward inflammation and auto merely because we've been as you can tell from the publications with be digging into that area understanding it they're still in need because this drug is different from the a other non kobe became hipsters it has a different set of kind a says it has different activities and we believe that if we're able to combine in francis with with the as with some these other drugs that are being developed for the be sell malignancies i like the network like france and stand now we believe we can see real activity there so there are for it that do not interfere with tospend
spk_2: that all get your question
spk_13: yes does very helpful thank you yeah
spk_6: aren't thank you
spk_0: thank you lisa a i for our next question the next question comes from a lovely watch that a cat of external on is open
spk_3: everyone version for the thanks for taking my questions just a couple here and personally i ever forgive some color around early activity eating even mana therapy i'm and after me and then and the rat pathway can you talk a bit more about wait can go at this guy named a wrath correlates with and the other mutations potentially on whether you see nano and kind of therapy potential here cause i'll thank her thanks rosemary for coming on us all star with isn't the me and maybe that's a hard one to jump in terms of early activity again it is very early in the after the trial on the mana therapy and as we sit in our presley's least we're beginning to see what we call had an initial and how leukemic activity you'll remember we're very conservative and what we say in terms of what we're seeing in the the clinic oh yes if you're ask us how we do see some level of last reductions we're not gonna be talking about how much your what we're seeing our the number of patients it's just very early that are we seeing hence of activity beginning yes it's early that we are he also asked about the rest mutations are find this one very exciting to tell you the truth because many the other drugs out there was there was a major skate pathways for other drugs is the rest pathway of him but we've seen activity crc our ages i mean these are real responses in patients have in rask a rest
spk_13: and also other mutations within the raft pathway so it's a real need that after i don't think people have highlighted enough in a a male because there has been a really good drug to treat these are but i am hoping we get more these patients i'm hoping that we see activity and these patients and maybe this will be another indication that we can look toward
spk_0: as an accelerated approval but the data will have to a point is no stretch i'm on a turnover doctor they harm if he has an additional comments and thought it was led by i think what is exciting that the activity and reputation it's reputation and real effort and really i mean can they get i can they do in the frontline setting even drive a kinetic lacks you can get sponsored can taste for them laughing at but i think i went to country that with typically an expanded and red color a new address cloud of that require that actually fit
spk_14: giggling network
spk_4: so the the ability to target casey could have and reputation is the not only did repercussions factory patient rapidly three patients the frontline and prevent the development of addition to the pathway that will help on that it had benefit from and go fish population and guilty of pointed out the activity in the after it failed star i did point out that patients began rolling and have to be a junior very it takes a month before the first it hasn't picked been there are certain takes place and then another month before the confirmatory that he takes place to were just about at that point now for the earliest patients and world so old millie say the least observed activity in terms of total blast productions and looking at that early look at the diner only but will have more data around at at get regular
spk_2: agora how rosemary did we answer questions i guess our thanks for coming off thank you as a reminder ladies and gentleman that star one one to ask the question please stand by for our next question
spk_3: our next question comes on the lawn of gregory runs up with rb c e on is sofa hi guys it's a nice on for greg congrats on the progress and thanks for taking my question just on paths are in considering the different ml mutations are so population studied and with the data to date and which type are you seeing the most responses and is a follow up in which subtype are you seen greater response
spk_2: the forty milligrams dosing edge men versus those that require greater exposure slash higher dose for responsive cats and how my these findings in radiant regulatory next up thanks so much i could close and but rap out you that know jumping on a second i could start a that and a great question i think that it it were very interested earning a rare limited by few things that first is patient numbers that even after being sixty playstation you don't necessarily have that many patient any particular genetic group when you open a studied or
spk_15: commit to we don't have large denominators with with their the be highly accurate about a response rate but we do see activity and patients they have these mutations that we would like advocated you get including an raf it again cp basically to be fifty three days of the ever get any these are all patients that are predicted to not do as well because he's ever seen cases they carry
spk_6: it could be a population great and medical need to be fair argue that iraqi him a patient operations our population great and that medical need as many are you can't be cured financial fair ability to go with join them for tramp at that point
spk_0: so the wanted interesting i think i mentioned and refugee fifty three for three patients that exhausted for three headers prior but the maybe others and in a become a nation imitating the matter for level and pm one answered remediation within a reasonable response we did that patient populations well and he added a study by rolling additional basis for really good at the confidence that we understand what this was pottery trying to population
spk_2: he would have without direct or to the the forty milligrams federal we've reported that that were two responses at that at that goes double for get very small numbers not really enough to discriminate whether he of what you have enough for some patients but not enough for others and it will have to really look at it became orchid to define what the optimal doses there even though we're thrilled to see activity at the forty and well said to thank you mexican
spk_0: thank you
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