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spk_0: hello everyone my name is chris not be a conference operator today at the standardized welcome everyone to accent she has business of day calls for the full year and a twenty twenty two all lines have been placed on mute to prevent any background noise after the speakers emerged there will be a question and answer session if you'd like to ask a question during the stance of the press star than the number one on your telephone keypad to withdraw your question please red star one again at the sounded like to introduce sarah sherman vice president investor relations sarah you may begin
spk_1: thank you operator a press release and i twenty ap wire issue this morning with our full year twenty twenty two financial results and business update these documents can be found on our website at www that investors that accent she had that i along with a presentation for today's my cast before we began i'd like to remind you that we may make forward looking statements on our car the blanket statements about are projected growth revenue business models preclinical and clinical results and business it actual results may differ materially from those indicated by the statement unless required by law accent she had is not undertake any obligation to update the statements regarding the future or chicken family statements in relation to actual results on today's call and joined by andrew hopkins chief executive officer and ben taylor cfl and she's strategy officer they palette chief scientific officer gary parody chief technology officer and my clam cheap quantitative medicine officer will also be available for the q and a session and with that i will now chemical over tandja
spk_2: thank you sarah
spk_3: twenty twenty two was another a transformational you have accent yeah we continue to validate so a driven precision medicine platform and strengthen our business accent his goal is to fundamentally transform the way our industry designs and develops drugs we believe our unique peridot excellent science with advanced computational experimental capabilities at every step of the already process differentiates outpatient first preseason midst approach our approach of modern driven adaptive burn and as an overarching technological principal enables us to innovate from discovery and into development to that end over market will progress to date is a testament centro company we are well capitalized with six hundred and eleven million dollars in cash at the end of year this provides us with several years runaway to advance only a tomb programs deeper know pipeline was also invest in a long term growth to that end we marked several significant milestone for out for you cross our internal and partner programs which we will provide more insight on today we will also highlight data with illustrates how we work and design and better drugs white patient by combining precision engineering with personalized medicine at a high level last he was significant for trajectory of a business with started you like sign in the collaboration with sanaa fifa fifteen targets and ended the year showcase in the value of a multi modal gene signature data for me or college he patient selection of isn't a while importantly with advanced or pipeline we highlight five comes across oncology and immunology an inflammation i been clinical stage or a in the enable and studies we have presented important data from out design and translational platforms across these programs are we are pleased we can now his targets and how the combined precision design the first lies medicine bow a to a candidate he accessed twenty one five or six or five or six last year with appointed top line healthy volunteer day to in june data confirmed a target propofol design including potency hi receptor cell activity unexpected low drain exposure with no cns adverse events reported this data provided support to move into a patient trial late last year we also the ccp a approval to initiate out phase one to try big night trial will examine the safety bomb cooks antics on could dynamics and efficacy of five or six when used in combination with anti pt one therapy envelops to factory renal cell carcinoma unknown small cell lung cancer during a trial we will be observation the validation of patients sex and biomarker aimed at in which and more likely to respond to five or six discovered preclinical the trial will go up to one hundred and ten patients and we continue to expect the first patient be dose in the first half of this year a vital component about a to a program is a bust biomarkers strategy as we believe the key to a successful a to a inhibitor is in which in from a white patients with high adenosine in the tumor microenvironment we presented relevant data at a small and medium quality annual congress in december identifying and novel patient selection multi team transcript signature the adenosine good in school or abs the biomarkers discovered preclinical use now patient issue platform and multi oh makes dataset integration from complex disease relevant model systems peek my trial will evaluate is jean signature to identify patients most likely to respond to five or six we look forward to present an additional tatum biological validation of the abs and of five or six wrote them at the upcoming a cr me to and next month in a lambda without cdc seven inhibitor g t h e access six one seven developed in partnership with gts perry on we remain on track to involve a first patient in our plan phase when to study in the first half as yeah this program also showcase what truly makes an he drug unique position design aiming to transform patient benefit and patients selection strategies we highlighted some his patients election data at the una congress in october to maximize understand some of the effect of six one seven using primary patient material for the first time we showed how we integrate machine learning data from primary human to miss samples and most you'll make sequencing capabilities to predict to my efficacy of six one seven using a deeper in in a ai and high content image of platform we've previously confirmed six one seven activity and primary humour samples data presented at a our lead us to generally defined two groups of patients are bulls effectively high and low responder groups when focusing on a burying council we believe that leverage in this information will enable us to dent five responders a and spawn ponders to six from seven a costume and types this is a key component or how we designed to face when to study we look forward to show more detail on the tumor types will investigate and shortly with both oh siddiqi seven and a to a programs we can now begin to see a hallmark of what an accent he a drug looks like a i you machine on is applied not just in the process of how we designed a drug but also how we didn't fiber white patients four hundred excelsior invented for first a i designed drug to ever and to the clinic since then we have made significant advancements now technology and they i capabilities we have developed a comprehensive physics based platform incomes in molecular dynamics and quantum mechanics which is combined with a ai generative an active learning capabilities we've also significantly progress or engineer and and data platforms enabling scale ability and robustness as you may seem or the past several weeks we've highlighted three new targets for the progress in the access for free when eight a clinical stage pjc cpt the compound bow was in licensed by bms he access seven four five pre nine our lsd one inhibitor and excess seven free five six five or more walt one protease inhibitor these embody what accent you can do in terms of a i generate a molecular design where we truly lead field these molecules are great examples of how of drug hunters use now a i consult complex problems such as kind cell activity in the case of ptc peter brain penetration couple who have a disability in the case of lsd one and alice eric inhibition in the gets a multi one allow spend a few minutes on each important programs throw new how we designed these compounds and what we have seen to date in federal of you monsieur bristol myers squibb initiate to the first and humor study of excess for free one eight a potential first in class selective pk sci fi to inhibitor be a mess will oversee clinical and commercial development and accent year is eligible for most on payments on if approved tiered royalties on the net products sales pcp the is an attractive a mean moderate and target was plays a critical role in the control of t cell function and the key drive of several highly common autoimmune diseases but as prove challenging to dose the target put a i was particular challenge and due to the need to balance stain high levels of target inhibition to drive efficacy with no daily dose and in humans pk cp to structurally similar to several the lady is makes it difficult to achieve a high loves the cell activity required to avoid off target effects our team of experts leverage you know a i design platform delivered a balance candidate with potent on target activity while maintaining high security and a favorable favorite index as demonstrated in the eye able to studies as you can see here previous molecules a failed of a challenge to design a candidate with quite potency as well as cell activity against of a close you later kindnesses we believe a well balanced molecule meets require properties to potentially provide benefit impatience this molecule oh supposed immunology and inflammation candidate to enter into clinic this is a significant milestone illustrated accent you strength efficiency and flexibility to precision design high quality outwitted candidates last week we should an update on our next generation lsd one and mode when inhibitors i'll highlight a few details but encourage everyone to visit our website and what's the video which detailed these candidates for it by pre nine is a differentiate lysine the mcaleese one or lsd one inhibitor precision designed to improve patient benefit and so challenging designed objectives a promise promises strong potential in both hematology and oncology to date of lsd one inhibitors in development elsewhere have fail so cheap a combination of appropriate pharmacokinetics good brain penetrance and the versatile mechanism of action our candidate has been designed to cheat suitable cns penetration to target blame it us to these common in certain cancer sub types in vivo studies have shown favorable activity also in small cell lung cancer seen got models with dose dependent inhibition of tumor growth in vivo studies have also shown a favorable of 's option distribution metabolism and excretion for file with shorter predicted human half life and some lsd one inhibitors currently in clinical trials we believe this may benefit on target talks management alone for platelets to recover following dose in given of abusable nature or five free night we believe exquisite control of lsd one inhibition and we superior management a platelets will be a critical differentiator for five free nine in the clinic particularly in combination with the standard of care that often has negative effects on platelets the flexibility to genuinely explore intimate and dose in regiments in the clinic and best maximise for therapeutic window is never reason we believe that five free nine is differentiated from other compounds in development here you can see the properties of five not against to other lsd one candidate specifically looking at factors such as cns penetration mechanism of action and predicted as an the case of five we nine or published clinical dose in regiments as you can see only five free nine that she's a unique combination of of a possible mechanism suitable cns penetration to target bring much as disease and predicted human half life aligned with once daily dose and our molecule also met a long list of our criteria such a cell activity against related enzymes hi bioavailability in preclinical species and in the west coast the in velvet models or se lc a potential indication with by free nine may have benefit importantly we were able to use a i find this highly different molecule of a specific target a poor file ultimately explore the new chemical space using afridi map in algorithms we didn't to fight target double features of each region of a protein we then used our free degenerative a i design outcomes to but he's privatized populations of molecules weekend specific optimization criteria machine in a models efficiently scored the compounds the seen as conference alongside optimize in multiple promises includes important see and out be properties by then apply an active learning methods we were able to select the most information which molecules to make and tested each design cycle usually around ten to twenty compounds this allowed us to find novel molecules outside established i'm a new applicability that would come to intuitive which enabled us to finding new starting point for design and cover envy chemo type ultimately led to five free night the result was that we were able to create molecules which achieved a target protocol fall but no compared to the morgue you have exhibited we believe five pre nine has the potential to become the first potent selective reversible am bring penetrance lsd one who better to meet significant unmet need in a range of oncological and he but logical indications look forward to highlight an obsession design of his compound as well as late latest bieber data at the ac our next month on the highlight another candidate would we say a availed almost one inhibitor he access same free five six five or five six five most one or the koza associated lymphoid tissue lymphoma translocation protein one is important proteus target with potential applications in hematology it aims to inhibit be uncontrolled perforation of malignant t and be cells in him it's logical cancers accent he has a i driven precision design approach was able to optimize the safety profile of agents targeted not one was also generate and potency and sensitivity when considering an optimal target put a porthole a team took into account the likely use of a moat one inhibitor in combination fat be such as became hipsters therefore in addition to potency cell activity in a bouncer to of properties we were mindful of potential drug drug interactions it leads to charge you you can see that in vivo studies of five six five have shown anti to activity in most models and favorable farm that both as mollify happy and in combination with a be it a toxicology studies have also shown an acceptable fabric index will the ability to maintain high levels of potency cell activity and safety benchmarks what's the boyden meaningful inhibition of huge eg one a one which can lead to excessive levels of below rubin and the know cause of drug drug interactions this shot you can pay five six five directly with published and patented molten scuffles from various groups five six five compares baby favorably posts all promises examining potency cellular activity android drug like properties five six five has very little activity at u yuji t one a one and is highly differentiated in this respect we would predict that many we have a compounds will likely inhibit huge t when they won to a meaningful degree and best present challenges in clinical development it's important to note in designing this compound it was the first time but we merged molecular dynamics with a i addicts yeah molecular dynamics of physics based method is just one of the tools that we have no text back today if a molecular dynamics simulations provided additional insight into critical bind and interactions within the alastair excite using a hotspot analyses allowed us to understand the alastair binding pocket highlighting key interactions need to for design molecular dynamics when enable us to understand my dynamic motion of abundant pocket and developer design strategy to improve the potency and water properties of compounds using data and knowledge of of alastair at most one inhibitors i'll generative design algorithm gambit was used to evolve novel molecules this resulted in a sweet of promising combat we believe at five six five can be developed to meet a significant medical need but exist today for potent i'm selective moat one proteus inhibition with potential for a meaningful safety differentiation in summary these compounds damage to the potential of accent your platform to efficiently deliver precision design compounds that may provide substantial benefit to patients better design we believe in a probability of success of reach and patience and when the average industry timeline to discovered developed and that takes around for a half years and sympathize and between two and half thousand to five posts and compounds it is remarkable that these two candidates were designed and fifteen to twenty months respectively and from synthesize and three hundred and forty four and four hundred and four thirteen season design compounds these stuff underscore hello ai driven approach is not only differentiate in terms of position design but also faster and more fish and by conventional methods i the enabling studies are underway for both is inhibitors of we expect provide an update on clinical develop plans leverage an accent he has i met medicine platform in the second half of twenty twenty three these compounds how potential poured application in oncology and hematology overall we have real revive recent month and look forward to save more details on a progress i'll hand over now to ban to walk through the financials thanks andor i'll now take a minute to close with highlights from our financial results full results are detailed in our press release and twenty off a review the results in us dollars using the december thirty first twenty twenty two constant currency rate of one point two zero seven seven dollars to the pound we ended the year with six hundred and eleven million dollars in cash equivalents and bank deposits we believe this provides us with several years of cash runway and the resources to continue investing in our growth at the same time we believe that the recent macro economic factors including bank defaults political trends and large farm announcements will cause twenty twenty three to be year of economic conservatism in the bio pharma industry as a side note sent your does not have any banking exposure to spp or credit suisse from a business model perspective we are well positioned to respond to the current market environment we have now repeatedly demonstrated that we can achieve better drug discovery outcomes faster and with less cost than traditional methods in order for the pharmaceutical industry to improve our ally in the face of great price and competitive pressures it needs the quality and efficiency that we bring we also believe that personalized medicine platform will help improve the probability of success in the clinic which in turn will further improve return on investment at accent yeah our partners continue to invest substantial resources in our projects are existing partnerships alone could contribute several hundred million in milestones or the next three years we expect a number of earlier milestones during twenty twenty three with a majority of the milestones occurring and twenty twenty four and twenty twenty five as we achieved development candidate goals we are also see an active interest in new business development in our reiterating are guidance of at least two deals this year we have seen a focus on innovative technologies and specific pipeline candidates from potential former partners and as a result we have begun to adjust some of our operations to focus on areas that we believe will have the highest near term impact and return in addition we believe it is important to respond to the macro economic environment by keeping our own operations as efficient as possible over the last six months we have reduced costs with several of our siro relationships and believe there is additional room for improvement without a loss of quality in addition we're evaluating multiple ways to apply technology or streamline our internal operations in order to drive greater efficiency we estimate the combination of these efforts will save tens of millions of dollars in operating costs over the course of twenty twenty three i also wanted to be clear that are guidance of several years cash runway allows us to take off for of are disclosed later stage internal programs including each way she decay seven hours one and mach one through initial proof of concept clinical trials if and when the clinical evidence and streets
spk_4: egypt business rationale support that decision
spk_5: with that i will turn the call back over dander
spk_3: thank you ben today we walked you through several examples of how we are working to produce better drugs faster by innovate in both discovery and in development we believe it or differentiated approach and our advancements this year is a valid eat out into and platform and distinguish our company as leaders in the field of a i based on discovery as you can see the have a never important your had the best position for the future
spk_6: we that will open up a call for questions nonsense
spk_0: thank you if you'd like ask a question at this time these breasts star than one on your toes on he dead
spk_7: the first question is from a grand prix hit with morgan stanley line is open
spk_3: hi good morning thanks for taking their questions to to our side of first for fighting on and tactic five or you slides mention that the molecules were developed and i believe fifty the twenty months or to the much longer industry average that development timeline and i was wondering if you could just walk through which components of early development you believe your platform helped to put timeline for the most and then secondly under topic of partnerships the business development going forward what would you be looking for in your next set of partnership or what kind of capability to be most added to the seek out and of congress they what also you think you can be bringing your partners or with an actor partnerships that you weren't able to i would be earlier that partnerships thanks it's can to to speak to again this is andreas am the guy actually so that says question i want to introduce gary paradise city you actually a cause i think yeah we sneak backgrounds have been a drug cancer and the technology actually will highlight and understand were actually accent is top of really brings value to the of to discover of design process sure i think sandra thanks to cram said the timelines we we we we put out of the time from starting a project with i hit molecule to identifying the candidate molecule said us molecule the that take food into into development typically industry average times around about four years that that here read the reason why our platform is ah so much more effective is because they're hot colonising the full power of using artificial intelligence is a multi plan to optimization and using generated designed to explore chemical space much more widely what that means in a nutshell is every optimization cycle with exploring more possibilities were affected
spk_8: the taking larger jumps at each step which is what's allowing us to cut the time down so dramatically and we seen this across all of our programs exits van carry and dave to an aunt bit more about a broader set of capabilities we have them yes nine hundred am i think it's important to realize that accent she operates a other interface between can of experiments and artificial intelligence and i guess the is that is the components of each that when they brought together the next the am make a significant event contribution to both timeline so it is very much in our interest to as you generate high quality data that canucks you didn't utilize in a machine learning environments and so that explains why i'm with created and country to grow our experimental serpent am but it's is ultimately and a placing experts
spk_3: with the right tools i need to have the right technology and that's going away see the acceleration of the timelines the com alert take your second part for questions while of a partnerships i think what's exciting about accent is development of the past couple of years is how well into him platform is really expanded we've gone upstream think about now how we think about target selection sickly incorporate in a patient tissue patients at july's approaches and tigers dyslexia and combine that thing with data science a pro which isn't deep loon approaches of really think that how to inch get a wealth of extol knowledge into his experiments and going all the way downstream our to think about how we design app decision medicine biomarkers for and selection use in the whole range of machine and approaches to multi modal oh makes you can see that with eat and sea birds and school and were look we jonesy to guess i'm and expect to see more of that going forward each year and we started to see now vaccine that the whole mark an accent you drug is one where we combine both precision designed with poor slice mets and go full it's not just a process of how we designed for drive but also how we think about embodied by kind of technology into the kind of late labels we as thinking about but i mean say we now have a much broader often and i think actually we think about the developments advances now we thinking about in clinical development and precision medicine i think the in a very strong position actually to offer a broad range the solutions to the pharmaceutical industry who off themselves face and of the challenges right now so we're very excited right now law discussions we have in which regards how we think about apply precision medicine with partners how we think about applying actually that model informed model driven adaptive learning processes that actually with also created in discovery how they also now apply in development the design of our trials so we really excited actually his accent your grows i think
spk_0: when a very strong position actually to continue to develop and strengthened the offering of solutions we can print off on the partners
spk_7: the next question is from michael right skin with bank of america line is open hi this book on from make thanks for taking the question so i'm starting up the not of battery died and by six five obviously quite exciting as well i know how to think about the incremental spend associated with these and other id enabling programs given the continued refinement scale up your prep platform item
spk_3: building up and victims question i don't know that follow up how are you thinking about your current capacity for parallel i'd be it like that is what it is a primary limiting factor to the number of for you can about i would want to the just a heads up anger their technical at you swap accent a good a speech again from i'm going to to do sir ben taylor actually transfers crusted a was nice to talk to you again so am couple things on and just thinking about our our budget of going ahead and operating expenses so as we think about twenty twenty two vs twenty twenty three twenty twenty two is really the year of scaling and putting a lot of the infrastructure in place that we would need to be able to execute on a broader pipeline both in the discovery phase as well as in development so when we look ahead at twenty twenty three i eat even though we are initiating a number of clinical trials we actually don't see that scaling of cost continuing i am would expect twenty twenty three to be much more level with what we saw in the fourth quarter so i think we've actually achieved a lot of that scale and infrastructure to be able to execute and i think that
spk_4: goes into your question of how we can handle our clinical programs moving forward the actual additional expense internally that we would need to do that is and is not substantial i think what we would look at his as those programs continue to get into later stage development that's where you really see the scale
spk_3: like ah in the expense and so am i think both on the discovery and the development side at were at a pretty good place right now out i also mentioned were we are finding a number of good efficiencies with our sierra relationships that's been a real change for us as well because we're now have a scale
spk_7: and doing enough projects where we can actually get economies of scale out of our zero relationships we can push that pricing dialogue without losing quality i answer that something that at has been a very powerful for as recently and i think you'll see that impact and twenty twenty three
spk_3: god much appreciated
spk_0: thank you have
spk_8: the next question is from peter lawson with barclays your line is open
spk_3: people take think the questions and
spk_9: i get him a question from ben just on the the back your comment about the
spk_3: potential
spk_10: air of them conservative this around a farmer and just how does that help or hinder collaboration
spk_3: it was your analysis or alone yeah so kind to be clear we still see a lot of interest out of former partners i think what we've seen as a bit of change in the focus of the former partner so back in twenty twenty a lot of the dialogue was around how can i scale my pipeline how can i i do and the really large pipeline deals i think what we're seeing in this sort of environment is a real focus on specific technologies and specific identified programs so from our perspective we can actually handle either and in fact sometimes the specific partnerships can be more profitable for us than the broad pipeline to us because there's less infrastructure required to execute on them i think also we are in a different position than we were two years ago because we've advanced enough amber of programs and technologies and platforms that we didn't have that and we've seen a lot of the former partners have interest in in those a later stage programs as well so i think am
spk_11: with this economically conservative environment the fact that we're still seeing a lot of interest set of from of partners i and hopefully this is a economic cycle as so if we're seeing this level of interest right now with feel pretty good if the economic cycle improved
spk_3: but thank you i didn't just a question on timing for today to i know but both of your adenosine and ctk seven patients eleven of trials and road the first patients in first half just your expectations for timing around those dataset a thanks for a fat i'm gonna introduce my cramps who leads out development efforts mike yeah are you a pubic you for the question and suitable we're using model informed drug development simulation got it didn't draw the line and experiments were we a crew in real time all data and look at the data at all times however the time at which we will actually amounts major findings were probably coincide with the
spk_12: it
spk_3: dd movement from the doors escalation face to add dose expansion face to face one to trials we haven't given guidance as to the exact timing of fat however am it will be similar to any of the sees one or two trials ducks are running in this field but importantly the trials that you're running are based on a model informed approaches where were you crew and analyze the data at all times but again and it could we expect a dream second half or is it is that to try to timeline
spk_13: we haven't given guidance on the exact timing and that's a i would think that the second half of twenty three is particularly given that because patients will come in the first off you can just go through the time
spk_0: yep
spk_7: gotcha okay thanks so much thank you peter again as a reminder that star one if you'd like ask a question to ask questions from chris she bhutanese it was goldman sachs lines open
spk_3: hi al is roger on per credit i'm so you've noted that you plan on moving toward antibiotic or that the company it towards using action learning techniques could develop our biologics i'm just wanted to kind of understand you know that such an area that challenging from both developer that economics you know what are the variable they make you believe that was kind of investment going forward it is worthwhile is it be you know the plethora of data that kind of feed them to the closed loop model lower competitive dynamics you just kind of one understand the other rational there hi roger hi david and know is a relatively small efforts in antivirals and panda preparedness we have no plans at all to move into antibiotics as a as a field right now we have a great collaboration and antivirals with the gates foundation that platinum out is focused on small molecules am and we move oh that's led by professor a a good fellow lv invested cambridge but damn important i will be bought up actually his accent he is development of a biologics platform we are as we announced last year developed any biologics design engine that county we are tested put the concept as we speak were also bills and out a new automated by logic slab actually to really speed up the sort of that make and test cycle for the generation of data so of a key areas are we see here xd is the ability actually each agenda is high quality data to drive machine and models and will give you an example of that we can we have a collaboration of oxford university level looking to generate a lot of are paid sequence data we believe actually we can create some a large databases the world and
spk_14: understanding the observable human antibody space and i've actually been gives a sort of the try as defined in a models swim it when evolve in and design and molecules and by a i resent design it's were human antibody space actually is when credibly excited by that actually it's led by professor charlotte dina hooks you an accent year or so how's chat oxford university ah
spk_0: and up later this year we look forward to bringing the use of the more news and information about how up biologics platform is developing but important thing we have a key advantage of as well with already shown that our patients centric precision medicine platform looks equally well for antibodies as it does a small molecules so we can they're also think about
spk_3: downstream how we can start of thing but applied precision medicine also to biologics and bring intervals to feels together and i think us going to be a unique set of attributes actually an outfit gotta thank you
spk_15: like surgeon
spk_0: there are no further questions at this time will turn over to andrew hawkins for any closing remarks
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