Surrozen, Inc.

Q4 2022 Earnings Conference Call


spk_0: good afternoon and welcome to the sorrows in corporate of a conference call my name's josh and i'll be your manager for this call our now turn the call over to crack parker theo sorokin to begin the call
spk_1: thanks josh and thank all of you for joining us today for this important corporate update as just said i'm craig parker ios or isn't and with me today is chuck williams the chief financial officer answers and will be providing corporate and are in the pipeline updates today and will then address questions
spk_2: side to
spk_1: i'll be making forward looking statements please consult are as he see filings in particular are twenty twenty two annual report on form ken k for a full discussion of our risk factors slide three as some of you know sir than is the preeminent innovator and using the went pathway the body's own physiologic mechanism for tissue repair to selectively stimulate tissue regeneration in a broad range of diseases we do this through our proprietary platform and technologies that combine and understanding of went pathway biology in specific disease settings with advanced antibody engineering techniques and proprietary antibody technologies our vision is the design and developed tissue selected antibodies that have the potential to regenerate tissue in many severe diseases it's this targeted approach to went modulation and the extremely broad potential therapeutic applications that distinguish our approach and are technologies the ultimate clinical promise of our approach is disease modifying benefit when signaling plays an essential role in regulating many biological processes including regenerative responses to tissue injury and we see mariette opportunities to regenerate tissue for clinical benefit we've invented several novel multi valence antibody based approaches to selectively modulating when signaling and have advanced to into the clinic we believe that the went pathways broad physiologic role for cans a role for went there appeared eggs and a wide range of severe an acute diseases our approach overcomes a significant limitation to most regenerative medicine approaches that are limited by availability of donor tissue or long term viability we're currently focused on to key clinical areas severe alcoholic hepatitis with our candidate as you know for three and inflammatory bowel disease with our candidate fc and thirteen twenty six today will provide you with corporate and pipeline updates including anticipated timelines for our lead clinical programs are prioritization efforts for the research pipeline update on our partner program with behringer ingelheim and our expectations around cash runway as we look toward key inflection points in our lead programs will also provide an overview of our initial evaluation of the trend them eight elevations observed in the phase one a studies and our approach to advancing both lead programs in november we disclosed several adverse events observed in clinical trials that had commenced and twenty twenty two one of the study is the phase one single a spending though study prescient thirteen twenty six was voluntarily paused pending further evaluation of grade three trans am an ace or liver enzyme elevations we're excited to be able to update you on progress for boat as yeah no for three and fc and thirteen twenty six phase one final trials both are currently open to enrollment for as yeah for three you even rolled our first patient and will provide more information later in the call
spk_3: slide for
spk_1: if when biology is so promising why the taken decades the drug this pathway there are many tactical on pet impediments when proteins themselves or insoluble promiscuous and not manufacturable so a typical recombinant need a protein strategy is just not possible saracens platform technologies and strategies have helped us overcome all of these limitations are candidate molecules are full length by specific antibodies that had desirable drug like properties such as soluble liddy stability and manufacture ability they're also highly targeted to tissue specific recep doors importantly we're mimicking a normal physiological response so our antibodies and a selective way are able to do it when pathway proteins do and all of our bodies and many issues either to maintain the tissue or respond to injury the novelty and breakthrough nature of our work is validated by are strong publication record and high impact peer reviewed journals including science nature spell chemical biology major scientific reports and nature communications we have filed are licensed over twenty patton family is related to our key discoveries involving the went pathway and it's modulation we recently received notice notices of allowance from the united states patent and trademark office for to patton families assigned to serve as and related to the at and thirteen twenty six program
spk_4: we think the breadth of our scientific discoveries and related patent application and claims can establish a dominant position for us in the use of antibody therapeutics the module eight went signaling
spk_1: slide five our proprietary technologies have led to two different lead programs that entered the clinic and twenty twenty two the licensing of the lead development candidate as the and for went three for treatment of retinal disease is to bangor ingelheim and the fourth quarter of twenty twenty two and a focus on to discovery pipeline programs for cornea and locker more gland our research programs focus on indications of high unmet need with no or few available treatments including a group of ophthalmology indications that will tell you more about we're excited today to provide an update on advancing both of our clinical programs as yeah no for three and fc and thirteen twenty six since or announcement in the fourth quarter of twenty twenty two regarding trans emanates elevations we've completed numerous studies to understand the mechanism of trans eighth elevation seen and this essay and thirteen twenty six programs and also to lower grade in the us yeah no for three program will provide you with an overview of our efforts to date and clinical program plans for as yeah know for three we're really excited with advance to the second phase of the study and chronic liver disease patients falling completion of dosing it to those levels and healthy volunteers for as the and thirteen twenty six we will progress are phase one single a spending go study at lower doses pursuing a dosing strategy frequently applied to first and clot antibodies are referred to as the mabel are minimal anticipated biological effect level additionally we look forward to the opportunity to advance another development candidate and twenty twenty three in collaboration with our partner bangor ingelheim with the potential to identify the final frizzell for targeted development candidate by year and a milestone that would trigger a payment to sir isn't
spk_2: finally we anticipate that are prioritization and restructuring will result in a cash runway into the second half of twenty twenty four allowing us to achieve multiple key milestones and catalysts
spk_1: slide seven se n o for three is our by specific multi vaillant an antibody that mimics the activity of our spawn then but importantly is specifically targeted to have had a site via it's a as she one binding as the yeah no for three specifically activates when signaling in the liver resulting in her passed by proliferation liver regeneration improvements in liver function and reduction in fibrosis we think the biological rationale and pre clinical data that support the concept of activating when signaling for the treatment of liver do severe liver diseases is compelling we developed a data driven clinical plan to align the molecules pharmacology with specific disease pathologies and advance into clinical trials and twenty twenty two as mentioned we observe some mild to moderate adverse events in the first to dope dose cohorts which will describe in more detail importantly these observations did not impact our ability to advance into the next stage of the phase one program in liver disease subjects
spk_2: we'll describe our plan next steps and the significant opportunity and severe alcoholic hepatitis
spk_1: flight eight it's important to point out that are sweet antibody platform on which oh for three is based allows for sell specific targeting of the wind activating mechanism after you know for three utilizes the well characterized have had a site specific receptor a sgr one to target oh for three the activity to have powder sites our sweet technology mimic the activity of a naturally occurring protein are spawn them our spawned and contribution to regeneration is well as described and we focused that it activity on her parasites with our technology we've confirmed to sell specific when pathway effects of the molecule and our animal toxicology studies showed no adverse effects up to one hundred and twenty five milligrams per kilogram does level let me explain why we think severe alcoholic hepatitis is the right indication for the molecule and for sir isn't alcoholic hepatitis is a severe clinical entity characterized by acute onset of jaundice and coagulate but the and patients with acute that with alcohol use disorder the incidents of alcoholic hepatitis is increasing over a recent years short term mortality of to the or a age remains very high twenty percent of patients with a to die within thirty days of admission to the hospital and thirty percent die within ninety days due to have slight loss and lack of sufficient regeneration to overcome that loss the medical management of alcoholic hepatitis has not evolved substantially in the last two decades with multiple potential therapeutic agents tested without success there are no approved drugs indicated for severe alcoholic hepatitis
spk_5: corticosteroids remain the only established treatment for a age but or contra indicated in more than half the patients liver transplants often are denied due to alcoholism and even if available or transplants are limited by donor organ availability cost i'm and limitations on medical centers with true
spk_1: plant capabilities hospitalization rates are very high and sir alcoholic hepatitis and represent about one hundred and thirty thousand hospitalizations per year people with severe age are typically admitted to the i see you so this is an identifiable population with an extremely high unmet need we are also aware that alcohol consumption increased by over thirty percent during the pandemic and hospitalizations also increased during the pandemic for alcoholic hepatitis we think that the critical medical need and this population the dearth of novel approaches and alignment of our mechanism with the disease path that physiology is reinforced by a word to sir as another several million dollar nih grant for this program importantly her parasite regeneration is known to correlate with improved survival furthermore we can utilize surrogates for response and survival such as the lil and meld scores to assess early signs of clinical benefit both of these tools are using clinical practice to assess response to treatment prognosis and eligibility for transplant they are objective and are calculated using common laboratory tests like bilirubin the will score at seven days is a well characterized margaret disease severely severity that is highly correlated with ninety day survival we expect ninety days survival to be the approvable and point in a registration trial because of the disease severity and on that medical need we believe there's an opportunity for favorable regulatory treatments such as break through therapy designation and a potentially rapid approval pathway as seen in other grievous diseases flight nine we've published data from multiple rodent liver injury model demonstrating that as you know for three rapidly proliferates mature her parasites resulting in functional improvements and a reduction and fibrosis these publications and abstract can be and found in investor section of our corporate website the efficacy of as you know for to be span injury models specific to our initial indication of alcoholic hepatitis to models of fibrosis that could ultimately provide translation to additional liver indications in the future slide ten we're excited to have completed to cohorts of patients in the phase one single spending though study and healthy volunteers and we've been rolled our first patient with chronic liver disease following the outcome of the mild to moderate key ale nations and the first cohort of healthy volunteers treated at three milligrams per kilogram we enrolled a stuck and cohort and six healthy volunteers at a lower dose of one milligram per kilogram we observed one case of mildly elevated great one trans am ammonite us that also result spontaneously following completion of cohort que in the face ones that and healthy volunteers we opened enrollment in the phase one sad and patients with chronic liver disease and as i said haven't enrolled our first patient we expect to enroll for subjects for dose group with an option to expand the cohorts we're proceeding with lower doses as our pre clinical data indicates that damaged tissue may be more sensitive to the beneficial a parasite proliferation effects of fc and for one oh for three patients and cohort one will be dosed at zero point five milligrams per kilogram importantly we anticipate having data from the phase one single ascending dose and chronic liver disease patients by year and twenty twenty three assuming acceptable safety we anticipate moving into a phase one be clinical study in severe alcoholic hepatitis patients and twenty twenty four with proof of concept data expected to be available and the second half of twenty twenty four
spk_6: in summary we believe that as you know for three mechanism and pre clinical data are ideally aligned with our initial target indication and that as you know for three has a well defined clinical development and regulatory pathway
spk_1: excuse me
spk_2: we look forward to advancing our understanding of the therapeutic potential of us you know for three as we initiate treatment of subjects with chronic liver disease and ultimately patients with severe alcoholic hepatitis
spk_1: five twelve as the and thirteen twenty six is based on our swap technology and were developing a and thirteen twenty six from moderate to severe inflammatory bowel disease based on a compelling fact and well established rodent models of collide us showing near complete healing of damage intestinal epithelial including reestablishment of the critical barrier function using water just one or two doses of as he entered his thirteen twenty six we design a clinical development plan leveraging the extensive experience of other biological agents and i b d in contrast to other biologic so our biology and pre clinical data suggest we have an opportunity to directly drive mucosal healing or his to logic permission in may twenty twenty two we commence dosing of se and thirteen twenty six and a healthy volunteer phase one single a spending though study several subjects and cohort one treated at twenty five milligrams experienced asymptomatic liver trans emanate elevations including two subjects with grade three l t and they have feel nations and two subjects with great one lt elevations there were no corresponding increases in total bilirubin nor any changes in other liver function markers and know whether clinically significant laboratory abnormalities the trans them and is elevations risk result spontaneously and all subjects no serious adverse events were observed during the study although the protocol did not require that we halt the study we announced a voluntary pause to enrollments in the phase one healthy volunteer portion of the study in november following this observation of following an observation of a great three lt elevation at a lower dose in order to give us an opera thirty to analyze the clinical data we have not observed trend them in a elevations or any other adversities at doses up to one hundred twenty five milligrams per kilogram and pilot or glp toxicology studies studies adverse events were unexpected and as such could not be characterized with non clinical data available the a time of the observed maps we've invested significantly in efforts to understand the mechanism of the t a elevations importantly a better understanding of the non clinical data and clinical data combined with a modified dosing strategy allows us now to proceed to dose additional healthy volunteers and phase one sad porsche the study which we expect to do and the next few weeks our initial rationale for dose levels for essien thirteen twenty six was based on goes doses tested in multiple models will collide us and the add an absence of any observed toxicities pre clinically such a dosing strategy is informed by the and away l or no observed adverse effect level as well as other indicators of activities such as a therapeutically active dose in light of the key a elevation observations were now pursuing a dose level strategy with fc and thirteen twenty six that as i said is commonly employed with agonising antibodies for first in human studies and that's a mabel or minimum anticipated biological effect level five thirteen so i probably don't need to reinforce for all of you the remaining unmet need in this significant market initially were developing se and thirteen twenty six for ulcerative colitis ulcerative colitis is a chronic immune mediated inflammatory disease of the large intestine it's frequently associated with inflation of the them but also extends proximal a to involve additional areas of the colon nearly one million individuals each in the us and you are affected peak incidents occurs between the ages of fifteen and forty five some patients with use the have persistent disease activity despite medical therapy and twenty percent will develop at least one episode of acute severe ulcerative colitis as hospitalization importantly although their medical therapies on the market and development there remains a significant unmet need and you see for the following rapid induction of current anti inflammatory biologics can take months to induce clinical remission improved efficacy especially his to logic remission as anti inflammatory biologics that she achieve clinical remission and less than fifty percent of patients at fifty two weeks and low rates of his to logic remission as low as twenty percent his the logic remission has been associated with a bit better clinical course additional mechanisms of action as an add additional medic unmet need as many patients fail first line anti inflammatory biologics and subsequently fail second third line therapies but fourteen so what's the rationale for a windmill medic inflammatory bowel disease a major component of the path of physiology of i the is an impaired epithelial barrier or got wall allowing for exposure of gut microbes to the guts immune system resulting in inflammation give inflammation further destroys the epithelial barrier se and thirteen twenty six can directly address this epithelial barrier dysfunction it binds to intestinal stem cells and the call encrypt replacing went like and that a normal circumstances are produced by the stromal cells but that disrupted and i bd this binding of thirteen twenty six leads to proliferation and differentiation of these cells as they move up and out of the call encrypt replacing the damaged epic sealand and restoring the epithelial barrier we've shown preclinical that this results in reduce inflammation and reduce disease activity five fifteen in preclinical studies we've demonstrated that thirteen twenty six restores when signaling in the damaged intestine repairs the damn call and epic feel am reduces inflammatory cytokine and reduces disease activity we've also shown that this activity and preclinical models of politesse compares favorably to approved biologics an immunosuppressant you can find abstracts are related to some of this preclinical data on our website slide sixteen over the last several months we've identified several potential hypotheses for the trans emanates elevations we've seen in the clinic and have established a rigorous science based investigation plan our in house expertise and capabilities have proved invaluable and expeditiously analyzing the available data and conducting additional experiment designed specifically addressed key questions let me describe some of these activities the data and our conclusions we've established additional in vitro and in vivo systems specifically employing human her sites in order to most closely model human physiology we've observed that are molecules do not have a direct toxic effect on human liver cells in multiple in vitro and in vivo experimental systems we have not observed a direct effect on ale key or a as he in vitro and importantly we have not seen any immune mediated effects using multiple experimental settings no cell death know immune activation know observed to parasite killing a fact and any of our studies that we've undertaken over the last few months although oh for three and thirteen twenty six employed different receptor systems for activity the downstream wind pathway of facts are shared
spk_7: we think the similarities in the patterns of trends emanate elevations between the two molecules in light of their different from a cook kinetics is supportive of the hypothesis that activation of went signaling and subsequent have parasite driven livery generation is at least partially responsible for the trans am on a
spk_1: the facts will continue to investigate additional models for up like ability to understanding the mechanism of these t elevations i'll also reminds you that this seems to be a liver specific effect and many of our molecules would not be expected to affect liver cells based on either receptor targeting or route of administration will be commencing dosing of se and thirteen twenty six in the next cohort of healthy volunteers at a dose of point o four milligrams or forty micrograms assuming acceptable safety in this and subsequent cohorts we anticipate proceeding to doses up to at least one milligram following acceptable safety we anticipate and rolling a proof of concept study and ulcerative colitis patients and twenty twenty four with proof of concept data expected to the it be available in the second half of twenty twenty four flight eighteen we have three research programs in late stages that lead optimization or candidate selection to wholly owned by sir isn't and one partnered with behringer ingelheim as i mentioned went signaling plays a central role and tissue regeneration and went responses cell types are found in tissues throughout the body we believe this broad physiologic role portends a role for went therapeutics in a wide range of severe and acute diseases the role of fizzled for mediated signaling and blood vessels in the retina has been validated through human genetics rodent models and our own and collaborators data and publications we've shown that are frazzled for targeted swap se and four one three could fill a unique mechanistic role in the treatment of rapid retinopathy is by simultaneously addressing vascular leakage and retinal non perfusion in two different models a retinal injury was shown that as the and four one three could reverse multiple manifestations of retinal injury including basket or leakage and areas in the areas in the retina they were not adequately vascularized and areas with characteristic half a logic near basket or tufts this and other data emulated interest from multiple parties in a nasty and four one three partnership and let us just fine a collaboration agreement with behringer ingelheim in october twenty twenty two five nineteen we also have a research program and regenerating cornea fuchs and feel your cell dystrophy is a disease characterized by corneal swelling and ultimately vision last and discomfort caused by excessive loss of corneal and of the oil cells the cause of corneal in the fuel cell loss is not well understood that has a genetic component current therapies are limited and the field transplant or reception at late stages of the disease there is a significant unmet need for therapies that mitigate disease progression and or improve surgical efficacy our strategy for treating coil diseased is to specifically activate when signaling in the tissue regenerate corneal and ophelia spells reduce corneal swelling and improve vision we've established a cornea research effort including in vitro and in vivo models that to date have demonstrated the following specific frazzled receptors are expressed in corneal and a feeling i'm above normal and fuchs human donors and can therefore be used in designing and targeting our swat molecules we can observe wind activation three specific swap that enhance proliferation or primary human corneal and feel your cells in vitro and we've established a corneal cryo injury model a measure the therapeutic effect of activating went signaling in the corneal and at the lamb in vivo as and wind activating molecules are efficacious in reducing cornell thickness and improving opacity the next step for a program is to optimize a lead molecule and select a development candidate slide twenty let me tell you about another off the melodic program that we're excited about were pursuing a potential treatment for severe dry eye with are swapped technology severe dry eye is characterized by ashraf the of the tear producing glands in the eye and insufficient regeneration the objective with the wind wind activating approach is to stimulate regeneration of the cheer producing cells in the locker more land and restore fluid secretion we've established multiple locker remote land injury models in rodents in which tear production as reduce one using interleukin one alpha to promote inflammation driven injury the other a lock ronald duct ligation model that results in the croesus to the gland an important first mechanistic step in restoring tear production as to regenerate the tear producing cells and the gland called the aston ourselves we've shown that a single injection of a swat molecule result in an increase in the weight a black mold land and a demonstrable proliferation of these ass and ourselves so we're having a clear of fact at the cellular level of increasing the number of target cells in the gland in the i'll want a induced injury model we've shown that swap molecules activate went signaling in the tissue which leads to an increase in tears secretion the method for measuring tier secretion this model doctor the same as that using clinical trials of agents for dry eye a phenol read thread and this model there's a statistically significant increase in tear production with swap molecules a days to three and four similarly and adopt ligation model a lock on the gland injury we've shown that treatment with the swat molecule restores tier production through activation of went signaling and proliferation of asner cells next step for the program is to optimize and finalize a lead molecule for development we expect at least one of these programs to move forward and development and twenty twenty three potentially in collaboration with a corporate partner both involved local administration of our antibodies to the affected tissue and therefore would not be at that expected to have any potential liver exposure liabilities five twenty one and i'm gonna turn the slide over to chuck
spk_8: thanks crowd that's correct outlined with made significant pro progress with our programs over the last few months and i wanted to highlight of few
spk_1: highlight a few the thing that we've accomplished from a corporate and capital structure perspective to establish never stronger foundation for continued future success the first a while i we executed a partnership with boehringer ingelheim in the fourth quarter of twenty twenty two to develop a when agonist as the and four one three for the treatment of people with retinal diseases we anticipate the potential to identify the lead prison for targeted when agonists candidate the by year end twenty twenty three would trigger a pencil pen my ten million dollar milestone payments secondly we implemented a restructuring and que one of the sheer or efforts were focused on maximizing shareholder value by one aligning resources and aren't the investments for the to lead clinical development programs with a focus on t proof of concept data to practising investment in the most advanced discovery preclinical programs like romulan cornea and thirdly reducing operating expenses of the old maintaining a strong balance sheet following the corporate privatization and restructuring activities we anticipate a reduction in operating expenses excluding noncash and nonrecurring charges of approximately fifteen percent in twenty twenty three compared with my money to cast cash equivalents and marketable securities were approximately seventy six million as of the end of
spk_9: twenty twenty two and we expect or cashman way to last and for the second half of twenty twenty four
spk_1: finally i wanted to highlight in the fourth quarter of twenty twenty two we entered into a security purchase agreement with continents
spk_9: given they decided that they were winding down there fun they were an overhang on our socks we entered into an agreement to repurchase approximately five point four million shares of our common
spk_1: and approximately one point three million warrant
spk_8: for a purchase price of approximately two point seven million following the repurchase it's no longer hold any shares of our common stock or wants to put plus there's and common stock
spk_1: works cited with the multiple opportunities that lie ahead of sarah's and twenty twenty three and twenty twenty four we've shared some of our key milestones and catalyst for twenty twenty four on that's why i should we share our thoughts when cash ronnie one way into the second half of twenty four as we think about our key upcoming milestone think cannolis and i'll briefly highlight of
spk_8: you these first for a piano for three is cried mention we've rolled the first patient for
spk_9: for chronic liver disease and expect to have data by the end of year in find initiate a phase one be clinical trial in twenty twenty four with potential proof of concept data in the second half of twenty twenty four
spk_8: as a relates to thirteen twenty six
spk_1: we've we've we've opened and role that for the fifth phase one in healthy volunteers and we expect to be able to have data by the end of the year and will initiate a phase one be trial and twenty twenty four you see patients and expect to have proof of concept data in the second half of twenty four
spk_8: as i've already mentioned with a him
spk_1: for one three which has partnered with boehringer ingelheim we expect on by the end of the year for them to nominate a a candidate which will trigger a ten million dollar milestone payment and as it relates to our research programs we expect to nominate an additional program into a partner that potential program
spk_0: for now i'd like to turn it back to the operated more open up the call for questions thank you as a reminder to ask a question please press star one one on your telephone and wait for your name to be announced to withdraw your question please press star one one again
spk_10: our first question goes on they got hung with people who may proceed good afternoon thanks her taken my questions and congrats for all the progress get to hear things are things are back in motion eight and your side of the table and maybe i'll just start with to before i hopped back in the queue regarding the all for three i don't hear anything
spk_11: lf can you guys hear me
spk_12: hello
spk_10: i can you oh you're coming loud and clear
spk_1: can you guys hear me now yes a crack ah great that they are taking my questions i'm combat another progress i wanted to ask two questions one was more of a clarification for the whole for three plan is there a change in the study plans because i thought the phase one next study was in early surat it patients but now it seems like chronic liver disease know whether a change or what was the yeah well as that i guess the nuance and i'm methane and based on the liver trans am an eight observations can you speak your confidence or strategy to mitigate similar observations and more have adequate impaired patients and i've got a follow up thanks to the questions they gone so yes you observed a a nuance in in the what we think are the patient likely to be enrolled in the study
spk_10: so
spk_1: the general little objective of the study well the primary objective the study is unchanged with the safety we think that an end about surat a patients are chronic liver disease patients and for many etiologies like patients would have see for example cirrhosis is defined in by and in part of fibrous can score or transit elastography score of seven point five and were taking patients with lower fibrous can score as so there will certainly have chronic liver disease they will have five fibrosis the whether they affect frank cirrhosis i think we'll just have to see so that that's the a nuance in the description of the at target population that you picked up eyes they may have fabrice can scores that are low enough that they would not be considered to be sir alex yet today certainly have fibrosis and have hepatic impairment got it and what about the ah they have particular impaired aspect how my the up be a pot potential complication for you guys are diaz strategies to mitigate that know we have not identified have a specific mechanism where one could you know mitigate for example by code ministering he also said something else on
spk_10: and so i think we're as i mentioned we've observed that damaged tissue tend to be more sensitive
spk_13: and so i think this is really gonna come down to the ah the dose response and these tissue
spk_1: yeah vs have vs healthy tissue so not there's no no specific mechanistic strategy at this point based on the data that we've generated that but but again you know it's possible that you know at at quite low doses there's a regenerative response that that he out that doesn't bring with it some have had a cellular injury and cat ah regarding bad may ball on aspect you are talking about ah so if we think about your thirteen twenty six study how many more goes cohorts are you going to be exploring i think i heard you say starting with point o for but go up to one milligram do those have you clarified how many course that would be and kind of by extension this notion of higher than expected exposure in humans vs animal studies is that also in effect for your oh for three molecule us law thanks so much yeah we'll we'll publish some other pharmacokinetic data some point for both molecules that but oh for three was roughly in line with our pk projections from animals you know what weird the dig on we're not going to disclose all the dosing cohorts but at the pretty typical
spk_10: dos level strategy
spk_14: and we can continue to go above one
spk_0: and it's possible for example that we could go up to two point five of where we've seen a one of these events
spk_15: with a different route of administration those the one potential hypothesis for example is that see max maybe a contributor we don't have pre clinical data suggesting that but it's seen with other molecules and we gave them all at were given molecule i the
spk_16: and and we may ultimately want to test whether there's a difference
spk_15: i'm at doses we've tested i with the subcutaneous dose so i said okay thank you very much all hope i can occur again thank you
spk_17: our next question comes from hannah yo yo with tv morgan you may proceed
spk_0: hi hannah on for eric thanks for taking the questions just a few from us
spk_18: i'm have you commented on the half life of thirteen funny as a far and as hell am i ever see kenny this decade it just like humans or frequency far i'm i'm not sending this study based on your preclinical an apple finding a far and shyly and fantasy am i'll can you confirm that the a that hand i
spk_19: i couldn't hear that i don't of others good
spk_15: oh okay i can repeat i'm i'm saying
spk_1: did i commented on the half life of baking twenty six and are able to speak to any affected dancing regimens or frequencies for a multiple are sending their study based on your preclinical and clinical finding a fire just how to see his arm he said he did a to give you comfort that the event eva deserved and
spk_20: thus far won't be seen over longer this the animals
spk_1: we able to get that glue one moment please the conference of the momentarily there with their ago i think we can go ahead hannah
spk_21: i can hear me now yes
spk_1: i am i gonna repeat and he having a guy you're just was asking about the half life of making twenty six am and you're expected to thing were given to frequencies for a month for an industry your the half life is about third thirteen twenty secs you're asking correct yes yeah the half life is
spk_22: about five days
spk_1: keep in mind though that am because there are a number of went pathway target genes that are activated when you activate the pathway that biological effects could be longer lasting then the
spk_23: what you might anticipate from the half life
spk_24: of the antibody
spk_0: and so on and say i do it with it's not as very it's not it's not a straightforward align the pk with the frequency of dosing so we think this could be and every other week or perhaps even less frequent dosing regimen we have not finalized that yet for said the phase one be portion
spk_14: and as a couple think hobbies and one as the all the human soul the human pk data different as levels
spk_25: okay a great make sense
spk_26: you at that have life by the way was
spk_27: the in primates out the fact that five days
spk_0: thank you
spk_1: thank you and as a reminder to ask a question you will need to press star one one on your telephone
spk_28: our next question comes from yeah things in a now with guggenheim you may proceed
spk_29: you guys get any yes you're coming in loud and clear at i can't hear him out there who are late club
spk_27: cracking you have enough
spk_1: once they get thing i'm from the company ask a question
spk_30: greg please give us the word when you can hear us
spk_1: i can hear you i can't hear you on ah
spk_29: now
spk_25: hello
spk_29: i think we are able to hear the know
spk_25: on the line with able to hear
spk_1: captain here us i can hear you cry can you hear young i know you can hear me yeah it
spk_31: did you translate question
spk_1: when will they let me plenty of ucla and and the asked the question chugs the you back in time maple self with regard to afford for the i phone you mention that you have and farm target engagement
spk_32: can you characterize that for us was that a dose response and how do you feel about zero point five told is that sufficient to elect either that for like a lawyer biological activity that's what and maybe a similar question but the other wonder that i don't think you said
spk_1: for ten to twenty six anything on be targeting a good yes of cracking early yeah i soon as we mentioned that we confirm target engagement and there was a dose response so i think you know for yeah that's been a super bowl programs know for throw for three specifically how we feel about your point five and the biological activity that we might see the in a similar question as it relates to thirteen twenty six an inmate yacht and me i can't hear you so make sure you them let or others know that you can hear me yeah we get those you know the doing price you can hear me okay i'm it as you noted we've confirmed target engagement with oh for three at least to be targeting str one receptor through a l p elevations of these are not i'm dumb adversities these are a p elevation that results from blocking a str one which is a scavenger receptor in the liver that takes
spk_25: they'll be out of the circulation
spk_33: i think your question is really about you know what kind of doses have a have we seen activity and animal models and are we in the range with point five
spk_27: and while we've typically employed a higher my higher doses an animal models
spk_1: we think we're in arrange that could be a therapeutically active dose and then i'll just also make the observation that obviously given that we had not seen any these adversities in other species the other species may not be that translate translator all for protecting predicting a dose response so we're we're we're we're in the range and wouldn't be overly concerned are focused on the exact dose in the mouth translating to human since that translate ability for for talks
spk_9: that has not been there
spk_1: for thirteen twenty six we do not have a target engagement as i am so it will take getting into you see patients and by asking the tissue to identify whether we'd activated when signaling so in that situation in that setting we have an ass save for a went target gene called accent
spk_34: to which will look for
spk_35: i'm to confirm that we'd activated the pathway
spk_1: but it every what one more question are check if he can translate damn this is funding it seems like at this point we not rule out ladder there on the phenomena that you are seeing actually funded miller like it either that he could target specific ah and we cannot rule that out how are you are saying that the terrorists tissues might be more sensitive so can you help us understand if that is a is there any threshold effect in all accident those who you might not see i'm just curious fair
spk_36: i'm like what gives you confidence i i can't the harry one still yeah been damaged tissue them more sense
spk_1: the fifteen or me yes okay so he he he yawns question as to do with we camp at this point i can't really rule out the liver issues or target specific and seen that the damage you know might be more sensitive is there is there any threshold the fact that certain doses that we see i might see based on a daily collected so in to him to answer the first part of your question yacht and no this does seem to be a oliver specific fact while are as the and thirteen twenty six is targeting frazzled five which is enriched in the intestinal epithelial am and ulcerative colitis patients it is expressed on her parasites so so that would be consistent with
spk_27: on a fact that similar to oh for three that mean meaning they're both hitting liver to some extent
spk_0: and i think
spk_1: as tiered the second question i think his head you know what what how do we find the therapeutic index is there what the likelihood of finding a therapeutic index
spk_0: and again i think we have to the

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