REBROADCAST : Inaugural INTERACT Eminent Speaker Series

REBROADCAST :   Inaugural INTERACT Eminent Speaker Series

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i'm burns harvest president of oklahoma state university and i want to welcome you to this first ever interact webinar we're glad you could join us we are pleased that interact is now the hub for one health research at osu merging plant animal and human science is a key mission for osu by uniting academic and industry expertise on one platform interact will speed the process to bringing new treatments to patients i visited the interact lab recently and i was amazed by the work done on a pet cancer patient today we are delighted to have with us dr phillip dormitzer from pfizer thank you for being with us and we want to offer a huge thanks to the entire pfizer team for its work on the colvid19 vaccine you are truly american heroes again welcome to oklahoma state university interact is proud to bring you this informative webinar interact is a university-wide effort housed in the college of veterinary medicine stillwater campus our college has several faculty members who perform basic and applied research under the leadership of dr ashish ranjan interact will provide these researchers an opportunity to translate their work into effective therapeutic approaches interact also aims to involve a variety of internal and external stakeholders for example last year we signed a memorandum of understanding with albert einstein college of medicine to promote one health research at oklahoma state university this and other partnerships across different disciplines are central to interact's mission and will help generate funds to perform clinical trials i would like to thank the deans of various oklahoma state university colleges for encouraging their faculties to participate in this important effort finally many thanks to dr phil dormitzer his leadership on covet vaccine development is commendable and we are grateful for his willingness to share the research with us our college's contributions to mitigate the impact of the covet pandemic were recognized by many including the washington post and his seminar is timely to our ongoing efforts thank you thank you all for joining today i would like to sincerely thank main campus administration dean riscoe dr muller founding members and the internal advisory committee for their great support in helping establish interact as dr risco and president hargis indicated interact aims to promote one health research by encouraging new research in clinical medicine utilizing devices therapeutics and diagnostic platforms towards these goals we have established the research infrastructure in the teaching hospital to support innovative projects under the leadership of dr brandow we have also put together an impressive list of speakers for the interact eminent speakers series please attend those seminars and learn more about the cutting edge research in size in the formative years interact will aim to bridge the gap between various scientific disciplines on campus and encourage new partnerships we hope that these will ultimately culminate into an extramurally funded center grant finally thank you very much dr darmiser for serving as an eminent speaker pfizer's vaccine has been a lifesaver and we applaud you for your leadership i sincerely hope we can host you again soon in person at the osu campus over to dr bix now good morning we're excited to have you as part of this inaugural event for for interact interact of course is our institute for translational and emerging research in advanced comparative therapy we're really pleased this morning to have dr dormitzer from pfizer speak to us it's a great launch of of this event and as dr ron john mentioned we hope you'll join us for additional events in this series we would like to welcome all of you from around the world we we have registrants from various international locations and we want to make sure that we recognize some of our oklahoma dignitaries that have joined us thank you so much for taking the time we want to thank our fellow university researchers faculty students for joining us and we also don't want to forget our cowboy fans right here at oklahoma state from across the campus for for joining us this morning i'm rosslyn biggs i am a faculty member here at the college of veterinary medicine and also a member of oklahoma cooperative extension service it's my pleasure this morning to introduce dr philip dormitzer hi dr dormitzer again thanks so much for being here i'm going to read your bio and it it's quite impressive so that our attendees can get a little bit of a snapshot before we before we get started on your presentation this morning so dr dormitor of course is vice president and chief scientific officer of viral vaccines with with pfizer and as we all know pfizer has done a tremendous job of the research and bringing bringing vaccine to us during this pandemic doctor dormie dormitor leads the firo viral vaccines research and development programs and including the pfizer bioin tech rna-based cova 19 pandemic vaccine as well as influenza vaccine collaborations the cova 19 vaccine as we know has been authorized for emergency use and mass vaccination campaigns are in progress really around the world a profusion f-based rsv vaccine to protect infants through maternal immunization has been advanced from discovery to global phase 3 as well in pregnant women as well as a cytomegalovirus vaccine candidate is preclinical before joining pfizer dr dormitzer held positions at novartis vaccine and that included the head of u.s research he was a founding member of the novartis viral vaccine research center in cambridge massachusetts and in 2009 his research team supported the development and licensure of three h1n1 influenza pandemic vaccines in what remains the most rapid vaccine response in in history in 2013 his team responded to the h7 in nine influenza outbreak by supplying u.s pre-pandemic stockpile with a vaccine generated from a synthesized virus before joining in industry dr dormitzer was an assistant professor of pediatrics at harvard medical school and led a structural virology laboratory which with collaborators determined the structure of the rhoda virus neutralization antigens he graduated summa laude in anthropology from harvard conducted paleontolog paleontological research in pakistan and zaire obtained a phd in cancer biology and an md at stanford he completed internal medicine training at massachusetts general hospital and completed the harvard infectious disease program clinical fellowship dr dormitor we're very pleased to have you today and and really we're we're ready to get into the presentation and um learn more about uh the effort that has uh really a a monumental effort during this pandemic time by you and your team well uh thank you so much rosalind i i really appreciate the invitation as especially to be the inaugural uh a speaker of this series uh so um yeah i'm looking forward to telling you a bit about how we developed the vaccine so i think if we're ready for the slides that we can we can start start showing them um i think they they start off probably with a really boring disclaimer slide um i'll give you the title application of new vaccine technologies to the kova 19 pandemic and there is a disclaimer if anyone cares to read it i'm sure it can be it can be viewed but maybe we can we can move on uh just as the introductory slide there is a an image of the vaccine coming off the uh the manufacturing line at our kalamazoo michigan fill finish facility um so this is where i know if you saw the news images a while back of the trucks pulling out on that first day and this is the facility for from which they left and so we'll tell a bit of the story about how we got to that point uh next slide please um this has been a collaboration uh with beyond tech our partner in germany and a lot is made about how rapid the uh uh development was and that's part of the story we'll tell but i think the other part of the story i really like to tell us how this sort of sprint to develop a vaccine during the pandemic built on research that actually started many years earlier so it didn't come out of nowhere and i'd like to tell a little bit about the story of of where this came from and in fact the collaboration with beyonce did not start this year or or 2020 with a pandemic but rather started in 2018 and at that time we decided that we would collaborate to make a rna-based influenza vaccine and one of the things that appealed to us so much about rna as a platform for flu was the ability to swap antigens in and out because with flu you're constantly changing the vaccine so the ability to change rapidly and readily was could make for perhaps better strain matches which is one of the determinants of how well flu vaccines work but that ability turned out to be very useful in january of this year it was at that time that following the outbreak in wuhan china the china cdc posted the sequence of the cyrus coronavirus to the causative agent of covet 19 um on the web and the gis data sharing platform and immediately our colleagues in germany epione tech began synthesizing uh the uh dna templates for the rnas and they actually made several at that time and of those one ultimately progressed to to become of the vaccine visor got more heavily involved in march it was by that time we had started to see cases in the u.s that did not have any obvious link to a traveler or to other known cases which indicated that this was spreading in ways that we were having trouble tracing and although certainly when i first heard about the outbreak and i hoped that this would be contained as if the related viruses sars the first tsars uh starts kobe 1 rather or the mers the middle east respiratory syndrome uh coronavirus were contained just through conventional public health measures but this sort of uh hard to trace spread made it clear that that was not going to be the case and that a vaccine would be needed and that pfizer's capability of large-scale development large-scale production and distribution was going to be needed for a global immunization campaign so in march we added to our existing collaboration on influenza vaccines a collaboration on a coven-19 vaccine our teams have been working very closely together for years uh at least since 2018 uh and things progressed very rapidly actually by april the first trial started in germany and in the us by may we progressed through phase one and two so that by july just a few months later we were in a large-scale pivotal global efficacy trial and by uh december we had our first approval in the uk excuse me first emergency use authorization we don't yet have approval it's only it's an emergency authorization for the pandemic we had our first emergency uh authorization in the uk followed later that month by emergency authorization in the united states and now of course we are in the midst of a global mass immunization campaign next slide please one of the things that really uh appealed to us about collaborating with biantec in addition to their capability for rna therapeutics and vaccines was a shared philosophy and that is we thought that some critical scientific questions even basic ones about what type of vaccine you're going to make are best answered with clinical data and that philosophy was reflected in the way we went about testing this vaccine in fact we did not enter the clinic with one vaccine candidate we ended with four and they included three different types of rna unmodified rna like ordinary cellular rna nucleoside modified rna that has a i'll say a bit more about this that can help evade innate immunity self amplifying rna that actually can can replicate in addition we had two alternative antigens one was the full length spike which you see depicted uh to the left under a spike protein but also just the receptor binding domain which can flop up and down on the molecule and it's in the up position in green and in the down position in blue and through that testing we found that at least at this stage of development the nucleoside modified rna provided us with the manufacturing reliability that we needed it gave us strong immune responses it was well tolerated and we found that while both the receptor binding domain alone which is how the virus grabs onto cells and it's a very dense source of targets of neutralizing antibodies it actually listed quite good neutralizing antibodies as did the full length spike but the foam-like spike gave us somewhat better t-cell responses and we thought it might be more robust to the possibility of variance and i'll come back to the variants that are emerging of this virus later so we selected a nucleoside modified rna expressing the full-length spike protein for further development the next slide please the now i'll talk a little bit about some of the basic science that went into that vaccine the first is this nucleoside modification and this is work that originated at the university of pennsylvania and instrumental in the work was katie carrico who's now actually at beyond tech and also drew weissman and they found that a modest change in uracil to make it pseudo-methyl uh uracil uh which you can see is just a a sort of inversion of two two uh two atoms still allow the rna to be translated by the ribosome to make protein however it made the rna no longer efficiently recognized by innate immune sensors such as toelic receptors now when rna is introduced into a cell not the normal weight coming out of the nucleus but from the outside it does trigger innate immunity it's a it's a sort of thing that a virus does and so this is the power of our antiviral defenses and the cell responds by shutting down expression and translation so by evading detection by these receptors as you can see in the graph on the left express in which rna is used to express luciferase the red line shows the expression level of luciferase with nucleoside modified rna in the blue line showing substantially lower expression from non-nucleoside modified rna and on the right you see interferon alpha production an indication of the inflammatory response and as you look from the unmodified and the left to in the middle the uh the pseudo methyl uh this is your pseudo urine and this not pseudomethyl uridine as we actually use in the vaccine you see much lower expression of this inflammatory mediator so not only do you have better expression it turns out it's better tolerated as well now this was not originally intended as a vaccine technology was intended as a technology to increase expression levels for example for therapeutic expression of proteins from rnas in the body and you can imagine that reducing innate immune responses might decrease image in a city but as it turns out the dominant effect is the increased expression and you actually get better adaptive immune responses when you quench the innate immune responses in this way next slide please there's another whole stream of science and really industrial application that went into this and that's depicted in very schematic form on this slide this slide comes from novartis and this was a glimpse of what happened during the 2009 pandemic where influenza cases peaked fell off and you can see the vaccine that was produced and delivered and you might think looking at this slide well look the vaccine started being delivered and the pandemic went away but that i'm afraid wouldn't actually be the case because you know there is no scale on that y-axis and in fact the number of vaccine doses delivered when that red line starts taking off was much too small to have had a significant impact on the pandemic which is not to say that the vaccine did not do some good it did particularly not in 2009 during the pandemic but during 2010 when the virus came back to the seasonal vaccine people at that time had time to get the vaccine and i'd note that this was not the first pandemic wave in 2009 this was the second pandemic wave the first occurring around spring break time and then the second occurring when everyone went back to school in the fall so not only did we miss the first pandemic wave we missed the second pandemic wave as well now during that time we had already tried some real uh innovation in how we could go faster and in fact i remember i was uh uh driving with my family to new york when i got the word from my boss who was in italy at the time that uh the uh uh virus had was now in san diego and the head of barta which is the u.s biomedical advanced research and

development authority had contacted my boss and we'd had a contract at that point for pandemic response he said well you need to deliver somewhere on the web but there the sequence has been posted now at that time the state of the art for starting a vaccine production was essentially to wait at the mailbox for someone to send you a virus someone from the who and in fact there's this large elaborate infrastructure global infrastructure to do surveillance to isolate viruses to make vaccine viruses for conventional flu vaccines we decided we're going to try something different then we're going to try to make the virus ourselves we tried to just synthesize it that didn't work but we could make it from cdna and actually we need to make it gmp as well at that time actually the experimentation had been done in rescuing viruses that the company had been a graduate student uh making viruses for most pathogenesis experiments but we used a laboratory for our collaborators the university of marburg in germany where they have a bsl4 laboratory and although it didn't need bsl4 containment that laboratory had the highly controlled circumstances that were very much like gmp or good manufacturing practice laboratories and as it turns out at about the same time that we received the virus from the world health organization we had not only rescued a virus ourselves but we had done so under close to gmp circumstances now we didn't end up using that virus when we since we had the virus that had the very standard provenance that had a much smoother regulatory path so we went with that but it taught us that if we could develop and make gmp a process to make our own viruses in the same amount of time we took the global system to send us a virus in the mail well if we weren't starting from scratch if we figured out how to do this couldn't we be much faster next slide please and so that led to a barta uh that same agency sponsored collaboration with the craig venter's group and we made a synthetic approach to generating flu seed viruses at the time you could either synthesize dna rapidly or you could synthesize it accurately but you really couldn't do both but really some of the innovation that came particularly from the vendor group was in how you could synthesize rapidly and accurately at the same time with enzymatic error correction and at the same time we had a separate stream of rna vaccine development not nucleoside modified rna but self-amplifying rna and these came together in a process that we developed under a barda contract and actually implemented because in 2013 there was a pre-pandemic outbreak it was h79 h7n9 outbreak in shanghai china again the chinese very promptly shared the data on this strain globally through gisid and we started synthesizing in fact in fact as i recall it was on easter sunday that we got the message and on monday our colleagues at the vendor group in california started synthesizing the genes on tuesday the genes had been synthesized uh uh actually says maybe maybe that was wednesday uh and uh i know it was tuesday uh it was shipped overnight to us in cambridge uh by fedex and by the next day we are starting to synthesize use the rna to rescue infectious virus and as a template to make rna by a week we actually had a sequence verified expression of the hemoglobin the virus we made went on to actually again back in back in germany in marburg to create the pre-pandemic vaccine that became part of the us pre-pandemic stockpile that was a pandemic that didn't happen it was scary but that one did not actually materialize but the rna that we made though it was an experimental batch not suitable for use in humans it actually contributed to that vaccine response because we needed to have antibodies against h7 um the a7 hemagglutinin and we got it by immunizing mice with that rna they produce the antibodies that we then use and you can see in that western blot on the right hand side on the bottom to detect that we had the right hemagglutinin being expressed from the vaccine virus that we that we generated also synthetically next slide please so that talks a little bit about how the technologies that went into the rna part of the uh vaccine and you can see that on the right uh and i won't go into great detail but it's a pretty standard rna except for the nucleoside modification another part of the technology that is extremely important is what you see on the left and that's the lip banana particle because if you just inject the rna it doesn't do that much you need to get it into cells and this lip and nanoparticle is another very fancy piece of biotechnology it it actually consists of four lipids they have different roles there's an ionizable amino lipid that changes its charge at different points in the production process and administration process so that at one point it encapsulates the rna it then protects it and then after uptake into cells fuses with the cell membrane after endocytosis to actually deliver the rna to cellularly a different rna makes up most of that outer layer with a another rna that is pegulated so that it's sort of shaggy and that coding helps preserve the particle when is the extracellular environment though it has to come off so it's actually designed to come off during uh for entry because the peg what preserves the particle extracellularly inhibits its uptake and finally the fourth lipid cholesterol is has a structural a bit of a lubricant keeping everything with with good physical properties so that's again another stream of technology about formulation science on how you actually deliver an rna molecule effectively right next slide there is another stream of technology that went to this as well and that's structural biology the notion that you could take viral vaccine antigens and engineer them to actually make them behave better not for the purpose of the virus in affecting for example cell entry but to function as vaccine antigens had its origin oh a decade or a decade a half ago and actually was sort of demonstrated to work initially with another virus respiratory systevirus these images show the real scientific breakthrough of jason mcclellan and his colleagues at the nih there had been 50 years of vaccine development against rsv with repeated failures and a key discovery was made through the breakthrough structure of a stabilized pre-fusion form of the protein because this vaccine antigen is in fact you almost think of it as a device that serves to fuse the viral envelope with the cell membrane to deliver viral rna into a cell and it does so by changing shape and i won't go into all the details of how it changes shape but suffice to say that on the far left is the pre-fusion structure the active form ready to attack a cell on the right hand side is the post fusion structure after it's done its job and you can see the molecule has turned itself inside out if you want to inhibit the function of the molecule thereby inhibiting the virus for example by binding an antibody to it you want to immunize with the thing on the left because there aren't that many patches of the thing on the right that are shared but the problem is it wants to flip so even if you have a fair amount of the stuff on the left in the beginning by the time it's in a vaccine vial it's all turned into the stuff in the right which doesn't work so well and what jason and his colleagues did was not only determine the structure but show that you could then use that structure to engineer stabilizing mutations to stabilize the structure on the left at pfizer we took that and we took it a step further on the next slide and i believe the next slide has some uh and the name animation oh it's good okay you can see it's you see it all there that's wonderful and in fact it was a huge effort to come up with an optimal structure we made more than 360 versions of that protein strength screened them for physical stability in the prefusion form coming up with our final candidate and when tested in monkeys the stabilized pre-fusion form in the graph on the right in blue elicited far higher neutralizing titers than the non-stabilized form which flipped to the post-fusion form as you can see in green and that vaccine is now in phase three trials uh really or in sites around the world being tested in pregnant women as a means to actually protect their infants by transferring antibodies transplacentally but that principle was applied also actually not initially for cyrus 2 but for one of its predecessors on the next slide you know we had two warning shots before this pandemic the first was sars kobe 1 the tsar's pandemic excuse me the stars stars epidemic they never became a pandemic because it was contained by conventional uh public health measures and then mers it was with mers the middle east respiratory syndrome virus that uh jason same guy jason and his team again applied their structural engineering you can see in that panel of electron micrographs down at the bottom on the left hand side you see at the top that long skinny rod and then the rest of it there's more globular kind of triangular molecules again it's a pre-fusion versus post-fusion transformation of a spike protein that affects entry of a virus the pre-fusion form is that more globular form that long skinny spike is part of the post region form the head kind of comes off of this molecule as it as it transforms and again the idea was to stabilize the pre-fusion form that was done by what you can see in the upper right that helix churn helix has to straighten out to go from pre-fusion to post-fusion by introducing prolines it was constrained so it could no longer do so stabilizing the prefusion form and in the graph on the lower right you can see the immune response solicited or the antibody response elicited in red by the pre-fusion stabilized form and in blue by the non-prefusion stabilized form and again you see that increase in immunogenicity so these are these multiple strains of technology that went in synthetic technology lipid formulation technology protein engineering um and now we come to how the clinical technologies uh that contribute to the vaccine development uh on the next slide we had two phase one studies one in germany led by our partners at beyond tech and the study in the us that would ultimately grow into the phase three study we applied principles that we'd used in our rsv vaccine development with very rapid large first in human studies with multiple arms to test many hypotheses simultaneously testing in younger and older adults testing as mentioned before multiple vaccine candidates multiple doses in an adaptive trial design in fact if we had more than 70 likes in the mid 70s the number of arms that that study would have had had we just tried to do everything without an adaptive component but we use the initial results that were facilitated by very rapid uh transportation of samples we we actually had i had a a plane that was devoted to getting the samples back and forth as fast as possible very rapid analysis so that we could take the initial results and adapt the study as we went and this required tremendous cooperation from the fda reviewing data reviewing modifications to plans very rapidly because of the the huge need to move quickly uh next slide please here's some of the data from that initial study these are neutralizing antibody titers elicited in purple on the left from 18 to 55 year olds and in blue on the right and those 65 to 85 years of age on the far right in gray are the antibody responses of people who actually had contracted infections with cyrus kobe 2 most of them simply symptomatic of cova 19 and what you can see is that in general the antibody responses to the vaccine are higher than the antibody responses actually listed by the virus itself and a very important point here that i'll come back to the vaccine was administered on days one and then again three weeks after that there's not much neutralizing antibody elicited before the second dose and so take note of that because it's key as we think about for example coverage of variance so it takes really two doses to get strong neutralizing antibody responses next slide please you also got very strong t cell responses in the light blue you have t cell responses from those who've been infected and in purple the t-cell responses from those have been immunized again the responses of those immunized of both t helper cells cd4 positive cells and toxic t cells cd8 positive cells are as great or in many cases greater than those elicited by infection next slide please the vaccine turned out to be tolerable with mild to moderate injection site pain some fevers and chills generally a greater reaction particularly for systemic reactions to the second dose than the first dose unfortunately lesser reactorgenicity in older adults who are perhaps depending on their overall health less able to tolerate a reactorgenic vaccine than younger adults but direct agency was reasonable and milder in older adults next slide gives a few details on well actually before we get to that um this study was a phase one two three study next slide and i'm not aware of any other vaccine trials that would have actually been phase one two three studies but this expanded from that initial part with an adapter design many groups do a very large study with the single final formulation and dose level let's start trial enrolled uh more than 46 000 participants and it is still ongoing today we'll follow um participants for two years and we are continuing to add arms that studies new questions arise and it was conducted at 153 locations around the world so a truly massive study we achieved good diversity both in terms of race and ethnicity in terms of age and in terms of underlying medical conditions next slide please and the results were actually there was a truly uh wonderful moment when we saw these results emerge when we unblinded uh for the fur the first unblinding in red on the graph are those who receive placebo and plotted is the cumulative incidence of covert 19. in blue are those who receive vaccine and as you can see for the first 12 days the two groups track each other and from that point on they diverge dramatically and i'll come back to the observation that they diverge at 12 days because recall even at 21 days there's very little neutralizing antibody present so we're seeing efficacy of the vaccine before there are high tides of neutralizing antibodies and what you see on the right is the actual vaccine efficacy and you see it's approximately 95 percent and that holds basically true to within a few percentage points across age ranges across racial and ethnic uh differences and is also true with a number of comorbidities so uh next slide please we got more data on reactogenicity we see pain at the injection site is reasonably common but mild to moderate in general not a lot of other local reactorgenicity next slide please systemic reactorgenicity you have the vaccine on the top placebo on the bottom also generally mild to moderate but you know people do feel somewhat fatigued and sometimes a bit of a headache some fever not a tremendous amount of fever but some fever less as you can see in older adults than younger adults and some chills but within the tolerable range and within the range of other vaccines in common use next slide one useful thing about directorgenesis is time course and that it's not that long you can see that for both younger and older adults it peaks on the day after immunization it's diminished substantially by two days after immunization and really is quite modest thereafter uh next slide so this leads us to the vaccine it is a two dose vaccine 30 micrograms per dose administered three weeks apart is indicated for the prevention of coven 19 in individuals 16 years of age and older it was rolled out as a five dose vial uh it turns out with a low dead volume syringe you can get six doses out of out of the vial and so that is how it's used now wherever uh uh people have access to the low low dead volume syringes uh it is distributed frozen uh it is distributed at the dry ice temperatures uh and then can be stored at the point of use for five days at ordinary refrigerator temperatures just recently we provided data package to the fda showing that in fact the vaccine also can be stored for two weeks at ordinary freezer temperatures which gives more flexibility in use and the fda has approved of the transportations and storage for two weeks uh at -20 in addition to these storage conditions this could be particularly useful in more rural areas or in parts of the world where maintaining in intense cold chain is difficult though the logistics group has done a remarkable job of being able to distribute associated distribution centers on dry ice uh with a very high success rate of delivering the vaccine in good condition uh to the sites of further distribution and next slide please now the vaccine campaign is underway and uh this slide has now been outdated uh it says that 12 million people in the us have received either one or two doses i i checked yesterday i think we're up to 14 million in the u.s and that is of course a fraction of the vaccine that's been produced much of it is being released is being uh vaccine campaigns are ongoing in the u.s and now in many other parts of the world uh as well to date the safety that we have seen with real world use is roughly the in fact very close to what we saw in the controlled phase three trial so uh we have not with widespread use seen a major change in the safety profile and in general most of the reactions that are seen after the rule of a vaccine or types of reactions are recognized within two to three months of vaccine rollout so we're getting past the point where is likely that new effects will be discovered because most of them just from historically have have turned up in the first two to three months after rollout all right next slide please so i'd like to say a few words about the emerging variants and obviously uh there's been a lot written about these among them are the uk variant uh the south african variant and the brazilian variant the virus does change over time it does accumulate mutation including some at the receptive binding site which is thought to be an important target for neutralizing antibodies but data i'll show make me optimistic that while we do need to prepare for the potential emergence of a variant that does escape vaccinated immunity it's not clear to me that we've seen that variant yet and i'll show you why on the next slide um these uh and are some real world effectiveness data from israel where they have rolled out the vaccine very effectively with a very high proportion of those in their 60s and above immunize and a good proportion of those below their 60s as well and i apologize for the small print um but we can see how is the vaccine doing with real world use and in israel most of the virus circulating is the uk variant you can see along the bottom row um against documented infection we have a 92 percent efficacy against symptomatic illness 94 against hospitalization 87 percent and against severe disease and it's a little small informatory here i believe it's 92 percent again um numbers very similar to what we're seeing in the controlled phase 3 trial and by the way these are data taken not so long after that second dose is rolled out so it is possible that they could even improve further with further observation as you give more time for the vaccine immediate immune response to develop and this tells you that in fact the vaccine covers the uk variant very well on the next slide we have some in vitro neutralization data versus the uk rather the south african variant on the right in red versus neutralization of the baseline this is the washington uh strain the one one of the first strings introduced to the u.s

on the left and there is a decrease in neutralization however every serum of of bnt 162 b2 immunized people each of those sera neutralizes the virus and it's important to note that the level of neutralization you see against the south african variant on the right is substantially higher than the level of neutralization seen after the first dose of vaccine where we saw protection in our phase 3 trial so we think it is likely that the vaccine will protect against even the south african variant which is the most distant variant that we have thus far though we need clinical data to be sure laboratory measures of immunity can give you clues as to what a clinical efficacy will be but you do have to actually make clinical observations to be sure even though we think it is likely that the vaccine will cover we need to be prepared because we now know this virus is changing and it's changing in ways that that do affect immune responses and so we are in fact making a uh a what we call a prototype vaccine to a variant strain and advancing that to at least a phase one safety and immunogenicity trial not because we think we need to change right now but because we need to demonstrate what a change looks like we have to go through the manufacturing steps see clinically what does uh how does the new vaccine behave and also smooth the regulatory path so that if a new variant emerges and we need to move fast we have everything in place to move very quickly taking advantage of the flexibility of the rna platform to make an updated vaccine next slide please and we also have another uh card to play and this comes from findings back from pre-pandemic studies with h5n1 highly pathogenic avian fluid in the graphs on the left you see the immune response to primary immunization sure that that wasn't h5 and one that was h5n3 so uh steering from quite some time back and you see that after the two doses indicated by the arrows you get a modest immune response just touching that dotted line which indicates the 1 to 40 uh neutralization threshold that people believe may be protective but if you come back years later with a booster dose or in this case two booster doses you can see in the middle and right hand graphs you get rapid and far higher immune responses and as it turns out those responses are very broad covering many strains so one possibility is that if you come back months later with a booster dose for sars kobe 2 you'll also get a very high and broad response we won't know until we test so we will be testing with both boosting with the updated variant and also with the original variant so we start to understand what are the rules of immunity for immunization including booster doses and variant immunization for cyrus kobe 2 as we have learned them for flu uh next slide please so based on this we think there's tremendous promise for the rna vaccine platform and we're eager to see what can be done certainly going back to flu to see how it does for flu vaccines next slide please and so our immediate goals are of course to continue ramping up production we've gone from the original projection of 1.3 billion doses produced this year to 2 billion doses and then time now but you know we have a network of manufacturing sites across the us and europe that are working together to increase production and we're continuing to get higher yields per batch be able to make more batches per unit time and exceeding our original production targets developing new formulations trying to get to the point where we no longer have to freeze the vaccine perhaps by doing things such as freeze drying in the plant so that the distributive vaccine doesn't need to be frozen we're exploring as i mentioned boosting for durability potentially for breath we're studying additional populations the vaccine is now being tested in adolescence from 12 up it's being tested in pregnant women we'll soon be starting a study in children under the age of 12 and of course preparing for the possibility that an emerging strain could require a vaccine update it may or may not well we will have to see uh next slide i'd let you can oh well this really does get us towards a vision i'm able to use these technologies to monitor viral outbreaks through widespread sequencing to exchange data rapidly through the internet rather than shipping viruses through the mail to synthesize our vaccines and then to have widely distributed manufacturing so that we have uh the ability to respond much more rapidly and maybe start to catch pandemics in the first waves rather than in the second or subsequent waves and then the final slide there's just there are many people to think of course the clinical many many clinical trial participants and their families the investigators and contract research organizations and other partners who've helped us develop the vaccine the government and regulatory authorities who have been working as hard as we are operation warp speed has been for us a place to exchange knowledge um and of course the many colleagues at beyond tech advisor who have been really working around the clock over this past year to deliver the vaccine and who are now particularly manufacturing sites working to get the vaccine produced and distributed also so thanks very much and that uh baby happy to take some questions all right thank you dr dormitor we do have a we do have a handful of questions and we would encourage our attendees if you're following us on social media live you can put those in the comments section and that will show show to us or you can follow your instructions for submission from your registration as well so give me just a moment we'll tee up our questions make sure we're ready to go here so doctor dormitory with with these emerging strains and and of course your extensive background in in vaccines you could you elaborate a little bit more for us you gave us certainly some hints but as a as a community um what what what does our future hold uh with with kovid as with the knowledge we have at this point so are you easy to predict everything uh but the future uh um but uh there there's some there's some sort of different possibilities you can play out one is the possibility that immunity turns out to be durable and broad either to the vaccine or to natural infection and that this becomes like the seasonal coronaviruses an annoyance but not that big a deal and if a vaccine is needed it'd be a pediatric vaccine a middle possibility is that this is a becomes a virus that needs a boost every few years and the rate of change starts to slow down and this becomes something more like pneumococcus where every number of years you need either a booster or or or a an updated uh vaccine that covers the the variants that have emerged the third possibility is it turns out to be like flu where it's constantly changing and every year you're updating and having to repeat immunize if i were to guess i would think it's more likely to be not quite like fluke chronoviruses are different they have a much lower rate of change i'm surprised by how much change we've seen and i wonder how much of it is really being driven by immunity and how much is being driven by this virus still adapting to growth in humans um so we'll find out i think the key is we're going to be we're going to be uh but we're going to be prepared uh for whatever it is we have to do well certainly that preparedness is is going to be important for us moving moving forward some reason i don't know if you can still hear me yes sir you can still hear me so this is a problem on my end well that would be disappointing uh if i can no longer hear you let me see what's going on here can you can you hear me there dr dormitor now i hear you yes okay wonderful wonderful all right so for our next question talk to us a little bit and you certainly covered some of this in the in the presentation but is there anything more to add on how how has the development process for cova 19 been different and how does that change us for both obviously you're coming coming to us from the college of veterinary medicine so those of us in in animal health are just as interested in in these technologies as well and really from a one health aspect where where does that lead us but how is this development process been different and how do you see that uh being implemented moving forward yeah so you know in in veterinary medicine and veterinary vaccines you've been doing this stuff for a long time i mean veterinary vaccines are wonderful because the things that in human vaccines you just talk about are being done in in veterinary vaccines i mean for example nucleic acid immunization is nothing new in veterinary vaccines there's a salmon vaccine that's been out for a long time uh that that's used uh uh dna technology and i believe that there are swine vaccines that are actually tailored to the individual farm with some rapid response to the specific strain in the specific facility so uh to some degree uh we in human medicine we're learning from what has been done in veterinary medicine um certainly the notion that when you have to you can do things in parallel use adaptive clinical trial designs um do things at risk are things that can be done in the future if necessary uh i know i don't have an illusion that all vaccine development will look like this because this has required a singular focus not just of the company but of regulators and others a kind of intensity of focus that in ordinary times can't be done because it means you have to not do a lot of other things in order to do this so an important point is no step steps have been skipped things have been done in parallel things have been done efficiently decision making has been accelerated there's been a very rapid cycle of turning around data and having it reviewed um so the steps are all being done but what we've shown is when it's really an emergency things can be done rapidly in parallel and not waiting for one step to finish before starting the next step for example scaling up manufacturing before you even know that the vaccine works which is of course a huge financial risk to build a whole manufacturing infrastructure before you know the vaccine works but this was a situation that called for that kind of response absolutely absolutely you mentioned uh you know we're we're here with with interact and we're particularly uh interested in you know our our institute here is for translational and emerging research in advanced comparative therapy hence our acronym interact but are there mechanisms where human and animal health collaborations can occur more readily in your opinion well yes i mean i certainly think of pandemic preparedness and and certainly for for flu understanding the uh both wild and domesticated uh poultry disease transmission as well as in swine is tremendously important and you know the epidemiology has not received the same level of attention that the epidemiology of the viruses in humans has but it's clear that not only is when it comes to virology it's sort of the global community we need we need to worry about because what is circulating elsewhere comes to us is absolutely true that the the animal community particularly animals with which we interact most are they we share we share our viruses with them so that human health and the animal health are intimately linked i have one i think we have time for i'm looking at the clock here one more question for you and and i will say on on behalf of someone that has family members that are now vaccinated thanks to uh the beyond tech team and pfizer we cannot say uh thank you enough and express our our appreciation for the efforts that undoubtedly have been round the clock with probably uh long long evenings and few weekends so with that tell us a little bit more about beyond tech what's distinguishing pfizer beyond tech from from other leading vaccine technologies and and where perhaps do we go go from here yeah so you know the partnership with beyond tech has been terrific i think beyond tech has been an ecology origin company a company that has been very innovative open to ideas and has that new nimbleness and innovative spirit that comes with biotech uh pfizer it's a very large pharmaceutical company has tremendous capabilities and i've been frankly amazed at how quickly and nimbly it can move because normally these giant institutions are it's kind of like turning an aircraft carrier but in this case it has moved quickly and we've been able to combine the strengths of the sort of very innovative spirit of beyond tech uh the capabilities and and and you know under albert barula who's the ceo the willingness to take a risk on saying we're going to just do whatever it takes to respond to this pandemic and so i think the final element of it is that the teamwork was established before the pandemic and so our research and development teams have been working together for about a year and a half at the time that the pandemic hit so we already knew how to work together we knew each other very well we trusted each other and that really has enabled us to work together as a very effective team well dr dormitzer on on behalf of oklahoma state university and and president hargis the college of veterinary medicine and and dean risco and of course our interact team here led by dr ron john we want to thank you again for for joining us today we have i apologize to our attendees we're we're limited with our time we have but as dr ron john said in his message hopefully we can have you back here in stillwater oklahoma at oklahoma state in person in in short order i think is everyone's goal and because we have definitely some continued interest on behalf of our faculty as well as uh those of us that excuse me those that have joined us today as far as attendance so thank you again please express our thanks and appreciation to the beyond tech team and and pfizer as a whole for their their monumental effort in in this pandemic response uh we do want to encourage our attendees to to stay tuned for more interact presentations and dr dorman so i don't think we could have uh had a better speaker today for our inaugural event and so thanks again we do encourage folks to take a look at our social media outlets as well as follow us on online at under research you can find our interact link you can be monitoring there for future presentations uh our team is already already hard at work at getting those lined out for hopefully comparable speakers to doctor dormitory that will be a hard a hard measure to reach i am sure but dr dormitzer again thanks so much and we again want to have you back in stillwater soon we'll share some orange power with you on on behalf of our cowboys here and again thanks to all those who have taken the time to join us it will be uh available at oh state tv for those that would like to to watch it again and with that i think we will will sign off for the day and hope everyone has a fantastic fantastic week and this wonderful start to march so thanks again dr dormitzer

2021-03-06 16:49

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